Corticosteroids for the common cold

BACKGROUND: The common cold is a frequent illness, which, although benign and self limiting, results in many consultations to primary care and considerable loss of school or work days. Current symptomatic treatments have limited benefit. Corticosteroids are an effective treatment in other upper respiratory tract infections and their anti‐inflammatory effects may also be beneficial in the common cold. This updated review has included one additional study. OBJECTIVES: To compare corticosteroids versus usual care for the common cold on measures of symptom resolution and improvement in children and adults. SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 4), which includes the Acute Respiratory Infections (ARI) Group's Specialised Register, the Database of Reviews of Effects (DARE) (2015, Issue 2), NHS Health Economics Database (2015, Issue 2), MEDLINE (1948 to May week 3, 2015) and EMBASE (January 2010 to May 2015). SELECTION CRITERIA: Randomised, double‐blind, controlled trials comparing corticosteroids to placebo or to standard clinical management. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. We were unable to perform meta‐analysis and instead present a narrative description of the available evidence. MAIN RESULTS: We included three trials (353 participants). Two trials compared intranasal corticosteroids to placebo and one trial compared intranasal corticosteroids to usual care; no trials studied oral corticosteroids. In the two placebo‐controlled trials, no benefit of intranasal corticosteroids was demonstrated for duration or severity of symptoms. The risk of bias overall was low or unclear in these two trials. In a trial of 54 participants, the mean number of symptomatic days was 10.3 in the placebo group, compared to 10.7 in those using intranasal corticosteroids (P value = 0.72). A second trial of 199 participants reported no significant differences in the duration of symptoms. The single‐blind trial in children aged two to 14 years, who were also receiving oral antibiotics, had inadequate reporting of outcome measures regarding symptom resolution. The overall risk of bias was high for this trial. Mean symptom severity scores were significantly lower in the group receiving intranasal steroids in addition to oral amoxicillin. One placebo‐controlled trial reported the presence of rhinovirus in nasal aspirates and found no differences. Only one of the three trials reported on adverse events; no differences were found. Two trials reported secondary bacterial infections (one case of sinusitis, one case of acute otitis media; both in the corticosteroid groups). A lack of comparable outcome measures meant that we were unable to combine the data. AUTHORS' CONCLUSIONS: Current evidence does not support the use of intranasal corticosteroids for symptomatic relief from the common cold. However, there were only three trials, one of which was very poor quality, and there was limited statistical power overall. Further large, randomised, double‐blind, placebo‐controlled trials in adults and children are required to answer this question

Recommendations of high-quality clinical practice guidelines related to the process of starting dialysis: A systematic review

Treatment guidelines; Chronic kidney disease; Database searchingPautas de tratamiento; Enfermedad renal cronica; Búsqueda de base de datosPautes de tractament; Malaltia renal crònica; Recerca de bases de dadesBackground The optimal time for initiation of dialysis and which modality to choose as the starting therapy is currently unclear. This systematic review aimed to assess the recommendations across high-quality clinical practice guidelines (CPGs) related to the start of dialysis. Methods We systematically searched MEDLINE, EMBASE, Web of Science, LILACS, and databases of organisations that develop CPGs between September 2008 to August 2021 for CPGs that addressed recommendations on the timing of initiation of dialysis, selection of dialysis modality, and interventions to support the decision-making process to select a dialysis modality. We used the Appraisal of Guidelines for Research and Evaluation instrument to assess the methodological quality of the CPGs and included only high-quality CPGs. This study is registered in PROSPERO, number CRD42018110325. Results We included 12 high-quality CPGs. Six CPGs addressed recommendations related to the timing of initiating dialysis, and all agreed on starting dialysis in the presence of symptoms or signs. Six CPGs addressed recommendations related to the selection of modality but varied greatly in their content. Nine CPGs addressed recommendations related to interventions to support the decision-making process. Eight CPGs agreed on recommended educational programs that include information about dialysis options. One CPG considered using patient decision aids a strong recommendation. Limitations We could have missed potentially relevant guidelines since we limited our search to CPGs published from 2008, and we set up a cut-off point of 60% in domains of the rigour of development and editorial independence. Conclusion High-quality CPGs related to the process of starting dialysis were consistent in initiating dialysis in the presence of symptoms or signs and offering patients education at the point of decision-making. There was variability in how CPGs addressed the issue of dialysis modality selection. CPGs should improve strategies on putting recommendations into practice and the quality of evidence to aid decision-making for patients. Registration The protocol of this systematic review has been registered in the international prospective register of systematic reviews (PROSPERO) under the registration number: CRD CRD42018110325. https://clinicaltrials.gov/ct2/show/CRD42018110325

Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children

BACKGROUND: Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide. OBJECTIVES: To describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomised, placebo-controlled trials and regulatory comments. SEARCH METHODS: We searched trial registries, electronic databases (to 22 July 2013) and regulatory archives, and corresponded with manufacturers to identify all trials. We also requested clinical study reports. We focused on the primary data sources of manufacturers but we checked that there were no published randomised controlled trials (RCTs) from non-manufacturer sources by running electronic searches in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE (Ovid), EMBASE, Embase.com, PubMed (not MEDLINE), the Database of Reviews of Effects, the NHS Economic Evaluation Database and the Health Economic Evaluations Database. SELECTION CRITERIA: Randomised, placebo-controlled trials on adults and children with confirmed or suspected exposure to naturally occurring influenza. DATA COLLECTION AND ANALYSIS: We extracted clinical study reports and assessed risk of bias using purpose-built instruments. We analysed the effects of zanamivir and oseltamivir on time to first alleviation of symptoms, influenza outcomes, complications, hospitalisations and adverse events in the intention-to-treat (ITT) population. All trials were sponsored by the manufacturers. MAIN RESULTS: We obtained 107 clinical study reports from the European Medicines Agency (EMA), GlaxoSmithKline and Roche. We accessed comments by the US Food and Drug Administration (FDA), EMA and Japanese regulator. We included 53 trials in Stage 1 (a judgement of appropriate study design) and 46 in Stage 2 (formal analysis), including 20 oseltamivir (9623 participants) and 26 zanamivir trials (14,628 participants). Inadequate reporting put most of the zanamivir studies and half of the oseltamivir studies at a high risk of selection bias. There were inadequate measures in place to protect 11 studies of oseltamivir from performance bias due to non-identical presentation of placebo. Attrition bias was high across the oseltamivir studies and there was also evidence of selective reporting for both the zanamivir and oseltamivir studies. The placebo interventions in both sets of trials may have contained active substances. Time to first symptom alleviation. For the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval (CI) 8.4 to 25.1 hours, P 1000) and nausea whilst on treatment (RD 4.15%, 95% CI 0.86 to 9.51); NNTH = 25 (95% CI 11 to 116). AUTHORS' CONCLUSIONS: Oseltamivir and zanamivir have small, non-specific effects on reducing the time to alleviation of influenza symptoms in adults, but not in asthmatic children. Using either drug as prophylaxis reduces the risk of developing symptomatic influenza. Treatment trials with oseltamivir or zanamivir do not settle the question of whether the complications of influenza (such as pneumonia) are reduced, because of a lack of diagnostic definitions. The use of oseltamivir increases the risk of adverse effects, such as nausea, vomiting, psychiatric effects and renal events in adults and vomiting in children. The lower bioavailability may explain the lower toxicity of zanamivir compared to oseltamivir. The balance between benefits and harms should be considered when making decisions about use of both NIs for either the prophylaxis or treatment of influenza. The influenza virus-specific mechanism of action proposed by the producers does not fit the clinical evidence

