Antibiotics Not Associated with Shorter Duration or Reduced Severity of Acute Lower Respiratory Tract Infection.

BACKGROUND: Antibiotic use remains common for the treatment of lower respiratory tract infections. The objective of this study was to evaluate the impact of antibiotic use on the duration and severity of acute lower respiratory tract infection (LRTI). PARTICIPANTS: Adult patients presenting to US primary or urgent care sites with a chief complaint of cough and symptoms consistent with LRTI. MAIN MEASURES: Collected data included demographics, comorbidities, symptoms, and 48 viral and bacterial respiratory pathogens by PCR. Severity of signs/symptoms was reported for up to 28 days using diaries and text messages. Interpolation was used where data were missing. KEY RESULTS: Of 718 patients with baseline data, 29% had an antibiotic prescribed at baseline. The most common antibiotics were amoxicillin-clavulanate, azithromycin, doxycycline, and amoxicillin in 85% of patients. Provision of an antibiotic had no effect on the duration or overall severity of cough, including in patients with viral, bacterial, and mixed infections. Receipt of an antibiotic did reduce the likelihood of a follow-up visit (14.1% vs 8.2%, aOR 0.47, 95% CI 0.26-0.84), perhaps by removing the motivation of getting an antibiotic at a follow-up visit. However, they were also more likely to receive a systemic corticosteroid (31.9% vs 4.5%, p < 0.001) and were also more likely to receive an albuterol inhaler (22.7% vs 7.6%, p < 0.001). Patients believed that receiving an antibiotic would reduce the duration of their illness by nearly 4 days. CONCLUSIONS: In this large prospective study in the US primary and urgent care setting, antibiotics had no measurable impact on the severity or duration of cough due to acute LRTI. Patients had unrealistic expectations regarding the duration of LRTI and the effect of antibiotics which should be the target of antibiotic stewardship efforts.

Identifying the Best Initial Oral Antibiotics for Adults with Community-Acquired Pneumonia: A Network Meta-Analysis.

BACKGROUND: The objective of this network meta-analysis was to compare rates of clinical response and mortality for empiric oral antibiotic regimens in adults with mild-moderate community-acquired pneumonia (CAP). METHODS: We searched PubMed, Cochrane, and the reference lists of systematic reviews and clinical guidelines. We included randomized trials of adults with radiologically confirmed mild to moderate CAP initially treated orally and reporting clinical cure or mortality. Abstracts and studies were reviewed in parallel for inclusion in the analysis and for data abstraction. We performed separate analyses by antibiotic medications and antibiotic classes and present the results through network diagrams and forest plots sorted by p-scores. We assessed the quality of each study using the Cochrane Risk of Bias framework, as well as global and local inconsistency. RESULTS: We identified 24 studies with 9361 patients: six at low risk of bias, six at unclear risk, and 12 at high risk. Nemonoxacin, levofloxacin, and telithromycin were most likely to achieve clinical response (p-score 0.79, 0.71, and 0.69 respectively), while penicillin and amoxicillin were least likely to achieve clinical response. Levofloxacin, nemonoxacin, azithromycin, and amoxicillin-clavulanate were most likely to be associated with lower mortality (p-score 0.85, 0.75, 0.74, and 0.68 respectively). By antibiotic class, quinolones and macrolides were most effective for clinical response (0.71 and 0.70 respectively), with amoxicillin-clavulanate plus macrolides and beta-lactams being less effective (p-score 0.11 and 0.22). Quinolones were most likely to be associated with lower mortality (0.63). All confidence intervals were broad and partially overlapping. CONCLUSION: We observed trends toward a better clinical response and lower mortality for quinolones as empiric antibiotics for CAP, but found no conclusive evidence of any antibiotic being clearly more effective than another. More trials are needed to inform guideline recommendations on the most effective antibiotic regimens for outpatients with mild to moderate CAP.

Clinically Important Benefits and Harms of Monoclonal Antibodies Targeting Amyloid for the Treatment of Alzheimer Disease: A Systematic Review and Meta-Analysis.

