Publications by authors named "David Simel"

53 Publications

Does This Patient With Acute Infectious Conjunctivitis Have a Bacterial Infection?: The Rational Clinical Examination Systematic Review.

JAMA 2022 06;327(22):2231-2237

Durham Veterans Affairs Medical Center, Durham, North Carolina.

Importance: Acute infectious conjunctivitis is characterized by ocular redness and discharge, and is a common clinical entity. Evidence-based tools to aid the clinical diagnosis of viral vs bacterial conjunctivitis are lacking and may contribute to overprescribing of topical antibiotics.

Objective: To determine the relative prevalence of viral vs bacterial conjunctivitis in adults and children, and to determine which symptoms or signs are suggestive of a viral vs bacterial etiology.

Data Sources: A MEDLINE search (January 1946-March 2022) yielded 1891 articles. Included articles were rated using a quality score based on a modified Rational Clinical Examination grading system. Methodological quality levels 1 through 4 required a microbiological reference standard for diagnosis, whereas quality level 5 (the lowest quality) used a clinical reference standard for diagnosis.

Study Selection: Consecutive series of patients presenting with acute infectious conjunctivitis and case series of viral or bacterial conjunctivitis alone. Thirty-two studies were included in a meta-analysis to determine prevalence and diagnostic accuracy measures; 27 used a microbiological reference standard for diagnosis and 5 used a clinical reference standard for diagnosis.

Results: In studies involving children (5 studies; 881 patients; mean age, 4.7 years [age range, 1 month-18 years]), the prevalence of bacterial conjunctivitis was higher than viral conjunctivitis (71% vs 16%, respectively, P = .01). In the only study of adults (n = 207 patients; mean age, 25.7 years), the prevalence of viral conjunctivitis was higher than bacterial conjunctivitis (78% vs 16%, respectively, P < .001). For the primary analysis of level 1 (n = 6) and level 2 (n = 5) studies (1725 patients total), the clinical findings that best distinguished a viral etiology for conjunctivitis from a bacterial etiology included pharyngitis (sensitivity range, 0.55-0.58; specificity range, 0.89-0.94; positive likelihood ratio [LR] range, 5.4-9.9), preauricular lymphadenopathy (sensitivity range, 0.17-0.31; specificity range, 0.93-0.94; positive LR range, 2.5-5.6), and contact with another person with red eye (sensitivity, 0.18 [95% CI, 0.14-0.22]; specificity, 0.93 [95% CI, 0.90-0.95]; positive LR, 2.5 [95% CI, 1.6-3.7]). Mucopurulent ocular discharge (sensitivity, 0.76 [95% CI, 0.60-0.87); specificity, 0.66 [95% CI, 0.58-0.73]; positive LR, 2.1 [95% CI, 1.7-2.6]) and otitis media (sensitivity, 0.24 [95% CI, 0.20-0.29]; specificity, 0.91 [95% CI, 0.85-0.94]; positive LR, 2.5 [95% CI, 1.5-4.4]) were associated with the presence of bacterial conjunctivitis.

Conclusions And Relevance: In this review, bacterial conjunctivitis was more common than viral conjunctivitis in children and viral conjunctivitis was more common than bacterial conjunctivitis in adults, although the prevalence estimates were based on limited evidence. Symptoms and signs associated with a higher likelihood of viral conjunctivitis in adults and children included concomitant pharyngitis, an enlarged preauricular node, and contact with another person with red eye, and signs associated with a higher likelihood of bacterial conjunctivitis included the presence of mucopurulent discharge and otitis media, but no single symptom or sign differentiated the 2 conditions with high certainty.
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http://dx.doi.org/10.1001/jama.2022.7687DOI Listing
June 2022

Does This Adult Patient Have Hypertension?: The Rational Clinical Examination Systematic Review.

JAMA 2021 07;326(4):339-347

Department of Medicine, Division of General Internal Medicine and Clinical Epidemiology, University of North Carolina at Chapel Hill.

Importance: Office blood pressure (BP) measurements are not the most accurate method to diagnose hypertension. Home BP monitoring (HBPM) and 24-hour ambulatory BP monitoring (ABPM) are out-of-office alternatives, and ABPM is considered the reference standard for BP assessment.

Objective: To systematically review the accuracy of oscillometric office and home BP measurement methods for correctly classifying adults as having hypertension, defined using ABPM.

Data Sources: PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and DARE databases and the American Heart Association website (from inception to April 2021) were searched, along with reference lists from retrieved articles.

Data Extraction And Synthesis: Two authors independently abstracted raw data and assessed methodological quality. A third author resolved disputes as needed.

Main Outcomes And Measures: Random effects summary sensitivity, specificity, and likelihood ratios (LRs) were calculated for BP measurement methods for the diagnosis of hypertension. ABPM (24-hour mean BP ≥130/80 mm Hg or mean BP while awake ≥135/85 mm Hg) was considered the reference standard.

Results: A total of 12 cross-sectional studies (n = 6877) that compared conventional oscillometric office BP measurements to mean BP during 24-hour ABPM and 6 studies (n = 2049) that compared mean BP on HBPM to mean BP during 24-hour ABPM were included (range, 117-2209 participants per analysis); 2 of these studies (n = 3040) used consecutive samples. The overall prevalence of hypertension identified by 24-hour ABPM was 49% (95% CI, 39%-60%) in the pooled studies that evaluated office measures and 54% (95% CI, 39%-69%) in studies that evaluated HBPM. All included studies assessed sensitivity and specificity at the office BP threshold of 140/90 mm Hg and the home BP threshold of 135/85 mm Hg. Conventional office oscillometric measurement (1-5 measurements in a single visit with BP ≥140/90 mm Hg) had a sensitivity of 51% (95% CI, 36%-67%), specificity of 88% (95% CI, 80%-96%), positive LR of 4.2 (95% CI, 2.5-6.0), and negative LR of 0.56 (95% CI, 0.42-0.69). Mean BP with HBPM (with BP ≥135/85 mm Hg) had a sensitivity of 75% (95% CI, 65%-86%), specificity of 76% (95% CI, 65%-86%), positive LR of 3.1 (95% CI, 2.2-4.0), and negative LR of 0.33 (95% CI, 0.20-0.47). Two studies (1 with a consecutive sample) that compared unattended automated mean office BP (with BP ≥135/85 mm Hg) with 24-hour ABPM had sensitivity ranging from 48% to 51% and specificity ranging from 80% to 91%. One study that compared attended automated mean office BP (with BP ≥140/90 mm Hg) with 24-hour ABPM had a sensitivity of 87.6% (95% CI, 83%-92%) and specificity of 24.1% (95% CI, 16%-32%).

Conclusions And Relevance: Office measurements of BP may not be accurate enough to rule in or rule out hypertension; HBPM may be helpful to confirm a diagnosis. When there is uncertainty around threshold values or when office and HBPM are not in agreement, 24-hour ABPM should be considered to establish the diagnosis.
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http://dx.doi.org/10.1001/jama.2021.4533DOI Listing
July 2021

Multivariable risk scores for predicting short-term outcomes for emergency department patients with unexplained syncope: A systematic review.

Acad Emerg Med 2021 05 28;28(5):502-510. Epub 2021 Jan 28.

Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

Objectives: Emergency department (ED) patients with unexplained syncope are at risk of experiencing an adverse event within 30 days. Our objective was to systematically review the accuracy of multivariate risk stratification scores for identifying adult syncope patients at high and low risk of an adverse event over the next 30 days.

Methods: We conducted a systematic review of electronic databases (MEDLINE, Cochrane, Embase, and CINAHL) from database creation until May 2020. We sought studies evaluating prediction scores of adults presenting to an ED with syncope. We included studies that followed patients for up to 30 days to identify adverse events such as death, myocardial infarction, stroke, or cardiac surgery. We only included studies with a blinded comparison between baseline clinical features and adverse events. We calculated likelihood ratios and confidence intervals (CIs).