B-type natriuretic peptide-guided treatment for heart failure

Background Heart failure is a condition in which the heart does not pump enough blood to meet all the needs of the body. Symptoms of heart failure include breathlessness, fatigue and fluid retention. Outcomes for patients with heart failure are highly variable; however on average, these patients have a poor prognosis. Prognosis can be improved with early diagnosis and appropriate use of medical treatment, use of devices and transplantation. Patients with heart failure are high users of healthcare resources, not only due to drug and device treatments, but due to high costs of hospitalisation care. B‐type natriuretic peptide levels are already used as biomarkers for diagnosis and prognosis of heart failure, but could offer to clinicians a possible tool to guide drug treatment. This could optimise drug management in heart failure patients whilst allaying concerns over potential side effects due to drug intolerance. Objectives To assess whether treatment guided by serial BNP or NT‐proBNP (collectively referred to as NP) monitoring improves outcomes compared with treatment guided by clinical assessment alone. Search methods Searches were conducted up to 15 March 2016 in the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (OVID), Embase (OVID), the Database of Abstracts of Reviews of Effects (DARE) and the NHS Economic Evaluation Database in the Cochrane Library. Searches were also conducted in the Science Citation Index Expanded, the Conference Proceedings Citation Index on Web of Science (Thomson Reuters), World Health Organization International Clinical Trials Registry and ClinicalTrials.gov. We applied no date or language restrictions. Selection criteria We included randomised controlled trials of NP‐guided treatment of heart failure versus treatment guided by clinical assessment alone with no restriction on follow‐up. Adults treated for heart failure, in both in‐hospital and out‐of‐hospital settings, and trials reporting a clinical outcome were included. Data collection and analysis Two review authors independently selected studies for inclusion, extracted data and evaluated risk of bias. Risk ratios (RR) were calculated for dichotomous data, and pooled mean differences (MD) (with 95% confidence intervals (CI)) were calculated for continuous data. We contacted trial authors to obtain missing data. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, we assessed the quality of the evidence and GRADE profiler (GRADEPRO) was used to import data from Review Manager to create a 'Summary of findings' table. Main results We included 18 randomised controlled trials with 3660 participants (range of mean age: 57 to 80 years) comparing NP‐guided treatment with clinical assessment alone. The evidence for all‐cause mortality using NP‐guided treatment showed uncertainty (RR 0.87, 95% CI 0.76 to 1.01; patients = 3169; studies = 15; low quality of the evidence), and for heart failure mortality (RR 0.84, 95% CI 0.54 to 1.30; patients = 853; studies = 6; low quality of evidence). The evidence suggested heart failure admission was reduced by NP‐guided treatment (38% versus 26%, RR 0.70, 95% CI 0.61 to 0.80; patients = 1928; studies = 10; low quality of evidence), but the evidence showed uncertainty for all‐cause admission (57% versus 53%, RR 0.93, 95% CI 0.84 to 1.03; patients = 1142; studies = 6; low quality of evidence). Six studies reported on adverse events, however the results could not be pooled (patients = 1144; low quality of evidence). Only four studies provided cost of treatment results, three of these studies reported a lower cost for NP‐guided treatment, whilst one reported a higher cost (results were not pooled; patients = 931, low quality of evidence). The evidence showed uncertainty for quality of life data (MD ‐0.03, 95% CI ‐1.18 to 1.13; patients = 1812; studies = 8; very low quality of evidence). We completed a 'Risk of bias' assessment for all studies. The impact of risk of bias from lack of blinding of outcome assessment and high attrition levels was examined by restricting analyses to only low 'Risk of bias' studies. Authors' conclusions In patients with heart failure low‐quality evidence showed a reduction in heart failure admission with NP‐guided treatment while low‐quality evidence showed uncertainty in the effect of NP‐guided treatment for all‐cause mortality, heart failure mortality, and all‐cause admission. Uncertainty in the effect was further shown by very low‐quality evidence for patient's quality of life. The evidence for adverse events and cost of treatment was low quality and we were unable to pool results.</p

The Evidence Base for Interventions Delivered to Children in Primary Care: An Overview of Cochrane Systematic Reviews