PURPOSE: We conducted a meta-analysis to evaluate clinically meaningful benefits and harms of monoclonal antibodies targeting amyloid in patients with Alzheimer dementia. METHODS: We searched PubMed, Cochrane CENTRAL, and 5 trial registries, as well as the reference lists of identified studies. We included randomized controlled trials comparing a monoclonal antibody with placebo at a dose consistent with that used in phase 3 trials or for Food and Drug Administration approval. Studies had to report at least 1 clinically relevant benefit or harm. Data were extracted independently by at least 2 researchers for random effects meta-analysis. Changes in cognitive and functional scales were compared between groups, and each difference was assessed to determine if it met the minimal clinically important difference (MCID). RESULTS: We identified 19 publications with 23,202 total participants that evaluated 8 anti-amyloid antibodies. There were small improvements over placebo in the Alzheimer's Disease Assessment Scale (ADAS)-Cog-11 to -14 score (standardized mean difference = -0.07; 95% CI, -0.10 to -0.04), Mini Mental State Examination score (0.32 points; 95% CI, 0.13 to 0.50), and Clinical Dementia Rating-Sum of Boxes scale score (mean difference =-0.18 points; 95% CI, -0.34 to -0.03), and the combined functional scores (standardized mean difference = 0.09; 95% CI, 0.05 to 0.13). None of the changes, including those for lecanemab, aducanumab, and donanemab, exceeded the MCID. Harms included significantly increased risks of amyloid-related imaging abnormalities (ARIA)-edema (relative risk [RR] = 10.29; number needed to harm [NNH] = 9), ARIA-hemorrhage (RR = 1.74; NNH = 13), and symptomatic ARIA-edema (RR = 24.3; NNH = 86). CONCLUSIONS: Although monoclonal antibodies targeting amyloid provide small benefits on cognitive and functional scales in patients with Alzheimer dementia, these improvements are far below the MCID for each outcome and are accompanied by clinically meaningful harms.

Prospective external validation of the FluScore risk score for influenza in outpatients.

BACKGROUND: Testing for influenza in patients with acute lower respiratory tract infection (LRTI) is common and in some cases is performed for all patients with LRTI. A more selective approach to testing could be more efficient. METHODS: We used data from two prospective studies in the US primary and urgent care settings that enrolled patients with acute LRTI or influenza-like illness. Data were collected in the 2016, 2019, 2021, and 2022 flu seasons. All patients underwent polymerase chain reaction (PCR) testing for influenza and the FluScore was calculated based on patient-reported symptoms at their initial visit. The probability of influenza in each risk group was reported, as well as stratum-specific likelihood ratios (SSLRs) for each risk level. RESULTS: The prevalence of influenza within risk groups varied based on overall differences in flu seasons and populations. However, the FluScore exhibited consistent performance across various seasons and populations based on the SSLRs. The FluScore had a consistent SSLR range of 0.20 to 0.23 for the low-risk group, 0.63 to 0.99 for the moderate-risk group, and 1.46 to 1.67 for the high-risk group. The diagnostic odds ratio based on the midpoints of these ranges was 7.25. CONCLUSIONS: The FluScore could streamline patient categorization, identifying patients who could be exempted from testing, while identifying candidates for rapid influenza tests. This has the potential to be more efficient than a "one size fits all" test strategy, as it strategically targets the use of tests on patients most likely to benefit. It is potentially usable in a telehealth setting.

Acute Uncomplicated UTIs in Adults: Rapid Evidence Review.

An acute uncomplicated urinary tract infection (UTI) is a bacterial infection of the lower urinary tract with no sign of systemic illness or pyelonephritis in a noncatheterized, nonpregnant adult with no urologic abnormalities or immunocompromise. In women, a self-diagnosis of a UTI with the presence of typical symptoms (e.g., frequency, urgency, dysuria/burning sensation, nocturia, suprapubic pain), without vaginal discharge, is accurate enough to diagnose an uncomplicated UTI without further testing. Urine culture and susceptibility testing should be reserved for women with recurrent infection, treatment failure, history of resistant isolates, or atypical presentation to make a definitive diagnosis and guide antibiotic selection. First-line antibiotics include nitrofurantoin for five days, fosfomycin in a single dose, trimethoprim for three days, or trimethoprim/sulfamethoxazole for three days. Symptomatic treatment with nonsteroidal anti-inflammatory drugs and delayed antibiotics may be considered because the risk of complications is low. Increased fluids, intake of cranberry products, and methenamine hippurate can prevent recurrent infections. Antibiotic prophylaxis is also effective in preventing recurrence but has a risk of adverse effects and antimicrobial resistance. Men with lower UTI symptoms should always receive antibiotics, with urine culture and susceptibility results guiding the antibiotic choice. Clinicians should also consider the possibility of urethritis and prostatitis in men with UTI symptoms. First-line antibiotics for men with uncomplicated UTI include trimethoprim, trimethoprim/sulfamethoxazole, and nitrofurantoin for seven days. Uncomplicated UTIs in nonfrail women and men 65 years and older with no relevant comorbidities also necessitate a urine culture with susceptibility testing to adjust the antibiotic choice after initial empiric treatment; first-line antibiotics and treatment durations do not differ from those recommended for younger adults.

