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Example sentences clinical presentation

Definition of 'clinical' clinical.

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Definition of 'present' present

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Tools for the Patient Presentation

The formal patient presentation.

  • Posing the Clinical Question
  • Searching the Medical Literature for EBM

Sources & Further Reading

First Aid for the Wards

Lingard L, Haber RJ.  Teaching and learning communications in medicine: a rhetorical approach .  Academic Medicine. 74(5):507-510 1999 May.

Lingard L, Haber RJ.  What do we mean by "relevance"? A clinical and rhetorical definition with implications for teaching and learning the case-presentation format . Academic Medicine. 74(10):S124-S127.

The Oral Presentation (A Practical Guide to Clinical Medicine, UCSD School of Medicine)  http://meded.ucsd.edu/clinicalmed/oral.htm

"Classically, the formal oral presentation is given in 7 minutes or less. Although it follows the same format as a written report, it is not simply regurgitation. A great presentation requires style as much as substance; your delivery must be succinct and smooth. No time should be wasted on superfluous information; one can read about such matters later in your admit note. Ideally, your presentation should be formulated so that your audience can anticipate your assessment and plan; that is, each piece of information should clue the listener into your thinking process and your most likely diagnosis."  [ Le, et al, p. 15 ]

Types of Patient Presentations

New Patient

New patients get the traditional H&P with assessment and plan.  Give the chief complaint and a brief and pertinent HPI.  Next give important PMH, PSH, etc.  The ROS is often left out, as anything important was in the HPI.  The PE is reviewed.  Only give pertinent positives and negatives.  The assessment and plan should include what you think is wrong and, briefly, why.  Then, state what you plan to do for the patient, including labs.  Be sure to know why things are being done: you will be asked.

The follow-up presentation differs from the presentation of a new patient.  It is an abridged presentation, perhaps referencing major patient issues that have been previously presented, but focusing on new information about these issues and/or what has changed. Give the patient’s name, age, date of admission, briefly review the present illness, physical examination and admitting diagnosis.  Then report any new finding, laboratory tests, diagnostic procedures and changes in medications.

The attending physician will ask the patient’s permission to have the medical student present their case.  After making the proper introductions the attending will let the patient know they may offer input or ask questions at any point.  When presenting at bedside the student should try to involve the patient.

Preparing for the Presentation

There are four things you must consider before you do your oral presentation

  • Occasion (setting and circumstances)

Ask yourself what do you want the presentation to do

  • Present a new patient to your preceptor : the amount of detail will be determined by your preceptor.  It is also likely to reflect your development and experience, with less detail being required as you progress.
  • Present your patient at working or teaching rounds : the amount of detail will be determined by the customs of the group. The focus of the presentation will be influenced by the learning objectives of working responsibilities of the group.
  • Request a consultant’s advice on a clinical problem : the presentation will be focused on the clinical question being posed to the consultant.
  • Persuade others about a diagnosis and plan : a shorter presentation which highlights the pertinent positives and negatives that are germane to the diagnosis and/or plan being suggested.
  • Enlist cooperation required for patient care : a short presentation focusing on the impact your audience can have in addressing the patient’s issues.

Preparation

  • Patient evaluation : history, physical examination, review of tests, studies, procedures, and consultants’ recommendations.
  • Selected reading : reference texts; to build a foundational understanding.
  • Literature search : for further elucidation of any key references from selected reading, and to bring your understanding up to date, since reference text information is typically three to seven years old.
  • Write-up : for oral presentation, just succinct notes to serve as a reminder or reference, since you’re not going to be reading your presentation.

Knowledge (Be prepared to answer questions about the following)

  • Pathophysiology
  • Complications
  • Differential diagnosis
  • Course of conditions
  • Diagnostic tests
  • Medications
  • Essential Evidence Plus

Template for Oral Presentations

Chief Complaint (CC)

The opening statement should give an overview of the patient, age, sex, reason for visit and the duration of the complaint. Give marital status, race, or occupation if relevant.  If your patient has a history of a major medical problem that bears strongly on the understanding of the present illness, include it.  For ongoing care, give a one sentence recap of the history.

History of Present Illness (HPI)

This will be very similar to your written HPI. Present the most important problem first. If there is more than one problem, treat each separately. Present the information chronologically.  Cover one system before going onto the next. Characterize the chief complaint – quality, severity, location, duration, progression, and include pertinent negatives. Items from the ROS that are unrelated to the present problem may be mentioned in passing unless you are doing a very formal presentation. When you do your first patient presentation you may be expected to go into detail.  For ongoing care, present any new complaints.

Review of Systems (ROS)

Most of the ROS is incorporated at the end of the HPI. Items that are unrelated to the present problem may be briefly mentioned.  For ongoing care, present only if new complaints.  

Past Medical History (PMH)

Discuss other past medical history that bears directly on the current medical problem.  For ongoing care, have the information available to respond to questions.

Past Surgical History

Provide names of procedures, approximate dates, indications, any relevant findings or complications, and pathology reports, if applicable.  For ongoing care, have the information available to respond to questions.

Allergies/Medications

Present all current medications along with dosage, route and frequency. For the follow-up presentation just give any changes in medication.  For ongoing care, note any changes.

Smoking and Alcohol (and any other substance abuse)

Note frequency and duration. For ongoing care, have the information available to respond to questions.

Social/Work History

Home, environment, work status and sexual history.  For ongoing care, have the information available to respond to questions.

Family History Note particular family history of genetically based diseases.  For ongoing care, have the information available to respond to questions.

Physical Exam/Labs/Other Tests

Include all significant abnormal findings and any normal findings that contribute to the diagnosis. Give a brief, general description of the patient including physical appearance. Then describe vital signs touching on each major system. Try to find out in advance how thorough you need to be for your presentation. There are times when you will be expected to give more detail on each physical finding, labs and other test results.  For ongoing care, mention only further positive findings and relevant negative findings.

Assessment and Plan

Give a summary of the important aspects of the history, physical exam and formulate the differential diagnosis. Make sure to read up on the patient’s case by doing a search of the literature. 

  • Include only the most essential facts; but be ready to answer ANY questions about all aspects of your patient.
  • Keep your presentation lively.
  • Do not read the presentation!
  • Expect your listeners to ask questions.
  • Follow the order of the written case report.
  • Keep in mind the limitation of your listeners.
  • Beware of jumping back and forth between descriptions of separate problems.
  • Use the presentation to build your case.
  • Your reasoning process should help the listener consider a differential diagnosis.
  • Present the patient as well as the illness .
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Overview and General Information about Oral Presentation

  • Daily Presentations During Work Rounds
  • The New Patient Presentation
  • The Holdover Admission Presentation
  • Outpatient Clinic Presentations
  • The structure of presentations varies from service to service (e.g. medicine vs. surgery), amongst subspecialties, and between environments (inpatient vs. outpatient). Applying the correct style to the right setting requires that the presenter seek guidance from the listeners at the outset.
  • Time available for presenting is rather short, which makes the experience more stressful.
  • Individual supervisors (residents, faculty) often have their own (sometimes quirky) preferences regarding presentation styles, adding another layer of variability that the presenter has to manage.
  • Students are evaluated/judged on the way in which they present, with faculty using this as one way of gauging a student’s clinical knowledge.
  • Done well, presentations promote efficient, excellent care. Done poorly, they promote tedium, low morale, and inefficiency.

General Tips:

  • Practice, Practice, Practice! Do this on your own, with colleagues, and/or with anyone who will listen (and offer helpful commentary) before you actually present in front of other clinicians. Speaking "on-the-fly" is difficult, as rapidly organizing and delivering information in a clear and concise fashion is not a naturally occurring skill.
  • Immediately following your presentations, seek feedback from your listeners. Ask for specifics about what was done well and what could have been done better – always with an eye towards gaining information that you can apply to improve your performance the next time.
  • Listen to presentations that are done well – ask yourself, “Why was it good?” Then try to incorporate those elements into your own presentations.
  • Listen to presentations that go poorly – identify the specific things that made it ineffective and avoid those pitfalls when you present.
  • Effective presentations require that you have thought through the case beforehand and understand the rationale for your conclusions and plan. This, in turn, requires that you have a good grasp of physiology, pathology, clinical reasoning and decision-making - pushing you to read, pay attention, and in general acquire more knowledge.
  • Think about the clinical situation in which you are presenting so that you can provide a summary that is consistent with the expectations of your audience. Work rounds, for example, are clearly different from conferences and therefore mandate a different style of presentation.
  • Presentations are the way in which we tell medical stories to one another. When you present, ask yourself if you’ve described the story in an accurate way. Will the listener be able to “see” the patient the same way that you do? Can they come to the correct conclusions? If not, re-calibrate.
  • It's O.K. to use notes, though the oral presentation should not simply be reduced to reading the admission note – rather, it requires appropriate editing/shortening.
  • In general, try to give your presentations on a particular service using the same order and style for each patient, every day. Following a specific format makes it easier for the listener to follow, as they know what’s coming and when they can expect to hear particular information. Additionally, following a standardized approach makes it easier for you to stay organized, develop a rhythm, and lessens the chance that you’ll omit elements.

Specific types of presentations

There are a number of common presentation-types, each with its own goals and formats. These include:

  • Daily presentations during work rounds for patients known to a service.
  • Newly admitted patients, where you were the clinician that performed the H&P.
  • Newly admitted patients that were “handed off” to the team in the morning, such that the H&P was performed by others.
  • Outpatient clinic presentations, covering several common situations.

Key elements of each presentation type are described below. Examples of how these would be applied to most situations are provided in italics. The formats are typical of presentations done for internal medicine services and clinics.

Note that there is an acceptable range of how oral presentations can be delivered. Ultimately, your goal is to tell the correct story, in a reasonable amount of time, so that the right care can be delivered. Nuances in the order of presentation, what to include, what to omit, etc. are relatively small points. Don’t let the pursuit of these elements distract you or create undue anxiety.

Daily presentations during work rounds of patients that you’re following:

  • Organize the presenter (forces you to think things through)
  • Inform the listener(s) of 24 hour events and plan moving forward
  • Promote focused discussion amongst your listeners and supervisors
  • Opportunity to reassess plan, adjust as indicated
  • Demonstrate your knowledge and engagement in the care of the patient
  • Rapid (5 min) presentation of the key facts

Key features of presentation:

  • Opening one liner: Describe who the patient is, number of days in hospital, and their main clinical issue(s).
  • 24-hour events: Highlighting changes in clinical status, procedures, consults, etc.
  • Subjective sense from the patient about how they’re feeling, vital signs (ranges), and key physical exam findings (highlighting changes)
  • Relevant labs (highlighting changes) and imaging
  • Assessment and Plan : Presented by problem or organ systems(s), using as many or few as are relevant. Early on, it’s helpful to go through the main categories in your head as a way of making sure that you’re not missing any relevant areas. The broad organ system categories include (presented here head-to-toe): Neurological; Psychiatric; Cardiovascular; Pulmonary; Gastrointestinal; Renal/Genitourinary; Hematologic/Oncologic; Endocrine/Metabolic; Infectious; Tubes/lines/drains; Disposition.

