Summary Background Antibiotic-associated diarrhoea (AAD) occurs most frequently in older (≥65 years) inpatients exposed to broad-spectrum antibiotics. When caused by Clostridium difficile , AAD can ...result in life-threatening illness. Although underlying disease mechanisms are not well understood, microbial preparations have been assessed in the prevention of AAD. However, studies have been mostly small single-centre trials with varying quality, providing insufficient data to reliably assess effectiveness. We aimed to do a pragmatic efficacy trial in older inpatients who would be representative of those admitted to National Health Service (NHS) and similar secondary care institutions and to recruit a sufficient number of patients to generate a definitive result. Methods We did a multicentre, randomised, double-blind, placebo-controlled, pragmatic, efficacy trial of inpatients aged 65 years and older and exposed to one or more oral or parenteral antibiotics. A computer-generated randomisation scheme was used to allocate participants (in a 1:1 ratio) to receive either a multistrain preparation of lactobacilli and bifidobacteria, with a total of 6 × 1010 organisms, one per day for 21 days, or an identical placebo. Patients, study staff, and specimen and data analysts were masked to assignment. The primary outcomes were occurrence of AAD within 8 weeks and C difficile diarrhoea (CDD) within 12 weeks of recruitment. Analysis was by modified intention-to-treat. This trial is registered, number ISRCTN70017204. Findings Of 17 420 patients screened, 1493 were randomly assigned to the microbial preparation group and 1488 to the placebo group. 1470 and 1471, respectively, were included in the analyses of the primary endpoints. AAD (including CDD) occurred in 159 (10·8%) participants in the microbial preparation group and 153 (10·4%) participants in the placebo group (relative risk RR 1·04; 95% CI 0·84–1·28; p=0·71). CDD was an uncommon cause of AAD and occurred in 12 (0·8%) participants in the microbial preparation group and 17 (1·2%) participants in the placebo group (RR 0·71; 95% CI 0·34–1·47; p=0·35). 578 (19·7%) participants had one or more serious adverse event; the frequency of serious adverse events was much the same in the two study groups and none was attributed to participation in the trial. Interpretation We identified no evidence that a multistrain preparation of lactobacilli and bifidobacteria was effective in prevention of AAD or CDD. An improved understanding of the pathophysiology of AAD is needed to guide future studies. Funding Health Technology Assessment programme; National Institute for Health Research, UK.
Abstract Background The optimal management of patients found to have multivessel disease while undergoing primary percutaneous coronary intervention (P-PCI) for ST-segment elevation myocardial ...infarction is uncertain. Objectives CvLPRIT (Complete versus Lesion-only Primary PCI trial) is a U.K. open-label randomized study comparing complete revascularization at index admission with treatment of the infarct-related artery (IRA) only. Methods After they provided verbal assent and underwent coronary angiography, 296 patients in 7 U.K. centers were randomized through an interactive voice-response program to either in-hospital complete revascularization (n = 150) or IRA-only revascularization (n = 146). Complete revascularization was performed either at the time of P-PCI or before hospital discharge. Randomization was stratified by infarct location (anterior/nonanterior) and symptom onset (≤3 h or >3 h). The primary endpoint was a composite of all-cause death, recurrent myocardial infarction (MI), heart failure, and ischemia-driven revascularization within 12 months. Results Patient groups were well matched for baseline clinical characteristics. The primary endpoint occurred in 10.0% of the complete revascularization group versus 21.2% in the IRA-only revascularization group (hazard ratio: 0.45; 95% confidence interval: 0.24 to 0.84; p = 0.009). A trend toward benefit was seen early after complete revascularization (p = 0.055 at 30 days). Although there was no significant reduction in death or MI, a nonsignificant reduction in all primary endpoint components was seen. There was no reduction in ischemic burden on myocardial perfusion scintigraphy or in the safety endpoints of major bleeding, contrast-induced nephropathy, or stroke between the groups. Conclusions In patients presenting for P-PCI with multivessel disease, index admission complete revascularization significantly lowered the rate of the composite primary endpoint at 12 months compared with treating only the IRA. In such patients, inpatient total revascularization may be considered, but larger clinical trials are required to confirm this result and specifically address whether this strategy is associated with improved survival. (Complete Versus Lesion-only Primary PCI Pilot Study CvLPRIT; ISRCTN70913605 )
This study provides 2-year data from the PARTNER trial, in which patients with aortic stenosis received transcatheter aortic-valve replacement (TAVR) or surgical replacement. Overall mortality was ...similar, but paravalvular leak increased mortality in the TAVR group.
