[Top 5 Research Studies of the month for Italian Primary Care Physicians: May 2024.] / La Top 5 di maggio 2024. Gli studi clinici che vale la pena conoscere se lavori nelle cure primarie in Italia.

This monthly article provides a collection of summaries of the most relevant studies identified as POEMs (patient-oriented evidence that matters) for Italian primary care physicians. 1) The 2023 updated American college of cardiology/American heart association guideline provide new recommendations for the diagnosis and treatment of atrial fibrillation. In a nutshell, screening is not recommended, and treatment decisions should be guided by risk assessment via CHA2DS2-VASC or a similar tool. For most patients, a direct oral anticoagulant (Doac) at a standard dose is recommended. 2) The use of gabapentin or pregabalin is associated with severe exacerbation of chronic obstructive pulmonary disease (Copd). Various government agencies warn about the use of those gabapentinoids in patients with respiratory risk factors. 3) In children 3 months to 5 years of age with an uncomplicated febrile urinary tract infection, 5 days of antibiotic treatment results in similar resolution of symptoms and 30-day recurrence rates as 10 days of treatment. 4) In adults with type 2 diabetes, bariatric surgery results in superior glycemic control and weight loss compared with medical plus lifestyle management. However, no significant differences occurred in major adverse cardiovascular events or all-cause mortality. Other (non-cardiovascular) adverse events occurred significantly more often in the surgery group, so it is uncertain whether the overall quality of life, morbidity or mortality are better or worse with surgery. 5) Prescribing a specific exercise program, whether aerobic or strength training, produces clinically meaningful and statistically significant benefits in patients with major depressive disorder. The advice can't be simply to "exercise more" but should be a specific exercise prescription, just like a medication prescription, specifying the frequency, intensity, time (duration), and type of exercise.

Prospective Validation of a Simple Risk Score to Predict Hospitalization during the Omicron Phase of COVID-19.

INTRODUCTION: We previously developed a simple risk score with 3 items (age, patient report of dyspnea, and any relevant comorbidity), and in this report validate it in a prospective sample of patients, stratified by vaccination status. METHODS: Data were abstracted from a structured electronic health record of primary care and urgent care 8 patients with COVID-19 in the Lehigh Valley Health Network from 11/21/2021 and 10/31/2022 9 (Omicron variant). Our previously derived risk score was calculated for each of 19,456 patients, 10 and the likelihood of hospitalization was determined. Area under the ROC curve was calculated. RESULTS: We were able to place 13,239 patients (68%) in a low-risk group with only a 0.16% risk of 13 hospitalization. The moderate risk group with 5622 patients had a 2.2% risk of hospitalization 14 and might benefit from close outpatient follow-up, whereas the high-risk group with only 574 15 patients (2.9% of all patients) had an 8.9% risk of hospitalization and may require further 16 evaluation. Area under the curve was 0.844. DISCUSSION: We prospectively validated a simple risk score for primary and urgent care patients with COVID1919 that can support outpatient triage decisions around COVID-19.

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.

Dipsticks and point-of-care Microscopy to reduce antibiotic use in women with an uncomplicated Urinary Tract Infection (MicUTI): protocol of a randomised controlled pilot trial in primary care.

INTRODUCTION: Uncomplicated urinary tract infections (uUTIs) in women are common infections encountered in primary care. Evidence suggests that rapid point-of-care tests (POCTs) to detect bacteria and erythrocytes in urine at presentation may help primary care clinicians to identify women with uUTIs in whom antibiotics can be withheld without influencing clinical outcomes. This pilot study aims to provide preliminary evidence on whether a POCT informed management of uUTI in women can safely reduce antibiotic use. METHODS AND ANALYSIS: This is an open-label two-arm parallel cluster-randomised controlled pilot trial. 20 general practices affiliated with the Bavarian Practice-Based Research Network (BayFoNet) in Germany were randomly assigned to deliver patient management based on POCTs or to provide usual care. POCTs consist of phase-contrast microscopy to detect bacteria and urinary dipsticks to detect erythrocytes in urine samples. In both arms, urine samples will be obtained at presentation for POCTs (intervention arm only) and microbiological analysis. Women will be followed-up for 28 days from enrolment using self-reported symptom diaries, telephone follow-up and a review of the electronic medical record. Primary outcomes are feasibility of patient enrolment and retention rates per site, which will be summarised by means and SDs, with corresponding confidence and prediction intervals. Secondary outcomes include antibiotic use for UTI at day 28, time to symptom resolution, symptom burden, number of recurrent and upper UTIs and re-consultations and diagnostic accuracy of POCTs versus urine culture as the reference standard. These outcomes will be explored at cluster-levels and individual-levels using descriptive statistics, two-sample hypothesis tests and mixed effects models or generalised estimation equations. ETHICS AND DISSEMINATION: The University of Würzburg institutional review board approved MicUTI on 16 December 2022 (protocol n. 109/22-sc). Study findings will be disseminated through peer-reviewed publications, conferences, reports addressed to clinicians and the local citizen's forums. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT05667207.

