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ObjectiveTo conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) of the effectiveness and safety of oral pre-exposure prophylaxis (PrEP) to prevent HIV.MethodsDatabases (PubMed, Embase and the Cochrane Register of Controlled Trials) were searched up to 5 July 2020. Search terms for ‘HIV’ were combined with terms for ‘PrEP’ or ‘tenofovir/emtricitabine’. RCTs were included that compared oral tenofovir-containing PrEP to placebo, no treatment or alternative medication/dosing schedule. The primary outcome was the rate ratio (RR) of HIV infection using a modified intention-to-treat analysis. Secondary outcomes included safety, adherence and risk compensation. All analyses were stratified a priori by population: men who have sex with men (MSM), serodiscordant couples, heterosexuals and people who inject drugs (PWIDs). The quality of individual studies was assessed using the Cochrane risk-of-bias tool, and the certainty of evidence was assessed using GRADE.ResultsOf 2803 unique records, 15 RCTs met our inclusion criteria. Over 25 000 participants were included, encompassing 38 289 person-years of follow-up data. PrEP was found to be effective in MSM (RR 0.25, 95% CI 0.1 to 0.61; absolute rate difference (RD) −0.03, 95% CI −0.01 to −0.05), serodiscordant couples (RR 0.25, 95% CI 0.14 to 0.46; RD −0.01, 95% CI −0.01 to −0.02) and PWID (RR 0.51, 95% CI 0.29 to 0.92; RD −0.00, 95% CI −0.00 to −0.01), but not in heterosexuals (RR 0.77, 95% CI 0.46 to 1.29). Efficacy was strongly associated with adherence (p<0.01). PrEP was found to be safe, but unrecognised HIV at enrolment increased the risk of viral drug resistance mutations. Evidence for behaviour change or an increase in sexually transmitted infections was not found.ConclusionsPrEP is safe and effective in MSM, serodiscordant couples and PWIDs. Additional research is needed prior to recommending PrEP in heterosexuals. No RCTs reported effectiveness or safety data for other high-risk groups, such as transgender women and sex workers.PROSPERO registration numberCRD42017065937.

Background Multimorbidity prevalence is increasing globally. People with multimorbidity have higher health care costs, which can create a financial burden. Objective To synthesize qualitative research exploring experience of financial burden for people with multimorbidity. Search strategy Six databases were searched in May 2019. A grey literature search and backward and forward citation checking were also conducted. Inclusion criteria Studies were included if they used a qualitative design, conducted primary data collection, included references to financial burden and had at least one community‐dwelling adult participant with two or more chronic conditions. Data extraction and synthesis Screening and critical appraisal were conducted by two reviewers independently. One reviewer extracted data from the results section; this was checked by a second reviewer. GRADE‐CERQual was used to summarize the certainty of the evidence. Data were analysed using thematic synthesis. Main results Forty‐six studies from six continents were included. Four themes were generated: the high costs people with multimorbidity experience, the coping strategies they use to manage these costs, and the negative effect of both these on their well‐being. Health insurance and government supports determine the manageability and level of costs experienced. Discussion Financial burden has a negative effect on people with multimorbidity. Continuity of care and an awareness of the impact of financial burden of multimorbidity amongst policymakers and health care providers may partially address the issue. Patient or public contribution Results were presented to a panel of people with multimorbidity to check whether the language and themes ‘resonated’ with their experiences.

ObjectivesTo examine the effectiveness of exercise interventions to improve long COVID symptoms and the tolerance of exercise interventions among people with long COVID.DesignSystematic review.Data sourcesMedline via EBSCOhost, Embase via OVID and CENTRAL via the Cochrane Library up to 28 February 2023.Eligibility criteria for selecting studiesInclusion criteria were: (1) participants with long COVID, as defined by study authors; (2) random assignment to either an exercise intervention or a comparison group and (3) a quantitative measure of at least 1 of the 12 core long COVID outcomes. Exclusion criteria were: (1) signs or symptoms not reasonably attributable to prior SARS-CoV-2 infection; (2) pre-exposure or postexposure prophylaxis for COVID-19 or the prevention of long COVID symptoms and (3) interventions where the primary exercise component is breathing or respiratory muscle training.Data extraction and synthesisTwo reviewers independently extracted data, and studies were narratively synthesised.ResultsEight studies were included. Follow-up periods ranged from 2 to 28 weeks (mean=8.5 weeks). Sample sizes ranged from 39 to 119 (mean=56). All studies were in adults (mean age=49.9 years) and both sexes (mean female proportion=53.9%). Four studies were at low risk of bias, two were unclear and two were high. The evidence suggests that exercise interventions lead to short-term improvements in dyspnoea, fatigue, physical function and the physical domain of quality of life among people with long COVID. Of the five studies that reported adverse events, rates were low and, when reported, mild. Of the seven studies that reported sufficient relevant information, 1 of 252 participants who received exercise discontinued the intervention due to tolerance-related issues.ConclusionAvailable evidence suggests that exercise interventions may be beneficial and tolerable among some people with long COVID. However, the evidence base consists of a limited number of studies with small sample sizes and short follow-up periods.

