Summary Local treatment of metastases such as metastasectomy or radiotherapy remains controversial in the treatment of metastatic renal cell carcinoma. To investigate the benefits and harms of ...various local treatments, we did a systematic review of all types of comparative studies on local treatment of metastases from renal cell carcinoma in any organ. Interventions included metastasectomy, radiotherapy modalities, and no local treatment. The results suggest that patients treated with complete metastasectomy have better survival and symptom control (including pain relief in bone metastases) than those treated with either incomplete or no metastasectomy. Nevertheless, the available evidence was marred by high risks of bias and confounding across all studies. Although the findings presented here should be interpreted with caution, they and the identified gaps in knowledge should provide guidance for clinicians and researchers, and directions for further research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background Financial incentives are increasingly considered to address socially patterned behaviours like smoking in pregnancy and breastfeeding. We investigated their mechanisms of action ...in relation to health inequalities to inform incentive intervention design. Methods The evidence syntheses we undertook were incentive effectiveness, delivery processes, barriers and facilitators to smoking cessation in pregnancy and also breastfeeding; and incentives for lifestyle behaviours. We searched Medline, Embase, CINAHL, PsycINFO, Web of Science, the Cochrane Library (all sections), MIDIRS, ASSIA, and the Trials Register of Promoting Health Interventions for studies published in English between Jan 1, 1990, and March 31, 2012, using a range of natural language, MeSH, and other index terms. Surveys were done with 1144 respondents from the general public and with 497 maternity and early-years health professionals. Qualitative interviews and focus groups were conducted with pregnant women, recent mothers, and partners in three UK settings (n=88); and with 53 service providers, 24 experts and decision makers, and 63 conference attendees. A discrete choice experiment (DCE) was conducted with 320 female current or ex-smokers. Findings Systematic reviews raised concerns about the reach of incentives, particularly to marginalised groups. Baseline characteristics for people who were eligible, approached, and recruited to studies were under-reported. Sample sizes were mostly small. Surveys revealed mixed acceptability. Less educated, white British, and women general public respondents disagreed (odds ratios OR 0·5≤OR<1·0) particularly with smoking cessation incentives. Universal incentives (55% net agreement) were preferred to targeting low income women (49% net agreement). DCE results showed that incentives, a quitting pal, and initial text or telephone support were statistically significant in increasing the reported likelihood that women would quit. Conflicting narratives of women's emotional, social and material environments and the push and pull of incentives were voiced. For some, unrestricted shopping vouchers offered rare opportunities for choice, reward for effort, and feeling valued amidst adversity. Women struggle on their own, even concealing behaviour, especially when people in personal networks smoke or formula feed. However layers of autonomy were revealed, with varying levels of resistance to the nanny state, and feeling judged, pressure, and stigma. How incentive interventions fit with life's challenges were incorporated into a logic model. Interpretation Financial incentives can help some women, but whether they will address inequalities is unclear because of concerns about reach and resistance to being pushed and pulled. Funding The project was funded by the Health Technology Assessment programme ( 10/31/02 ) and will be published in full in Health Technology Assessment . The Chief Scientist Office of the Scottish Government Health and Social Care Directorates funds the Nursing Midwifery and Allied Health Professional Research Unit, University of Stirling; and the Health Services Research Unit and the Health Economics Research Unit, University of Aberdeen.
