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BACKGROUND Randomised controlled trials (RCTs) investigated analgesics, herbal formulations, delayed prescription of antibiotics and placebo to prevent overprescription of antibiotics in women with uncomplicated urinary tract infections (uUTI). OBJECTIVES To estimate the effect of these strategies and to identify symptoms, signs or other factors that indicate a benefit from these strategies. DATA SOURCES MEDLINE, EMBASE, Web of Science, LILACS, Cochrane Database of Systematic Reviews and of Controlled Trials, and ClinicalTrials. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS RCTs investigating any strategies to reduce antibiotics versus immediate antibiotics in adult women with uUTI in primary care. DATA SYNTHESIS We extracted individual participant data (IPD) if available, otherwise aggregate data (AD). Bayesian random-effects meta-analysis of the AD was used for pairwise comparisons. Candidate moderators and prognostic indicators of treatment effects were investigated using generalised linear mixed models based on IPD. RESULTS We analysed IPD of 3524 patients from eight RCTs and AD of 78 patients. Non-antibiotic strategies increased the rates of incomplete recovery (odds ratio [OR] 3.0; 95% credible interval [CI] 1.7-5.5; Bayesian p-value pB=0.0017; τ=0.6), subsequent antibiotic treatment (OR 3.5 [95% CI 2.1, 5.8; pB=0.0003) and pyelonephritis (OR 5.6; 95% CI 2.3, 13.9; pB=0.0003). Conversely, they decreased overall antibiotic use by 63%. In patients positive for urinary erythrocytes and urine culture were at increased risk for incomplete recovery (OR 4.7; 95% CI 2.1-10.8; pB =0.0010), but no difference was apparent where both were negative (OR 0.8; 95% CI 0.3-2.0; pB =0.667). In patients treated with using non-antibiotic strategies, urinary erythrocytes and positive urine culture were independent prognostic indicators for subsequent antibiotic treatment and pyelonephritis. CONCLUSIONS AND RELEVANCE Compared to immediate antibiotics, non-antibiotic strategies reduce overall antibiotic use but result in poorer clinical outcomes. The presence of erythrocytes and tests to confirm bacteria in urine could be used to target antibiotic prescribing.

Abstract The microbial ecology of arctic and sub-arctic soils is an important aspect of the global carbon cycle, due to the sensitivity of the large soil carbon stocks to ongoing climate warming. These regions are characterized by strong climatic seasonality, but the emphasis of most studies on the short vegetation growing season could potentially limit our ability to predict year-round ecosystem functions. We compiled a database of studies from arctic, subarctic, and boreal environments that include sampling of microbial community and functions outside the growing season. We found that for studies comparing across seasons, in most environments, microbial biomass and community composition vary intra-annually, with the spring thaw period often identified by researchers as the most dynamic time of year. This seasonality of microbial communities will have consequences for predictions of ecosystem function under climate change if it results in: seasonality in process kinetics of microbe-mediated functions; intra-annual variation in the importance of different (a)biotic drivers; and/or potential temporal asynchrony between climate change-related perturbations and their corresponding effects. Future research should focus on (i) sampling throughout the entire year; (ii) linking these multi-season measures of microbial community composition with corresponding functional or physiological measurements to elucidate the temporal dynamics of the links between them; and (iii) identifying dominant biotic and abiotic drivers of intra-annual variation in different ecological contexts.

Cachexia is a commonly observed but frequently neglected extra-pulmonary manifestation in patients with chronic obstructive pulmonary disease (COPD). Cachexia is a multifactorial syndrome characterized by severe loss of body weight, muscle, and fat, as well as increased protein catabolism. COPD cachexia places a high burden on patients (eg, increased mortality risk and disease burden, reduced exercise capacity and quality of life) and the healthcare system (eg, increased number, length, and cost of hospitalizations). The etiology of COPD cachexia involves a complex interplay of non-modifiable and modifiable factors (eg, smoking, hypoxemia, hypercapnia, physical inactivity, energy imbalance, and exacerbations). Addressing these modifiable factors is needed to prevent and treat COPD cachexia. Oral nutritional supplementation combined with exercise training should be the primary multimodal treatment approach. Adding a pharmacological agent might be considered in some, but not all, patients with COPD cachexia. Clinicians and researchers should use longitudinal measures (eg, weight loss, muscle mass loss) instead of cross-sectional measures (eg, low body mass index or fat-free mass index) where possible to evaluate patients with COPD cachexia. Lastly, in future research, more detailed phenotyping of cachectic patients to enable a better comparison of included patients between studies, prospective longitudinal studies, and more focus on the impact of exacerbations and the role of biomarkers in COPD cachexia, are highly recommended.

Snow is an important driver of ecosystem processes in cold biomes. Snow accumulation determines ground temperature, light conditions, and moisture availability during winter. It also affects the growing season’s start and end, and plant access to moisture and nutrients. Here, we review the current knowledge of the snow cover’s role for vegetation, plant-animal interactions, permafrost conditions, microbial processes, and biogeochemical cycling. We also compare studies of natural snow gradients with snow experimental manipulation studies to assess time scale difference of these approaches. The number of tundra snow studies has increased considerably in recent years, yet we still lack a comprehensive overview of how altered snow conditions will affect these ecosystems. Specifically, we found a mismatch in the timing of snowmelt when comparing studies of natural snow gradients with snow manipulations. We found that snowmelt timing achieved by snow addition and snow removal manipulations (average 7.9 days advance and 5.5 days delay, respectively) were substantially lower than the temporal variation over natural spatial gradients within a given year (mean range 56 days) or among years (mean range 32 days). Differences between snow study approaches need to be accounted for when projecting snow dynamics and their impact on ecosystems in future climates.

The article describes some of the achievements of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA), after eight years in operation. These results were achieved thanks to the collaborative work of the action groups (AGs) and reference sites (RSs). RS regional ecosystems include key organisations committed to investing in innovation to foster active and healthy ageing. The AGs are groups of professionals committed to sharing their knowledge and skills in active and healthy ageing. This article reports on the approach used by the EIP on AHA to bring together experts and regions in identifying and addressing these challenges. Synergies between AGs offered substantial support to RSs, allowing regional health and care priorities and challenges to be identified and pursued through AG commitments. Building upon the experiences of the EIP on AHA, the Reference Sites Collaborative Network has set up a number of thematic action groups that bring together multidisciplinary experts from across Europe to address the main health and social care challenges at regional, national and European level.

Obstructive sleep apnoea is a challenging medical problem due to its prevalence, its impact on quality of life and performance in school and professionally, the implications for risk of accidents, and comorbidities and mortality. Current research has carved out a broad spectrum of clinical phenotypes and defined major pathophysiological components. These findings point to the concept of personalised therapy, oriented on both the distinct clinical presentation and the most relevant pathophysiology in the individual patient. This leads to questions of whether sufficient therapeutic options other than positive airway pressure (PAP) alone are available, for which patients they may be useful, if there are specific indications for single or combined treatment, and whether there is solid scientific evidence for recommendations. This review describes our knowledge on PAP and non-PAP therapies to address upper airway collapsibility, muscle responsiveness, arousability and respiratory drive. The spectrum is broad and heterogeneous, including technical and pharmaceutical options already in clinical use or at an advanced experimental stage. Although there is an obvious need for more research on single or combined therapies, the available data demonstrate the variety of effective options, which should replace the unidirectional focus on PAP therapy.