Results: We screened 13,788 abstracts. We included 17 studies evaluating nine risk stratification scores on 24,234 patient visits, where 7.5% (95% CI = 5.3% to 10%) experienced an adverse event. A Canadian Syncope Risk Score (CSRS) of 4 or more was associated with a high likelihood of an adverse event (LR  = 11, 95% CI = 8.9 to 14). A CSRS of 0 or less (LR  = 0.10, 95% CI = 0.07 to 0.20) was associated with a low likelihood of an adverse event. Other risk scores were not validated on an independent sample, had low positive likelihood ratios for identifying patients at high risk, or had high negative likelihood ratios for identifying patients at low risk.

Conclusion: Many risk stratification scores are not validated or not sufficiently accurate for clinical use. The CSRS is an accurate validated prediction score for ED patients with unexplained syncope. Its impact on clinical decision making, admission rates, cost, or outcomes of care is not known.
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http://dx.doi.org/10.1111/acem.14203DOI Listing
May 2021

Does This Patient Have Hip Osteoarthritis?: The Rational Clinical Examination Systematic Review.

JAMA 2019 Dec;322(23):2323-2333

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom.

Importance: Hip osteoarthritis (OA) is a common cause of pain and disability.

Objective: To identify the clinical findings that are most strongly associated with hip OA.

Data Sources: Systematic search of MEDLINE, PubMed, EMBASE, and CINAHL from inception until November 2019.

Study Selection: Included studies (1) quantified the accuracy of clinical findings (history, physical examination, or simple tests) and (2) used plain radiographs as the reference standard for diagnosing hip OA.

Data Extraction And Synthesis: Studies were assigned levels of evidence using the Rational Clinical Examination scale and assessed for risk of bias using the Quality Assessment of Diagnostic Accuracy Studies tool. Data were extracted using individual hips as the unit of analysis and only pooled when findings were reported in 3 or more studies.

Main Outcomes And Measures: Sensitivity, specificity, and likelihood ratios (LRs).

Results: Six studies were included, with data from 1110 patients and 1324 hips, of which 509 (38%) showed radiographic evidence of OA. Among patients presenting to primary care physicians with hip or groin pain, the affected hip showed radiographic evidence of OA in 34% of cases. A family history of OA, personal history of knee OA, or pain on climbing stairs or walking up slopes all had LRs of 2.1 (sensitivity range, 33%-68%; specificity range, 68%-84%; broadest LR range: 95% CI, 1.1-3.8). To identify patients most likely to have OA, the most useful findings were squat causing posterior pain (sensitivity, 24%; specificity, 96%; LR, 6.1 [95% CI, 1.3-29]), groin pain on passive abduction or adduction (sensitivity, 33%; specificity, 94%; LR, 5.7 [95% CI, 1.6-20]), abductor weakness (sensitivity, 44%; specificity, 90%; LR, 4.5 [95% CI, 2.4-8.4]), and decreased passive hip adduction (sensitivity, 80%; specificity, 81%; LR, 4.2 [95% CI, 3.0-6.0]) or internal rotation (sensitivity, 66%; specificity, 79%; LR, 3.2 [95% CI, 1.7-6.0]) as measured by a goniometer or compared with the contralateral leg. The presence of normal passive hip adduction was most useful for suggesting the absence of OA (negative LR, 0.25 [95% CI, 0.11-0.54]).

Conclusions And Relevance: Simple tests of hip motion and observing for pain during that motion were helpful in distinguishing patients most likely to have OA on plain radiography from those who will not. A combination of findings efficiently detects those most likely to have severe hip OA.
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http://dx.doi.org/10.1001/jama.2019.19413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583647PMC
December 2019

Pain Management With Opioids in 2019-2020.

JAMA 2019 Nov;322(19):1912-1913

Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

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http://dx.doi.org/10.1001/jama.2019.15802DOI Listing
November 2019

Did This Patient Have Cardiac Syncope?: The Rational Clinical Examination Systematic Review.

JAMA 2019 06;321(24):2448-2457

Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

Importance: Syncope can result from a reduction in cardiac output from serious cardiac conditions, such as arrhythmias or structural heart disease (cardiac syncope), or other causes, such as vasovagal syncope or orthostatic hypotension.

Objective: To perform a systematic review of studies of the accuracy of the clinical examination for identifying patients with cardiac syncope.

Study Selection: Studies of adults presenting to primary care, emergency departments, or referred to specialty clinics.

Data Extraction And Synthesis: Relevant data were abstracted from articles in databases through April 9, 2019, and methodologic quality was assessed. Included studies had an independent comparison to a reference standard.

Main Outcomes And Measures: Sensitivity, specificity, and likelihood ratios (LRs).

Results: Eleven studies of cardiac syncope (N = 4317) were included. Age at first syncope of at least 35 years was associated with greater likelihood of cardiac syncope (n = 323; sensitivity, 91% [95% CI, 85%-97%]; specificity, 72% [95% CI, 66%-78%]; LR, 3.3 [95% CI, 2.6-4.1]), while age younger than 35 years was associated with a lower likelihood (LR, 0.13 [95% CI, 0.06-0.25]). A history of atrial fibrillation or flutter (n = 323; sensitivity, 13% [95% CI, 6%-20%]; specificity, 98% [95% CI, 96%-100%]; LR, 7.3 [95% CI, 2.4-22]), or known severe structural heart disease (n = 222; range of sensitivity, 35%-51%, range of specificity, 84%-93%; range of LR, 3.3-4.8; 2 studies) were associated with greater likelihood of cardiac syncope. Symptoms prior to syncope that were associated with lower likelihood of cardiac syncope were mood change or prodromal preoccupation with details (n = 323; sensitivity, 2% [95% CI, 0%-5%]; specificity, 76% [95% CI, 71%-81%]; LR, 0.09 [95% CI, 0.02-0.38]), feeling cold (n = 412; sensitivity, 2% [95% CI, 0%-5%]; specificity, 89% [95% CI, 85%-93%]; LR, 0.16 [95% CI, 0.06-0.64]), or headache (n = 323; sensitivity, 3% [95% CI, 0%-7%]; specificity, 80% [95% CI, 75%-85%]; LR, 0.17 [95% CI, 0.06-0.55]). Cyanosis witnessed during the episode was associated with higher likelihood of cardiac syncope (n = 323; sensitivity, 8% [95% CI, 2%-14%]; specificity, 99% [95% CI, 98%-100%]; LR, 6.2 [95% CI, 1.6-24]). Mood changes after syncope (n = 323; sensitivity, 3% [95% CI, 0%-7%]; specificity, 83% [95% CI, 78%-88%]; LR, 0.21 [95% CI, 0.06-0.65]) and inability to remember behavior prior to syncope (n = 323; sensitivity, 5% [95% CI, 0%-9%]; specificity, 82% [95% CI, 77%-87%]; LR, 0.25, [95% CI, 0.09-0.69]) were associated with lower likelihood of cardiac syncope. Two studies prospectively validated the accuracy of the multivariable Evaluation of Guidelines in Syncope Study (EGSYS) score, which is based on 6 clinical variables. An EGSYS score of less than 3 was associated with lower likelihood of cardiac syncope (n = 456; range of sensitivity, 89%-91%, range of specificity, 69%-73%; range of LR, 0.12-0.17; 2 studies). Cardiac biomarkers show promising diagnostic accuracy for cardiac syncope, but diagnostic thresholds require validation.

Conclusions And Relevance: The clinical examination, including the electrocardiogram as part of multivariable scores, can accurately identify patients with and without cardiac syncope.
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http://dx.doi.org/10.1001/jama.2019.8001DOI Listing
June 2019

Strategies to Identify Patient Risks of Prescription Opioid Addiction When Initiating Opioids for Pain: A Systematic Review.

JAMA Netw Open 2019 05 3;2(5):e193365. Epub 2019 May 3.

Department of Medicine, University of British Columbia, St Paul's Hospital, Vancouver, British Columbia, Canada.

Importance: Although prescription opioid use disorder is associated with substantial harms, strategies to identify patients with pain among whom prescription opioids can be safely prescribed have not been systematically reviewed.