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Abstract Background Incentives for smoking cessation in pregnancy are attractive to policy makers because evidence of effectiveness for other interventions is scarce. Our aims were to establish the ...effectiveness of incentive interventions delivered within or outside the NHS to individuals, families, or organisations that are designed to increase and sustain smoking cessation in pregnancy; investigate how incentive delivery processes work, their acceptability, and how they fit with existing barriers, facilitators, and intrinsic and extrinsic motivators to behaviour change; and work in partnership with mother-and-baby groups to inform the design of incentive trials. Methods This study combines a mixed methods evidence synthesis with primary qualitative and survey research to investigate the perspectives of service users, care providers, the general public, experts, and policy makers. Uniquely, two mother-and-baby groups in areas serving disadvantaged populations in Aberdeen and Blackpool, UK, are study coapplicants, and are providing broad, dynamic, and longitudinal service-user contributions. Researchers attend mother-and-baby groups every 4–6 weeks to feedback findings from evidence synthesis, and record and transcribe discussions of included studies that will iteratively inform future qualitative data collection and analysis, guided by a grounded theory approach. Evidence synthesis follows Cochrane guidance. Detailed searches were done in Medline, Medline-in-Process, Embase, CINAHL, PsycINFO, Web of Science, CENTRAL, Cochrane Database of Systematic Reviews, DARE, HTA, MIDIRS, Applied Social Sciences Index and Abstracts, and the Trials Register of Promoting Health Interventions. 1469 abstracts were identified and 215 full-text reports were screened by two researchers. 21 studies—20 incentivising individuals, one incentivising an organisation—were included in quantitative data analysis and quality assessed with instruments such as Cochrane Risk of Bias and guidance from the Centre for Reviews and Dissemination (dependent on whether the population was randomised). All studies and one survey of attitudes to incentives were included in the delivery processes evidence synthesis, with quality assessment with a Mixed Methods Appraisal Tool. Therefore, one mixed methods coding and data extraction form (MMF) was designed iteratively through piloting with four information-rich studies with form modification after discussion between quantitative and qualitative team members. Quantitative data were extracted from full texts and crosschecked by a second reviewer. Two qualitative researchers independently identified themes that were coded by one with the MMF, with a sample crosschecked by the second. Interpretive themes emerged through discussion and a final thematic framework incorporating continuing service user perspectives is under construction, assisted by NVivo 9 data management software. Findings Incentive interventions identified were multifaceted. 14 (70%) of the 20 patient-level studies verified smoking cessation biochemically rather than relying on self-report. Incentives ranged from four packets of gum to larger incentives—eg, US$50 per month of abstinence. Incentives were often combined with additional smoking cessation components, with varying intensity: 13 (65%) included counselling or behavioural support, 13 (65%) included self-help guides or educational materials, six (30%) included advice to quit, and six (30%) involved social support (eg, including partners or peers) through education materials or encouragement. Few studies were directly comparable, with only four suitable for inclusion in a formal meta-analysis. The relative risk of cessation was 2·77 (95% CI 1·69–4·24), indicating that incentives were effective. Several key themes emerge for delivery processes and acceptability: individual or relational focus; certain or lottery incentives; hedonic or utilitarian incentives; programme bureaucracy meeting chaotic lifestyles; health professional or independent providers; continuity of care; and targeted interventions. Interpretation Incentives show promise for smoking cessation in pregnancy and contextual factors probably moderate effectiveness. Funding Project funded by the HTA programme (10/31/02) and will be published in full in Health Technology Assessment.
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Men are underrepresented in obesity services, suggesting current weight loss service provision is suboptimal. This systematic review evaluated evidence-based strategies for treating obesity in men. ...Eight bibliographic databases and four clinical trials’ registers were searched to identify randomized controlled trials (RCTs) of weight loss interventions in men only, with mean/median body mass index of ≥30 kg/m2 (or ≥28 kg/m2 with cardiac risk factors), with a minimum mean/median duration of ≥52 weeks. Interventions included diet, physical activity, behavior change techniques, orlistat, or combinations of these; compared against each other, placebo, or a no intervention control group; in any setting. Twenty-one reports from 14 RCTs were identified. Reducing diets produced more favorable weight loss than physical activity alone (mean weight change after 1 year from a reducing diet compared with an exercise program −3.2 kg, 95% confidence interval −4.8 to −1.6 kg, reported p < .01). The most effective interventions combined reducing diets, exercise, and behavior change techniques (mean difference in weight at 1 year compared with no intervention was −4.9 kg, 95% confidence interval −5.9 to −4.0, reported p < .0001). Group interventions produced favorable weight loss results. The average reported participant retention rate was 78.2%, ranging from 44% to 100% retention, indicating that, once engaged, men remained committed to a weight loss intervention. Weight loss for men is best achieved and maintained with the combination of a reducing diet, increased physical activity, and behavior change techniques. Strategies to increase engagement of men with weight loss services to improve the reach of interventions are needed.