Example of a daily presentation for a patient known to a team:

  • Opening one liner: This is Mr. Smith, a 65 year old man, Hospital Day #3, being treated for right leg cellulitis
  • MRI of the leg, negative for osteomyelitis
  • Evaluation by Orthopedics, who I&D’d a superficial abscess in the calf, draining a moderate amount of pus
  • Patient appears well, states leg is feeling better, less painful
  • T Max 101 yesterday, T Current 98; Pulse range 60-80; BP 140s-160s/70-80s; O2 sat 98% Room Air
  • Ins/Outs: 3L in (2 L NS, 1 L po)/Out 4L urine
  • Right lower extremity redness now limited to calf, well within inked lines – improved compared with yesterday; bandage removed from the I&D site, and base had small amount of purulence; No evidence of fluctuance or undrained infection.
  • Creatinine .8, down from 1.5 yesterday
  • WBC 8.7, down from 14
  • Blood cultures from admission still negative
  • Gram stain of pus from yesterday’s I&D: + PMNS and GPCs; Culture pending
  • MRI lower extremity as noted above – negative for osteomyelitis
  • Continue Vancomycin for today
  • Ortho to reassess I&D site, though looks good
  • Follow-up on cultures: if MRSA, will transition to PO Doxycycline; if MSSA, will use PO Dicloxacillin
  • Given AKI, will continue to hold ace-inhibitor; will likely wait until outpatient follow-up to restart
  • Add back amlodipine 5mg/d today
  • Hep lock IV as no need for more IVF
  • Continue to hold ace-I as above
  • Wound care teaching with RNs today – wife capable and willing to assist. She’ll be in this afternoon.
  • Set up follow-up with PMD to reassess wound and cellulitis within 1 week

The Brand New Patient (admitted by you)

  • Provide enough information so that the listeners can understand the presentation and generate an appropriate differential diagnosis.
  • Present a thoughtful assessment
  • Present diagnostic and therapeutic plans
  • Provide opportunities for senior listeners to intervene and offer input
  • Chief concern: Reason why patient presented to hospital (symptom/event and key past history in one sentence). It often includes a limited listing of their other medical conditions (e.g. diabetes, hypertension, etc.) if these elements might contribute to the reason for admission.
  • The history is presented highlighting the relevant events in chronological order.
  • 7 days ago, the patient began to notice vague shortness of breath.
  • 5 days ago, the breathlessness worsened and they developed a cough productive of green sputum.
  • 3 days ago his short of breath worsened to the point where he was winded after walking up a flight of stairs, accompanied by a vague right sided chest pain that was more pronounced with inspiration.
  • Enough historical information has to be provided so that the listener can understand the reasons that lead to admission and be able to draw appropriate clinical conclusions.
  • Past history that helps to shed light on the current presentation are included towards the end of the HPI and not presented later as “PMH.” This is because knowing this “past” history is actually critical to understanding the current complaint. For example, past cardiac catheterization findings and/or interventions should be presented during the HPI for a patient presenting with chest pain.
  • Where relevant, the patient's baseline functional status is described, allowing the listener to understand the degree of impairment caused by the acute medical problem(s).
  • It should be explicitly stated if a patient is a poor historian, confused or simply unaware of all the details related to their illness. Historical information obtained from family, friends, etc. should be described as such.
  • Review of Systems (ROS): Pertinent positive and negative findings discovered during a review of systems are generally incorporated at the end of the HPI. The listener needs this information to help them put the story in appropriate perspective. Any positive responses to a more inclusive ROS that covers all of the other various organ systems are then noted. If the ROS is completely negative, it is generally acceptable to simply state, "ROS negative.”
  • Other Past Medical and Surgical History (PMH/PSH): Past history that relates to the issues that lead to admission are typically mentioned in the HPI and do not have to be repeated here. That said, selective redundancy (i.e. if it’s really important) is OK. Other PMH/PSH are presented here if relevant to the current issues and/or likely to affect the patient’s hospitalization in some way. Unrelated PMH and PSH can be omitted (e.g. if the patient had their gall bladder removed 10y ago and this has no bearing on the admission, then it would be appropriate to leave it out). If the listener really wants to know peripheral details, they can read the admission note, ask the patient themselves, or inquire at the end of the presentation.
  • Medications and Allergies: Typically all meds are described, as there’s high potential for adverse reactions or drug-drug interactions.
  • Family History: Emphasis is placed on the identification of illnesses within the family (particularly among first degree relatives) that are known to be genetically based and therefore potentially heritable by the patient. This would include: coronary artery disease, diabetes, certain cancers and autoimmune disorders, etc. If the family history is non-contributory, it’s fine to say so.
  • Social History, Habits, other → as relates to/informs the presentation or hospitalization. Includes education, work, exposures, hobbies, smoking, alcohol or other substance use/abuse.
  • Sexual history if it relates to the active problems.
  • Vital signs and relevant findings (or their absence) are provided. As your team develops trust in your ability to identify and report on key problems, it may become acceptable to say “Vital signs stable.”
  • Note: Some listeners expect students (and other junior clinicians) to describe what they find in every organ system and will not allow the presenter to say “normal.” The only way to know what to include or omit is to ask beforehand.
  • Key labs and imaging: Abnormal findings are highlighted as well as changes from baseline.
  • Summary, assessment & plan(s) Presented by problem or organ systems(s), using as many or few as are relevant. Early on, it’s helpful to go through the main categories in your head as a way of making sure that you’re not missing any relevant areas. The broad organ system categories include (presented here head-to-toe): Neurological; Psychiatric; Cardiovascular; Pulmonary; Gastrointestinal; Renal/Genitourinary; Hematologic/Oncologic; Endocrine/Metabolic; Infectious; Tubes/lines/drains; Disposition.
  • The assessment and plan typically concludes by mentioning appropriate prophylactic considerations (e.g. DVT prevention), code status and disposition.
  • Chief Concern: Mr. H is a 50 year old male with AIDS, on HAART, with preserved CD4 count and undetectable viral load, who presents for the evaluation of fever, chills and a cough over the past 7 days.
  • Until 1 week ago, he had been quite active, walking up to 2 miles a day without feeling short of breath.
  • Approximately 1 week ago, he began to feel dyspneic with moderate activity.
  • 3 days ago, he began to develop subjective fevers and chills along with a cough productive of red-green sputum.
  • 1 day ago, he was breathless after walking up a single flight of stairs and spent most of the last 24 hours in bed.
  • Diagnosed with HIV in 2000, done as a screening test when found to have gonococcal urethritis
  • Was not treated with HAART at that time due to concomitant alcohol abuse and non-adherence.
  • Diagnosed and treated for PJP pneumonia 2006
  • Diagnosed and treated for CMV retinitis 2007
  • Became sober in 2008, at which time interested in HAART. Started on Atripla, a combination pill containing: Efavirenz, Tonofovir, and Emtricitabine. He’s taken it ever since, with no adverse effects or issues with adherence. Receives care thru Dr. Smiley at the University HIV clinic.
  • CD4 count 3 months ago was 400 and viral load was undetectable.
  • He is homosexual though he is currently not sexually active. He has never used intravenous drugs.
  • He has no history of asthma, COPD or chronic cardiac or pulmonary condition. No known liver disease. Hepatitis B and C negative. His current problem seems different to him then his past episode of PJP.
  • Review of systems: negative for headache, photophobia, stiff neck, focal weakness, chest pain, abdominal pain, diarrhea, nausea, vomiting, urinary symptoms, leg swelling, or other complaints.
  • Hypertension x 5 years, no other known vascular disease
  • Gonorrhea as above
  • Alcohol abuse above and now sober – no known liver disease
  • No relevant surgeries
  • Atripla, 1 po qd
  • Omeprazole 20 mg, 1 PO, qd
  • Lisinopril 20mg, qd
  • Naprosyn 250 mg, 1-2, PO, BID PRN
  • No allergies
  • Both of the patient's parents are alive and well (his mother is 78 and father 80). He has 2 brothers, one 45 and the other 55, who are also healthy. There is no family history of heart disease or cancer.
  • Patient works as an accountant for a large firm in San Diego. He lives alone in an apartment in the city.
  • Smokes 1 pack of cigarettes per day and has done so for 20 years.
  • No current alcohol use. Denies any drug use.
  • Sexual History as noted above; has sex exclusively with men, last partner 6 months ago.
  • Seated on a gurney in the ER, breathing through a face-mask oxygen delivery system. Breathing was labored and accessory muscles were in use. Able to speak in brief sentences, limited by shortness of breath
  • Vital signs: Temp 102 F, Pulse 90, BP 150/90, Respiratory Rate 26, O2 Sat (on 40% Face Mask) 95%
  • HEENT: No thrush, No adenopathy
  • Lungs: Crackles and Bronchial breath sounds noted at right base. E to A changes present. No wheezing or other abnormal sounds noted over any other area of the lung. Dullness to percussion was also appreciated at the right base.
  • Cardiac: JVP less than 5 cm; Rhythm was regular. Normal S1 and S2. No murmurs or extra heart sounds noted.
  • Abdomen and Genital exams: normal
  • Extremities: No clubbing, cyanosis or edema; distal pulses 2+ and equal bilaterally.
  • Skin: no eruptions noted.
  • Neurological exam: normal
  • WBC 18 thousand with 10% bands;
  • Normal Chem 7 and LFTs.
  • Room air blood gas: pH of 7.47/ PO2 of 55/PCO2 of 30.
  • Sputum gram stain remarkable for an abundance of polys along with gram positive diplococci.
  • CXR remarkable for dense right lower lobe infiltrate without effusion.
  • Monitored care unit, with vigilance for clinical deterioration.
  • Hypertension: given significant pneumonia and unclear clinical direction, will hold lisinopril. If BP > 180 and or if clear not developing sepsis, will consider restarting.
  • Low molecular weight heparin
  • Code Status: Wishes to be full code full care, including intubation and ICU stay if necessary. Has good quality of life and hopes to return to that functional level. Wishes to reconsider if situation ever becomes hopeless. Older brother Tom is surrogate decision maker if the patient can’t speak for himself. Tom lives in San Diego and we have his contact info. He is aware that patient is in the hospital and plans on visiting later today or tomorrow.
  • Expected duration of hospitalization unclear – will know more based on response to treatment over next 24 hours.

The holdover admission (presenting data that was generated by other physicians)

  • Handoff admissions are very common and present unique challenges
  • Understand the reasons why the patient was admitted
  • Review key history, exam, imaging and labs to assure that they support the working diagnostic and therapeutic plans
  • Does the data support the working diagnosis?
  • Do the planned tests and consults make sense?
  • What else should be considered (both diagnostically and therapeutically)?
  • This process requires that the accepting team thoughtfully review their colleagues efforts with a critical eye – which is not disrespectful but rather constitutes one of the main jobs of the accepting team and is a cornerstone of good care *Note: At some point during the day (likely not during rounds), the team will need to verify all of the data directly with the patient.
  • 8-10 minutes
  • Chief concern: Reason for admission (symptom and/or event)
  • Temporally presented bullets of events leading up to the admission
  • Review of systems
  • Relevant PMH/PSH – historical information that might affect the patient during their hospitalization.
  • Meds and Allergies
  • Family and Social History – focusing on information that helps to inform the current presentation.
  • Habits and exposures
  • Physical exam, imaging and labs that were obtained in the Emergency Department
  • Assessment and plan that were generated in the Emergency Department.
  • Overnight events (i.e. what happened in the Emergency Dept. and after the patient went to their hospital room)? Responses to treatments, changes in symptoms?
  • How does the patient feel this morning? Key exam findings this morning (if seen)? Morning labs (if available)?
  • Assessment and Plan , with attention as to whether there needs to be any changes in the working differential or treatment plan. The broad organ system categories include (presented here head-to-toe): Neurological; Psychiatric; Cardiovascular; Pulmonary; Gastrointestinal; Renal/Genitourinary; Hematologic/Oncologic; Endocrine/Metabolic; Infectious; Tubes/lines/drains; Disposition.
  • Chief concern: 70 yo male who presented with 10 days of progressive shoulder pain, followed by confusion. He was brought in by his daughter, who felt that her father was no longer able to safely take care for himself.
  • 10 days ago, Mr. X developed left shoulder pain, first noted a few days after lifting heavy boxes. He denies falls or direct injury to the shoulder.
  • 1 week ago, presented to outside hospital ER for evaluation of left shoulder pain. Records from there were notable for his being afebrile with stable vitals. Exam notable for focal pain anteriorly on palpation, but no obvious deformity. Right shoulder had normal range of motion. Left shoulder reported as diminished range of motion but not otherwise quantified. X-ray negative. Labs remarkable for wbc 8, creat 2.2 (stable). Impression was that the pain was of musculoskeletal origin. Patient was provided with Percocet and told to see PMD in f/u
  • Brought to our ER last night by his daughter. Pain in shoulder worse. Also noted to be confused and unable to care for self. Lives alone in the country, home in disarray, no food.
  • ROS: negative for falls, prior joint or musculoskeletal problems, fevers, chills, cough, sob, chest pain, head ache, abdominal pain, urinary or bowel symptoms, substance abuse
  • Hypertension
  • Coronary artery disease, s/p LAD stent for angina 3 y ago, no symptoms since. Normal EF by echo 2 y ago
  • Chronic kidney disease stage 3 with creatinine 1.8; felt to be secondary to atherosclerosis and hypertension
  • aspirin 81mg qd, atorvastatin 80mg po qd, amlodipine 10 po qd, Prozac 20
  • Allergies: none
  • Family and Social: lives alone in a rural area of the county, in contact with children every month or so. Retired several years ago from work as truck driver. Otherwise non-contributory.
  • Habits: denies alcohol or other drug use.
  • Temp 98 Pulse 110 BP 100/70
  • Drowsy though arousable; oriented to year but not day or date; knows he’s at a hospital for evaluation of shoulder pain, but doesn’t know the name of the hospital or city
  • CV: regular rate and rhythm; normal s1 and s2; no murmurs or extra heart sounds.
  • Left shoulder with generalized swelling, warmth and darker coloration compared with Right; generalized pain on palpation, very limited passive or active range of motion in all directions due to pain. Right shoulder appearance and exam normal.
  • CXR: normal
  • EKG: sr 100; nl intervals, no acute changes
  • WBC 13; hemoglobin 14
  • Na 134, k 4.6; creat 2.8 (1.8 baseline 4 m ago); bicarb 24
  • LFTs and UA normal
  • Vancomycin and Zosyn for now
  • Orthopedics to see asap to aspirate shoulder for definitive diagnosis
  • If aspiration is consistent with infection, will need to go to Operating Room for wash out.
  • Urine electrolytes
  • Follow-up on creatinine and obtain renal ultrasound if not improved
  • Renal dosing of meds
  • Strict Ins and Outs.
  • follow exam
  • obtain additional input from family to assure baseline is, in fact, normal
  • Since admission (6 hours) no change in shoulder pain
  • This morning, pleasant, easily distracted; knows he’s in the hospital, but not date or year
  • T Current 101F Pulse 100 BP 140/80
  • Ins and Outs: IVF Normal Saline 3L/Urine output 1.5 liters
  • L shoulder with obvious swelling and warmth compared with right; no skin breaks; pain limits any active or passive range of motion to less than 10 degrees in all directions
  • Labs this morning remarkable for WBC 10 (from 13), creatinine 2 (down from 2.8)
  • Continue with Vancomycin and Zosyn for now
  • I already paged Orthopedics this morning, who are en route for aspiration of shoulder, fluid for gram stain, cell count, culture
  • If aspirate consistent with infection, then likely to the OR
  • Continue IVF at 125/h, follow I/O
  • Repeat creatinine later today
  • Not on any nephrotoxins, meds renaly dosed
  • Continue antibiotics, evaluation for primary source as above
  • Discuss with family this morning to establish baseline; possible may have underlying dementia as well
  • SC Heparin for DVT prophylaxis
  • Code status: full code/full care.