Objective: To review the evidence examining factors associated with opioid addiction and screening tools for identifying adult patients at high vs low risk of developing symptoms of prescription opioid addiction when initiating prescription opioids for pain.

Data Sources: MEDLINE and Embase (January 1946 to November 2018) were searched for articles investigating risks of prescription opioid addiction.

Study Selection: Original studies that were included compared symptoms, signs, risk factors, and screening tools among patients who developed prescription opioid addiction and those who did not.

Data Extraction And Synthesis: Two investigators independently assessed quality to exclude biased or unreliable study designs and extracted data from higher quality studies. The Preferred Reporting Items for Systematic Reviews and Meta-analyses of Diagnostic Accuracy Studies (PRISMA-DTA) reporting guideline was followed.

Main Outcomes And Measures: Likelihood ratios (LRs) for risk factors and screening tools were calculated.

Results: Of 1287 identified studies, 6 high-quality studies were included in the qualitative synthesis and 4 were included in the quantitative synthesis. The 4 high-quality studies included in the quantitative synthesis were all retrospective studies including a total of 2 888 346 patients with 4470 cases that met the authors' definitions of prescription opioid addiction. A history of opioid use disorder (LR range, 17-22) or other substance use disorder (LR range, 4.2-17), certain mental health diagnoses (eg, personality disorder: LR, 27; 95% CI, 18-41), and concomitant prescription of certain psychiatric medications (eg, atypical antipsychotics: LR, 17; 95% CI, 15-18) appeared useful for identifying patients at high risk of opioid addiction. Among individual findings, only the absence of a mood disorder (negative LR, 0.50; 95% CI, 0.45-0.52) was associated with a lower risk of opioid addiction. Despite their widespread use, most screening tools involving combinations of questions were based on low-quality studies or, when diagnostic performance was assessed among high-quality studies, demonstrated poor performance in helping to identify patients at high vs low risk.

Conclusions And Relevance: While a history of substance use disorder, certain mental health diagnoses, and concomitant prescription of certain psychiatric medications appeared useful for identifying patients at higher risk, few quality studies were available and no symptoms, signs, or screening tools were particularly useful for identifying those at lower risk.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.3365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503484PMC
May 2019

Does This Patient Have a Severe Snake Envenomation?: The Rational Clinical Examination Systematic Review.

JAMA Surg 2019 04;154(4):346-354

Department of Emergency Medicine and Rocky Mountain Poison and Drug Center, Denver Health, Denver, Colorado.

Importance: Venomous snakebite severity ranges from an asymptomatic dry bite to severe envenomation and death. The clinical evaluation aids in prognosis and is essential to determine the risks and potential benefits of antivenom treatment.

Objectives: To identify historical features, clinical examination findings, basic laboratory testing, and clinical grading scales that will risk-stratify patients with pit viper snake envenomation for severe systemic envenomation, severe tissue injury, and/or severe hematologic venom effects.

Data Sources: We conducted a structured search of PubMed (1966-October 3, 2017) and Embase database (1980-October 3, 2017) to identify English-language studies that evaluated clinical features predictive of severe envenomation.

Study Selection: We included studies that evaluated the test performance of at least 1 clinical finding with an acceptable reference standard of severe envenomation for venomous snakes of the Western Hemisphere. Only studies involving the most common subfamily, Crotalinae (pit vipers), were evaluated. Seventeen studies with data were available for abstraction.

Data Extraction And Synthesis: The clinical features assessed and severity outcome measures were extracted from each original study. We assessed severity in 3 categories: systemic toxicity, tissue injury, and hematologic effects. Differences were resolved by author consensus.

Results: The pooled prevalence of severe systemic envenomation was 14% (95% CI, 9%-21%). The pooled prevalence of severe tissue injury and severe hematologic venom effects were 14% (95% CI, 12%-16%) and 18% (95% CI, 8%-27%), respectively. Factors increasing the likelihood of severe systemic envenomation included the time from bite to care of 6 or more hours (likelihood ratio [LR], 3.4 [95% CI, 1.1-6.4]), a patient younger than 12 years (LRs, 3.2 [95% CI, 1.5-7.1] and 2.9 [95% CI, 1.3-6.2]), large snake size (LR, 3.1 [95% CI, 1.5-5.7]), and ptosis (LRs, 1.4 [95% CI, 1.0-2.1] and 3.8 [95% CI, 1.8-8.3]). Envenomation by the genus Agkistrodon (copperhead and cottonmouth), as opposed to rattlesnakes, decreased the likelihood of severe systemic envenomation (LR, 0.28 [95% CI, 0.10-0.78]). Initial hypofibrinogenemia (LR, 5.1 [95% CI, 1.7-15.0]) and thrombocytopenia (LR, 3.7 [95% CI, 1.9-7.3]) increased the likelihood of severe hematologic venom effects. Other clinical features from history, physical examination, or normal laboratory values were not discriminative.

Conclusions: Clinical features can identify patients at increased risk of severe systemic envenomation and severe hematologic venom effects, but there are few features that are associated with severe tissue injury or can confidently exclude severe envenomation. Physicians should monitor patients closely and be wary of progression from nonsevere to a severe envenomation and have a low threshold to escalate therapy as needed.
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http://dx.doi.org/10.1001/jamasurg.2018.5069DOI Listing
April 2019

Will This Patient Be Difficult to Intubate?: The Rational Clinical Examination Systematic Review.

JAMA 2019 Feb;321(5):493-503

Interdepartmental Division of Critical Care Medicine and Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

Importance: Recognizing patients in whom endotracheal intubation is likely to be difficult can help alert physicians to the need for assistance from a clinician with airway training and having advanced airway management equipment available.

Objective: To identify risk factors and physical findings that predict difficult intubation.

Data Sources: The databases of MEDLINE and EMBASE were searched from 1946 to June 2018 and from 1947 to June 2018, respectively, and the reference lists from the retrieved articles and previous reviews were searched for additional studies.

Study Selection: Sixty-two studies with high (level 1-3) methodological quality that evaluated the accuracy of clinical findings for identifying difficult intubation were reviewed.

Data Extraction And Synthesis: Two authors independently abstracted data. Bivariate random-effects meta-analyses were used to calculate summary positive likelihood ratios across studies or univariate random-effects models when bivariate models failed to converge.

Results: Among the 62 high-quality studies involving 33 559 patients, 10% (95% CI, 8.2%-12%) of patients were difficult to intubate. The physical examination findings that best predicted a difficult intubation included a grade of class 3 on the upper lip bite test (lower incisors cannot extend to reach the upper lip; positive likelihood ratio, 14 [95% CI, 8.9-22]; specificity, 0.96 [95% CI, 0.93-0.97]), shorter hyomental distance (range of <3-5.5 cm; positive likelihood ratio, 6.4 [95% CI, 4.1-10]; specificity, 0.97 [95% CI, 0.94-0.98]), retrognathia (mandible measuring <9 cm from the angle of the jaw to the tip of the chin or subjectively short; positive likelihood ratio, 6.0 [95% CI, 3.1-11]; specificity, 0.98 [95% CI, 0.90-1.0]), and a combination of physical findings based on the Wilson score (positive likelihood ratio, 9.1 [95% CI, 5.1-16]; specificity, 0.95 [95% CI, 0.90-0.98]). The widely used modified Mallampati score (≥3) had a positive likelihood ratio of 4.1 (95% CI, 3.0-5.6; specificity, 0.87 [95% CI, 0.81-0.91]).

Conclusions And Relevance: Although several simple clinical findings are useful for predicting a higher likelihood of difficult endotracheal intubation, no clinical finding reliably excludes a difficult intubation. An abnormal upper lip bite test, which is easily assessed by clinicians, raises the probability of difficult intubation from 10% to greater than 60% for the average-risk patient.
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http://dx.doi.org/10.1001/jama.2018.21413DOI Listing
February 2019

Does This Patient Have Acute Mountain Sickness?: The Rational Clinical Examination Systematic Review.

JAMA 2017 11;318(18):1810-1819

Service of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland.