Development and internal validation of risk scores to diagnose infectious mononucleosis among college students.

BACKGROUND: Individual symptoms and signs of infectious mononucleosis (IM) are of limited value for diagnosis. OBJECTIVE: To develop and validate risk scores based on signs and symptoms with and without haematologic parameters for the diagnosis of IM. DESIGN AND SETTING: Data were extracted from electronic health records of a university health centre and were divided into derivation (9/1/2015-10/31/2017) and a prospective temporal internal validation (11/1/2017-1/31/2019) cohort. METHOD: Independent predictors for the diagnosis of IM were identified in univariate analysis using the derivation cohort. Logistic regression models were used to develop 2 risk scores: 1 with only symptoms and signs (IM-NoLab) and 1 adding haematologic parameters (IM-Lab). Point scores were created based on the regression coefficients, and patients were grouped into risk groups. Primary outcomes were area under the receiver operating characteristic curve (AUROCC) and classification accuracy. RESULTS: The IM-NoLab model had 4 predictors and identified a low-risk group (7.9% with IM) and a high-risk group (22.2%) in the validation cohort. The AUROCC was 0.75 in the derivation cohort and 0.69 in the validation cohort. The IM-Lab model had 3 predictors and identified a low-risk group (3.6%), a moderate-risk group (12.5%), and a high-risk group (87.6%). The AUROCC was 0.97 in the derivation cohort and 0.93 in the validation cohort. CONCLUSION: We derived and internally validated the IM-NoLab and IM-Lab risk scores. The IM-Lab score in particular had very good discrimination and have the potential to reduce the need for diagnostic testing for IM.

Top 20 Research Studies of 2022 for Primary Care Physicians.

This article summarizes the top 20 research studies of 2022 identified as POEMs (patient-oriented evidence that matters), excluding COVID-19. Statins for primary prevention of cardiovascular disease produce only a small absolute reduction in a person's likelihood of dying (0.6%), having a myocardial infarction (0.7%), or having a stroke (0.3%) over three to six years. Supplemental vitamin D does not reduce the risk of a fragility fracture, even in people with low baseline vitamin D levels or a previous fracture. Selective serotonin reuptake inhibitors are preferred medical therapy for panic disorder, and patients who discontinue antidepressants are more likely to relapse (number needed to harm = 6) compared with those who continue. Combination therapy using a selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor, or tricyclic antidepressant with mirtazapine or trazodone is more effective than monotherapy for first-line treatment of acute severe depression and when monotherapy fails. Using hypnotic agents for insomnia in adults comes with a significant trade-off between effectiveness and tolerability. In patients with moderate to severe asthma, using a combination of albuterol and glucocorticoid inhalers as rescue therapy reduces exacerbations and need for systemic steroids. Observational research shows an increased risk of gastric cancer in patients taking proton pump inhibitors (number needed to harm = 1,191 over 10 years). The American College of Gastroenterology updated its guideline for gastroesophageal reflux disease, and a new guideline provides sound advice for the evaluation and management of irritable bowel syndrome. Adults older than 60 years with prediabetes are more likely to become normoglycemic than to develop diabetes mellitus or die. Treatment of prediabetes via intensive lifestyle intervention or metformin has no impact on long-term cardiovascular outcomes. Persons with painful diabetic peripheral neuropathy have similar degrees of improvement with monotherapy using amitriptyline, duloxetine, or pregabalin and greater improvement with combination therapy. When communicating with patients about disease risk, most patients prefer numbers over words because people overestimate word-based probabilities. In terms of drug therapy, the duration of an initial varenicline prescription should be 12 weeks. Many drugs can interact with cannabidiol. No important difference was found among ibuprofen, ketorolac, and diclofenac for treatment of acute nonradicular low back pain in adults.

External Validation of the COVID-NoLab and COVID-SimpleLab Prognostic Tools.

Our objective was to externally validate 2 simple risk scores for mortality among a mostly inpatient population with COVID-19 in Canada (588 patients for COVID-NoLab and 479 patients for COVID-SimpleLab). The mortality rates in the low-, moderate-, and high-risk groups for COVID-NoLab were 1.1%, 9.6%, and 21.2%, respectively. The mortality rates for COVID-SimpleLab were 0.0%, 9.8%, and 20.0%, respectively. These values were similar to those in the original derivation cohort. The 2 simple risk scores, now successfully externally validated, offer clinicians a reliable way to quickly identify low-risk inpatients who could potentially be managed as outpatients in the event of a bed shortage. Both are available online (https://ebell-projects.shinyapps.io/covid_nolab/ and https://ebell-projects.shinyapps.io/COVID-SimpleLab/).