Outpatient-based presentations

There are 4 main types of visits that commonly occur in an outpatient continuity clinic environment, each of which has its own presentation style and purpose. These include the following, each described in detail below.

  • The patient who is presenting for their first visit to a primary care clinic and is entirely new to the physician.
  • The patient who is returning to primary care for a scheduled follow-up visit.
  • The patient who is presenting with an acute problem to a primary care clinic
  • The specialty clinic evaluation (new or follow-up)

It’s worth noting that Primary care clinics (Internal Medicine, Family Medicine and Pediatrics) typically take responsibility for covering all of the patient’s issues, though the amount of energy focused on any one topic will depend on the time available, acuity, symptoms, and whether that issue is also followed by a specialty clinic.

The Brand New Primary Care Patient

Purpose of the presentation

  • Accurately review all of the patient’s history as well as any new concerns that they might have.
  • Identify health related problems that need additional evaluation and/or treatment
  • Provide an opportunity for senior listeners to intervene and offer input

Key features of the presentation

  • If this is truly their first visit, then one of the main reasons is typically to "establish care" with a new doctor.
  • It might well include continuation of therapies and/or evaluations started elsewhere.
  • If the patient has other specific goals (medications, referrals, etc.), then this should be stated as well. Note: There may well not be a "chief complaint."
  • For a new patient, this is an opportunity to highlight the main issues that might be troubling/bothering them.
  • This can include chronic disorders (e.g. diabetes, congestive heart failure, etc.) which cause ongoing symptoms (shortness of breath) and/or generate daily data (finger stick glucoses) that should be discussed.
  • Sometimes, there are no specific areas that the patient wishes to discuss up-front.
  • Review of systems (ROS): This is typically comprehensive, covering all organ systems. If the patient is known to have certain illnesses (e.g. diabetes), then the ROS should include the search for disorders with high prevalence (e.g. vascular disease). There should also be some consideration for including questions that are epidemiologically appropriate (e.g. based on age and sex).
  • Past Medical History (PMH): All known medical conditions (in particular those requiring ongoing treatment) are listed, noting their duration and time of onset. If a condition is followed by a specialist or co-managed with other clinicians, this should be noted as well. If a problem was described in detail during the “acute” history, it doesn’t have to be re-stated here.
  • Past Surgical History (PSH): All surgeries, along with the year when they were performed
  • Medications and allergies: All meds, including dosage, frequency and over-the-counter preparations. Allergies (and the type of reaction) should be described.
  • Social: Work, hobbies, exposures.
  • Sexual activity – may include type of activity, number and sex of partner(s), partner’s health.
  • Smoking, Alcohol, other drug use: including quantification of consumption, duration of use.
  • Family history: Focus on heritable illness amongst first degree relatives. May also include whether patient married, in a relationship, children (and their ages).
  • Physical Exam: Vital signs and relevant findings (or their absence).
  • Key labs and imaging if they’re available. Also when and where they were obtained.
  • Summary, assessment & plan(s) presented by organ system and/or problems. As many systems/problems as is necessary to cover all of the active issues that are relevant to that clinic. This typically concludes with a “health care maintenance” section, which covers age, sex and risk factor appropriate vaccinations and screening tests.

The Follow-up Visit to a Primary Care Clinic

  • Organize the presenter (forces you to think things through).
  • Accurately review any relevant interval health care events that might have occurred since the last visit.
  • Identification of new symptoms or health related issues that might need additional evaluation and/or treatment
  • If the patient has no concerns, then verification that health status is stable
  • Review of medications
  • Provide an opportunity for listeners to intervene and offer input
  • Reason for the visit: Follow-up for whatever the patient’s main issues are, as well as stating when the last visit occurred *Note: There may well not be a “chief complaint,” as patients followed in continuity at any clinic may simply be returning for a visit as directed by their doctor.
  • Events since the last visit: This might include emergency room visits, input from other clinicians/specialists, changes in medications, new symptoms, etc.
  • Review of Systems (ROS): Depth depends on patient’s risk factors and known illnesses. If the patient has diabetes, then a vascular ROS would be done. On the other hand, if the patient is young and healthy, the ROS could be rather cursory.
  • PMH, PSH, Social, Family, Habits are all OMITTED. This is because these facts are already known to the listener and actionable aspects have presumably been added to the problem list (presented at the end). That said, these elements can be restated if the patient has a new symptom or issue related to a historical problem has emerged.
  • MEDS : A good idea to review these at every visit.
  • Physical exam: Vital signs and pertinent findings (or absence there of) are mentioned.
  • Lab and Imaging: The reason why these were done should be mentioned and any key findings mentioned, highlighting changes from baseline.
  • Assessment and Plan: This is most clearly done by individually stating all of the conditions/problems that are being addressed (e.g. hypertension, hypothyroidism, depression, etc.) followed by their specific plan(s). If a new or acute issue was identified during the visit, the diagnostic and therapeutic plan for that concern should be described.

The Focused Visit to a Primary Care Clinic

  • Accurately review the historical events that lead the patient to make the appointment.
  • Identification of risk factors and/or other underlying medical conditions that might affect the diagnostic or therapeutic approach to the new symptom or concern.
  • Generate an appropriate assessment and plan
  • Allow the listener to comment

Key features of the presentation:

  • Reason for the visit
  • History of Present illness: Description of the sequence of symptoms and/or events that lead to the patient’s current condition.
  • Review of Systems: To an appropriate depth that will allow the listener to grasp the full range of diagnostic possibilities that relate to the presenting problem.
  • PMH and PSH: Stating only those elements that might relate to the presenting symptoms/issues.
  • PE: Vital signs and key findings (or lack thereof)
  • Labs and imaging (if done)
  • Assessment and Plan: This is usually very focused and relates directly to the main presenting symptom(s) or issues.

The Specialty Clinic Visit

Specialty clinic visits focus on the health care domains covered by those physicians. For example, Cardiology clinics are interested in cardiovascular disease related symptoms, events, labs, imaging and procedures. Orthopedics clinics will focus on musculoskeletal symptoms, events, imaging and procedures. Information that is unrelated to these disciples will typically be omitted. It’s always a good idea to ask the supervising physician for guidance as to what’s expected to be covered in a particular clinic environment.

  • Highlight the reason(s) for the visit
  • Review key data
  • Provide an opportunity for the listener(s) to comment
  • 5-7 minutes
  • If it’s a consult, state the main reason(s) that the patient was referred as well as who referred them.
  • If it’s a return visit, state the reasons why the patient is being followed in the clinic and when the last visit took place
  • If it’s for an acute issue, state up front what the issue is Note: There may well not be a “chief complaint,” as patients followed in continuity in any clinic may simply be returning for a return visit as directed
  • For a new patient, this highlights the main things that might be troubling/bothering the patient.
  • For a specialty clinic, the history presented typically relates to the symptoms and/or events that are pertinent to that area of care.
  • Review of systems , focusing on those elements relevant to that clinic. For a cardiology patient, this will highlight a vascular ROS.
  • PMH/PSH that helps to inform the current presentation (e.g. past cardiac catheterization findings/interventions for a patient with chest pain) and/or is otherwise felt to be relevant to that clinic environment.
  • Meds and allergies: Typically all meds are described, as there is always the potential for adverse drug interactions.
  • Social/Habits/other: as relates to/informs the presentation and/or is relevant to that clinic
  • Family history: Focus is on heritable illness amongst first degree relatives
  • Physical Exam: VS and relevant findings (or their absence)
  • Key labs, imaging: For a cardiology clinic patient, this would include echos, catheterizations, coronary interventions, etc.
  • Summary, assessment & plan(s) by organ system and/or problems. As many systems/problems as is necessary to cover all of the active issues that are relevant to that clinic.
  • Reason for visit: Patient is a 67 year old male presenting for first office visit after admission for STEMI. He was referred by Dr. Goins, his PMD.
  • The patient initially presented to the ER 4 weeks ago with acute CP that started 1 hour prior to his coming in. He was found to be in the midst of a STEMI with ST elevations across the precordial leads.
  • Taken urgently to cath, where 95% proximal LAD lesion was stented
  • EF preserved by Echo; Peak troponin 10
  • In-hospital labs were remarkable for normal cbc, chem; LDL 170, hdl 42, nl lfts
  • Uncomplicated hospital course, sent home after 3 days.
  • Since home, he states that he feels great.
  • Denies chest pain, sob, doe, pnd, edema, or other symptoms.
  • No symptoms of stroke or TIA.
  • No history of leg or calf pain with ambulation.
  • Prior to this admission, he had a history of hypertension which was treated with lisinopril
  • 40 pk yr smoking history, quit during hospitalization
  • No known prior CAD or vascular disease elsewhere. No known diabetes, no family history of vascular disease; He thinks his cholesterol was always “a little high” but doesn’t know the numbers and was never treated with meds.
  • History of depression, well treated with prozac
  • Discharge meds included: aspirin, metoprolol 50 bid, lisinopril 10, atorvastatin 80, Plavix; in addition he takes Prozac for depression
  • Taking all of them as directed.
  • Patient lives with his wife; they have 2 grown children who are no longer at home
  • Works as a computer programmer
  • Smoking as above
  • ETOH: 1 glass of wine w/dinner
  • No drug use
  • No known history of cardiovascular disease among 2 siblings or parents.
  • Well appearing; BP 130/80, Pulse 80 regular, 97% sat on Room Air, weight 175lbs, BMI 32
  • Lungs: clear to auscultation
  • CV: s1 s2 no s3 s4 murmur
  • No carotid bruits
  • ABD: no masses
  • Ext; no edema; distal pulses 2+
  • Cath from 4 weeks ago: R dominant; 95% proximal LAD; 40% Cx.
  • EF by TTE 1 day post PCI with mild Anterior Hypokinesis, EF 55%, no valvular disease, moderate LVH
  • Labs of note from the hospital following cath: hgb 14, plt 240; creat 1, k 4.2, lfts normal, glucose 100, LDL 170, HDL 42.
  • EKG today: SR at 78; nl intervals; nl axis; normal r wave progression, no q waves
  • Plan: aspirin 81 indefinitely, Plavix x 1y
  • Given nitroglycerine sublingual to have at home.
  • Reviewed symptoms that would indicate another MI and what to do if occurred
  • Plan: continue with current dosages of meds
  • Chem 7 today to check k, creatinine
  • Plan: Continue atorvastatin 80mg for life
  • Smoking cessation: Doing well since discharge without adjuvant treatments, aware of supports.
  • Plan: AAA screening ultrasound

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INTRODUCTION

The definition, classification, etiology, and pathophysiology of shock are discussed in this review. The clinical presentation and diagnostic evaluation of undifferentiated shock and the evaluation of patients with specific forms of shock are discussed separately. (See "Evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock" and "Evaluation and management of suspected sepsis and septic shock in adults" and "Clinical manifestations and diagnosis of cardiogenic shock in acute myocardial infarction" and "Etiology, clinical manifestations, and diagnosis of volume depletion in adults" and "Approach to shock in the adult trauma patient" and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism" .)