Importance: Acute mountain sickness (AMS) affects more than 25% of individuals ascending to 3500 m (11 500 ft) and more than 50% of those above 6000 m (19 700 ft). AMS may progress from nonspecific symptoms to life-threatening high-altitude cerebral edema in less than 1% of patients. It is not clear how to best diagnose AMS.

Objective: To systematically review studies assessing the accuracy of AMS diagnostic instruments, including the visual analog scale (VAS) score, which quantifies the overall feeling of sickness at altitude (VAS[O]; various thresholds), Acute Mountain Sickness-Cerebral score (AMS-C; ≥0.7 indicates AMS), and the clinical functional score (CFS; ≥2 indicates AMS) compared with the Lake Louise Questionnaire Score (LLQS; score of ≥5).

Data Extraction And Synthesis: Searches of MEDLINE and EMBASE from inception to May 2017 identified 1245 publications of which 91 were suitable for prevalence analysis (66 944 participants) and 14 compared at least 2 instruments (1858 participants) using a score of 5 or greater on the LLQS as a reference standard. To determine the prevalence of AMS for establishing the pretest probability of AMS, a random-effects meta-regression was performed based on the reported prevalence of AMS as a function of altitude.

Main Outcomes And Measures: AMS prevalence, likelihood ratios (LRs), sensitivity, and specificity of screening instruments.

Results: The final analysis included 91 articles (comprising 66 944 study participants). Altitude predicted AMS and accounted for 28% of heterogeneity between studies. For each 1000-m (3300-ft) increase in altitude above 2500 m (8200 ft), AMS prevalence increased 13% (95% CI, 9.5%-17%). Testing characteristics were similar for VAS(O), AMS-C, and CFS vs a score of 5 or greater on the LLQS (positive LRs: range, 3.2-8.2; P = .22 for comparisons; specificity range, 67%-92%; negative LRs: range, 0.30-0.36; P = .50 for comparisons; sensitivity range, 67%-82%). The CFS asks a single question: "overall if you had any symptoms, how did they affect your activity (ordinal scale 0-3)?" For CFS, moderate to severe reduction in daily activities had a positive LR of 3.2 (95% CI, 1.4-7.2) and specificity of 67% (95% CI, 37%-97%); no reduction to mild reduction in activities had a negative LR of 0.30 (95% CI, 0.22-0.39) and sensitivity of 82% (95% CI, 77%-87%).

Conclusions And Relevance: The prevalence of acute mountain sickness increases with higher altitudes. The visual analog scale for the overall feeling of sickness at altitude, Acute Mountain Sickness-Cerebral, and clinical functional score perform similarly to the Lake Louise Questionnaire Score using a score of 5 or greater as a reference standard. In clinical and travel settings, the clinical functional score is the simplest instrument to use. Clinicians evaluating high-altitude travelers who report moderate to severe limitations in activities of daily living (clinical functional score ≥2) should use the Lake Louise Questionnaire Score to assess the severity of acute mountain sickness.
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http://dx.doi.org/10.1001/jama.2017.16192DOI Listing
November 2017

Urinalysis in the Evaluation of Proliferative Glomerulonephritis.

JAMA 2017 Oct;318(13):1276-1277

Division of Nephrology, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1001/jama.2017.14482DOI Listing
October 2017

Does This Child Have Pneumonia?: The Rational Clinical Examination Systematic Review.

JAMA 2017 Aug;318(5):462-471

Division of Emergency Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.

Importance: Pneumonia is a leading cause of morbidity and mortality in children. It is important to identify the clinical symptoms and physical examination findings associated with pneumonia to improve timely diagnosis, prevent significant morbidity, and limit antibiotic overuse.

Objective: To systematically review the accuracy of symptoms and physical examination findings in identifying children with radiographic pneumonia.

Data Sources And Study Selection: MEDLINE and Embase (1956 to May 2017) were searched, along with reference lists from retrieved articles, to identify diagnostic studies of pediatric pneumonia across a broad age range that had to include children younger than age 5 years (although some studies enrolled children up to age 19 years); 3644 unique articles were identified, of which 23 met inclusion criteria.

Data Extraction And Synthesis: Two authors independently abstracted raw data and assessed methodological quality. A third author resolved disputes.

Main Outcomes And Measures: Likelihood ratios (LRs), sensitivity, and specificity were calculated for individual symptoms and physical examination findings for the diagnosis of pneumonia. An infiltrate on chest radiograph was considered the reference standard for the diagnosis of pneumonia.

Results: Twenty-three prospective cohort studies of children (N = 13 833) with possible pneumonia were included (8 from North America), with a range of 78 to 2829 patients per study. The prevalence of radiographic pneumonia in North American studies was 19% (95% CI, 11%-31%) and 37% (95% CI, 26%-50%) outside of North America. No single symptom was strongly associated with pneumonia; however, the presence of chest pain in 2 studies that included adolescents was associated with pneumonia (LR, 1.5-5.5; sensitivity, 8%-14%; specificity, 94%-97%). Vital sign abnormalities such as fever (temperature >37.5°C [LR range, 1.7-1.8]; sensitivity, 80%-92%; specificity, 47%-54%) and tachypnea (respiratory rate >40 breaths/min; LR, 1.5 [95% CI, 1.3-1.7]; sensitivity, 79%; specificity, 51%) were not strongly associated with pneumonia diagnosis. Similarly, auscultatory findings were not associated with pneumonia diagnosis. The presence of moderate hypoxemia (oxygen saturation ≤96%; LR, 2.8 [95% CI, 2.1-3.6]; sensitivity, 64%; specificity, 77%) and increased work of breathing (grunting, flaring, and retractions; positive LR, 2.1 [95% CI, 1.6-2.7]) were signs most associated with pneumonia. The presence of normal oxygenation (oxygen saturation >96%) decreased the likelihood of pneumonia (LR, 0.47 [95% CI, 0.32-0.67]).

Conclusions And Relevance: Although no single finding reliably differentiates pneumonia from other causes of childhood respiratory illness, hypoxia and increased work of breathing are more important than tachypnea and auscultatory findings.
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http://dx.doi.org/10.1001/jama.2017.9039DOI Listing
August 2017

Improving Timely Resident Follow-Up and Communication of Results in Ambulatory Clinics Utilizing a Web-Based Audit and Feedback Module.

J Grad Med Educ 2017 Apr;9(2):195-200

Background: Failure to follow up and communicate test results to patients in outpatient settings may lead to diagnostic and therapeutic delays. Residents are less likely than attending physicians to report results to patients, and may face additional barriers to reporting, given competing clinical responsibilities.

Objective: This study aimed to improve the rates of communicating test results to patients in resident ambulatory clinics.

Methods: We performed an internal medicine, residency-wide, pre- and postintervention, quality improvement project using audit and feedback. Residents performed audits of ambulatory patients requiring laboratory or radiologic testing by means of a shared online interface. The intervention consisted of an educational module viewed with initial audits, development of a personalized improvement plan after Phase 1, and repeated real-time feedback of individual relative performance compared at clinic and program levels. Outcomes included results communicated within 14 days and prespecified "significant" results communicated within 72 hours.

Results: A total of 76 of 86 eligible residents (88%) reviewed 1713 individual ambulatory patients' charts in Phase 1, and 73 residents (85%) reviewed 1509 charts in Phase 2. Follow-up rates were higher in Phase 2 than Phase 1 for communicating results within 14 days and significant results within 72 hours (85% versus 78%,  < .001; and 82% versus 70%,  = .002, respectively). Communication of "significant" results was more likely to occur via telephone, compared with communication of nonsignificant results.

Conclusions: Participation in a shared audit and feedback quality improvement project can improve rates of resident follow-up and communication of results, although communication gaps remained.
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http://dx.doi.org/10.4300/JGME-D-16-00460.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5398151PMC
April 2017

Splenectomy as a Destination: Improving Quality of Care Among Asplenic Veterans Through a Travel Clinic.

Am J Med 2017 07 14;130(7):856-861. Epub 2017 Feb 14.

Department of Medicine, Durham Veterans Affairs Medical Center, NC.