Evidence reversals in primary care research: a study of randomized controlled trials.

BACKGROUND: Evidence-Based Medicine is built on the premise that clinicians can be more confident when their decisions are grounded in high-quality evidence. Furthermore, evidence from studies involving patient-oriented outcomes is preferred when making decisions about tests or treatments. Ideally, the findings of relevant and valid trials should be stable over time, that is, unlikely to be reversed in subsequent research. OBJECTIVE: To evaluate the stability of evidence from trials relevant to primary healthcare and to identify study characteristics associated with their reversal. METHODS: We studied synopses of randomized controlled trials (RCTs) published from 2002 to 2005 as "Daily POEMs" (Patient Oriented Evidence that Matters). The initial evidence (E1) from these POEMs (2002-2005) was compared with the updated evidence (E2) on that same topic in a summary resource (DynaMed 2019). Two physician-raters independently categorized each POEM-RCT as (i) reversed when E1 ≠ E2, or as (ii) not reversed, when E1 = E2. For all "Evidence Reversals" (E1 ≠ E2), we assessed the direction of change in the evidence. RESULTS: We evaluated 408 POEMs on RCTs. Of those, 35 (9%; 95% confidence interval [6-12]) were identified as reversed, 359 (88%) were identified as not reversed, and 14 (3%) were indeterminate. On average, this represents about 2 evidence reversals per annum for POEMs about RCTs. CONCLUSIONS: Over 12-17 years, 9% of RCTs summarized as POEMs are reversed. Information alerting services that apply strict criteria for relevance and validity of clinical information are likely to identify RCTs whose findings are stable over time.

We studied the extent to which evidence from randomized controlled trials (RCTs) relevant to primary care is contradicted in subsequent research. When it was, we identified this event as an evidence reversal. In addition, we sought to identify characteristics of RCTs associated with their reversal. From 408 RCTs published during the period 2002­2005, study characteristics such as sample size were identified and extracted. Subsequently, we compared the evidence reported in each of these RCTs with the evidence on that same topic in an online summary resource in 2019. This allowed us to classify each RCT in one of the following 3 categories: evidence confirmed, reversed, or uncertain if this evidence is confirmed or reversed. Over 12­17 years of follow-up time, the findings of about 9 in 10 RCTs summarized as POEMs are stable. We found no statistically significant associations between trial characteristics and their subsequent reversal. This low rate of evidence reversal is good news for the RCTs that are used to inform decision-making.

Top 20 Research Studies of 2021 for Primary Care Physicians.

This article summarizes the top 20 research studies of 2021 identified as POEMs (patient-oriented evidence that matters) that did not address the COVID-19 pandemic. Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists prevent adverse cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and also reduce all-cause and cardiovascular mortality. Most older adults (mean age, 75 years) with prediabetes do not progress to diabetes. Among patients in this age group with type 2 diabetes treated with medication, an A1C level of less than 7% is associated with increased risk of hospitalization for hypoglycemia, especially when using a sulfonylurea or insulin. For patients with chronic low back pain, exercise, nonsteroidal anti-inflammatory drugs, duloxetine, and opioids were shown to be more effective than control in achieving a 30% reduction in pain, but self-discontinuation of duloxetine and opioids was common. There is no clinically important difference between muscle relaxants and placebo in the treatment of nonspecific low back pain. In patients with chronic pain, low- to moderate-quality evidence supports exercise, yoga, massage, and mindfulness-based stress reduction. For acute musculoskeletal pain, acetaminophen, 1,000 mg, plus ibuprofen, 400 mg, without an opioid is a good option. Regarding screening for colorectal cancer, trial evidence supports performing fecal immunochemical testing every other year. For chronic constipation, evidence supports polyethylene glycol, senna, fiber supplements, magnesium-based products, and fruit-based products. The following abdominal symptoms carry a greater than 3% risk of cancer or inflammatory bowel disease: dysphagia or change in bowel habits in men; rectal bleeding in women; and abdominal pain, change in bowel habits, or dyspepsia in men and women older than 60 years. For secondary prevention in those with established arteriosclerotic cardiovascular disease, 81 mg of aspirin daily appears to be effective. The Framingham Risk Score and the Pooled Cohort Equations both overestimate the risk of cardiovascular events. Over 12 years, no association between egg consumption and cardiovascular events was demonstrated. Gabapentin, pregabalin, duloxetine, and venlafaxine provide clinically meaningful improvements in chronic neuropathic pain. In patients with moderate to severe depression, initial titration above the minimum starting dose of antidepressants in the first eight weeks of treatment is not more likely to increase response. In adults with iron deficiency anemia, adding vitamin C to oral iron has no effect. In children with pharyngitis, rhinosinusitis, acute bronchitis, or acute otitis media, providing education combined with a take-and-hold antibiotic prescription results in 1 in 4 of those children eventually taking an antibiotic.