EPIDEMIOLOGY

In the emergency department (ED), the percentage of each type of shock seen depends upon the population served by the ED [ 3,4 ]. As an example, busy, urban, level-I trauma centers will see a higher percentage of hemorrhagic shock. In one study of 103 patients with undifferentiated shock presenting to a busy, urban ED, 36 percent of patients had hypovolemic shock, 33 percent had septic shock, 29 percent had cardiogenic shock, and 2 percent had other forms of shock [ 3 ].

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Clinical Presentation

  • Dengue can range from asymptomatic infection or mild illness to severe disease.
  • An estimated 1 in 4 dengue virus infections are symptomatic. Symptomatic dengue virus infection most commonly presents as a mild to moderate, nonspecific, acute febrile illness.
  • Infection with one of the four dengue viruses will induce long-lived immunity for that specific virus.
  • Because there are four dengue viruses, people can be infected with DENV multiple times in their life.
  • The second infection with DENV is a risk factor for severe dengue.
  • Early clinical findings are nonspecific but require a high index of suspicion because recognizing early signs of shock and promptly initiating intensive supportive therapy can reduce risk of death among patients with severe dengue to <0.5%.
  • See Box 3-01  for information regarding the World Health Organization (WHO) guidelines for classifying dengue.

In November 2009, WHO issued a new guideline that classifies symptomatic cases as dengue or severe dengue.

Dengue is defined by a combination of ≥2 clinical findings in a febrile person who traveled to or lives in a dengue-endemic area. Clinical findings include nausea, vomiting, rash, aches and pains, a positive tourniquet test, leukopenia, and the following warning signs: abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy, restlessness, and liver enlargement. The presence of a warning sign may predict severe dengue in a patient.

Severe dengue is defined by dengue with any of the following symptoms: severe plasma leakage leading to shock or fluid accumulation with respiratory distress; severe bleeding; or severe organ impairment such as elevated transaminases ≥1,000 IU/L, impaired consciousness, or heart impairment.

From 1975 through 2009, symptomatic dengue virus infections were classified according to the WHO guidelines as dengue fever, dengue hemorrhagic fever (DHF), and dengue shock syndrome (the most severe form of DHF). The case definition was changed to the 2009 clinical classification after reports that the case definition of DHF was both too difficult to apply in resource-limited settings and too specific, as it failed to identify a substantial proportion of severe dengue cases, including cases of hepatic failure and encephalitis. The 2009 clinical classification has been criticized for being overly inclusive, as it allows several different ways to qualify for severe dengue, and nonspecific warning signs are used as diagnostic criteria for dengue. Lastly, the new guidelines have been criticized because they do not define the clinical criteria for establishing severe dengue (with the exception of providing laboratory cutoff values for transaminase levels), thereby leaving severity determination up to individual clinical judgment.

Dengue begins abruptly after a typical incubation period of 5–7 days, and the course follows 3 phases: febrile, critical, and convalescent.

Febrile Phase

  • Fever typically lasts 2–7 days and can be biphasic.
  • Other signs and symptoms may include severe headache; retro-orbital eye pain; muscle, joint, and bone pain; macular or maculopapular rash; and minor hemorrhagic manifestations including petechia, ecchymosis, purpura, epistaxis, bleeding gums, hematuria, or a positive tourniquet test result.
  • Some patients have injected oropharynx and facial erythema in the first 24–48 hours after onset.

Emergency room sign outside of a hospital

Warning Signs

Warning signs of progression to severe dengue occur in the late febrile phase around the time of defervescence, and include persistent vomiting, severe abdominal pain, fluid accumulation, mucosal bleeding, difficulty breathing, lethargy/restlessness, postural hypotension, liver enlargement, and progressive increase in hematocrit (i.e., hemoconcentration).

Critical Phase

  • The critical phase of dengue begins at defervescence and typically lasts 24–48 hours.
  • Most patients clinically improve during this phase, but those with substantial plasma leakage can, within a few hours, develop severe dengue as a result of a marked increase in vascular permeability.
  • Initially, physiologic compensatory mechanisms maintain adequate circulation, which narrows pulse pressure as diastolic blood pressure increases.
  • Patients with severe plasma leakage may have pleural effusions, ascites, hypoproteinemia, or hemoconcentration.
  • Patients may appear to be well despite early signs of shock. However, once hypotension develops, systolic blood pressure rapidly declines, and irreversible shock and death may ensue despite resuscitation.
  • Patients can also develop severe hemorrhagic manifestations, including hematemesis, bloody stool, or menorrhagia, especially if they have been in prolonged shock. Uncommon manifestations include hepatitis, myocarditis, pancreatitis, and encephalitis.

Convalescent Phase

  • As plasma leakage subsides, the patient enters the convalescent phase and begins to reabsorb extravasated intravenous fluids and pleural and abdominal effusions.
  • As a patient’s well-being improves, hemodynamic status stabilizes (although he or she may manifest bradycardia), and diuresis ensues. The patient’s hematocrit stabilizes or may fall because of the dilutional effect of the reabsorbed fluid, and the white cell count usually starts to rise, followed by a recovery of platelet count.
  • The convalescent-phase rash may desquamate and be pruritic.

Laboratory findings commonly include leukopenia, thrombocytopenia, hyponatremia, elevated aspartate aminotransferase and alanine aminotransferase, and a normal erythrocyte sedimentation rate.

Dengue During Pregnancy

  • Data are limited on health outcomes of dengue in pregnancy and effects of maternal infection on the developing fetus.
  • Perinatal transmission can occur, and peripartum maternal infection may increase the likelihood of symptomatic infection in the newborn.
  • Of 41 perinatal transmission cases described in the literature, all developed thrombocytopenia, most had evidence of plasma leakage evidenced by ascites or pleural effusions, and fever was absent in only two cases. Nearly 40% had a hemorrhagic manifestation, and 1 in 4 had hypotension.
  • Perinatally infected neonates typically become ill during the first week of life.
  • Placental transfer of maternal IgG against dengue virus (from a previous maternal infection) may increase risk for severe dengue among infants infected at 6–12 months of age, when the protective effect of these antibodies wanes.

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A Review of Difficult-to-Treat Rheumatoid Arthritis: Definition, Clinical Presentation, and Management

  • Published: 30 September 2023
  • Volume 25 , pages 285–294, ( 2023 )

Cite this article

  • Carly Conran 1 ,
  • Jason Kolfenbach 2 ,
  • Kristine Kuhn 2 ,
  • Christopher Striebich 2 &
  • Larry Moreland 2  

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Purpose of Review

A subset of patients with rheumatoid arthritis (RA) who fail multiple biologic therapies are deemed to have “difficult-to-treat” (D2T) RA. In 2021, a European Alliance of Associations for Rheumatology (EULAR) task force proposed a clinical definition of D2T RA. Here we review RA phenotypes and clinical assessment of RA, propose a different definition of D2T RA, discuss possible D2T RA risk factors, and summarize existing literature on the management of D2T RA.

Recent Findings

High disease activity at the time of diagnosis or prior to treatment with a biologic is associated with the development of D2T RA. Prolonged time from diagnosis to beginning treatment has been consistently associated with the development of D2T RA. Other clinical factors such as burden of disease, extraarticular disease, obesity, smoking, pain, fatigue, and psychological conditions have inconsistent associations with D2T RA according to current literature.

D2T RA is a relatively new concept that represents an area of great need for research regarding the characterization of those with the disease as well as how best to treat the disease. With this gained knowledge, rheumatologists will be able to better identify patients at the time of diagnosis that are likely to develop D2T RA to help guide management.

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Papers of particular interest, published recently, have been highlighted as: • Of importance

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Thank you to Dr. Ted Mikuls, University of Nebraska Medical Center, for providing the review of this article.

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Jason Kolfenbach, Kristine Kuhn, Christopher Striebich & Larry Moreland

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Conran, C., Kolfenbach, J., Kuhn, K. et al. A Review of Difficult-to-Treat Rheumatoid Arthritis: Definition, Clinical Presentation, and Management. Curr Rheumatol Rep 25 , 285–294 (2023). https://doi.org/10.1007/s11926-023-01117-6

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News Details

Moderna advances multiple vaccine programs to late-stage clinical trials.

Announces next-generation COVID-19 vaccine candidate as fourth respiratory vaccine to successfully meet its Phase 3 endpoints

Expects two more Phase 3 readouts in 2024, including combination vaccine against flu and COVID-19, and vaccine against CMV

Announces positive clinical trial data from three new vaccines against viruses that cause significant burden (Epstein-Barr virus, Varicella-Zoster virus, norovirus) and advances programs toward Phase 3 development

Anticipates U.S. launch of vaccine against RSV following FDA approval and ACIP recommendation in 2024

Announces development and commercialization funding agreement with Blackstone Life Sciences for up to $750 million to advance flu program

"Our mRNA platform continues a remarkable track record across our broad vaccine portfolio. Today, we are excited to share that four vaccines in our pipeline have achieved successful clinical readouts across our respiratory, latent and other virus franchises," said Stéphane Bancel, Chief Executive Officer of Moderna. "With five vaccines in Phase 3, and three more moving toward Phase 3, we have built a very large and diverse portfolio addressing significant unmet medical needs. We are focused on execution to further build momentum across our pipeline and business, and to deliver for patients who are impacted by these infectious diseases."

Portfolio Overview

The vaccine portfolio seeks to address infectious diseases that cause considerable health burdens and includes 28 vaccines addressing respiratory, latent and other pathogens.

Latent and Other Vaccine Portfolio

Moderna is advancing five vaccine candidates against viruses that cause latent infections, all of which are in clinical trials. When latent, a virus is present in the body but exists in a resting state, typically without causing any noticeable symptoms. Latent viruses can reactivate and cause clinical symptoms as a person ages, during times of stress or when immunity is compromised. The capacity for latency is a defining feature of members of the Herpesviridae family, including cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV) and Varicella-Zoster virus (VZV).

Cytomegalovirus (CMV)

CMV is the most common infectious cause of birth defects in the U.S. and is responsible for several billion dollars in annual healthcare costs. One in 200 babies in the U.S. are born with a congenital CMV infection, and of those affected, one in five will have severe, life-altering health problems. Possible short- and long-term sequelae of CMV infection include microcephaly, chorioretinitis, seizures, sensorineural hearing loss, cognitive impairment and cerebral palsy. There is currently no approved vaccine to prevent congenital CMV.

CMVictory is a pivotal Phase 3 trial evaluating mRNA-1647 against primary CMV infection in women 16 to 40 years of age. The trial is a randomized, observer-blind, placebo-controlled study designed to evaluate the efficacy, safety and immunogenicity of mRNA-1647. The trial is fully enrolled with approximately 7,300 participants from 290 clinical sites globally.