Background: Asplenic patients are at risk for severe infections, but adherence to recommended preventive education and vaccination is poor. The goal of this study was to demonstrate that a targeted intervention can improve vaccination rates in a population of asplenic veterans.

Methods: Surgically asplenic patients actively receiving care in our health care system were identified via a database search. Patients were contacted via mailed letters and encouraged to attend an existing travel clinic with a new process designed for asplenic patients. In the clinic, patients were educated on the risks of asplenia and proper preventive precautions, a vaccination history was taken, and patients were administered any additional indicated vaccines.

Results: The database search yielded 113 patients; an additional 14 asplenic patients were identified and referred to the clinic by providers, and 2 were referred prior to planned splenectomy. Among all asplenic patients, the first-year referral rate to clinic was 38/129 (29%). During the first year of the intervention, there were increases in the rates of 3 of 4 recommended vaccinations: pneumococcal conjugate, 19% to 55% (P <.001); Haemophilus influenzae type B, 19% to 35% (P = .007); and meningococcal vaccine, 24% to 43% (P = .002). The pneumococcal polysaccharide vaccination rate increased from 91% to 93% (P = .62).

Conclusions: Targeted interventions can improve guideline-based care for asplenic patients. The creation of a clinic designed for asplenic patients led to increases in 3 of 4 recommended vaccinations. This strategy may be applicable to other health care systems with similar numbers of asplenic patients.
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http://dx.doi.org/10.1016/j.amjmed.2017.01.024DOI Listing
July 2017

Predicting low testosterone in aging men: a systematic review.

CMAJ 2016 Sep 20;188(13):E321-E330. Epub 2016 Jun 20.

Department of Medicine (Millar, Tomlinson, Detsky, Lipscombe) and Institute of Health Policy, Management and Evaluation (Tomlinson, Detsky, Lipscombe), University of Toronto, Toronto, Ont.; Department of Medicine (Millar, Lau, Tomlinson, Kraguljac, Detsky), Mount Sinai Hospital and University Health Network, Toronto, Ont.; Durham Veterans Affairs Medical Center (Simel), Durham, NC; Department of Medicine (Simel), Duke University, Durham, NC; Department of Medicine (Lipscombe), Women's College Research Institute of Women's College Hospital, Toronto, Ont.

Background: Physicians diagnose and treat suspected hypogonadism in older men by extrapolating from the defined clinical entity of hypogonadism found in younger men. We conducted a systematic review to estimate the accuracy of clinical symptoms and signs for predicting low testosterone among aging men.

Methods: We searched the MEDLINE and Embase databases (January 1966 to July 2014) for studies that compared clinical features with a measurement of serum testosterone in men. Three of the authors independently reviewed articles for inclusion, assessed quality and extracted data.

Results: Among 6053 articles identified, 40 met the inclusion criteria. The prevalence of low testosterone ranged between 2% and 77%. Threshold testosterone levels used for reference standards also varied substantially. The summary likelihood ratio associated with decreased libido was 1.6 (95% confidence interval [CI] 1.3-1.9), and the likelihood ratio for absence of this finding was 0.72 (95% CI 0.58-0.85). The likelihood ratio associated with the presence of erectile dysfunction was 1.5 (95% CI 1.3-1.8) and with absence of erectile dysfunction was 0.83 (95% CI 0.76-0.91). Of the multiple-item instruments, the ANDROTEST showed both the most favourable positive likelihood ratio (range 1.9-2.2) and the most favourable negative likelihood ratio (range 0.37-0.49).

Interpretation: We found weak correlation between signs, symptoms and testosterone levels, uncertainty about what threshold testosterone levels should be considered low for aging men and wide variation in estimated prevalence of the condition. It is therefore difficult to extrapolate the method of diagnosing pathologic hypogonadism in younger men to clinical decisions regarding age-related testosterone decline in aging men.
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http://dx.doi.org/10.1503/cmaj.150262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026531PMC
September 2016

Does This Patient With Chest Pain Have Acute Coronary Syndrome?: The Rational Clinical Examination Systematic Review.

JAMA 2015 Nov;314(18):1955-65

Division of Cardiology, Duke University, Durham, North Carolina2Department of Medicine, Duke University, Durham, North Carolina4Duke Clinical Research Institute, Duke University, Durham, North Carolina.

Importance: About 10% of patients with acute chest pain are ultimately diagnosed with acute coronary syndrome (ACS). Early, accurate estimation of the probability of ACS in these patients using the clinical examination could prevent many hospital admissions among low-risk patients and ensure that high-risk patients are promptly treated.

Objective: To review systematically the accuracy of the initial history, physical examination, electrocardiogram, and risk scores incorporating these elements with the first cardiac-specific troponin.

Study Selection: MEDLINE and EMBASE were searched (January 1, 1995-July 31, 2015), along with reference lists from retrieved articles, to identify prospective studies of diagnostic test accuracy among patients admitted to the emergency department with symptoms suggesting ACS.

Data Extraction And Synthesis: We identified 2992 unique articles; 58 met inclusion criteria.

Main Outcomes And Measures: Sensitivity, specificity, and likelihood ratio (LR) of findings for the diagnosis of ACS. The reference standard for ACS was either a final hospital diagnosis of ACS or occurrence of a cardiovascular event within 6 weeks.

Results: The clinical findings and risk factors most suggestive of ACS were prior abnormal stress test (specificity, 96%; LR, 3.1 [95% CI, 2.0-4.7]), peripheral arterial disease (specificity, 97%; LR, 2.7 [95% CI, 1.5-4.8]), and pain radiation to both arms (specificity, 96%; LR, 2.6 [95% CI, 1.8-3.7]). The most useful electrocardiogram findings were ST-segment depression (specificity, 95%; LR, 5.3 [95% CI, 2.1-8.6]) and any evidence of ischemia (specificity, 91%; LR, 3.6 [95% CI,1.6-5.7]). Both the History, Electrocardiogram, Age, Risk Factors, Troponin (HEART) and Thrombolysis in Myocardial Infarction (TIMI) risk scores performed well in diagnosing ACS: LR, 13 (95% CI, 7.0-24) for the high-risk range of the HEART score (7-10) and LR, 6.8 (95% CI, 5.2-8.9) for the high-risk range of the TIMI score (5-7). The most useful for identifying patients less likely to have ACS were the low-risk range HEART score (0-3) (LR, 0.20 [95% CI, 0.13-0.30]), low-risk range TIMI score (0-1) (LR, 0.31 [95% CI, 0.23-0.43]), or low to intermediate risk designation by the Heart Foundation of Australia and Cardiac Society of Australia and New Zealand risk algorithm (LR, 0.24 [95% CI, 0.19-0.31]).

Conclusions And Relevance: Among patients with suspected ACS presenting to emergency departments, the initial history, physical examination, and electrocardiogram alone did not confirm or exclude the diagnosis of ACS. Instead, the HEART or TIMI risk scores, which incorporate the first cardiac troponin, provided more diagnostic information.
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http://dx.doi.org/10.1001/jama.2015.12735DOI Listing
November 2015

Guideline-based decision support has a small, non-sustained effect on transthoracic echocardiography ordering frequency.

BMJ Qual Saf 2016 Jan 24;25(1):57-62. Epub 2015 Sep 24.

Department of Medicine, Durham VA Medical Center, Durham, North Carolina, USA Department of Medicine, Duke University Health System, Durham, North Carolina, USA.

Background: Guidance for appropriate utilisation of transthoracic echocardiograms (TTEs) can be incorporated into ordering prompts, potentially affecting the number of requests.

Methods: We incorporated data from the 2011 Appropriate Use Criteria for Echocardiography, the 2010 National Institute for Clinical Excellence Guideline on Chronic Heart Failure, and American College of Cardiology Choosing Wisely list on TTE use for dyspnoea, oedema and valvular disease into electronic ordering systems at Durham Veterans Affairs Medical Center. Our primary outcome was TTE orders per month. Secondary outcomes included rates of outpatient TTE ordering per 100 visits and frequency of brain natriuretic peptide (BNP) ordering prior to TTE. Outcomes were measured for 20 months before and 12 months after the intervention.