Top 20 Research Studies of 2020 for Primary Care Physicians.

This article summarizes the top 20 research studies of 2020 identified as POEMs (patient-oriented evidence that matters), including the two most highly rated guidelines of the year on gout and chronic obstructive pulmonary disease (COPD). Regarding COVID-19, handwashing and social distancing through stay-at-home orders or quarantine measures are effective at slowing the spread of illness. Use of proper face masks (not gaiters or bandanas) is also effective at preventing trans- mission. This is important because the virus can infect others during the presymptomatic phase. Aspirin can no longer be recommended for the primary prevention of cardiovascular disease. Human papillomavirus vaccination is strongly associated with reduced risk of invasive cervical cancer, especially in women who were vaccinated before 17 years of age. When a woman who is postmenopausal has a screening bone mineral density test, rechecking the test after three years does not help to identify those who will have a fragility fracture. A higher daily step count is associated with lower all-cause mortality. After one year of follow-up, physical therapy is preferred to glucocorticoid injections for osteoarthritis of the knee; acetaminophen is ineffective for acute low back pain or pain due to knee or hip osteoarthritis; and adding a muscle relaxant to ibuprofen does not improve functional outcomes or pain in people reporting moderate to severe back pain one week after starting treatment. Although short-term antibiotics and steroids are effective in treating acute exacerbations of COPD, not much else is. Successful communication with patients seeking an antibiotic for a flulike illness can be achieved with combinations of messaging, including information on antibiotic resistance and the self-limiting nature of the illness. A new prediction rule effectively identifies patients with a history of penicillin allergy who have a low likelihood of positive findings on allergy testing. Low-value screening tests in asymptomatic, low-risk patients often lead to further testing, diagnostic procedures, or referrals. A new tool helps determine the amount of change needed to signify a real difference between two laboratory values in the same person over time. Finally, a pillar of our specialty, continuity of care, is associated with decreased all-cause mortality.

Cancer-Specific Mortality, All-Cause Mortality, and Overdiagnosis in Lung Cancer Screening Trials: A Meta-Analysis.

PURPOSE: Benefit of lung cancer screening using low-dose computed tomography (LDCT) in reducing lung cancer-specific and all-cause mortality is unclear. We undertook a meta-analysis to assess its associations with outcomes. METHODS: We searched the literature and previous systematic reviews to identify randomized controlled trials comparing LDCT screening with usual care or chest radiography. We performed meta-analysis using a random effects model. The primary outcomes were lung cancer-specific mortality, all-cause mortality, and the cumulative incidence ratio of lung cancer between screened and unscreened groups as a measure of overdiagnosis. RESULTS: Meta-analysis was based on 8 trials with 90,475 patients that had a low risk of bias. There was a significant reduction in lung cancer-specific mortality with LDCT screening (relative risk = 0.81; 95% CI, 0.74-0.89); the estimated absolute risk reduction was 0.4% (number needed to screen = 250). The reduction in all-cause mortality was not statistically significant (relative risk = 0.96; 95% CI, 0.92-1.01), but the absolute reduction was consistent with that for lung cancer-specific mortality (0.34%; number needed to screen = 294). In the studies with the longest duration of follow-up, the incidence of lung cancer was 25% higher in the screened group, corresponding to a 20% rate of overdiagnosis. CONCLUSIONS: This meta-analysis showing a significant reduction in lung cancer-specific mortality, albeit with a tradeoff of likely overdiagnosis, supports recommendations to screen individuals at elevated risk for lung cancer with LDCT.

A comparison of contemporary versus older studies of aspirin for primary prevention.