To date, 50 primary infection cases have accrued and are undergoing confirmation. The first interim analysis for the evaluation of vaccine efficacy, which will be triggered when both 81 confirmed per-protocol cases and 12 median months of safety follow-up have occurred, is expected as early as the end of 2024.

Moderna's CMV vaccine candidate mRNA-1647 has advanced to indication expansion studies in adolescents 9 to 15 years of age and adult transplant patients, both of which have begun enrollment.

Epstein-Barr virus (EBV)

EBV is a major cause of infectious mononucleosis (IM) in the U.S., accounting for more than 90% of IM cases annually. Importantly, EBV and IM are associated with a higher lifetime risk of more serious sequelae including certain cancers such as gastric carcinoma, nasopharyngeal carcinoma and multiple types of lymphoma. The lifetime risk of developing multiple sclerosis (MS) is increased by 32-fold after EBV infection. There is currently no approved vaccine to prevent EBV.

Moderna's EBV vaccine candidates are designed to tackle multiple EBV-associated conditions, including prevention of IM (mRNA-1189) and MS and post-transplant lymphoproliferative disorder, a subcategory of lymphoma in solid organ transplant patients (mRNA-1195) . The Phase 1 trial for mRNA-1189 was designed to test the safety, reactogenicity and immunogenicity of four different dose levels in participants 12 to 30 years of age in the U.S. The randomized, observer-blind, placebo-controlled study showed mRNA-1189 was immunogenic and generally well tolerated across all dose levels. The Company is advancing mRNA-1189 toward a pivotal Phase 3 trial.

The Phase 1 trial for mRNA-1195 was designed to test the safety, reactogenicity and immunogenicity of two drug products at four different dose levels in healthy EBV seropositive participants 18 to 55 years of age in the U.S. The randomized, observer-blind, placebo-controlled study is fully enrolled.

Herpes simplex virus (HSV)

Herpes simplex virus type 2 (HSV-2) infects approximately 13% of adults globally and is the primary cause of genital herpes. There are an estimated four billion people globally infected with HSV, of which 491 million cases are HSV-2. Recurrent genital herpes causes a reduction in quality of life, which antivirals (current standard of care) only partially restore. Moderna expects that if an HSV vaccine candidate could deliver similar efficacy as a suppressive antiviral treatment, compliance with recommended therapy and associated quality of life would improve. There is currently no approved vaccine to treat HSV-2.

The first in human, fully enrolled Phase 1/2 trial of mRNA-1608 is designed to test safety and immunogenicity and to establish a proof-of-concept of clinical benefit in adults 18 to 55 years of age with recurrent HSV-2 genital herpes. The randomized 1:1:1:1, observer-blind, controlled study is fully enrolled with 300 participants in the U.S.

Varicella-Zoster virus (VZV)

Herpes zoster, also known as shingles, is caused by reactivation of latent VZV, the same virus that causes chickenpox. Declining immunity in older adults decreases immunity against VZV, allowing reactivation of the virus from latently infected neurons, causing painful and itchy lesions. Herpes Zoster occurs in one out of three adults in the U.S. in their lifetime and the incidence increases at 50 years of age. There is potential to reach a growing and underserved patient population.

Moderna's VZV vaccine candidate mRNA-1468 has initial data available from a Phase 1/2 trial, which was designed to test safety and immunogenicity in healthy adults 50 years of age and older in the U.S. The randomized 1:1:1:1:1, observer-blind, active-controlled study of mRNA-1468 elicited strong antigen-specific T cell responses at one month after the second dose and was generally well tolerated. Results of the first interim analysis support the further clinical development of mRNA-1468 for the prevention of shingles. Additional results from the ongoing Phase 1/2 study will be available later this year, including persistence data. The Company is planning for a pivotal Phase 3 trial. Norovirus

Enteric viruses, including norovirus, are a leading cause of diarrheal diseases, resulting in significant morbidity and mortality worldwide, particularly among young children and older adults. Norovirus is highly contagious and a leading cause of diarrheal disease globally, associated with 18% of all acute gastroenteritis (AGE), resulting in approximately 200,000 deaths per year and substantial healthcare costs. Given the wide diversity of norovirus genotypes, a broadly effective norovirus vaccine will require a multivalent vaccine design. There is currently no approved vaccine to prevent norovirus.

The randomized, observer-blind, placebo-controlled Phase 1 trial was designed to evaluate the safety, reactogenicity and immunogenicity of trivalent  (mRNA-1403)  and pentavalent  (mRNA-1405) norovirus vaccine candidates in 664 participants 18 to 49 years of age and 60 to 80 years of age in the U.S. An interim analysis showed that a single dose of mRNA-1403 elicited a robust immune response across all dose levels evaluated with a clinically acceptable reactogenicity and safety profile. The Company is advancing mRNA-1403 toward a pivotal Phase 3 trial.

Respiratory Vaccine Portfolio

Moderna's approach to ease the global burden of respiratory infections includes vaccine candidates against major causative pathogens, including SARS-CoV-2, respiratory syncytial virus (RSV) and influenza virus. Respiratory infections are a top cause of death in the U.S. and are particularly harmful to the young, immunocompromised, and older adults who experience more severe illness, greater incidence of hospitalization, and greater mortality than younger adults.

Moderna's respiratory pipeline includes Phase 3 trials for investigational vaccines including a next-generation COVID-19 vaccine, an RSV vaccine, a flu vaccine, and a flu and COVID-19 combination vaccine. The pipeline includes three additional flu vaccine candidates with expanded antigen coverage as well as combination vaccine programs.

Moderna continues to address the needs of the endemic COVID-19 market by focusing on public health efforts to increase vaccination coverage rates to reduce the substantial burden of COVID-19 as well as by advancing next-generation vaccines. The Company's mRNA platform can produce variant-matched vaccines on an accelerated time horizon, consistent with recent U.S. Food and Drug Administration (FDA) comments on the timing of potential strain selection for the fall booster season.

A recent announcement of positive interim results from the NEXTCove Phase 3 trial showed that mRNA-1283 elicited a higher immune response against both the Omicron BA.4/BA.5 and original virus strains of SARS-CoV-2 compared to mRNA-1273.222, Moderna's licensed COVID-19 vaccine. mRNA-1283 is designed to be refrigerator-stable and paves the way for a combination vaccine against influenza and COVID-19, mRNA-1083, enhancing the Company's overall respiratory portfolio. This is Moderna's fourth infectious disease vaccine program with Phase 3 data.

Respiratory Syncytial Virus (RSV)

RSV is the leading cause of respiratory illness in young children, and older adults are at increased risk relative to younger adults for severe outcomes. In addition to acute mortality and morbidity, RSV infection is associated with long-term sequelae such as asthma and impaired lung function in pediatric populations, and exacerbation of chronic obstructive pulmonary disease in older adults. Annually, there are approximately two million medically attended RSV infections and 58,000 to 80,000 hospitalizations in children younger than five years old in the U.S. In the U.S., each year there are up to 160,000 hospitalizations and 10,000 deaths in adults 65 years and older due to RSV. Across high-income countries in 2019, RSV caused an estimated 5.2 million cases, 470,000 hospitalizations and 33,000 in-hospital deaths in adults 60 years and older.

Moderna's RSV vaccine candidate, mRNA-1345, is in an ongoing Phase 2/3, randomized, observer-blind, placebo-controlled case-driven trial (ConquerRSV) in adults over 60 years of age. In this study, approximately 37,000 participants from 22 countries were randomized 1:1 to receive one dose of mRNA-1345 or placebo.

Based on positive data from the ConquerRSV trial, Moderna has filed for regulatory approvals for mRNA-1345 for the prevention of RSV-associated lower respiratory tract disease (RSV-LRTD) and acute respiratory disease (ARD) in adults over 60 years of age.

The trial met both its primary efficacy endpoints, with a vaccine efficacy (VE) of 83.7% (95.88% CI: 66.1%, 92.2%; p<0.0001) against RSV-LRTD as defined by two or more symptoms, and a VE of 82.4% (96.36% CI: 34.8%, 95.3%; p=0.0078) against RSV-LRTD defined by three or more symptoms. These data were published in the New England Journal of Medicine in December 2023.

A subsequent analysis from the ConquerRSV study with a longer median follow-up duration of 8.6 months (versus 3.7 months in the primary analysis), with a range of 15 days to 530 days, and including subjects from the Northern and Southern Hemispheres was recently presented at the RSVVW'24 conference . In this supplemental analysis, mRNA-1345 maintained durable efficacy, with sustained VE of 63.3% (95.88% CI: 48.7%, 73.7%) against RSV-LRTD including two or more symptoms. VE was 74.6% (95% CI: 50.7%, 86.9%) against RSV-LRTD with ≥2 symptoms, including shortness of breath and 63.0% (95% CI: 37.3%, 78.2%) against RSV-LRTD including three of more symptoms. The stringent statistical criterion of the study, a lower bound on the 95% CI of >20%, continued to be met for both endpoints.

mRNA-1345 has been granted Breakthrough Therapy designation by the FDA for the prevention of RSV-LRTD in adults over 60 years of age. The Company is awaiting regulatory approvals and the U.S. ACIP recommendation in 2024.

Indication expansion studies for mRNA-1345

mRNA-1345 has the potential to protect all vulnerable populations from RSV. Moderna has initiated multiple Phase 3 expansion studies in adults over 50 years of age to evaluate co-administration and revaccination. Additional trials (Phase 1 - Phase 3) have been initiated for high-risk adults, as well as maternal and pediatric populations. Interim data from these studies could be available as early as 2024.

Influenza (Flu)

Worldwide, influenza leads to 3-5 million severe cases of flu and 290,000-650,000 flu-related respiratory deaths annually. Two main types of influenza viruses (A and B) cause seasonal flu epidemics, and the influenza A viruses lead to most flu-related hospitalization in older adults.

The Company has several seasonal influenza vaccine candidates in clinical development. Moderna's seasonal flu vaccine, mRNA-1010 , demonstrated consistently acceptable safety and tolerability across three Phase 3 trials. In the most recent Phase 3 trial (P303), which was designed to test the immunogenicity and safety of an optimized vaccine composition, mRNA-1010 met all immunogenicity primary endpoints, demonstrating higher antibody titers compared to a currently licensed standard-dose flu vaccine. In an older adult extension study of P303, mRNA-1010 is being studied against high dose Fluzone HD ® ; the trial is fully enrolled. The Company is in ongoing discussions with regulators and intends to file in 2024.

Combination Respiratory Vaccines

Moderna's combination vaccine candidates cover respiratory viruses associated with the largest disease burden in the category. The Phase 3 combination study of the Company's investigational combination vaccine against flu and COVID-19 (mRNA-1083) for adults aged 50 years and older is fully enrolled and data are expected in 2024. mRNA-1083 was granted Fast Track designation by the FDA in May 2023.

Commercial Updates

Respiratory viruses in addition to latent and other viruses represent large unmet or underserved medical needs, and the human and economic costs from these infectious diseases highlight the need for effective vaccines. To help address this need, Moderna expects multiple vaccine product launches in the next few years, each with significant addressable markets.

The 2024 global endemic COVID-19 vaccine market alone is estimated by Moderna to be approximately $10 billion. COVID-19 continues to show a high burden of disease, and while COVID-19 hospitalizations remain high relative to RSV and flu, the risks of Long COVID are also becoming better understood. Moderna is focused on improving education and awareness to increase vaccination rates as Long COVID data suggests even traditionally low-risk groups should be vaccinated. Moderna is also working with health authorities to align the timing of COVID-19 and flu vaccine launches to help improve public health.

For RSV, Moderna estimates the peak annual market to be approximately $10 billion. The Company expects a strong RSV vaccine launch into a large market in 2024. As the only mRNA investigational vaccine with positive Phase 3 data, Moderna's RSV vaccine candidate has a strong profile with consistently strong efficacy across vulnerable and older populations, a well-established safety and tolerability profile, and ease of administration with a ready-to-use, pre-filled syringe formulation, which could relieve some of the burden that falls on pharmacies during the fall vaccination season.