Results: The number of TTEs ordered did not decrease (338±32 TTEs/month prior vs 320±33 afterwards, p=0.12). Rates of outpatient TTE ordering decreased minimally post intervention (2.28 per 100 primary care/cardiology visits prior vs 1.99 afterwards, p<0.01). Effects on TTE ordering and ordering rate significantly interacted with time from intervention (p<0.02 for both), as the small initial effects waned after 6 months. The percentage of TTE orders with preceding BNP increased (36.5% prior vs 42.2% after for inpatients, p=0.01; 10.8% prior vs 14.5% after for outpatients, p<0.01).

Conclusions: Ordering prompts for TTEs initially minimally reduced the number of TTEs ordered and increased BNP measurement at a single institution, but the effect on TTEs ordered was likely insignificant from a utilisation standpoint and decayed over time.
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http://dx.doi.org/10.1136/bmjqs-2015-004284DOI Listing
January 2016

Reductions in telemetry order duration do not reduce telemetry utilization.

J Hosp Med 2014 Dec 29;9(12):795-6. Epub 2014 Sep 29.

Department of Medicine, Durham Veterans Affairs Medical Center, Durham, North Carolina; Department of Medicine, Duke University Health System, Durham, North Carolina.

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http://dx.doi.org/10.1002/jhm.2264DOI Listing
December 2014

Does this adult patient have early HIV infection?: The Rational Clinical Examination systematic review.

JAMA 2014 Jul;312(3):278-85

Durham Veterans Affairs Medical Center, Durham, North Carolina7Duke University Medical Center, Durham, North Carolina.

Importance: Timely identification of human immunodeficiency virus (HIV) infection in adults can contribute to reduced mortality and likelihood of further HIV transmission. During the first 6 months after infection, known as early HIV infection, patients often report a well-described constellation of symptoms and signs. However, the literature examining utility of the clinical examination in identifying early infection has not been systematically assessed.

Objective: To assess the accuracy of symptoms and signs in identifying early HIV infection among adults.

Data Sources: We searched MEDLINE and EMBASE (1981-May, 2014) for articles investigating symptoms and signs of early HIV infection in adults and searched reference lists of retrieved articles.

Study Selection: We retained original studies that compared symptoms and signs among patients with early HIV infection in comparison to HIV-negative individuals.

Data Extraction And Synthesis: Data were extracted and used to calculate sensitivity, specificity, and likelihood ratios (LRs), and meta-analysis was used to calculate summary LRs.

Results: Of 1356 studies, 16 studies included data that were eligible for meta-analysis and included a total of 24,745 patients and 1253 cases of early HIV infection. Symptoms that increased the likelihood of early HIV infection the most included genital ulcers (LR, 5.4; 95% CI, 2.5-12), weight loss (LR, 4.7; 95% CI, 2.1-7.2), vomiting (LR, 4.6; 95% CI, 2.5-8.0), and swollen lymph nodes (LR, 4.6; 95% CI, 1.3-8.0). No symptoms had an LR that was 0.5 or lower, but the absence of recent fever (LR, 0.74; 95% CI, 0.64-0.84) slightly decreased the likelihood of early HIV infection. The presence of lymphadenopathy on physical examination was the most useful sign (LR, 3.1; 95% CI, 1.0-5.2). No sign had an LR of 0.5 or less, but the absence of lymphadenopathy slightly decreased the likelihood of early HIV infection (LR, 0.70, 95% CI, 0.49-0.92). Using data from studies that considered combinations of findings (range of possible findings, 4-17), the summary LR for individuals with 0 findings was 0.47 (95% CI, 0.38-0.58).

Conclusions And Relevance: The limited utility of the clinical examination to detect or rule out early HIV infection highlights the importance of routine testing for HIV infection among adults.
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http://dx.doi.org/10.1001/jama.2014.5954DOI Listing
July 2014

Does this patient have obstructive sleep apnea?: The Rational Clinical Examination systematic review.

JAMA 2013 Aug;310(7):731-41

Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.

Importance: Obstructive sleep apnea is a common disease, responsible for daytime sleepiness. Prior to referring patients for definitive testing, the likelihood of obstructive sleep apnea should be established in the clinical examination.

Objective: To systematically review the clinical examination accuracy in diagnosing obstructive sleep apnea.

Data Sources: MEDLINE and reference lists from articles were searched from 1966 to June 2013. Titles and abstracts (n = 4449) were reviewed for eligibility and appraised for evidence levels.

Study Selection: For inclusion, studies must have used full, attended nocturnal polysomnography for the reference standard (n = 42).

Main Outcomes And Measures: Community and referral-based prevalence of obstructive sleep apnea; accuracy of symptoms and signs for the diagnosis of obstructive sleep apnea.

Results: The prevalence of sleep apnea in community-screened patients is 2% to 14% (sample sizes 360-1741) and 21% to 90% (sample sizes 42-2677) for patients referred for sleep evaluation. The prevalence varies based on the apnea-hypopnea index (AHI) threshold used for the evaluation (≥5 events/h, prevalence 14%; ≥15/h, prevalence 6%) and whether the disease definition requires symptoms in addition to an abnormal AHI (≥5/h with symptoms, prevalence 2%-4%). Among patients referred for sleep evaluation, those with sleep apnea weighed more (summary body mass index, 31.4; 95% CI, 30.5-32.2) than those without sleep apnea (summary BMI, 28.3; 95% CI, 27.6-29.0; P < .001 for the comparison). The most useful observation for identifying patients with obstructive sleep apnea was nocturnal choking or gasping (summary likelihood ratio [LR], 3.3; 95% CI, 2.1-4.6) when the diagnosis was established by AHI ≥10/h). Snoring is common in sleep apnea patients but is not useful for establishing the diagnosis (summary LR, 1.1; 95% CI, 1.0-1.1). Patients with mild snoring and body mass index lower than 26 are unlikely to have moderate or severe obstructive sleep apnea (LR, 0.07; 95% CI, 0.03-0.19 at threshold of AHI ≥15/h).

Conclusions And Relevance: Nocturnal gasping or choking is the most reliable indicator of obstructive sleep apnea, whereas snoring is not very specific. The clinical examination of patients with suspected obstructive sleep apnea is useful for selecting patients for more definitive testing.
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http://dx.doi.org/10.1001/jama.2013.276185DOI Listing
August 2013

Does this patient with shoulder pain have rotator cuff disease?: The Rational Clinical Examination systematic review.

JAMA 2013 Aug;310(8):837-47

Department of Orthopaedic Surgery, Erasmus MC University Medical Centre Rotterdam, Rotterdam, The Netherlands.

Importance: Rotator cuff disease (RCD) is the most common cause of shoulder pain seen by physicians.

Objective: To perform a meta-analysis to identify the most accurate clinical examination findings for RCD.

Data Sources: Structured search in MEDLINE, EMBASE, and CINAHL from their inception through May 2013.

Study Selection: For inclusion, a study must have met the following criteria: (1) description of history taking, physical examination, or clinical tests concerning RCD; (2) detailing of sensitivity and specificity; (3) use of a reference standard with diagnostic criteria prespecified; (4) presentation of original data, or original data could be obtained from the authors; and (5) publication in a language mastered by one of the authors (Danish, Dutch, English, French, German, Norwegian, Spanish, Swedish).

Main Outcomes And Measures: Likelihood ratios (LRs) of symptoms and signs of RCD or of a tear, compared with an acceptable reference standard; quality scores assigned using the Rational Clinical Examination score and bias evaluated with the Quality Assessment of Diagnostic Accuracy Studies tool.