Aortic stenosis is associated with high mortality after the appearance of cardiac symptoms.
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Nevertheless, many patients do not undergo surgical aortic-valve replacement owing to real or perceived increased risks associated with surgery.
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Transcatheter aortic-valve replacement (TAVR) has emerged as an alternative therapy in high-risk patients with aortic stenosis.
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Observational registries from various countries have reported 1-month and 1-year outcomes after TAVR,
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but there are limited long-term follow-up data.
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The Placement of Aortic Transcatheter Valves (PARTNER) trial was a randomized trial comparing TAVR with standard-of-care therapies in high-risk patients with aortic stenosis. One-year mortality outcomes from PARTNER showed . . .
This study examines use of an expandable bovine pericardial prosthetic valve inserted with a catheter system for valvular aortic stenosis. Outcomes were noninferior to those of surgical aortic-valve ...replacement, but the risk of stroke, aortic regurgitation, and vascular complications was substantial.
After the appearance of symptoms, aortic stenosis is associated with a high rate of death if left untreated.
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Although surgical aortic-valve replacement improves symptoms and survival,
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observational studies have identified various subgroups of patients (i.e., those with an advanced age and those with poor left ventricular function or other coexisting disorders) who are at increased risk for operative complications or death.
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In such patients, a less invasive treatment may be a desirable alternative.
Transcatheter aortic-valve replacement treats aortic stenosis by displacing and functionally replacing the native valve with a bioprosthetic valve delivered on a catheter through the . . .
There has been evidence demonstrating that China has had a persistently low and below-replacement level fertility since early 1990s, causing concerns of a rapidly aging population and sustainability ...of the Chinese economy. To avoid adverse effects of excessively low fertility, the Chinese government has recently changed its family planning policy from "one-child policy" to "two-child policy." Nonetheless, the effectiveness of the newly initiated two-child policy is questionable if women's average desired number of children or desired fertility for their lifetime is below the threshold fertility allowed by the two-child policy. Therefore, this study argues that it would be interesting and pertinent to know women's fertility desires under the circumstances of no policy restrictions and understand major factors that may affect their desired fertility. Based on a multi-stage stratified cluster sampling survey with 2,516 women respondents in rural Shaanxi, this study tries to estimate desired fertility of rural women and evaluate the impact of important socioeconomic factors on their desired fertility. The results of this study reveal that the average lifetime desired fertility for rural women of childbearing age in Shaanxi is about 1.71, below the total fertility rate at the replacement level. The findings of this study suggest that women's marriage age, the pecuniary costs of having children, women's income forgone for having children, and social security benefits available for rural residents at retirement age, are significantly and negatively related to desired fertility. However, rural women's cultural views towards fertility are significantly but positively related to their desired fertility. This study further confirms that China has entered an era of low fertility, and thus, any policy restrictions on fertility may no longer be necessary. Instead, government programs which support childbearing and childrearing are needed to prevent excessive low fertility and rapid aging of the population.
Background:
Health anxiety may be an increasing problem because of the focus on monitoring health and increasing use of the Internet for self-diagnosis (cyberchondria). There is very little ...information about changes in the prevalence of health anxiety.
Aim:
We compared the prevalence of health anxiety in four medical clinics in one hospital over a 4-year period using the Health Anxiety Inventory (HAI) as a diagnostic marker.