An interim analysis from an ongoing time and motion study evaluating differences in preparation time between a pre-filled syringe (PFS) presentation and vaccines that require reconstitution showed that a PFS presentation could relieve some of the burden that falls on pharmacies during the fall vaccination season. Results from this study suggest that pharmacies may be capable of preparing up to four times as many doses of PFS in an hour compared to vaccines requiring reconstitution.

Moderna estimates flu vaccines represent an approximately $7 billion market in 2024. The market is expected to grow with the rise of more effective vaccines and there is an opportunity to expand the market with next-generation premium flu vaccines as well as combination respiratory vaccines, adding increased value to the health ecosystem.

CMV is expected to be a $2-5 billion annual market. With no vaccine currently on the market and a potential vaccine launch in 2026, Moderna could be the first CMV vaccine in multi-billion-dollar latent vaccine market. In addition, EBV has the potential to address and reduce the burden and cost of EBV infection in multiple populations, while VZV provides the opportunity to enter a large and growing market, which could be $5-6 billion annually. The market for norovirus vaccines is similar to that of rotavirus in pediatrics with opportunity to expand into the adult population, and represents a $3-6 billion annual market.

Moderna's vaccine portfolio targets large addressable markets, with an estimated total addressable market (TAM) of $52 billon for Moderna infectious disease vaccines, which includes a respiratory vaccines TAM of more than $27 billion and a latent and other vaccines TAM of more than $25 billion.

Manufacturing

The Company's manufacturing innovation supports expanding commercialization of a diverse pipeline through efficiency and productivity gains. Its mRNA manufacturing platform enables benefits such as quality, speed, scale and cost efficiency across a footprint that broadly includes the manufacture of plasmid, mRNA, lipid nanoparticles, as well as fill/finish and quality control capabilities.

As the Company continues to build its footprint for the future, it is developing an agile global manufacturing network to meet commercial demand and support its growing pipeline. Pre-clinical through commercial manufacturing occurs at the Moderna Technology Center in Norwood, Massachusetts, which remains central to the Company's network. New facilities being constructed in Australia, Canada and the UK are expected to come online in 2025, and drug product capacity is achieved through a flexible contract manufacturing network. Additionally, the Company has purchased and started build-out of a manufacturing site in Marlborough, Massachusetts, to enable commercial scale of its individualized neoantigen therapy program.

By continuing to pioneer new technologies, including advanced robotics, applying AI and other digital solutions, and driving network and capital efficiency, Moderna's manufacturing network is expected to also drive more predictable cost of sales.

Research and Development Investment Strategy

Today's updates provide further evidence that Moderna's mRNA technology platform is working, and with a rate of success higher than industry standard. Looking ahead, research and development will continue to be the Company's top capital allocation priority.

As Moderna looks to create value through the research and development strategy for its vaccine portfolio, it is taking three prioritization parameters into consideration: pipeline advancement, revenue diversification and risk reduction. As part of its strategy, the funding options Moderna considers are self-funding, project financing and partnerships.

Moderna recently entered into a development and commercialization funding agreement with Blackstone Life Sciences to advance the Company's flu program. As part of the agreement, Blackstone will fund up to $750 million with a return based on cumulative commercial milestones and low-single digit royalties. Moderna expects to recognize the funding as a reduction in research and development expenses and will retain full rights and control of the Company's flu program. This funding does not result in any change to Moderna's 2024 research and development framework spending of approximately $4.5 billion.

About Moderna

Moderna is a leader in the creation of the field of mRNA medicine. Through the advancement of mRNA technology, Moderna is reimagining how medicines are made and transforming how we treat and prevent disease for everyone. By working at the intersection of science, technology and health for more than a decade, the company has developed medicines at unprecedented speed and efficiency, including one of the earliest and most effective COVID-19 vaccines.


Moderna's mRNA platform has enabled the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases and autoimmune diseases. With a unique culture and a global team driven by the Moderna values and mindsets to responsibly change the future of human health, Moderna strives to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.

INDICATION (U.S.)

SPIKEVAX (COVID-19 Vaccine, mRNA) is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 18 years of age and older.

IMPORTANT SAFETY INFORMATION

  • Do not administer to individuals with a known history of severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine.
  • Appropriate medical treatment to manage immediate allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of the vaccine.
  • Postmarketing data demonstrate increased risks of myocarditis and pericarditis, particularly within 7 days following the second dose. The observed risk is higher among males under 40 years of age than among females and older males. The observed risk is highest in males 18 through 24 years of age.
  • Syncope (fainting) may occur in association with administration of injectable vaccines. Procedures should be in place to avoid injury from fainting.
  • Immunocompromised persons, including individuals receiving immunosuppressive therapy, may have a diminished response to the vaccine.
  • The vaccine may not protect all vaccine recipients.
  • Adverse reactions reported in clinical trials following administration of the vaccine include pain at the injection site, fatigue, headache, myalgia, arthralgia, chills, nausea/vomiting, axillary swelling/tenderness, fever, swelling at the injection site, and erythema at the injection site, and rash.
  • The vaccination provider is responsible for mandatory reporting of certain adverse events to the Vaccine Adverse Event Reporting System (VAERS) online at https://vaers.hhs.gov/reportevent.html or by calling 1-800-822-7967.
  • Please see the SPIKEVAX Full Prescribing Information . For information regarding authorized emergency uses of the Moderna COVID-19 Vaccine, please see the EUA Fact Sheet .

Spikevax ® is a registered trademark of Moderna. Fluzone ® is a registered trademark of Sanofi Pasteur. Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding: the advancement of Moderna's programs under clinical development; the timing for anticipated approvals of vaccine candidates; the efficacy, safety and tolerability of vaccine candidates; the total addressable markets for programs under development; the efficiencies and advantages of Moderna's mRNA platform; future capital allocation and financing efforts; and anticipated spending for R&D in 2024. In some cases, forward-looking statements can be identified by terminology such as "will," "may," "should," "could," "expects," "intends," "plans," "aims," "anticipates," "believes," "estimates," "predicts," "potential," "continue," or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna's control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties, and other factors include, among others, those risks and uncertainties described under the heading "Risk Factors" in Moderna's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, filed with the U.S. Securities and Exchange Commission (SEC), and in subsequent filings made by Moderna with the SEC, which are available on the SEC's website at www.sec.gov . Except as required by law, Moderna disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this presentation in the event of new information, future developments or otherwise. These forward-looking statements are based on Moderna's current expectations and speak only as of the date of this press release.

Moderna Contacts

Media: Chris Ridley Head, Global Media Relations +1 617-800-3651 [email protected]

Investors: Lavina Talukdar Senior Vice President & Head of Investor Relations +1 617-209-5834 [email protected]

SOURCE: Moderna, Inc.

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  • Continuing Education Activity

Anemia is a reduction in hemoglobin (Hb) or hematocrit (HCT) or RBC count. It is a presentation of an underlying condition and can be subdivided into macrocytic, microcytic, or normocytic. Patients with anemia typically present with vague symptoms such as lethargy, weakness, and tiredness. Severe anemia may present with syncope, shortness of breath, and reduced exercise tolerance. This activity outlines the evaluation and treatment of anemia and explains the role of the interprofessional team in managing patients with this condition.

  • Summarize the etiology of anemia.
  • Describe the pathophysiology of anemia.
  • Outline the use of dietary supplements in the treatment of anemia.
  • Explain the importance of collaboration and communication among the interprofessional team to improve outcomes for patients affected by anemia.
  • Introduction

Anemia is described as a reduction in the proportion of the red blood cells. Anemia is not a diagnosis, but a presentation of an underlying condition. Whether or not a patient becomes symptomatic depends on the etiology of anemia, the acuity of onset, and the presence of other comorbidities, especially the presence of cardiovascular disease. Most patients experience some symptoms related to anemia when the hemoglobin drops below 7.0 g/dL. 

Erythropoietin (EPO), which is made in the kidney, is the major stimulator of red blood cell (RBC) production. Tissue hypoxia is the major stimulator of EPO production, and levels of EPO are generally inversely proportional to the hemoglobin concentration. In other words, an individual who is anemic with low hemoglobin has elevated levels of EPO. However, levels of EPO are lower than expected in anemic patients with renal failure. In anemia of chronic disease (AOCD), EPO levels are generally elevated, but not as high as they should be, demonstrating a relative deficiency of EPO.

Normal Hemoglobin (Hgb)-specific laboratory cut-offs will differ slightly, but in general, the normal ranges are as follows:

  • 13.5 to 18.0 g/dL in men
  • 12.0 to 15.0 g/dL in women
  • 11.0 to 16.0 g/dL in children
  • Varied in pregnancy depending on the trimester, but generally greater than 10.0 g/dL

The etiology of anemia depends on whether the anemia is hypoproliferative (i.e., corrected reticulocyte count <2%) or hyperproliferative (i.e., corrected reticulocyte count >2%).

Hypoproliferative anemias are further divided by the mean corpuscular volume into microcytic anemia (MCV<80 fl), normocytic anemia (MCV 80-100 fl), and macrocytic anemia (MCV>100 fl). 

  1) Hypoproliferative Microcytic Anemia (MCV<80 fl)

  • Iron deficiency anemia  [1]
  • Anemia of chronic disease (AOCD)
  • Sideroblastic anemia  [2]  (may be associated with an elevated MCV as well, resulting in a dimorphic cell population)
  • Thalassemia
  • Lead poisoning 

2) Hypoproliferative Normocytic Anemia (MCV 80-100 fL)

  • Renal failure
  • Aplastic anemia
  • Pure red cell aplasia
  • Myelofibrosis or myelophthisic processes
  • Multiple myeloma

Macrocytic anemia can be caused by either a hypoproliferative disorder, hemolysis, or both. Thus, it is important to calculate the corrected reticulocyte count when evaluating a patient with macrocytic anemia. In hypoproliferative macrocytic anemia, the corrected reticulocyte count is <2%, and the MCV is greater than 100 fl. But, if the reticulocyte count is > 2%, hemolytic anemia should be considered.

3) Hypoproliferative Macrocytic Anemia (MCV>100 fL)

  • Liver disease
  • Hypothyroidism
  • Folate and Vitamin B12 deficiency  [3]
  • Refractory anemia (RA)
  • Refractory anemia with ringed sideroblasts (RA-RS)
  • Refractory anemia with excess blasts (RA-EB)
  • Refractory anemia with excess blasts in transformation
  • Chronic myelomonocytic leukemia (CMML)
  • Diuretics 
  • Chemotherapeutic agents
  • Hypoglycemic agents
  • Antiretroviral agents
  • Antimicrobials
  • Anticonvulsants

  4) Hemolytic anemia Hemolytic anemia (HA) is divided into extravascular and intravascular causes.

  • Hemoglobinopathies (sickle cell, thalassemias)
  • Enzyemopathies (G6PD deficiency, pyruvate kinase deficiency)
  • Membrane defects (hereditary spherocytosis, hereditary elliptocytosis)
  • Drug-induced
  • Transfusion reactions
  • Snake bites/venom
  • Epidemiology

Anemia is an extremely common disease affecting up to one-third of the global population. In many cases, it is mild and asymptomatic and requires no management. 

The prevalence increases with age and is more common in women of reproductive age, pregnant women, and the elderly.

The prevalence is more than 20% of individuals who are older than the age of 85. The incidence of anemia is 50%-60% in the nursing home population. In the elderly, approximately one-third of patients have a nutritional deficiency as the cause of anemia, such as iron, folate, and vitamin B12 deficiency. In another one-third of patients, there is evidence of renal failure or chronic inflammation.  [4]

Classically, mild iron-deficiency anemia is seen in women of childbearing age, usually due to poor dietary intake of iron and monthly loss with the menstrual cycles. Anemia is also common in elderly patients, often due to poor nutrition, especially of iron and folic acid. Other at-risk groups include alcoholics, the homeless population, and those experiencing neglect or abuse.

New-onset anemia, especially in those over 55 years of age, needs investigating and should be considered cancer until proven otherwise. This is especially true in men of any age who present with anemia. 

Apart from age and sex, the race is also an important determinant of anemia, with the prevalence increasing in the African American population.  