ObjectivesIndividuals with multimorbidity use more health services and take more medicines. This can lead to high out-of-pocket (OOP) healthcare expenditure. This study, therefore, aimed to assess the association between multimorbidity (two or more chronic conditions) and OOP healthcare expenditure in a nationally representative sample of adults aged 50 years or over.DesignCross-sectional analysis of data collected in 2016 from wave 4 of The Irish Longitudinal Study on Ageing.SettingIreland.ParticipantsCommunity-dwelling adults aged 50 years and over.MethodA generalised linear model with log-link and gamma distributed errors was fitted to assess the association between multimorbidity and OOP healthcare expenditure (including general practitioner, emergency department, outpatients, specialist consultations, hospital admissions, home care and prescription drugs).ResultsOverall, 3453 (58.5%) participants had multimorbidity. Among those with any OOP healthcare expenditure, individuals with multimorbidity spent more on average per annum (€806.8 for two conditions, €885.8 for three or more conditions), than individuals with no conditions (€580.3). Pharmacy-dispensed medicine expenditure was the largest component of expenditure. People with multimorbidity on average spent more of their equivalised household income on healthcare (7.1% for two conditions, 9.7% for three or more conditions), than people with no conditions (5.0%). A strong positive association was found between number of conditions and OOP healthcare expenditure (p<0.001) and between having private health insurance and OOP healthcare expenditure (p<0.001). A strong negative association was found between eligibility for free primary/hospital care and heavily subsidised medicines and OOP healthcare expenditure (p<0.001).ConclusionsThis study suggests that having multimorbidity in Ireland increases OOP healthcare expenditure, which is problematic for those with more conditions who have lower incomes. This highlights the need for this financial burden to be considered when designing healthcare/funding systems to address multimorbidity, so that access to essential healthcare can be maximised for those with greatest need.

Background People with multimorbidity (i.e., two or more chronic conditions) experience increased out-of-pocket healthcare costs and are vulnerable to cost-related non-adherence to recommended treatment. The aim of this study was to understand how people with multimorbidity prioritise different healthcare services when faced with tighter budget constraints and how they experience cost-related non-adherence. Methods A national cross-sectional online survey incorporating a choice experiment was conducted. Participants were adults aged 40 years or over with at least one chronic condition, recruited in Ireland (December 2021 to March 2022). The survey included questions about real-life experiences of cost-related non-adherence and financial burden. The choice experiment element involved participants identifying how they would prioritise their real-world healthcare utilisation if their monthly personal healthcare budget was reduced by 25%. Results Among the 962 participants, 64.9% ( n  = 624) had multimorbidity. Over one third (34.5%, n  = 332) of participants reported cost-related non-adherence in the previous 12 months, which included not attending a healthcare appointment and/or not accessing medication. Similar findings on prioritisation were observed on the choice task. When presented with the hypothetical tighter budget constraint, participants reduced expenditure on ‘other healthcare (hospital visits, specialist doctors, etc.)’ by the greatest percentage (50.2%) and medicines by the lowest percentage (24.8%). Participants with multimorbidity tended to have a condition they prioritised over others. On average, they reduced expenditure for their top-priority condition by 71% less than would be expected if all conditions were valued equally, while they reduced expenditure for their least prioritised condition by 60% more than would be expected. Independence, symptom control and staying alive were rated as the most important influencing factors when making prioritisation decisions (median score = 5 out of 5). Conclusion When faced with tighter financial constraints, people with multimorbidity tended to have a condition they prioritised over others. Participants were also more likely to prioritise medicines over other aspects of healthcare. Researchers, policymakers and clinicians should take greater consideration of the different ways people respond to tighter financial constraints. This could involve reducing the payment barriers to accessing care or clinicians discussing healthcare costs and coverage with patients as part of cost-of-care conversations.

Self-management (SM) is defined as the provision of interventions to increase patients’ skills and confidence, empowering the individual to take an active part in their disease management. There is uncertainty regarding the optimal format and the short- and long-term benefits of chronic obstructive pulmonary disease (COPD) SM interventions in adults. Therefore, a high-quality overview of reviews was updated to examine their clinical effectiveness. Sixteen reviews were identified, interventions were broadly classified as education or action plans, complex interventions with an SM focus, pulmonary rehabilitation (PR), telehealth and outreach nursing. Systematic review and meta-analysis quality and the risk of bias of underlying primary studies were assessed. Strong evidence was found that PR is associated with significant improvements in health-related quality of life (HRQoL). Limited to moderate evidence for complex interventions (SM focus) with limited evidence for education, action plans, telehealth interventions and outreach nursing for HRQoL was found. There was strong evidence that education is associated with a significant reduction in COPD-related hospital admissions, moderate to strong evidence that telehealth interventions and moderate evidence that complex interventions (SM focus) are associated with reduced health care utilization. These findings from a large body of evidence suggesting that SM, through education or as a component of PR, confers significant health gains in people with COPD in terms of HRQoL. SM supported by telehealth confers significant reductions in healthcare utilization, including hospitalization and emergency department visits.

