Treatments for subacute cough in primary care: systematic review and meta-analyses of randomised clinical trials.

BACKGROUND: Subacute cough following a non-specific viral infection lasting 3-8 weeks is common. However, despite many treatment options there are no systematic reviews evaluating these. AIM: To provide a systematic overview of treatment options and outcomes evaluated in randomised clinical trials (RCTs). DESIGN AND SETTING: Systematic review and meta-analyses assessing the overall effects of any treatment for subacute cough. METHOD: The authors systematically searched PubMed/MEDLINE and the Cochrane Central Register of Controlled Trials (last search March 2017) for RCTs in adult patients with subacute cough. The authors considered trials evaluating any outcome of any drug or non-drug treatments, apart from traditional Chinese and Asian medicines. They combined treatment effects on cough-related outcomes in random effects meta-analyses. RESULTS: Six eligible RCTs including 724 patients were identified. These assessed montelukast, salbutamol plus ipratropium bromide, gelatine, fluticasone propionate, budesonide, and nociception opioid 1 receptor agonist and codeine. Five studies reported effects on various cough severity scores at various timepoints. No treatment option was associated with a clear benefit on cough recovery or other patient-relevant outcomes in any of the studies or in meta-analyses for cough outcomes at 14 days and 28 days. Reported adverse events were rather mild and reported for 14% of patients across all treatments. CONCLUSION: Evidence on treatment options for subacute cough is weak. There is no treatment showing clear patient-relevant benefits in clinical trials.

Procalcitonin, pyuria and proadrenomedullin in the management of urinary tract infections--'triple p in uti': study protocol for a randomized controlled trial.

BACKGROUND: Urinary tract infections (UTIs) are among the most common infectious diseases and drivers of antibiotic use and in-hospital days. A reduction of antibiotic use potentially lowers the risk of antibiotic resistance. An early and adequate risk assessment combining medical, biopsychosocial and functional risk scores has the potential to optimize site-of-care decisions and thus allocation of limited health-care resources. The aim of this factorial design study is twofold: first, for Intervention A, it investigates antibiotic exposure of patients treated with a protocol based on the type of UTI, procalcitonin (PCT) and pyuria. Second, for Intervention B, it investigates the usefulness of the prognostic biomarker proadrenomedullin (ProADM) integrated into an interdisciplinary assessment bundle for site-of-care decisions. METHODS AND DESIGN: This randomized controlled open-label trial has a factorial design (2 × 2). Randomization of patients will be based on a pre-specified computer-generated randomization list and independent for the two interventions. Adults with UTI presenting to the emergency department (ED) will be screened and enrolled after providing informed consent. For our first Intervention (A), we developed a protocol based on previous observational research to recommend initiation and duration of antibiotic use based on the clinical presentation of UTI, pyuria and PCT levels. For our second intervention (B), an algorithm was developed to support site-of care decisions based on the prognostic marker ProADM and distinct nursing factors on days 1 and 3. Both interventions will be compared with a control group conforming to the guidelines. The primary endpoints for the two interventions will be: (A) overall exposure to antibiotics and (B) length of physician-led hospitalization within a follow-up of 30 days. Endpoints are assessed at discharge from hospital, and 30 and 90 days after admission. We plan to screen 300 patients and enroll 250 for an anticipated estimated loss of follow-up of 20%. This will provide adequate power for the two interventions. DISCUSSION: This trial investigates two strategies for improved individualized medical care in patients with UTI. The minimally effective duration of antibiotic therapy is not known for UTIs, which is important for reducing the selection pressure for antibiotic resistance, costs and drug-related side effects. Triage decisions must be improved to reflect the true medical, biopsychosocial and functional risks in order to allocate patients to the most appropriate care setting and reduce hospital-acquired disability. TRIAL REGISTRATION NUMBER: ISRCTN13663741.