Summary Background Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndrome is a rare autosomal recessive disorder of unknown cause. We aimed to identify the ...genetic basis of this syndrome by sequencing most coding exons in affected individuals. Methods Through a search of available case studies and communication with collaborators, we identified families that included at least one individual with at least three of the five main features of the DOORS syndrome: deafness, onychodystrophy, osteodystrophy, intellectual disability, and seizures. Participants were recruited from 26 centres in 17 countries. Families described in this study were enrolled between Dec 1, 2010, and March 1, 2013. Collaborating physicians enrolling participants obtained clinical information and DNA samples from the affected child and both parents if possible. We did whole-exome sequencing in affected individuals as they were enrolled, until we identified a candidate gene, and Sanger sequencing to confirm mutations. We did expression studies in human fibroblasts from one individual by real-time PCR and western blot analysis, and in mouse tissues by immunohistochemistry and real-time PCR. Findings 26 families were included in the study. We did exome sequencing in the first 17 enrolled families; we screened for TBC1D24 by Sanger sequencing in subsequent families. We identified TBC1D24 mutations in 11 individuals from nine families (by exome sequencing in seven families, and Sanger sequencing in two families). 18 families had individuals with all five main features of DOORS syndrome, and TBC1D24 mutations were identified in half of these families. The seizure types in individuals with TBC1D24 mutations included generalised tonic-clonic, complex partial, focal clonic, and infantile spasms. Of the 18 individuals with DOORS syndrome from 17 families without TBC1D24 mutations, eight did not have seizures and three did not have deafness. In expression studies, some mutations abrogated TBC1D24 mRNA stability. We also detected Tbc1d24 expression in mouse phalangeal chondrocytes and calvaria, which suggests a role of TBC1D24 in skeletogenesis. Interpretation Our findings suggest that mutations in TBC1D24 seem to be an important cause of DOORS syndrome and can cause diverse phenotypes. Thus, individuals with DOORS syndrome without deafness and seizures but with the other features should still be screened for TBC1D24 mutations. More information is needed to understand the cellular roles of TBC1D24 and identify the genes responsible for DOORS phenotypes in individuals who do not have a mutation in TBC1D24. Funding US National Institutes of Health, the CIHR (Canada), the NIHR (UK), the Wellcome Trust, the Henry Smith Charity, and Action Medical Research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The risk of severe COVID-19 if an individual becomes infected is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at ...increased risk of severe COVID-19 and how this varies between countries should inform the design of possible strategies to shield or vaccinate those at highest risk.
We estimated the number of individuals at increased risk of severe disease (defined as those with at least one condition listed as “at increased risk of severe COVID-19” in current guidelines) by age (5-year age groups), sex, and country for 188 countries using prevalence data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 and UN population estimates for 2020. The list of underlying conditions relevant to COVID-19 was determined by mapping the conditions listed in GBD 2017 to those listed in guidelines published by WHO and public health agencies in the UK and the USA. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. To help interpretation of the degree of risk among those at increased risk, we also estimated the number of individuals at high risk (defined as those that would require hospital admission if infected) using age-specific infection–hospitalisation ratios for COVID-19 estimated for mainland China and making adjustments to reflect country-specific differences in the prevalence of underlying conditions and frailty. We assumed males were twice at likely as females to be at high risk. We also calculated the number of individuals without an underlying condition that could be considered at increased risk because of their age, using minimum ages from 50 to 70 years. We generated uncertainty intervals (UIs) for our estimates by running low and high scenarios using the lower and upper 95% confidence limits for country population size, disease prevalences, multimorbidity fractions, and infection–hospitalisation ratios, and plausible low and high estimates for the degree of clustering, informed by multimorbidity studies.
We estimated that 1·7 billion (UI 1·0–2·4) people, comprising 22% (UI 15–28) of the global population, have at least one underlying condition that puts them at increased risk of severe COVID-19 if infected (ranging from <5% of those younger than 20 years to >66% of those aged 70 years or older). We estimated that 349 million (186–787) people (4% 3–9 of the global population) are at high risk of severe COVID-19 and would require hospital admission if infected (ranging from <1% of those younger than 20 years to approximately 20% of those aged 70 years or older). We estimated 6% (3–12) of males to be at high risk compared with 3% (2–7) of females. The share of the population at increased risk was highest in countries with older populations, African countries with high HIV/AIDS prevalence, and small island nations with high diabetes prevalence. Estimates of the number of individuals at increased risk were most sensitive to the prevalence of chronic kidney disease, diabetes, cardiovascular disease, and chronic respiratory disease.