  • Pathophysiology

The pathophysiology of anemia varies greatly depending on the primary cause. For instance, in acute hemorrhagic anemia, it is the restoration of blood volume with intracellular and extracellular fluid that dilutes the remaining red blood cells (RBCs), which results in anemia. A proportionate reduction in both plasma and red cells results in falsely normal hemoglobin and hematocrit. 

RBC are produced in the bone marrow and released into circulation. Approximately 1% of RBC are removed from circulation per day. Imbalance in production to removal or destruction of RBC leads to anemia.  [5]

The main mechanisms involved in anemia are listed below:

1. Increased RBC destruction

  • Acute- hemorrhage, surgery, trauma, menorrhagia
  • Chronic- heavy menstrual bleeding, chronic gastrointestinal blood losses  [6] (in the setting of hookworm infestation, ulcers, etc.), urinary losses (BPH, renal carcinoma, schistosomiasis)
  • Acquired- immune-mediated, infection, microangiopathic, blood transfusion-related, and secondary to hypersplenism
  • Hereditary- enzymopathies, disorders of hemoglobin (sickle cell), defects in red blood cell metabolism (G6PD deficiency, pyruvate kinase deficiency), defects in red blood cell membrane production (hereditary spherocytosis and elliptocytosis)

2. Deficient/defective erythropoiesis

  • Normocytic, normochromic
  • History and Physical

A thorough history and physical must be performed.

Some important questions to obtain in a history:

  • Obvious bleeding- per rectum or heavy menstrual bleeding, black tarry stools, hemorrhoids
  • Thorough dietary history
  • Consumption of nonfood substances
  • Bulky or fatty stools with foul odor to suggest malabsorption
  • Thorough surgical history, with a concentration on abdominal and gastric surgeries
  • Family history of hemoglobinopathies, cancer, bleeding disorders
  • Careful attention to the medications taken daily

1) Symptoms of anemia

Classically depends on the rate of blood loss. Symptoms usually include the following: 

  • Restless legs
  • Shortness of breath, especially on exertion, near syncope
  • Chest pain and reduced exercise tolerance- with more severe anemia
  • Pica- desire to eat unusual and nondietary substances 
  • Mild anemia may otherwise be asymptomatic 

2) Signs of anemia

  • Skin may be cool to touch
  • Hypotension (orthostatic)
  • Pallor of the conjunctiva                                                                                                                                                                                               
  • “Boxcars” or “sausaging” of retinal veins: suggestive of hyperviscosity which can be seen in myelofibrosis                                                               
  • Jaundice- elevated bilirubin is seen in several hemoglobinopathies, liver diseases and other forms of hemolysis                                         
  • Lymphadenopathy: suggestive of lymphoma or leukemia                                                                                                                                           
  • Glossitis (inflammation of the tongue) and cheilitis (swollen patches on the corners of the mouth): iron/folate deficiency, alcoholism, pernicious anemia 
  • Splenomegaly: hemolysis, lymphoma, leukemia, myelofibrosis                                                                                                                                         
  • Hepatomegaly: alcohol, myelofibrosis                                                                                                                                                                 
  • Scar from gastrectomy: decreased absorptive surface with the loss of the terminal ileum leads to vitamin B12 deficiency                                                       
  • Scar from cholecystectomy: Cholesterol and pigmented gallstones are commonly seen in sickle cell anemia are hereditary spherocytosis
  • Tachycardia                                                                                                                                                                                                           
  • Systolic flow murmur                                                                                                                                                                                                   
  • Severe anemia may lead to high output heart failure
  • Neurologic exam: Decreased proprioception/vibration: vitamin B12 deficiency
  • Pallor of the mucous membranes/nail bed or palmar creases: suggests hemoglobin < 9 mg/dL                                                                                   
  • Petechiae: thrombocytopenia, vasculitis                                                                                                                                                               
  • Dermatitis herpetiformis (in iron deficiency due to malabsorption- Celiac disease)                                                                                                         
  • Koilonychia (spooning of the nails): iron deficiency
  • Rectal and pelvic exam: These examinations are usually overlooked and underperformed in the evaluation of anemia. If a patient has heavy rectal bleeding, one must evaluate for the presence of hemorrhoids or hard masses that suggest neoplasm as causes of bleeding.

Approach to anemia includes identification of the type of anemia:  [7] [8]

1. Complete blood count (CBC) including differential

2. Calculate the corrected reticulocyte count = percent reticulocytes x (patient's HCT/normal HCT)

For normal HCT, use 45% in men and 40% in women

If result > 2, this suggests hemolysis or acute blood loss, while results < 2 suggests hypoproliferation.

3. After calculating the reticulocyte count, check the MCV.

  • Iron deficiency- decreased serum iron, percent saturation of iron, with increased total iron-binding capacity (TIBC), transferrin levels, and soluble transferrin receptor 
  • Lead poisoning- basophilic stippling on the peripheral blood smear, ringed sideroblasts in bone marrow, elevated lead levels 
  • AOCD- may be normocytic
  • Thalassemia- RBC count may be normal/high, low MCV, target cells, and basophilic stippling are on peripheral smear. Alpha thalassemia is differentiated from beta-thalassemia by a normal Hgb electrophoresis in alpha thalassemia.  Elevated Hgb A2/HgbF is seen in the beta-thalassemia trait.
  • Sideroblastic anemia- elevated serum iron and transferrin with ringed sideroblasts in the bone marrow 
  • Renal failure: BUN/Creatinine 
  • Aplastic anemia- ask for drug exposure, check for infections (EBV, hepatitis, CMV, HIV), test for hematologic malignancies and paroxysmal nocturnal hemoglobinuria (PNH)
  • Myelofibrosis/myelophthisis- check bone marrow biopsy 
  • Multiple myeloma- serum and urine electrophoresis 
  • Pure red cell aplasia- test for Parvovirus B19, exclude thymoma
  • B12/folate levels- B12 and folate deficiency can be differentiated by an elevated methylmalonic and homocysteine level in B12 deficiency and only an elevated homocysteine level in folate deficiency. Methylmalonic levels are relatively normal.  
  • MDS- hyposegmented PMNs on peripheral smear, bone marrow biopsy 
  • Hypothyroidism- TSH, free T4
  • Liver disease- check liver function 
  • Alcohol- assess alcohol intake 

Steps to evaluate for hemolytic anemia

1) Confirm the presence of hemolysis- elevated LDH, corrected reticulocyte count >2%, elevated indirect bilirubin and decreased/low haptoglobin

2) Determine extra vs. intravascular hemolysis- 

  • Spherocytes present
  • Urine hemosiderin negative
  • Urine hemoglobin negative  
  • Urine hemosiderin elevated
  • Urine hemoglobin elevated

3) Examine the peripheral blood smear  [9]

  • Spherocytes: immune hemolytic anemia (Direct antiglobulin test DAT+) vs. hereditary spherocytosis (DAT-)
  • Bite cells: G6PD deficiency 
  • Target cells: hemoglobinopathy or liver disease 
  • Schistocytes: TTP/HUS, DIC, prosthetic valve, malignant HTN
  • Acanthocytes: liver disease
  • Parasitic inclusions: malaria, babesiosis, bartonellosis

4) If spherocytes +, check if DAT is + 

  • DAT(+): Immune hemolytic anemia (AIHA)
  • DAT (-): Hereditary spherocytosis 

Other investigations that might be warranted include esophagogastroduodenoscopy for the determination of an upper GI bleed, colonoscopy for the determination of a lower GI bleed, and imaging studies if malignancy, or internal hemorrhage is suspected. If a menstruating woman has heavy vaginal bleeding, evaluate the presence of fibroids with a pelvic ultrasound. 

  • Treatment / Management

Management depends primarily on treating the underlying cause of anemia.

1) Anemia due to acute blood loss- Treat with IV fluids, crossmatched packed red blood cells, oxygen. Always remember to obtain at least two large-bore IV lines for the administration of fluid and blood products. Maintain hemoglobin of > 7 g/dL in a majority of patients. Those with cardiovascular disease require a higher hemoglobin goal of > 8 g/dL.

2) Anemia due to nutritional deficiencies: Oral/IV iron, B12, and folate. 

  • Oral supplementation of iron is by far the most common method of iron repletion. The dose of iron administered depends on the patient's age, calculated iron deficit, the rate of correction required, and the ability to tolerate side effects. The most common side effects include metallic taste and gastrointestinal side effects such as constipation and black tarry stools. For such individuals, they are advised to take oral iron every other day, in order to aid in improved GI absorption. The hemoglobin will usually normalize in 6-8 weeks, with an increase in reticulocyte count in just 7-10 days.  
  •  IV iron may be beneficial in patients requiring a rapid increase in levels. Patients with acute and ongoing blood loss or patients with intolerable side effects are candidates for IV iron.

3) Anemia due to defects in the bone marrow and stem cells: Conditions such as aplastic anemia require bone marrow transplantation.

4) Anemia due to chronic disease: Anemia in the setting of renal failure, responds to erythropoietin. Autoimmune and rheumatological conditions causing anemia require treatment of the underlying disease. 

5) Anemia due to increased red blood cell destruction:

  • Hemolytic anemia caused by faulty mechanical valves will need replacement.
  • Hemolytic anemia due to medications requires the removal of the offending drug.
  • Persistent hemolytic anemia requires splenectomy.
  • Hemoglobinopathies such as sickle anemia require blood transfusions, exchange transfusions, and even hydroxyurea to decrease the incidence of sickling. 
  • DIC, which is characterized by uncontrolled coagulation and thrombosis, requires the removal of the offending stimulus. Patients with life-threatening bleeding require the use of antifibrinolytic agents. 
  • Differential Diagnosis

Hemolysis during phlebotomy and significant hemodilution due to large volume fluid resuscitation may lead to a falsely low red cell count.

In acute blood loss from trauma, anemia may not immediately be present on laboratory testing, as the fluid shifts have not had time to occur to normalize the circulating volume, thus diluting the number of red blood cells remaining

Anemia of chronic disease: consider renal failure, underlying malignancies, and autoimmune conditions

Bone marrow infiltration: consider in a patient with weight loss, fatigue.

Macrocytic anemia with B12/folate deficiency: consider in a patient with paresthesias, vegans/vegetarians or in patients with recent gastric bypass surgeries

Hemolytic anemia: consider in all patients with jaundice, dark urine. Always question the recent use of medications. 

Acute upper or lower GI bleed: trauma, carcinoma, peptic ulcer disease, use of NSAIDs.

The prognosis for anemia depends on the cause of anemia.

Nutritional replacements of (iron, B12, folate) should begin immediately. In iron deficiency, replacements must continue for at least three months after the normalization of iron levels, in order to restore iron stores. Usually, nutritional deficiencies have a good prognosis if treated early and adequately.

Anemia, due to acute blood loss, if treated and stopped early, has a good prognosis.

  • Complications

Anemia, if undiagnosed or left untreated for a prolonged period of time can lead to multiorgan failure and can even death.

Pregnant women with anemia can go into premature labor and give birth to babies with low birth weight  [10] . Anemia during pregnancy also increases the risk of anemia in the baby and increased blood loss during pregnancy. 

Complications are more predominant in the older population due to multiple comorbidities  [11] . The cardiovascular system is the most commonly affected in chronic anemia. Myocardial infarction, angina, and high output heart failure are common complications. Other cardiac complications include the development of arrhythmias and cardiac hypertrophy.

Severe iron deficiency is associated with restless leg syndrome and esophageal webs.

Severe anemia from a young age may lead to impaired neurological development in the form of cognitive, mental, and developmental delays. These complications are unlikely to be amenable to medical management. 

  • Consultations
  • Gastroenterologist if a gastrointestinal bleed is suspected
  • Nephrologist if anemia of chronic disease in the setting of renal failure is suspected
  • Hematologist if a bone marrow disorder is suspected
  • Gynecologist if intractable menorrhagia is suspected
  • Cardiologist if severe anemia leads to angina, myocardial infarction, heart failure, or arrhythmias
  • Deterrence and Patient Education

Patients with nutritional anemia due to iron deficiency should be educated on food which is rich in iron. Foods such as green leafy vegetables, tofu, red meats, raisins, and dates contain a lot of iron. Vitamin C helps to increase dietary iron absorption. Patients must be advised to avoid excess tea or coffee, as these can decrease iron absorption. Patients on oral iron supplementation must be educated that there is an increased risk of constipation and of the risk of passing black tarry stools. Patients must be advised to contact their doctor if there is severe intolerance to oral iron, as they may be candidates for IV iron supplementation. 