BACKGROUND: Recent aspirin trials have not shown similar benefits for primary prevention as older studies. OBJECTIVE: To compare benefits and harms of aspirin for primary prevention before and after widespread use of statins and colorectal cancer screening. METHODS: We compared studies of aspirin for primary prevention that recruited patients from 2005 onward with previous individual patient data (IPD) meta-analyses that recruited patients from 1978 to 2002. Data for contemporary studies were synthesized using random-effects models. We report vascular [major adverse cardiovascular events (MACE), myocardial infarction (MI) and stroke], bleeding, cancer and mortality outcomes. RESULTS: The IPD analyses of older studies included 95 456 patients for CV prevention and 25 270 for cancer mortality, while the four newer studies had 61 604 patients. Relative risks for vascular outcomes for older versus newer studies follow: MACE: 0.89 [95% confidence interval (CI) 0.83-0.95] versus 0.93 (0.86-0.99); fatal haemorrhagic stroke: 1.73 (1.11-2.72) versus 1.06 (0.66-1.70); any ischaemic stroke: 0.86 (0.74-1.00) versus 0.86 (0.75-0.98); any MI: 0.84 (0.77-0.92) versus 0.88 (0.77-1.00); and non-fatal MI: 0.79 (0.71-0.88) versus 0.94 (0.83-1.08). Cancer death was not significantly decreased in newer studies (1.11, 0.92-1.34). Major haemorrhage was significantly increased (older studies RR 1.48, 95% CI 1.25-1.76 versus newer studies RR 1.37, 1.24-1.53). There was no effect on all-cause mortality, cardiovascular mortality, fatal stroke or fatal MI. CONCLUSIONS: Per 1200 persons taking aspirin for primary prevention for 5 years, there will be 4 fewer MACEs, 3 fewer ischaemic strokes, 3 more intracranial haemorrhages and 8 more major bleeding events. Aspirin should no longer be recommended for primary prevention.

Defining adequate contact for transmission of Mycobacterium tuberculosis in an African urban environment.

BACKGROUND: The risk of infection from respiratory pathogens increases according to the contact rate between the infectious case and susceptible contact, but the definition of adequate contact for transmission is not standard. In this study we aimed to identify factors that can explain the level of contact between tuberculosis cases and their social networks in an African urban environment. METHODS: This was a cross-sectional study conducted in Kampala, Uganda from 2013 to 2017. We carried out an exploratory factor analysis (EFA) in social network data from tuberculosis cases and their contacts. We evaluated the factorability of the data to EFA using the Kaiser-Meyer-Olkin Measure of Sampling Adequacy (KMO). We used principal axis factoring with oblique rotation to extract and rotate the factors, then we calculated factor scores for each using the weighted sum scores method. We assessed construct validity of the factors by associating the factors with other variables related to social mixing. RESULTS: Tuberculosis cases (N = 120) listed their encounters with 1154 members of their social networks. Two factors were identified, the first named "Setting" captured 61% of the variance whereas the second, named 'Relationship' captured 21%. Median scores for the setting and relationship factors were 10.2 (IQR 7.0, 13.6) and 7.7 (IQR 6.4, 10.1) respectively. Setting and Relationship scores varied according to the age, gender, and nature of the relationship among tuberculosis cases and their contacts. Family members had a higher median setting score (13.8, IQR 11.6, 15.7) than non-family members (7.2, IQR 6.2, 9.4). The median relationship score in family members (9.9, IQR 7.6, 11.5) was also higher than in non-family members (6.9, IQR 5.6, 8.1). For both factors, household contacts had higher scores than extra-household contacts (p < .0001). Contacts of male cases had a lower setting score as opposed to contacts of female cases. In contrast, contacts of male and female cases had similar relationship scores. CONCLUSIONS: In this large cross-sectional study from an urban African setting, we identified two factors that can assess adequate contact between tuberculosis cases and their social network members. These findings also confirm the complexity and heterogeneity of social mixing.

Top POEMs of 2019 Consistent with the Principles of the Choosing Wisely Campaign.

In this article, we discuss the POEMs (patient-oriented evidence that matters) of 2019 judged to be most consistent with the principles of Choosing Wisely, an international campaign to reduce unnecessary testing and treatments. We selected these POEMs through a crowdsourcing strategy of the daily POEMs information service for the Canadian Medical Association's physician members. We present recommendations from these top POEMs of primary research or meta-analysis that identify interventions to encourage or consider avoiding in practice. The recommendations cover musculoskeletal conditions (e.g., do not recommend platelet-rich plasma injections for rotator cuff disease or knee osteoarthritis), respiratory disease (e.g., in clinically stable patients with community-acquired pneumonia, antibiotics can be stopped after five days), screening or preventive care (e.g., patients who take their blood pressure at home or in a pharmacy should know what to do when they have an elevated reading), and miscellaneous topics (e.g., in healthy adults treated for dermatophyte infection, do not obtain baseline or follow-up alanine transaminase level, aspartate transaminase level, or complete blood count). These POEMs describe interventions whose benefits are not superior to other options, are sometimes more expensive, or put patients at increased risk of harm. Knowing more about these POEMs and their connection with the Choosing Wisely campaign will help clinicians and patients engage in conversations better informed by high-quality evidence.