Method:
Patients attending cardiology, endocrine, gastroenterology and respiratory medicine clinics at King’s Mill Hospital, North Nottinghamshire, completed the HAI while waiting for their appointments. There were eight research assistants involved in collecting data, two in the 2006–2008 period and six in the 2008–2010 period. As a consequence, more data were collected on the second occasion.
Results:
There was an increase in the prevalence of health anxiety from 14.9% in 2006–2008 (54 positive of 362 assessed) to 19.9% (1,132 positive out of 5,704 assessed) in 2008–2010. This increase was primarily noted in gastroenterology clinics (increase of 10%) and not shown in endocrine ones.
Conclusion:
The prevalence of health anxiety is increasing in those who attend medical out-patient clinics. Reasons are given that this may be a possible result of cyberchondria, as the excessive use of the Internet to interpret troubling symptoms is growing. Further studies are needed in other populations, but there is reason to be concerned at this trend as it is likely to increase the number of medical consultations unnecessarily.
The conventional reporting of composite endpoints in clinical trials has an inherent limitation in that it emphasizes each patient's first event, which is often the outcome of lesser clinical ...importance. To overcome this problem, we introduce the concept of the win ratio for reporting composite endpoints. Patients in the new treatment and control groups are formed into matched pairs based on their risk profiles. Consider a primary composite endpoint, e.g. cardiovascular (CV) death and heart failure hospitalization (HF hosp) in heart failure trials. For each matched pair, the new treatment patient is labelled a 'winner' or a 'loser' depending on who had a CV death first. If that is not known, only then they are labelled a 'winner' or 'loser' depending on who had a HF hosp first. Otherwise they are considered tied. The win ratio is the total number of winners divided by the total numbers of losers. A 95% confidence interval and P-value for the win ratio are readily obtained. If formation of matched pairs is impractical then an alternative win ratio can be obtained by comparing all possible unmatched pairs. This method is illustrated by re-analyses of the EMPHASIS-HF, PARTNER B, and CHARM trials. The win ratio is a new method for reporting composite endpoints, which is easy to use and gives appropriate priority to the more clinically important event, e.g. mortality. We encourage its use in future trial reports.
Summary Background WHO estimates exposure to air pollution from cooking with solid fuels is associated with over 4 million premature deaths worldwide every year including half a million children ...under the age of 5 years from pneumonia. We hypothesised that replacing open fires with cleaner burning biomass-fuelled cookstoves would reduce pneumonia incidence in young children. Methods We did a community-level open cluster randomised controlled trial to compare the effects of a cleaner burning biomass-fuelled cookstove intervention to continuation of open fire cooking on pneumonia in children living in two rural districts, Chikhwawa and Karonga, of Malawi. Clusters were randomly allocated to intervention and control groups using a computer-generated randomisation schedule with stratification by site, distance from health centre, and size of cluster. Within clusters, households with a child under the age of 4·5 years were eligible. Intervention households received two biomass-fuelled cookstoves and a solar panel. The primary outcome was WHO Integrated Management of Childhood Illness (IMCI)-defined pneumonia episodes in children under 5 years of age. Efficacy and safety analyses were by intention to treat. The trial is registered with ISRCTN, number ISRCTN59448623. Findings We enrolled 10 750 children from 8626 households across 150 clusters between Dec 9, 2013, and Feb 28, 2016. 10 543 children from 8470 households contributed 15 991 child-years of follow-up data to the intention-to-treat analysis. The IMCI pneumonia incidence rate in the intervention group was 15·76 (95% CI 14·89–16·63) per 100 child-years and in the control group 15·58 (95% CI 14·72–16·45) per 100 child-years, with an intervention versus control incidence rate ratio (IRR) of 1·01 (95% CI 0·91–1·13; p=0·80). Cooking-related serious adverse events (burns) were seen in 19 children; nine in the intervention and ten (one death) in the control group (IRR 0·91 95% CI 0·37–2·23; p=0·83). Interpretation We found no evidence that an intervention comprising cleaner burning biomass-fuelled cookstoves reduced the risk of pneumonia in young children in rural Malawi. Effective strategies to reduce the adverse health effects of household air pollution are needed. Funding Medical Research Council, UK Department for International Development, and Wellcome Trust.