Results: Twenty-eight studies assessed the examination of referred patients by specialists. Only 5 studies reached Rational Clinical Examination quality scores of level 1-2. The studies with quality scores of level 1-2 included 30 to 203 shoulders with the prevalence of RCD ranging from 33% to 81%. Among pain provocation tests, a positive painful arc test result was the only finding with a positive LR greater than 2.0 for RCD (3.7 [95% CI, 1.9-7.0]), and a normal painful arc test result had the lowest negative LR (0.36 [95% CI, 0.23-0.54]). Among strength tests, a positive external rotation lag test (LR, 7.2 [95% CI, 1.7-31]) and internal rotation lag test (LR, 5.6 [95% CI, 2.6-12]) were the most accurate findings for full-thickness tears. A positive drop arm test result (LR, 3.3 [95% CI, 1.0-11]) might help identify patients with RCD. A normal internal rotation lag test result was most accurate for identifying patients without a full-thickness tear (LR, 0.04 [95% CI, 0.0-0.58]).

Conclusions And Relevance: Because specialists performed all the clinical maneuvers for RCD in each of the included studies with no finding evaluated in more than 3 studies, the generalizability of the results to a nonreferred population is unknown. A positive painful arc test result and a positive external rotation resistance test result were the most accurate findings for detecting RCD, whereas the presence of a positive lag test (external or internal rotation) result was most accurate for diagnosis of a full-thickness rotator cuff tear.
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http://dx.doi.org/10.1001/jama.2013.276187DOI Listing
August 2013

Do findings on routine examination identify patients at risk for primary open-angle glaucoma? The rational clinical examination systematic review.

JAMA 2013 May;309(19):2035-42

Department of Ophthalmology, Queen’s University, Kingston, Ontario, Canada.

Importance: Glaucoma is the second leading cause of blindness worldwide, and its insidious onset is often associated with diagnostic delay. Since glaucoma progression can often be effectively diminished when treated, identifying individuals at risk for glaucoma could potentially lead to earlier detection and prevent associated vision loss.

Objective: To quantify the diagnostic accuracy of examination findings and relevant risk factors in identifying individuals with primary open-angle glaucoma (POAG), the most common form of glaucoma in North America.

Data Sources: Structured Medline (January 1950-January 2013) search and a hand search of references and citations of retrieved articles yielding 57 articles from 41 studies.

Study Selection: Population-based studies of high-level methods relating relevant examination findings of cup-to-disc ratio (CDR), CDR asymmetry, intraocular pressure (IOP), and demographic risk factors to the presence of POAG.

Results: The summary prevalence of glaucoma in the highest-quality studies was 2.6% (95% CI, 2.1%-3.1%). Among risk factors evaluated, high myopia (≥6 diopters; odds ratio [OR], 5.7; 95% CI, 3.1-11) and family history (OR, 3.3; 95% CI, 2.0-5.6) had the strongest association with glaucoma. Black race (OR, 2.9; 95% CI, 1.4-5.9) and increasing age (especially age >80 years; OR, 2.9; 95% CI, 1.9-4.3) were also associated with an increased risk. As CDR increased, the likelihood for POAG increased with a likelihood ratio (LR) of 14 (95% CI, 5.3-39) for CDR of 0.7 or greater. Increasing CDR asymmetry was also associated with an increased likelihood for POAG (CDR asymmetry ≥0.3; LR, 7.3; 95% CI, 3.3-16). No single threshold for CDR or asymmetry ruled out glaucoma. The presence of a disc hemorrhage (LR, 12; 95% CI, 2.9-48) was highly suggestive of glaucoma, but the absence of a hemorrhage was nondiagnostic (LR, 0.94; 95% CI, 0.83-0.98). At the commonly used cutoff for high IOP (≥22), the LR was 13 (95% CI, 8.2-17), while lower IOP made glaucoma less likely (LR, 0.65; 95% CI, 0.55-0.76). We found no studies of screening examinations performed by generalist physicians in a routine setting.

Conclusions And Relevance: Individual findings of increased CDR, CDR asymmetry, disc hemorrhage, and elevated IOP, as well as demographic risk factors of family history, black race, and advanced age are associated with increased risk for POAG, but their absence does not effectively rule out POAG. The best available data support examination by an ophthalmologist as the most accurate way to detect glaucoma.
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http://dx.doi.org/10.1001/jama.2013.5099DOI Listing
May 2013

Likelihood ratios, sensitivity, and specificity values can be back-calculated when the odds ratios are known.

J Clin Epidemiol 2013 Apr 27;66(4):458-60. Epub 2012 Sep 27.

Department of Medicine, Durham Veterans Affairs Medical Center and Duke University, Durham, NC 27705, USA.

Objective: To provide a solution for calculating the true-positive, false-positive, false-negative, and true-negative results from studies where only the odds ratios (ORs), number of patients with the finding, and number of patients with the target condition are given.

Results: The quadratic formula shown here allows investigators conducting systematic reviews to back-calculate the sensitivity, specificity, and likelihood ratios (LRs) from the OR. A spreadsheet that requires only the OR, and the row and column total from the 2 × 2 table enables the back-calculation of the individual true positives, false positives, false negatives, and true negatives. Solutions are also available for the special situations when the OR = 1 or the OR is nonestimable because of zero false positives or false negatives.

Conclusions: A simple spreadsheet enables those conducting systematic reviews of diagnostic tests to include studies that report only the OR. This approach should enrich the number of studies retained in meta-analyses of diagnostic tests where the desire is to create summary sensitivity, specificity, or LRs.
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http://dx.doi.org/10.1016/j.jclinepi.2012.07.014DOI Listing
April 2013

Does this adult patient have a blunt intra-abdominal injury?

JAMA 2012 Apr;307(14):1517-27

Department of Emergency Medicine, University of California Davis School of Medicine, Sacramento, USA.

Context: Blunt abdominal trauma often presents a substantial diagnostic challenge. Well-informed clinical examination can identify patients who require further diagnostic evaluation for intra-abdominal injuries after blunt abdominal trauma.

Objective: To systematically assess the precision and accuracy of symptoms, signs, laboratory tests, and bedside imaging studies to identify intra-abdominal injuries in patients with blunt abdominal trauma.

Data Sources: We conducted a structured search of MEDLINE (1950-January 2012) and EMBASE (1980-January 2012) to identify English-language studies examining the identification of intra-abdominal injuries. A separate, structured search was conducted for studies evaluating bedside ultrasonography.

Study Selection: We included studies of diagnostic accuracy for intra-abdominal injury that compared at least 1 finding with a reference standard of abdominal computed tomography, diagnostic peritoneal lavage, laparotomy, autopsy, and/or clinical course for intra-abdominal injury. Twelve studies on clinical findings and 22 studies on bedside ultrasonography met inclusion criteria for data extraction.

Data Extraction: Critical appraisal and data extraction were independently performed by 2 authors.

Data Synthesis: The prevalence of intra-abdominal injury in adult emergency department patients with blunt abdominal trauma among all evidence level 1 and 2 studies was 13% (95% CI, 10%-17%), with 4.7% (95% CI, 2.5%-8.6%) requiring therapeutic surgery or angiographic embolization of injuries. The presence of a seat belt sign (likelihood ratio [LR] range, 5.6-9.9), rebound tenderness (LR, 6.5; 95% CI, 1.8-24), hypotension (LR, 5.2; 95% CI, 3.5-7.5), abdominal distention (LR, 3.8; 95% CI, 1.9-7.6), or guarding (LR, 3.7; 95% CI, 2.3-5.9) suggest an intra-abdominal injury. The absence of abdominal tenderness to palpation does not rule out an intra-abdominal injury (summary LR, 0.61; 95% CI, 0.46-0.80). The presence of intraperitoneal fluid or organ injury on bedside ultrasound assessment is more accurate than any history and physical examination findings (adjusted summary LR, 30; 95% CI, 20-46); conversely, a normal ultrasound result decreases the chance of injury detection (adjusted summary LR, 0.26; 95% CI, 0.19-0.34). Test results increasing the likelihood of intra-abdominal injury include a base deficit less than -6 mEq/L (LR, 18; 95% CI, 11-30), elevated liver transaminases (LR range, 2.5-5.2), hematuria (LR range, 3.7-4.1), anemia (LR range, 2.2-3.3), and abnormal chest radiograph (LR range, 2.5-3.8). Symptoms and signs may be most useful in combination, particularly in identification of patients who do not need further diagnostic workup.