Vegan and vegetarian patients, who may be deficient in B12 must be advised to consume food fortified with vitamin B12, such as certain plant and soy products. Patients who had gastric sleeve operations and sleeve gastrectomies are at an increased risk of vitamin B12 and folate deficiency, due to the loss of absorptive surface at the terminal ileum.

  • Pearls and Other Issues

Always send blood films in patients with an unclear etiology of anemia.

Start haematinics early (iron, B12, and folate).

Inform patients of the side effects of iron therapy, including constipation and black, tarry stools.

Consider screening for sickle cell and thalassemia in patients with unexplained anemia or with a family history of these diseases.

Vitamin C aids iron absorption, so coadministration of vitamin C with iron, or encouraging the patients to take iron supplements with orange juice, will aid therapy.

  • Enhancing Healthcare Team Outcomes

Anemia is a heterogeneous condition caused by a variety of diseases. Identifying the cause of anemia and treating it appropriately is very crucial in the management of anemia. This requires interprofessional teamwork between the patient, the patient's primary care provider, and consultant physician based on the cause, such as a gastroenterologist, nephrologist, cardiologist, hematologist, or gynecologist. Taking all necessary medications along with lifestyle modifications and frequent follow up with the team of doctors is essential to prevent the development of complications. Pharmacists provide education to patients about compliance and side effects of medication, as well as checking for drug interactions. Nurses assist with the education of patients and arrange followup laboratory evaluations and appointments. Only with collaborative interprofessional care can anemia cases achieve optimal outcomes. [Level 5]

  • Review Questions
  • Access free multiple choice questions on this topic.
  • Comment on this article.

Aplastic anemia bone marrow Contributed by Ruozhi Xiao

Macrocytic anemia Contributed by Ruozhi Xiao via SlideShare, “Anemia Overview,”

Iron deficiency anemia Image courtesy S Bhimji MD

Sideroblastic anemia Image courtesy S Bhimji MD

Hypochromic Microcytic Anemia Image courtesy S Bhimji MD

Disclosure: Jake Turner declares no relevant financial relationships with ineligible companies.

Disclosure: Meghana Parsi declares no relevant financial relationships with ineligible companies.

Disclosure: Madhu Badireddy declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

  • Cite this Page Turner J, Parsi M, Badireddy M. Anemia. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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  • Anemia management and outcomes from 12 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS). [Am J Kidney Dis. 2004] Anemia management and outcomes from 12 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Pisoni RL, Bragg-Gresham JL, Young EW, Akizawa T, Asano Y, Locatelli F, Bommer J, Cruz JM, Kerr PG, Mendelssohn DC, et al. Am J Kidney Dis. 2004 Jul; 44(1):94-111.
  • Serum erythropoietin concentrations in patients with anemia--preliminary hemoglobin-related reference ranges. [Clin Lab. 2002] Serum erythropoietin concentrations in patients with anemia--preliminary hemoglobin-related reference ranges. Vogeser M, Schiel X. Clin Lab. 2002; 48(11-12):595-8.
  • Anemia in kidney transplants without erythropoietic agents: levels of erythropoietin and iron parameters. [Transplant Proc. 2012] Anemia in kidney transplants without erythropoietic agents: levels of erythropoietin and iron parameters. Florit EA, Hadad F, Rodriguez Cubillo B, De la Flor JC, Valga F, Perez Flores I, Calvo Romero N, Valero San Cecilio R, Barrientos Guzman A, Sanchez Fructuoso A. Transplant Proc. 2012 Nov; 44(9):2590-2.
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What is Good Friday? What the holy day means for Christians around the world

def clinical presentation

Christians around the world observe Good Friday two days before Easter, but what is it, and why do they commemorate the holy day?

The holiday is part of Holy Week, which leads up to Easter Sunday. Palm Sunday kicks off the series of Christian holy days that commemorate the Crucifixion and celebrate Jesus Christ's resurrection.

"Good Friday has been, for centuries now, the heart of the Christian message because it is through the death of Jesus Christ that Christians believe that we have been forgiven of our sins," Daniel Alvarez, an associate teaching professor of religious studies at Florida International University, told USA TODAY.

What is Holy Saturday? What the day before Easter means for Christians around the world

When is Good Friday?

Good Friday is always the Friday before Easter. It's the second-to-last day of Holy Week.

In 2024, Good Friday will fall on March 29.

What is Good Friday?

Good Friday is the day Christ was sacrificed on the cross. According to Britannica , it is a day for "sorrow, penance, and fasting."

"Good Friday is part of something else," Gabriel Radle, an assistant professor of theology at the University of Notre Dame, previously told USA TODAY. "It's its own thing, but it's also part of something bigger."

Are Good Friday and Passover related?

Alvarez says that Good Friday is directly related to the Jewish holiday, Passover.

Passover , or Pesach, is a major Jewish holiday that celebrates the Israelites’ exodus from Egypt.

"The whole Christian idea of atoning for sin, that Jesus is our atonement, is strictly derived from the Jewish Passover tradition," said Alvarez.

How is that possible?

According to the professor, Passover celebrates the day the "Angel of Death" passed over the homes of Israelites who were enslaved by the Egyptians. He said that the Bible states when the exodus happened, families were told to paint their doors with lamb's blood so that God would spare the lives of their firstborn sons.

Alvarez says this is why Christians call Jesus the "lamb of God." He adds that the symbolism of the "blood of the lamb" ties the two stories together and is why Christians believe God sacrificed his firstborn son. Because, through his blood, humanity is protected from the "wrath of a righteous God that cannot tolerate sin."

He adds that the stories of the exodus and the Crucifixion not only further tie the stories together but also emphasize just how powerful the sacrifice of the firstborn and the shedding of blood are in religion.

"Jesus is the firstborn, so the whole idea of the death of the firstborn is crucial," said Alvarez.

He adds that the sacrifice of the firstborn, specifically a firstborn son, comes from an ancient and "primitive" idea that the sacrifice unleashes "tremendous power that is able to fend off any kind of force, including the wrath of God."

Why Is Good Friday so somber?

Alavarez says people might think this holiday is more depressing or sad than others because of how Catholics commemorate the Crucifixion.

"I think [it's] to a level that some people might think is morbid," said Alvarez.

He said Catholics not only meditate on Jesus' death, but primarily focus on the suffering he faced in the events that led up to his Crucifixion. That's what makes it such a mournful day for people.

But, the professor says that Jesus' suffering in crucial to Christianity as a whole.

"The suffering of Christ is central to the four Gospels," said Alvarez. "Everything else is incidental."

According to the professor, statues that use blood to emphasize the way Jesus and Catholic saints suffered is very common in Spanish and Hispanic Countries, but not as prevalent in American churches.

Do you fast on Good Friday?

Father Dustin Dought, the executive director of the Secretariat of Divine Worship of the United States Conference of Catholic Bishops, previously told USA TODAY that Good Friday and Ash Wednesday are the two days in the year that Roman Catholics are obliged to fast.

"This practice is a way of emptying ourselves so that we can be filled with God," said Dought.

What do you eat on Good Friday?

Many Catholics do not eat meat on any Friday during Lent. Anything with flesh is off-limits. Dought says this practice is to honor the way Jesus sacrificed his flesh on Good Friday.

Meat that is off limits includes:

Instead, many Catholics will eat fish. According to the Marine Stewardship Council , this is allowed because fish is considered to be a different type of flesh.

Contributing: Jordan Mendoza ; USA TODAY

COMMENTS

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  12. UC San Diego's Practical Guide to Clinical Medicine

    Key elements of each presentation type are described below. Examples of how these would be applied to most situations are provided in italics. The formats are typical of presentations done for internal medicine services and clinics. Note that there is an acceptable range of how oral presentations can be delivered.

  13. Definition, classification, etiology, and pathophysiology of ...

    The definition, classification, etiology, and pathophysiology of shock are discussed in this review. The clinical presentation and diagnostic evaluation of undifferentiated shock and the evaluation of patients with specific forms of shock are discussed separately.

  14. Clinical Presentation

    In November 2009, WHO issued a new guideline that classifies symptomatic cases as dengue or severe dengue. Dengue is defined by a combination of ≥2 clinical findings in a febrile person who traveled to or lives in a dengue-endemic area. Clinical findings include nausea, vomiting, rash, aches and pains, a positive tourniquet test, leukopenia, and the following warning signs: abdominal pain or ...

  15. Pathology: The Clinical Description of Human Disease

    By definition, these philosophers, theologians, and physicians had access and assets to allow a written record, and materials and storage sufficient for the written records to survive. ... Pathologists diagnose disease by generating a differential diagnosis, then finding the best fit for the clinical presentation, the radiographic appearance ...

  16. CLINICAL PRESENTATION collocation

    Examples of CLINICAL PRESENTATION in a sentence, how to use it. 16 examples: This review describes the causative organisms, pathogenesis, clinical presentation, epidemiology…

  17. Osteoporosis: Definition and Clinical Presentation : Spine

    In this definition, it is recognized that there is a strong association between bone mineral density and the likelihood of fracture. 4,22,28 According to the criteria, approximately 0.6% of young women have osteoporosis and approximately 16% have low bone mass. By age 75, an estimated 38% of white women will have osteoporosis and 94% will have low bone mass. 20,21,25,26 Although the definition ...

  18. PDF Complex Clinical Presentations and their Models

    A complex clinical presentation model diseasescomprises related clinical entities and ; clinical data are excluded from this definition because they are elements of a disease model. Many other algorithms employ tree and network structures that extend from cause of disease to clinical

  19. Presentation (medical)

    This definition of medical jargon appears to be a dictionary definition. Please rewrite it to present the subject from an encyclopedic point of view. (May 2023) In medicine, a presentation is the appearance in a patient of illness or disease—or signs or symptoms thereof—before a medical professional.

  20. Clinical presentation and management of COVID‐19

    Clinical presentation. Similar to other coronaviruses, SARS‐CoV‐2 is predominantly spread by respiratory droplets, although spread by contact with contaminated fomites also occurs, as does transmission by aerosols in certain circumstances.1 Based on the experience in China, the typical incubation period of COVID‐19 infection has been estimated to be a median of 5.1 days (95% CI, 4.5-5. ...

  21. A Review of Difficult-to-Treat Rheumatoid Arthritis: Definition

    Purpose of Review A subset of patients with rheumatoid arthritis (RA) who fail multiple biologic therapies are deemed to have "difficult-to-treat" (D2T) RA. In 2021, a European Alliance of Associations for Rheumatology (EULAR) task force proposed a clinical definition of D2T RA. Here we review RA phenotypes and clinical assessment of RA, propose a different definition of D2T RA, discuss ...

  22. Clinical Data on the Impact of Sotagliflozin on Stroke and

    In a post-hoc analysis of data from the 10,584 patients in the SCORED Phase 3 clinical trial, 213 all-cause stroke events occurred, including 29 (13.6%) fatal events. Sotagliflozin reduced the ...

  23. Moderna Advances Multiple Vaccine Programs to Late-Stage Clinical Trials

    Announces next-generation COVID-19 vaccine candidate as fourth respiratory vaccine to successfully meet its Phase 3 endpoints Expects two more Phase 3 readouts in 2024, including combination vaccine against flu and COVID-19, and vaccine against CMV Announces positive clinical trial data from three new vaccines against viruses that cause significant burden (Epstein-Barr virus, Varicella-Zoster ...

  24. Anemia

    Anemia is described as a reduction in the proportion of the red blood cells. Anemia is not a diagnosis, but a presentation of an underlying condition. Whether or not a patient becomes symptomatic depends on the etiology of anemia, the acuity of onset, and the presence of other comorbidities, especially the presence of cardiovascular disease. Most patients experience some symptoms related to ...

  25. What is Good Friday? What the holy day means for Christians wordwide

    What is Good Friday? Good Friday is the day Christ was sacrificed on the cross. According to Britannica, it is a day for "sorrow, penance, and fasting." "Good Friday is part of something else ...