The presence of SARS-CoV-2 in raw wastewaters has been demonstrated in many countries affected by this pandemic. Nevertheless, virus presence and infectivity in treated wastewaters, but also in the ...receiving water bodies are still poorly investigated. In this study, raw and treated samples from three wastewater treatment plants, and three river samples within the Milano Metropolitan Area, Italy, were surveyed for SARS-CoV-2 RNA detection by means of real time RT-PCR and infectivity test on culture cells. SARS-CoV-2 RNA was detected in raw, but not in treated wastewaters (four and two samples, respectively, sampled in two dates). The isolated virus genome was sequenced, and belonged to the strain most spread in Europe and similar to another found in the same region. RNA presence in raw wastewater samples decreased after eight days, probably following the epidemiological trend estimated for the area. Virus infectivity was always null, indicating the natural decay of viral pathogenicity in time from emission. Samples from receiving rivers (three sites, sampled in the same dates as wastewaters) showed in some cases a positivity to real time RT-PCR, probably due to non-treated, or inefficiently treated discharges, or to the combined sewage overflows. Nevertheless, also for rivers infectivity was null. Risks for public health should be limited, although a precautionary approach to risk assessment is here advocated, giving the preliminary nature of the presented data.
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•SARS-CoV-2 RNA presence and infectivity in wastewaters and receptors was assessed.•Viral RNA was detectable in the inflow but not in the outflow wastewaters.•Viral RNA was present in receptors due to sewage overflows or inefficient treatment.•SARS-CoV-2 infectivity was null both in wastewaters and receptors.•A precautionary approach in the assessment of contagious risk is advocated.
The evaluation of imprecision is a key dimension of the grading of the confidence in the estimate. Grading of Recommendations Assessment, Development and Evaluation (GRADE) gives recommendations on ...how to downgrade evidence for imprecision, but authors vary in their use. Trial Sequential Analysis (TSA) has been advocated for a more reliable assessment of imprecision. We aimed to evaluate reporting of and adherence to GRADE and to compare the assessment of imprecision of intervention effects assessed by GRADE and TSA in Cochrane systematic reviews.
In this cross-sectional study, we included 100 Cochrane reviews irrespective of type of intervention with a key dichotomous outcome meta-analyzed and assessed by GRADE. The methods and results sections of each review were assessed for adequacy of imprecision evaluation. We re-analyzed imprecision following the GRADE Handbook and the TSA Manual.
Overall, only 13.0% of reviews stated the criteria they applied to assess imprecision. The most common dimensions were the 95% width of the confidence intervals and the optimal information size. Review authors downgraded 48.0% of key outcomes due to imprecision. When imprecision was re-analyzed following the GRADE Handbook, 64% of outcomes were downgraded. Agreement between review authors' assessment and assessment by the authors of this study was moderate (kappa 0.43, 95% confidence interval CI 0.23 to 0.58). TSA downgraded 69.0% outcomes due to imprecision. Agreement between review authors' GRADE assessment and TSA, irrespective of downgrading levels, was moderate (kappa 0.43, 95% CI 0.21 to 0.57). Agreement between our GRADE assessment following the Handbook and TSA was substantial (kappa 0.66, 95% CI 0.49 to 0.79).
In a sample of Cochrane reviews, methods for assessing imprecision were rarely reported. GRADE according to Handbook guidelines and TSA led to more severe judgment of imprecision rather than GRADE adopted by reviews' authors. Cochrane initiatives to improve adherence to GRADE Handbook are warranted. TSA may transparently assist in such development.
To assess the relationship between surgical delay and mortality in elderly patients with hip fracture. Systematic review and meta-analysis of retrospective and prospective studies published from 1948 ...to 2011. Medline (from 1948), Embase (from 1974) and CINAHL (from 1982), and the Cochrane Library. Odds ratios (OR) and 95% confidence intervals for each study were extracted and pooled with a random effects model. Heterogeneity, publication bias, bayesian analysis, and meta-regression analyses were done. Criteria for inclusion were retro- and prospective elderly population studies, patients with operated hip fractures, indication of timing of surgery and survival status.