Top 20 Research Studies of 2019 for Primary Care Physicians.

In 2019, regular surveillance of 110 English-language research journals identified 254 studies that met the criteria to become POEMs (patient-oriented evidence that matters). Physician members of the Canadian Medical Association rated these POEMs for their relevance to patients in their practices. This article summarizes the clinical questions and bottom-line answers from the top 20 POEMs of 2019. Taking blood pressure medications at night results in a large mortality reduction over six years compared with morning dosing. Automated devices are the best way to measure blood pressure. Nonfasting lipid profiles are preferred over fasting lipid profiles, and nonfasting and fasting lipid profiles are equally effective at predicting risk. The benefit of statins for primary prevention in people 75 years and older is uncertain at best. Aspirin has no net benefit for primary prevention of cardiovascular disease and has no effect on cancer outcomes. An Italian study found fecal immunochemical testing over five biennial screening cycles has a similar colorectal cancer yield as screening colonoscopy, whereas a meta-analysis found that taking aspirin, an anticoagulant, or a nonsteroidal anti-inflammatory drug has no impact on the positive predictive value of fecal immunochemical testing. Regarding infections, a meta-analysis showed that patients presenting with symptoms of acute respiratory tract infection are unlikely to have pneumonia if vital signs and the lung examination findings are normal. For streptococcal pharyngitis (strep throat), penicillin V at a dosage of 800 mg four times a day for five days is at least as effective as a dosage of 1,000 mg three times a day for 10 days. A primary care study in the United Kingdom reinforced that clinicians should counsel parents of children with lower respiratory tract symptoms to be patient, because these infections can take three weeks or more to fully resolve. Among direct oral anticoagulants, apixaban has the lowest bleeding risk, and cotreating with a proton pump inhibitor significantly reduces bleeding risk. Single ibuprofen doses from 400 to 800 mg significantly reduce acute pain to a similar degree. The two-dose recombinant zoster vaccine is much more effective than the single-dose live, attenuated vaccine but with a greater risk of injection site pain. Exercise helps reduce the risk of falls in older adults. Practice guidelines from 2019 on antithrombotics for atrial fibrillation, the management of type 2 diabetes mellitus, and screening for breast cancer were judged to be especially relevant.

Short-Term Systemic Corticosteroids: Appropriate Use in Primary Care.

Short-term systemic corticosteroids, also known as steroids, are frequently prescribed for adults in the outpatient setting by primary care physicians. There is a lack of supporting evidence for most diagnoses for which steroids are prescribed, and there is evidence against steroid use for patients with acute bronchitis, acute sinusitis, carpal tunnel, and allergic rhinitis. There is insufficient evidence supporting routine use of steroids for patients with acute pharyngitis, lumbar radiculopathy, carpal tunnel, and herpes zoster. There is evidence supporting use of short-term steroids for Bell palsy and acute gout. Physicians might assume that short-term steroids are harmless and free from the widely known long-term effects of steroids; however, even short courses of systemic corticosteroids are associated with many possible adverse effects, including hyperglycemia, elevated blood pressure, mood and sleep disturbance, sepsis, fracture, and venous thromboembolism. This review considers the evidence for short-term steroid use for common conditions seen by primary care physicians.

A Risk Classification Model to Predict Mortality Among Laboratory-Confirmed Avian Influenza A H7N9 Patients: A Population-Based Observational Cohort Study.