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.

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.

[Top 4 Research Studies of the month for Italian Primary Care Physicians: December 2023.] / La Top 4 di dicembre 2023. Gli studi clinici che vale la pena conoscere se lavori nelle cure primarie in Italia.

This monthly article provides a collection of summaries of the most relevant studies identified as POEMs (patient-oriented evidence that matters) for Italian primary care physicians. 1) According to a high-quality network meta-analysis, oral isotretinoin is the most effective therapy for decreasing the number of inflammatory and non-inflammatory skin lesions in patients with acne vulgaris. 2) Non-steroidal anti-inflammatory drug (Nsaid) use is associated with a small increase (0.004%) in the risk of venous thromboembolism. Combining Nsaid use with a medium-risk hormonal contraceptive increases the risk to 0.011%; the addition of a high-risk hormonal contraceptive increases the risk to 0.023%. 3) For adults who wish to quit smoking, nicotine delivery via e-cigarettes, plus counseling, may be more effective than other means of nicotine replacement, or counseling alone for long-term smoking cessation. 4) We can reassure our patients that nonerosive gastroesophageal reflux disease (Gerd) does not increase the likelihood of esophageal cancer. Erosive Gerd, however, is associated with a doubled - but still low - risk of developing cancer, with the likelihood increasing over time.

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.

Using microbiological data to improve the use of antibiotics for respiratory tract infections: A protocol for an individual patient data meta-analysis.

BACKGROUND: Resistance to antibiotics is rising and threatens future antibiotic effectiveness. 'Antibiotic targeting' ensures patients who may benefit from antibiotics receive them, while being safely withheld from those who may not. Point-of-care tests may assist with antibiotic targeting by allowing primary care clinicians to establish if symptomatic patients have a viral, bacterial, combined, or no infection. However, because organisms can be harmlessly carried, it is important to know if the presence of the virus/bacteria is related to the illness for which the patient is being assessed. One way to do this is to look for associations with more severe/prolonged symptoms and test results. Previous research to answer this question for acute respiratory tract infections has given conflicting results with studies has not having enough participants to provide statistical confidence. AIM: To undertake a synthesis of IPD from both randomised controlled trials (RCTs) and observational cohort studies of respiratory tract infections (RTI) in order to investigate the prognostic value of microbiological data in addition to, or instead of, clinical symptoms and signs. METHODS: A systematic search of Cochrane Central Register of Controlled Trials, Ovid Medline and Ovid Embase will be carried out for studies of acute respiratory infection in primary care settings. The outcomes of interest are duration of disease, severity of disease, repeated consultation with new/worsening illness and complications requiring hospitalisation. Authors of eligible studies will be contacted to provide anonymised individual participant data. The data will be harmonised and aggregated. Multilevel regression analysis will be conducted to determine key outcome measures for different potential pathogens and whether these offer any additional information on prognosis beyond clinical symptoms and signs. TRIAL REGISTRATION: PROSPERO Registration number: CRD42023376769.

[Top 4 Research Studies of the month for Italian Primary Care Physicians: November 2023.] / La Top 4 di novembre 2023. Gli studi clinici che vale la pena conoscere se lavori nelle cure primarie in Italia.

This monthly article provides a collection of summaries of the most relevant studies identified as POEMs (patient-oriented evidence that matters) for Italian primary care physicians. 1) Based on efficacy, safety, and cost, a regimen of terbinafine 250 mg once daily for 12 weeks, followed by a 12-week period of no therapy, and then a 4-week booster of terbinafine 250 mg is preferred for onychomycosis in adults for the outcome of complete cure at 1 year. 2) A high-quality randomized trial found that standard-course antibiotic therapy for children with uncomplicated urinary tract infection was superior to short-course therapy. However, the number needed to treat of 28 suggests that offering short-course therapy is not unreasonable, especially if there is good follow-up in the subsequent weeks. 3) An updated guideline of the American College of Physicians on screening of colorectal cancer adds 2 new recommendations. One is to consider not screening patients aged 45 to 49 years. The other recommendation is against screening using stool Dna, computed tomography colonography, capsule endoscopy, urine, or serum screening tests for colorectal cancer. 4) The US Preventive Services Task Force found additional evidence on the benefit of folic acid supplementation for preventing neural tube defects. Since the critical period starts at least 1 month before conception, the task force recommends a daily supplement of 0.4 mg to 0.8 mg folic acid for all women who plan to or could become pregnant.