There were 35 independent studies, with 191,873 participants and 34,448 deaths. The majority considered a cut-off between 24 and 48 hours. Early hip surgery was associated with a lower risk of death (pooled odds ratio (OR) 0.74, 95% confidence interval (CI) 0.67 to 0.81; P<0.000) and pressure sores (0.48, 95% CI 0.38 to 0.60; P<0.000). Meta-analysis of the adjusted prospective studies gave similar results. The bayesian probability predicted that about 20% of future studies might find that early surgery is not beneficial for decreasing mortality. None of the confounders (e.g. age, sex, data source, baseline risk, cut-off points, study location, quality and year) explained the differences between studies.
Surgical delay is associated with a significant increase in the risk of death and pressure sores. Conservative timing strategies should be avoided. Orthopaedic surgery services should ensure the majority of patients are operated within one or two days.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The coronavirus disease 2019 (COVID-19) pandemic and antimicrobial resistance (AMR) are parallel and interacting health emergencies that provide the opportunity for mutual learning. As their measures ...and consequences are comparable, the COVID-19 pandemic helps to illustrate the potential long-term impact of AMR, which is less acute but not less crucial. They may also impact each other as there is a push to use existing antimicrobials to treat critically ill COVID-19 patients in the absence of specific treatments. Attempts to manage the spread of COVID-19 may also lead to a slowdown in AMR. Understanding how COVID-19 affects AMR trends and what we can expect if these trends remain the same or worsen will help us to plan the next steps for tackling AMR. Researchers should start collecting data to measure the impact of current COVID-19 policies and programs on AMR.
In stroke patients, upper limb paresis affects many activities of daily life. Reducing disability is therefore a major aim of rehabilitation programmes for hemiparetic patients. Constraint-induced ...movement therapy (CIMT) is a current approach to stroke rehabilitation that implies the forced use and the massed practice of the affected arm by restraining the unaffected arm.
To assess the efficacy of CIMT, modified CIMT (mCIMT), or forced use (FU) for arm management in hemiparetic patients.
We searched the Cochrane Stroke Group trials register (last searched June 2008), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2008), MEDLINE (1966 to June 2008), EMBASE (1980 to June 2008), CINAHL (1982 to June 2008), and the Physiotherapy Evidence Database (PEDro) (June 2008).
Randomised control trials (RCTs) and quasi-RCTs (qRCTs) comparing CIMT, mCIMT or FU with other rehabilitative techniques, or none.
Two review authors independently classified the identified trials according to the inclusion and exclusion criteria, assessed methodological quality and extracted data. The primary outcome was disability.
We included 19 studies involving 619 participants. The trials included participants who had some residual motor power of the paretic arm, the potential for further motor recovery and with limited pain or spasticity, but tended to use the limb little if at all. Only five studies had adequate allocation concealment. The majority of studies were underpowered (median number of included patients was 15) and we cannot rule out small-trial bias. Six trials (184 patients) assessed disability immediately after the intervention, indicating a significant standard mean difference (SMD) of 0.36, 95% confidence interval (CI) 0.06 to 0.65. For the most frequently reported outcome, arm motor function (11 studies involving 373 patients), the SMD was 0.72 (95% CI 0.32 to 1.12). There were only two studies that explored disability improvement after a few months of follow up and found no significant difference, SMD -0.07 (95% CI -0.53 to 0.40).
CIMT is a multifaceted intervention: the restriction to the normal limb is accompanied by a certain amount of exercise of the appropriate quality. It is associated with a moderate reduction in disability assessed at the end of the treatment period. However, for disability measured some months after the end of treatment, there was no evidence of persisting benefit. Further randomised trials, with larger sample sizes and longer follow up, are justified.
Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is associated with increased morbidity and mortality, but the identification of LVAD candidates at risk for ...RVF remains challenging. We undertook a systematic review and meta‐analysis of observational studies of risk factors associated with RVF after LVAD implant. Thirty‐six studies published between 1 January 1995 and 30 April 2015, comprising 995 RVF patients out of a pooled final population of 4428 patients, were identified. Meta‐analysed prevalence of post‐LVAD RVF was 35%. A need for mechanical ventilation odds ratio (OR) 2.99, or continuous renal replacement therapy (CRRT; OR 4.61, area under the curve 0.78, specificity 0.91) were the clinical variables with the highest effect size (ES) in predicting RVF. International normalized ratio INR; standardized mean difference (SMD) 0.49 and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) (SMD 0.52) were the biochemical markers that best discriminated between RVF and No‐RVF populations, though NT‐proBNP was highly heterogeneous. Right ventricular stroke work index (RVSWI) and central venous pressure (CVP) (SMD −0.58 and 0.47, respectively) were the haemodynamic measures with the highest ES in identifying patients at risk of post‐LVAD RVF; CVP was particularly useful in risk stratifying patients undergoing continuous‐flow LVAD implant (SMD 0.59, P < 0.001, I2 = 20.9%). Finally, pre‐implant moderate to severe right ventricular (RV) dysfunction, as assessed qualitatively (OR 2.82), or a greater RV/LV diameter ratio (SMD 0.51) were the standard echocardiographic measurements with the highest ES in comparing RVF with No‐RVF patients. Longitudinal systolic strain of the RV free wall had the highest ES (SMD 0.73) but also the greatest heterogeneity (I2 = 74%) and was thus only marginally significant (P = 0.05). Patients on ventilatory support or CRRT are at high risk for post‐LVAD RVF, similarly to patients with slightly increased INR, high NT‐proBNP or leukocytosis. High CVP, low RVSWI, an enlarged right ventricle with concomitant low RV strain also identify patients at higher risk.
Introduction: Five anti-tumor necrosis factor (anti-TNF) agents have received regulatory approval for use in rheumatology: adalimumab, golimumab, infliximab, certolizumab, and etanercept. Apart from ...their well-documented therapeutic value, it is still uncertain to what extent they are associated with an increased risk of infectious adverse events.
Areas covered: We conducted a systematic review and meta-analysis of published randomized studies to determine the effect of anti-TNF drugs on the occurrence of infectious adverse events (serious infections; tuberculosis; opportunistic infections; any infection). We searched Medline, Embase, and the Cochrane Library up to May 2014 to identify eligible studies in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis that evaluated anti-TNF drugs compared with placebo or no treatment.
Expert opinion: Our study encompassed data from 71 randomized controlled trials involving 22,760 participants (range of follow-up: 1-36 months) and seven open label extension studies with 2,236 participants (range of follow-up: 6-48 months). Quantitative synthesis of the available data found statistically significant increases in the occurrence of any infections (20%), serious infections (40%), and tuberculosis (250%) associated with anti-TNF drug use, while the data for opportunistic infections were scarce. The quality of synthesized evidence was judged as moderate. Further evidence from registries and long-term epidemiological studies are needed to better define the relationship between anti-TNF agents and infection complications.
Advanced Computerized Decision Support Systems (CDSSs) assist clinicians in their decision-making process, generating recommendations based on up-to-date scientific evidence. Although this technology ...has the potential to improve the quality of patient care, its mere provision does not guarantee uptake: even where CDSSs are available, clinicians often fail to adopt their recommendations. This study examines the barriers and facilitators to the uptake of an evidence-based CDSS as perceived by diverse health professionals in hospitals at different stages of CDSS adoption.
Qualitative study conducted as part of a series of randomized controlled trials of CDSSs. The sample includes two hospitals using a CDSS and two hospitals that aim to adopt a CDSS in the future. We interviewed physicians, nurses, information technology staff, and members of the boards of directors (n = 30). We used a constant comparative approach to develop a framework for guiding implementation.
We identified six clusters of experiences of, and attitudes towards CDSSs, which we label as "positions." The six positions represent a gradient of acquisition of control over CDSSs (from low to high) and are characterized by different types of barriers to CDSS uptake. The most severe barriers (prevalent in the first positions) include clinicians' perception that the CDSSs may reduce their professional autonomy or may be used against them in the event of medical-legal controversies. Moving towards the last positions, these barriers are substituted by technical and usability problems related to the technology interface. When all barriers are overcome, CDSSs are perceived as a working tool at the service of its users, integrating clinicians' reasoning and fostering organizational learning.
Barriers and facilitators to the use of CDSSs are dynamic and may exist prior to their introduction in clinical contexts; providing a static list of obstacles and facilitators, irrespective of the specific implementation phase and context, may not be sufficient or useful to facilitate uptake. Factors such as clinicians' attitudes towards scientific evidences and guidelines, the quality of inter-disciplinary relationships, and an organizational ethos of transparency and accountability need to be considered when exploring the readiness of a hospital to adopt CDSSs.