Conclusions: Bedside ultrasonography has the highest accuracy of all individual findings, but a normal result does not rule out an intra-abdominal injury. Combinations of clinical findings may be most useful to determine which patients do not require further evaluation, but the ideal combination of variables for identifying patients without intra-abdominal injury requires further study.
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http://dx.doi.org/10.1001/jama.2012.422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966670PMC
April 2012

Does this patient with liver disease have cirrhosis?

JAMA 2012 Feb;307(8):832-842

Context: Among adult patients with liver disease, the ability to identify those most likely to have cirrhosis noninvasively is challenging.

Objective: To identify simple clinical indicators that can exclude or detect cirrhosis in adults with known or suspected liver disease.

Data Sources: We searched MEDLINE and EMBASE (1966 to December 2011) and reference lists from retrieved articles, previous reviews, and physical examination textbooks.

Study Selection: We retained 86 studies of adequate quality that evaluated the accuracy of clinical findings for identifying histologically proven cirrhosis.

Data Extraction: Two authors independently abstracted data (sensitivity, specificity, and likelihood ratios [LRs]) and assessed methodological quality. Random-effects meta-analyses were used to calculate summary LRs across studies.

Results: Among the 86 studies, 19,533 patients were included in this meta-analysis, among whom 4725 had biopsy-proven cirrhosis (prevalence rate, 24%; 95% CI, 20%-28%). Many physical examination and simple laboratory tests increase the likelihood of cirrhosis, though the presence of ascites (LR, 7.2; 95% CI, 2.9-12), a platelet count <160 x 10(3)/μL (LR, 6.3; 95% CI, 4.3-8.3), spider nevi (LR, 4.3; 95% CI 2.4-6.2), or a combination of simple laboratory tests with the Bonacini cirrhosis discriminant score >7 (LR, 9.4; 95% CI, 2.6-37) are the most frequently studied, reliable, and informative results. For lowering the likelihood of cirrhosis, the most useful findings are a Lok index <0.2 (a score created from the platelet count, serum aspartate aminotransferase and alanine aminotransferase, and prothrombin international normalized ratio; LR, 0.09; 95% CI, 0.03-0.31); a platelet count ≥160 x 10(3)/μL (LR, 0.29; 95% CI, 0.20-0.39); or the absence of hepatomegaly (LR, 0.37; 95% CI, 0.24-0.51). The overall impression of the clinician was not as informative as the individual findings or laboratory combinations.

Conclusions: For identifying cirrhosis, the presence of a variety of clinical findings or abnormalities in a combination of simple laboratory tests that reflect the underlying pathophysiology increase its likelihood. To exclude cirrhosis, combinations of normal laboratory findings are most useful.
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http://dx.doi.org/10.1001/jama.2012.186DOI Listing
February 2012

A meta-analysis and systematic review of computed tomography angiography as a diagnostic triage tool for patients with chest pain presenting to the emergency department.

J Nucl Cardiol 2012 Apr;19(2):364-76

Division of Cardiovascular Medicine, Duke University Medical Center (DUMC), Durham, NC 27710, USA.

Background: To assess clinical utility of computed tomography angiography (CTA) in the diagnosis of chest pain patients presenting to emergency departments (EDs), we conducted a meta-analysis of CTA in patients with suspected acute coronary syndromes (ACSs).

Methods: 386 studies were identified on initial review of literature. Inclusion criteria were: (1) prospective study with ≥1 month follow-up, (2) use of CTA in the ED setting, (3) use of ACC/AHA definitions for ACS and robust assessment of major adverse cardiac events, (4) ≥30 patients, and (5) study population with initial non-diagnostic ECGs and negative biomarkers.

Results: Nine studies (N = 1349) formed the data set. The pooled patient population was 52 ± 2 years of age, 51% male, with low to intermediate pretest probability for ACS. Risk factors included 12% diabetes, 42% hypertension, 35% smokers, 29% had hyperlipidemia, and 7% known CAD. ACS was subsequently diagnosed in 10% of patients. The bivariate summary estimate of sensitivity of CTA for ACS diagnosis was 95% (95% CI 88-100) and specificity was 87% (95% CI 83-92), yielding a negative likelihood ratio of 0.06 (95% CI 0-0.14) and positive likelihood ratio of 7.4 (95% CI 4.8-10). The 30-day event rate included no deaths and no additional MIs.

Conclusion: Coronary CTA demonstrates a high sensitivity and a low negative likelihood ratio of 0.06, and is effective in ruling out the presence of ACS in low to intermediate risk patients presenting to the ED with acute chest pain.
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http://dx.doi.org/10.1007/s12350-012-9520-2DOI Listing
April 2012

NICE guideline for management of chronic heart failure in adults.

Authors:
David L Simel

Ann Intern Med 2012 Jan;156(1 Pt 1):69-70; author reply 70

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http://dx.doi.org/10.7326/0003-4819-156-1-201201030-00024DOI Listing
January 2012

Autopsy and grief: a case of transformative postmortem examination.

J Palliat Med 2012 Feb 4;15(2):251-3. Epub 2011 Aug 4.

Department of Medicine, Duke University Medical Center, Durham, NC, USA.

Background: A physician's obligations to deliver compassionate care do not end with a patient's death. When a patient dies there remains a responsibility to assist grieving family members. Unfortunately, many physicians feel ill prepared to assist in the bereavement process, not knowing what to say or how to say it. Although underutilized, the medical autopsy can play an important role in families' grief processes, particularly in those cases wherein uncertainties exist regarding the ultimate cause of death.

Discussion: Here we postulate a role for the medical autopsy in assisting families through the grief process, which we demonstrate via an illustrative case. Effective communication of these results to family members is the key to its therapeutic effect.
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http://dx.doi.org/10.1089/jpm.2011.0044DOI Listing
February 2012

Does this patient have malaria?

JAMA 2010 Nov 5;304(18):2048-56. Epub 2010 Nov 5.

Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina, USA.

Context: Malaria commonly infects residents of and travelers to tropical regions. The clinical features of infection are notoriously nonspecific but have not been comprehensively evaluated.

Objective: To systematically review and synthesize data related to the predictive value of clinical findings for the diagnosis of malaria in endemic areas and in travelers returning from endemic areas.

Data Sources, Study Selection, And Data Extraction: The databases of MEDLINE and EMBASE (1950-July 2010) were searched to identify studies published in the English language of endemic and "imported" (acquired during travel) malaria. Additional studies were identified from reference lists. Studies were included that had patients suspected of having acute malaria (usually because of fever) and compared the presence or absence of clinical findings with blood smear confirmation. Two authors independently identified studies, appraised study quality, and extracted data on the patient population, outcome assessment, and clinical findings. Differences between reviewers were resolved by consensus.

Data Synthesis: Fourteen studies for endemic malaria were identified that met review criteria. Individual symptoms are of limited diagnostic utility but presence of splenomegaly (summary likelihood ratio [LR], 3.3; 95% confidence interval [CI], 2.0-4.7) or hepatomegaly (summary LR, 2.4; 95% CI, 1.6-3.6) make malaria more likely. Combinations of findings can affect the likelihood of malaria, but their performance varies by setting. Seven studies of imported malaria were identified. The presence of fever (LR, 5.1; 95% CI, 4.9-5.3), splenomegaly (summary LR, 6.5; 95% CI, 3.9-11.0), hyperbilirubinemia (LR, 7.3; 95% CI, 5.5-9.6), or thrombocytopenia (summary LR, 5.6; 95% CI, 4.1-7.5) make malaria more likely.

Conclusions: In endemic areas, the likelihood of malaria is increased by the presence of splenomegaly and hepatomegaly but individual findings are of limited utility and cannot reliably exclude malaria; combinations of findings may be useful to stratify risk in patients. In returning travelers, the clinical assessment can provide substantial diagnostic benefit, although all patients still require laboratory testing because malaria can be rapidly fatal.
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http://dx.doi.org/10.1001/jama.2010.1578DOI Listing
November 2010
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