The purpose of this study is to assess the level of knowledge, attitudes, and willingness to organ donation among the general public in China.
The study population consisted of 4274 participants from ...Eastern, Central and Western China. The participants' knowledge, attitudes and willingness to organ donation were collected by a self-designed questionnaire consisting of 30 items. Knowledge is measured by 10 items and presented as a 10 point score, attitudes is measured by 20 items using a 5-step Likert scale and total score ranged between 0 and 80; while the willingness to donate is assessed as binary variable (0 = No; 1 = Yes). A logistic regression model was used to assess the association of knowledge and attitudes with willingness to organ donation, controlling for demographic and socioeconomic confounders.
The questionnaire response rate was 94.98%. The mean score (± SD) of the general public's knowledge to organ donation was 6.84 ± 1.76, and the mean score (± SD) of attitudes to organ donation was 47.01 ± 9.07. The general public's knowledge and attitudes were the highest in Eastern China, followed by West and Central China. The logistic regression model indicated a positive association between knowledge and the willingness to organ donation (OR = 1.12, 95%CI: 1.08, 1.17; P < 0.001); attitudes were also positively potential determinant of more willingness to organ donation (OR = 1.08, 95%CI: 1.07, 1.09; P < 0.001).
Knowledge and attitudes were found to be positively associated with the Chinese general public's willingness to organ donation. Knowledge about the concept of brain death and the transplant procedure may help raise the rate of willingness to organ donation.
Considerable attention has focused on the role of omega-3 polyunsaturated fatty acids (PUFA) in the prevention of cardiometabolic diseases, which has led to dietary recommendations to increase ...omega-3 fatty acid intake. A meta-analysis was conducted to summarize evidence from prospective studies regarding associations between omega-3 PUFA biomarkers and risk of developing major chronic diseases.
Four electronic databases were searched for articles from inception to March 1, 2022. Random-effects model was used to estimate the pooled relative risk (RR) and 95% confidence intervals (CIs) for the association of omega-3 PUFAs, including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), with risk of developing type 2 diabetes (T2D), cardiovascular disease (CVD), including coronary heart disease (CHD) and stroke, cancer, and mortality. The Grades of Recommendation, Assessment, Development and Evaluation assessment tool was used to rates the confidence in estimates.
A total of 67 prospective studies comprised of 310,955 participants were identified. Individual omega-3 PUFAs showed divergent associations with the study outcomes of interest. A significant inverse association with T2D risk was observed across categories of ALA (relative risk RR: 0.89, 95% confidence interval CI: 0.82–0.96), EPA (RR: 0.85, 95% CI: 0.72–0.99) and DPA (RR: 0.84, 95% CI: 0.73–0.96) biomarkers. The marine-origin omega-3 fatty acids biomarkers but not ALA was significantly associated with lower risks of total CVD, CHD, and overall mortality, with RRs ranging from 0.70 for DHA-CHD association to 0.85 for EPA-CHD association. A lower risk of colorectal cancer was observed at higher levels of DPA (RR: 0.76, 95% CI: 0.59–0.98) and DHA (RR: 0.80; 95% CI: 0.65–0.99), whereas no association was noted for other outcomes. In addition, a dose–response relationship was observed between an increasing level of EPA, DPA, or DHA biomarker and lower risk of CVD.
Higher concentrations of marine-derived omega-3 PUFA biomarkers were associated with a significantly reduced risk of total CVD, CHD, and total mortality. Levels of ALA were inversely associated with a lower risk of T2D but not CVD-related outcomes. These data support the dietary recommendations advocating the role of omega-3 PUFAs in maintaining an overall lower risk of developing cardiovascular disease and premature deaths.
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