Background: As a first step in developing a framework to evaluate and improve the quality of care of children in primary care there is a need to identify the evidence base underpinning interventions relevant to child health. Our objective was to identify all Cochrane systematic reviews relevant to the management of childhood conditions in primary care and to assess the extent to which Cochrane reviews reflect the burden of childhood illness presenting in primary care.Methodology/Principal Findings: We used the Cochrane Child Health Field register of child-relevant systematic reviews to complete an overview of Cochrane reviews related to the management of children in primary care. We compared the proportion of systematic reviews with the proportion of consultations in Australia, US, Dutch and UK general practice in children. We identified 396 relevant systematic reviews; 385 included primary studies on children while 251 undertook a meta-analysis. Most reviews (n=218, 55%) focused on chronic conditions and over half (n=216, 57%) evaluated drug interventions. Since 2000, the percentage of pediatric primary care relevant reviews only increased by 2% (7% to 9%) compared to 18% (10% to 28%) in all child relevant reviews. Almost a quarter of reviews (n=78, 23%) were published on asthma treatments which only account for 3-5% of consultations. Conversely, 15-23% of consultations are due to skin conditions yet they represent only 7% (n=23) of reviews.Conclusions/Significance: Although Cochrane systematic reviews focus on clinical trials and do not provide a comprehensive picture of the evidence base underpinning the management of children in primary care, the mismatch between the focus of the published research and the focus of clinical activity is striking. Clinical trials are an important component of the evidence based and the lack of trial evidence to demonstrate intervention effectiveness in substantial areas of primary care for children should be addressed.</p

Does cranberry extract reduce antibiotic use for symptoms of acute uncomplicated urinary tract infections (CUTI)?:A feasibility randomised trial

Objectives To determine the feasibility of conducting a randomised trial of the effectiveness of cranberry extract in reducing antibiotic use by women with symptoms of acute, uncomplicated urinary tract infection (UTI). Design Open-label feasibility randomised parallel group trial. Setting Four general practices in Oxfordshire. Participants Women aged 18 years and above presenting to general practice with symptoms of acute, uncomplicated UTI. Interventions Women were randomly assigned using Research Electronic Data Capture in a 1:1:1 ratio to: (1) immediate antibiotics alone (n=15); (2) immediate antibiotics and immediate cranberry capsules for up to 7 days (n=15); or (3) immediate cranberry capsules and delayed antibiotics for self-initiation in case of non-improvement or worsening of symptoms (n=16). Primary and secondary outcome measures The primary outcome measures were: rate of recruitment of participants; numbers lost to follow-up; proportion of electronic diaries completed by participants; and acceptability of the intervention and study procedures to participants and recruiters. Secondary outcomes included an exploration of differences in symptom burden and antibiotic use between groups. Results Four general practitioner practices (100%) were opened and recruited participants between 1 July and 2 December 2019, with nine study participants recruited per month on average. 68.7% (46/67) of eligible participants were randomised (target 45) with a mean age of 48.4 years (SD 19.9, range 18–81). 89.1% (41/46) of diaries contained some participant entered data and 69.6% (32/46) were fully complete. Three participants (6.5%) were lost to follow-up and two (4.4%) withdrew. Of women randomly assigned to take antibiotics alone (controls), one-third of respondents reported consuming cranberry products (33.3%, 4/12). There were no serious adverse events. Conclusions It appears feasible to conduct a randomised trial of the use of cranberry extract in the treatment of acute, uncomplicated UTI in general practice. Trial registration number ISRCTN Registry (ID: 10399299)

Impact of Changes to National Hypertension Guidelines on Hypertension Management and Outcomes in the United Kingdom.

In recent years, national and international guidelines have recommended the use of out-of-office blood pressure monitoring for diagnosing hypertension. Despite evidence of cost-effectiveness, critics expressed concerns this would increase cardiovascular morbidity. We assessed the impact of these changes on the incidence of hypertension, out-of-office monitoring and cardiovascular morbidity using routine clinical data from English general practices, linked to inpatient hospital, mortality, and socio-economic status data. We studied 3 937 191 adults with median follow-up of 4.2 years (49% men, mean age=39.7 years) between April 1, 2006 and March 31, 2017. Interrupted time series analysis was used to examine the impact of changes to English hypertension guidelines in 2011 on incidence of hypertension (primary outcome). Secondary outcomes included rate of out-of-office monitoring and cardiovascular events. Across the study period, incidence of hypertension fell from 2.1 to 1.4 per 100 person-years. The change in guidance in 2011 was not associated with an immediate change in incidence (change in rate=0.01 [95% CI, -0.18-0.20]) but did result in a leveling out of the downward trend (change in yearly trend =0.09 [95% CI, 0.04-0.15]). Ambulatory monitoring increased significantly in 2011/2012 (change in rate =0.52 [95% CI, 0.43-0.60]). The rate of cardiovascular events remained unchanged (change in rate =-0.02 [95% CI, -0.05-0.02]). In summary, changes to hypertension guidelines in 2011 were associated with a stabilisation in incidence and no increase in cardiovascular events. Guidelines should continue to recommend out-of-office monitoring for diagnosis of hypertension

Self-Screening and Non-Physician Screening for Hypertension in Communities: A Systematic Review.