Statins may prevent recurrent ischemic events after ischemic stroke. Determining which statin to use remains controversial. We aimed to summarize the evidence for the use of statins in secondary ...prevention for patients with ischemic stroke by comparing benefits and harms of various statins.
We searched for randomized controlled trials (RCTs) assessing statins in patients with ischemic stroke or transient ischemic attack (TIA) in MEDLINE, EMBASE, and CENTRAL up to July 2017. Two authors extracted data and appraised risks of bias. We performed pairwise meta-analyses and trial sequential analyses (TSA) to compare statins versus placebo/no statin, and network meta-analyses using frequentist random-effects models to compare statins through indirect evidence. We used GRADE to rate the overall certainty of evidence. Primary outcomes were all-cause mortality and all strokes. Secondary outcomes were different types of strokes, cardiovascular events, and adverse events.
We identified nine trials (10,741 patients). No head-to-head RCTs were found. The median follow-up period was 2.5 years. Statins did not seem to modify all stroke and all-cause mortality outcomes; they were associated with a decreased risk of ischemic stroke (odds ratio, OR, 0.81 95% CI, 0.70 to 0.93; absolute risk difference, ARD, - 1.6% 95% CI, - 2.6 to - 0.6%), ischemic stroke or TIA (OR, 0.75 95% CI, 0.64 to 0.87; ARD, - 4.2% 95% CI, - 6.2 to - 2.1%), and cardiovascular event (OR, 0.75 95% CI, 0.69 to 0.83; ARD, - 5.4% 95% CI, - 6.8 to - 3.6%), and did not seem to modify rhabdomyolysis, myalgia, or rise in creatine kinase. In the comparison of different statins, moderate- to high-quality evidence indicated that differences between pharmaceutical products seemed modest, with high doses (e.g., atorvastatin 80 mg/day and simvastatin 40 mg/day) associated with the greatest benefits. TSA excluded random error as a cause of the findings for ischemic stroke and cardiovascular event outcomes. Evidence for increased risk of hemorrhagic stroke was sensitive to the exclusion of the SPARCL trial.
Evidence strongly suggests that statins are associated with a reduction in the absolute risk of ischemic strokes and cardiovascular events. Differences in effects among statins were modest, signaling potential therapeutic equivalence.
PROSPERO CRD42018079112.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Increasing availability of competing biosimilar alternatives makes it challenging to make treatment decisions. The purpose of this review is to evaluate the comparative efficacy and safety ...of ultra-long-/long-/intermediate-acting insulin products and biosimilar insulin compared to human/animal insulin in adults with type 1 diabetes mellitus (T1DM).
Methods
MEDLINE, EMBASE, CENTRAL, and grey literature were searched from inception to March 27, 2019. Randomized controlled trials (RCTs), quasi-experimental studies, and cohort studies of adults with T1DM receiving ultra-long-/long-/intermediate-acting insulin, compared to each other, as well as biosimilar insulin compared to human/animal insulin were eligible for inclusion. Two reviewers independently screened studies, abstracted data, and appraised risk-of-bias. Pairwise meta-analyses and network meta-analyses (NMA) were conducted. Summary effect measures were mean differences (MD) and odds ratios (OR).
Results
We included 65 unique studies examining 14,200 patients with T1DM. Both ultra-long-acting and long-acting insulin were superior to intermediate-acting insulin in reducing A1c, FPG, weight gain, and the incidence of major, serious, or nocturnal hypoglycemia. For fasting blood glucose, long-acting once a day (od) was superior to long-acting twice a day (bid) (MD - 0.44, 95% CI: - 0.81 to - 0.06) and ultra-long-acting od was superior to long-acting bid (MD - 0.73, 95% CI - 1.36 to - 0.11). For weight change, long-acting od was inferior to long-acting bid (MD 0.58, 95% CI: 0.05 to 1.10) and long-acting bid was superior to long-action biosimilar od (MD - 0.90, 95% CI: - 1.67 to - 0.12).
Conclusions
Our results can be used to tailor insulin treatment according to the desired results of patients and clinicians and inform strategies to establish a competitive clinical market, address systemic barriers, expand the pool of potential suppliers, and favor insulin price reduction.
PROSPERO Registration
CRD42017077051
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