About one in five individuals worldwide could be at increased risk of severe COVID-19, should they become infected, due to underlying health conditions, but this risk varies considerably by age. Our estimates are uncertain, and focus on underlying conditions rather than other risk factors such as ethnicity, socioeconomic deprivation, and obesity, but provide a starting point for considering the number of individuals that might need to be shielded or vaccinated as the global pandemic unfolds.
UK Department for International Development, Wellcome Trust, Health Data Research UK, Medical Research Council, and National Institute for Health Research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary Background The use of prophylactic radiotherapy to prevent procedure-tract metastases (PTMs) in malignant pleural mesothelioma remains controversial, and clinical practice varies worldwide. ...We aimed to compare prophylactic radiotherapy with deferred radiotherapy (given only when a PTM developed) in a suitably powered trial. Methods We did a multicentre, open-label, phase 3, randomised controlled trial in 22 UK hospitals of patients with histocytologically proven mesothelioma who had undergone large-bore pleural interventions in the 35 days prior to recruitment. Eligible patients were randomised (1:1), using a computer-generated sequence, to receive immediate radiotherapy (21 Gy in three fractions within 42 days of the pleural intervention) or deferred radiotherapy (same dose given within 35 days of PTM diagnosis). Randomisation was minimised by histological subtype, surgical versus non-surgical procedure, and pleural procedure (indwelling pleural catheter vs other). The primary outcome was the incidence of PTM within 7 cm of the site of pleural intervention within 12 months from randomisation, assessed in the intention-to-treat population. This trial is registered with ISRCTN, number ISRCTN72767336. Findings Between Dec 23, 2011, and Aug 4, 2014, we randomised 203 patients to receive immediate radiotherapy (n=102) or deferred radiotherapy (n=101). The patients were well matched at baseline. No significant difference was seen in PTM incidence in the immediate and deferred radiotherapy groups (nine 9% vs 16 16%; odds ratio 0·51 95% CI 0·19–1·32; p=0·14). The only serious adverse event related to a PTM or radiotherapy was development of a painful PTM within the radiotherapy field that required hospital admission for symptom control in one patient who received immediate radiotherapy. Common adverse events of immediate radiotherapy were skin toxicity (grade 1 in 50 54% and grade 2 in four 4% of 92 patients vs grade 1 in three 60% and grade 2 in two 40% of five patients in the deferred radiotherapy group who received radiotherapy for a PTM) and tiredness or lethargy (36 39% in the immediate radiotherapy group vs two 40% in the deferred radiotherapy group) within 3 months of receiving radiotherapy. Interpretation Routine use of prophylactic radiotherapy in all patients with mesothelioma after large-bore thoracic interventions is not justified. Funding Research for Patient Benefit Programme from the UK National Institute for Health Research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
As therapies are developed for rare disorders, challenges of early diagnosis become particularly relevant. This article focuses on clinical recognition of mucopolysaccharidoses (MPS), a group of rare ...genetic diseases related to abnormalities in lysosomal function. As quality of outcomes with current therapies is impacted by timing of intervention, minimizing time to diagnosis is critical. The objective of this study was to characterize how, when, and to whom patients with MPS first present and develop tools to stimulate earlier recognition of MPS. A tripartite approach was used, including a systematic literature review yielding 194 studies, an online physician survey completed by 209 physicians who described 859 MPS cases, and a global panel of MPS experts who distilled the findings. Red flag signs/symptoms were identified for cardiology, pediatric neurology, otorhinolaryngology, rheumatology, orthopedics, pediatrics, and general medicine and converted into simple, specialty-specific tools intended to facilitate early diagnosis of MPS, enabling improved patient outcomes.
The mucopolysaccharidosis (MPS) disorders are rare genetic diseases caused by deficiencies in lysosomal enzymes involved in the degradation of glycosaminoglycans, leading to pulmonary, cardiac and ...neurological dysfunctions, skeletal anomalies, impaired vision, and/or hearing and shortened life spans. Whereas in the past, few individuals with MPS reached adulthood, better diagnosis, multidisciplinary care, and new therapies have led to an increasing number of adult patients with MPS. Therefore, fertility and pregnancy questions in this patient population are becoming more important. Management of fertility issues and pregnancy in patients with MPS is challenging due to the lack of documented cases and a dearth in the literature on this topic. This review presents multidisciplinary expert opinions on managing fertility and pregnancy based on case studies and clinical experience presented at a meeting of MPS specialists held in Berlin, Germany, in April 2015. An overview of the existing literature on this subject is also included.
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