BACKGROUND: Community-based self-screening may provide opportunities to increase detection of hypertension, and identify raised blood pressure (BP) in populations who do not access healthcare. This systematic review aimed to evaluate the effectiveness of non-physician screening and self-screening of BP in community settings. METHODS: We searched the Cochrane Central Trials Register, Medline, Embase, CINAHL, and Science Citation Index & Conference Proceedings Citation Index-Science to November 2013 to identify studies reporting community-based self-screening or non-physician screening for hypertension in adults. Results were stratified by study site, screener, and the cut-off used to define high screening BP. RESULTS: We included 73 studies, which described screening in 9 settings, with pharmacies (22%) and public areas/retail (15%) most commonly described. We found high levels of heterogeneity in all analyses, despite stratification. The highest proportions of eligible participants screened were achieved by mobile units (range 21%-88%) and pharmacies (range 40%-90%). Self-screeners had similar median rates of high BP detection (25%-35%) to participants in studies using other screeners. Few (16%) studies reported referral to primary care after screening. However, where participants were referred, a median of 44% (range 17%-100%) received a new hypertension diagnosis or antihypertensive medication. CONCLUSIONS: Community-based non-physician or self-screening for raised BP can detect raised BP, which may lead to the identification of new cases of hypertension. However, current evidence is insufficient to recommend specific approaches or settings. Studies with good follow-up of patients to definitive diagnosis are needed.This article presents independent research funded by a National Institute for Health Research Programme Grant RP-PG-1209–10051.This is the final version of the article. It was first available from Oxford University Press via http://dx.doi.org/10.1093/ajh/hpv02

Accuracy of blood pressure monitors used for BP checks in retail pharmacies

BACKGROUND: Free blood pressure (BP) checks offered by community pharmacies offer a potentially useful opportunity to diagnose and/or manage hypertension, but the accuracy of the sphygmomanometers in use is currently unknown. AIM: To assess the accuracy of validated automatic BP monitors used for BP checks in a UK retail pharmacy chain. Design and Setting 52 pharmacies from one chain were visited in a range of locations (inner city, suburban, rural) in central England. METHOD: Monitor accuracy was compared to a calibrated reference device (Omron PA-350), at 50 mmHg intervals across the range 0-300 mmHg (static pressure test), with a difference from the reference monitor of +/-3 mmHg at any interval considered a failure. The results were analysed by usage rates and length of time in service. RESULTS: Eight (13%) monitors failed (i.e. were more than 3mmHg from reference), all underestimating BP. Monitor failure rate from the reference monitor of +/- 3 mmHg at any testing interval varied by length of time in use (2/38, 5% before 18 months vs. 4/14, 29% after 18 months; p=0.038) and to some extent but non-significantly by usage rates (4/22, 18% in monitors used more than once daily vs. 2/33, 6% in those used less frequently; p=0.204). CONCLUSION: BP monitors within a pharmacy setting fail at similar rates to those in general practice. Annual calibration checks for blood pressure monitors are needed, even for new monitors, since these data indicate declining performance from 18 months onwards.This work represents independent research commissioned by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research funding scheme (RP-PG-0407–10347). The views expressed in this study are those of the authors and not necessarily of the NHS, the NIHR or the Department of Health. RJM is supported by an NIHR Professorship (NIHR-RP-02-12-015) and by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) Oxford at Oxford Health NHS Foundation Trust. FDRH is part funded as Director of the National Institute for Health Research (NIHR) School for Primary Care Research (SPCR), Theme Leader of the NIHR Oxford Biomedical Research Centre (BRC), and Director of the NIHR CLAHRC Oxford