BACKGROUND: Avian influenza A H7N9 (A/H7N9) is characterized by rapid progressive pneumonia and respiratory failure. Mortality among laboratory-confirmed cases is above 30%; however, the clinical course of disease is variable and patients at high risk for death are not well characterized. METHODS: We obtained demographic, clinical, and laboratory information on all A/H7N9 patients in Zhejiang province from China Centers for Disease Control and Prevention electronic databases. Risk factors for death were identified using logistic regression and a risk score was created using regression coefficients from multivariable models. We externally validated this score in an independent cohort from Jiangsu province. RESULTS: Among 305 A/H7N9 patients, 115 (37.7%) died. Four independent predictors of death were identified: older age, diabetes, bilateral lung infection, and neutrophil percentage. We constructed a score with 0-13 points. Mortality rates in low- (0-3), medium- (4-6), and high-risk (7-13) groups were 4.6%, 32.1%, and 62.7% (Ptrend < .0001). In a validation cohort of 111 A/H7N9 patients, 61 (55%) died. Mortality rates in low-, medium-, and high-risk groups were 35.5%, 55.8, and 67.4% (Ptrend = .0063). CONCLUSIONS: We developed and validated a simple-to-use, predictive risk score for clinical use, identifying patients at high mortality risk.

Meta-analysis of Calibration, Discrimination, and Stratum-Specific Likelihood Ratios for the CRB-65 Score.

BACKGROUND: The CRB-65 score is recommended as a decision support tool to help identify patients with community-acquired pneumonia (CAP) who can safely be treated as outpatients. OBJECTIVE: To perform an updated meta-analysis of the accuracy, discrimination, and calibration of the CRB-65 score using a novel approach to calculation of stratum-specific likelihood ratios. DESIGN: Meta-analysis of accuracy, discrimination, and calibration. METHODS: We searched PubMed, Google, previous systematic reviews, and reference lists of included studies. Data was abstracted and quality assessed in parallel by two investigators. The quality assessment used an adaptation of the TRIPOD and PROBAST criteria. Measures of discrimination, calibration, and stratum-specific likelihood ratios are reported. KEY RESULTS: Twenty-nine studies met our inclusion criteria and provided usable data. Most studies were set in Europe, none in North America, and 12 were judged to be at low risk of bias. The pooled estimate of area under the receiver operating characteristic curve was 0.74 (95% CI 0.71-0.77) for all studies. Calibration was good although there was significant heterogeneity; the pooled estimate of the ratio of observed to expected mortality for all studies was 1.04 (95% CI 0.91-1.19). The corresponding values for studies at low risk of bias where patients could be treated as outpatients or inpatients were 0.76 (0.70-0.81) and 0.88 (0.69-1.13). Summary estimates of stratum-specific likelihood ratios for all studies were 0.19 for the low-risk group, 1.1 for the moderate-risk group, and 4.5 for the high-risk group, and 0.13, 1.3, and 5.6 for studies at low risk of bias where patients could be treated as outpatients or inpatients. CONCLUSIONS: The CRB-65 is useful for identifying low-risk patients for outpatient therapy. Given a 4% overall mortality risk, patients classified as low risk by the CRB-65 had an outpatient mortality risk of no more than 0.5%.

Accuracy of Signs and Symptoms for the Diagnosis of Acute Rhinosinusitis and Acute Bacterial Rhinosinusitis.

PURPOSE: To evaluate the accuracy of signs and symptoms for the diagnosis of acute rhinosinusitis (ARS). METHODS: We searched Medline to identify studies of outpatients with clinically suspected ARS and sufficient data reported to calculate the sensitivity and specificity. Of 1,649 studies initially identified, 17 met our inclusion criteria. Acute rhinosinusitis was diagnosed by any valid reference standard, whereas acute bacterial rhinosinusitis (ABRS) was diagnosed by purulence on antral puncture or positive bacterial culture. We used bivariate meta-analysis to calculate summary estimates of test accuracy. RESULTS: Among patients with clinically suspected ARS, the prevalence of imaging confirmed ARS is 51% and ABRS is 31%. Clinical findings that best rule in ARS are purulent secretions in the middle meatus (positive likelihood ratio [LR+] 3.2) and the overall clinical impression (LR+ 3.0). The findings that best rule out ARS are the overall clinical impression (negative likelihood ratio [LR-] 0.37), normal transillumination (LR- 0.55), the absence of preceding respiratory tract infection (LR- 0.48), any nasal discharge (LR- 0.49), and purulent nasal discharge (LR- 0.54). Based on limited data, the overall clinical impression (LR+ 3.8, LR- 0.34), cacosmia (fetid odor on the breath) (LR+ 4.3, LR- 0.86) and pain in the teeth (LR+ 2.0, LR- 0.77) are the best predictors of ABRS. While several clinical decision rules have been proposed, none have been prospectively validated. CONCLUSIONS: Among patients with clinically suspected ARS, only about one-third have ABRS. The overall clinical impression, cacosmia, and pain in the teeth are the best predictors of ABRS. Clinical decision rules, including those incorporating C-reactive protein, and use of urine dipsticks are promising, but require prospective validation.