Intermittent pneumatic compression (IPC) is designed to aid wound healing and limb salvage for patients with critical limb ischaemia who are not candidates for revascularisation. We conducted a systematic review of the literature to identify and critically appraise the evidence supporting its use in this population. A search was conducted in Embase, MEDLINE and clinical trial registries up to the end of March 2013. No date or language restrictions were applied. Quality assessment was performed by two people independently. Quality was assessed using the Cochrane risk of bias tool and the NICE case-series assessment tool. Two controlled before-and-after (CBA) studies and six case series were identified. One retrospective CBA study involving compression of the calf reported improved limb salvage and wound healing (OR 7.00, 95% CI 1.82 to 26.89, p<0.01). One prospective CBA study involving sequential compression of the foot and calf reported statistically significant improvements in claudication distances and SF-36 quality of life scores. No difference in all-cause mortality was found. Complications included pain associated with compression, as well as skin abrasion and contact rash as a result of the cuff rubbing against the skin. All studies had a high risk of bias. In conclusion, the limited available results suggest that IPC may be associated with improved limb salvage, wound healing and pain management. However, in the absence of additional well-designed analytical studies examining the effect of IPC in critical limb ischaemia, this treatment remains unproven.

Although no known asteroid poses a threat to Earth for at least the next century, the catalogue of near-Earth asteroids is incomplete for objects whose impacts would produce regional devastation 1 , 2 . Several approaches have been proposed to potentially prevent an asteroid impact with Earth by deflecting or disrupting an asteroid 1 – 3 . A test of kinetic impact technology was identified as the highest-priority space mission related to asteroid mitigation 1 . NASA’s Double Asteroid Redirection Test (DART) mission is a full-scale test of kinetic impact technology. The mission’s target asteroid was Dimorphos, the secondary member of the S-type binary near-Earth asteroid (65803) Didymos. This binary asteroid system was chosen to enable ground-based telescopes to quantify the asteroid deflection caused by the impact of the DART spacecraft 4 . Although past missions have utilized impactors to investigate the properties of small bodies 5 , 6 , those earlier missions were not intended to deflect their targets and did not achieve measurable deflections. Here we report the DART spacecraft’s autonomous kinetic impact into Dimorphos and reconstruct the impact event, including the timeline leading to impact, the location and nature of the DART impact site, and the size and shape of Dimorphos. The successful impact of the DART spacecraft with Dimorphos and the resulting change in the orbit of Dimorphos 7 demonstrates that kinetic impactor technology is a viable technique to potentially defend Earth if necessary. The impact of the DART spacecraft on the asteroid Dimorphos is reported and reconstructed, demonstrating that kinetic impactor technology is a viable technique to potentially defend Earth from asteroids.

Objective PubReMiner is a text‐mining tool that analyses a seed set of citations to assess word frequency in titles, s, and Medical Subject Headings (MeSH). This study aimed to determine the sensitivity and precision of search strategies developed using the PubReMiner tool compared to conventional search strategies developed by a librarian at our institution. Methods Twelve consecutive reviews conducted at our center were included from September 2023 to January 2025. These reviews included various types of evidence synthesis, including rapid reviews and systematic reviews, covering a variety of topics. One librarian developed a comprehensive search strategy, which included a conventional MEDLINE search for each review. Separately, two librarians independently developed MEDLINE search strategies using PubReMiner‐generated word frequency tables (PubReMiner 1 and PubReMiner 2). All search strategies were constructed by experienced librarians using predefined work instructions. Primary outcomes were sensitivity and precision. Secondary outcomes included the number needed to read, the number of unique references retrieved, and the time taken to construct each strategy. Results Sensitivity of PubReMiner strategies was generally lower than that of conventional strategies; however, in one review, PubReMiner achieved a higher sensitivity (83.87%) than the conventional strategy (58.06%). Only the sensitivity outcome showed a statistically significant difference between search methods (Friedman test p = 0.0065). No statistically significant difference in precision between the searches was identified. PubReMiner strategies were typically faster to construct but yielded inconsistent performance across reviews and between librarians. Conclusion While PubReMiner offers efficiency advantages, its inconsistent performance in retrieving relevant studies suggests that it should not replace conventional search strategies. The study illustrates the value of multi‐review SWARs in producing evidence that informs evidence synthesis practices.

In this study we aim to examine gene–environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10−3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10−4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.