Long-term health outcomes in a British cohort of breast, colorectal and prostate cancer survivors: a database study

BACKGROUND: The community-based incidence of cancer treatment-related long-term consequences is uncertain. We sought to establish the burden of health outcomes that have been associated with treatment among British long-term cancer survivors. METHODS: We identified 26,213 adults from the General Practice Research Database who have survived 5 years or more following breast, colorectal or prostate cancer. Four age-, sex- and general practice-matched non-cancer controls were selected for each survivor. We considered the incidence of treatment-associated health outcomes using Cox proportional hazards models. RESULTS: Breast cancer survivors had an elevated incidence of heart failure (hazards ratio (HR) 1.95, 95% confidence interval (CI) 1.27-3.01), coronary artery disease (HR 1.27, 95% CI 1.11-1.44), hypothyroidism (HR 1.26, 95% CI 1.02-1.56) and osteoporosis (HR 1.26, 95% CI 1.13-1.40). Among colorectal cancer survivors, there was increased incidence of dementia (HR 1.68, 95% CI 1.20-2.35), diabetes (HR 1.39, 95% CI 1.12-1.72) and osteoporosis (HR 1.41, 95% CI 1.15-1.73). Prostate cancer survivors had the highest risk of osteoporosis (HR 2.49, 95% CI 1.93-3.22). CONCLUSIONS: The study confirms the occurrence of increased incidence of chronic illnesses in long-term cancer survivors attributable to underlying lifestyle and/or cancer treatments. Although the absolute risk of the majority of late effects in the cancer survivors cohort is low, identifying prior risk of osteoporosis by bone mineral density scanning for prostate survivors should be considered. There is an urgent need to improve primary care recording of cancer treatmen

Development of a Patient-Centred, Psychosocial Support Intervention for Multi-Drug-Resistant Tuberculosis (MDR-TB) Care in Nepal

Multi-drug-resistant tuberculosis (MDR-TB) poses a major threat to public health worldwide, particularly in low-income countries. The current long (20 month) and arduous treatment regime uses powerful drugs with side-effects that include mental ill-health. It has a high loss-to-follow-up (25%) and higher case fatality and lower cure-rates than those with drug sensitive tuberculosis (TB). While some national TB programmes provide small financial allowances to patients, other aspects of psychosocial ill-health, including iatrogenic ones, are not routinely assessed or addressed. We aimed to develop an intervention to improve psycho-social well-being for MDR-TB patients in Nepal. To do this we conducted qualitative work with MDR-TB patients, health professionals and the National TB programme (NTP) in Nepal. We conducted semi-structured interviews (SSIs) with 15 patients (10 men and 5 women, aged 21 to 68), four family members and three frontline health workers. In addition, three focus groups were held with MDR-TB patients and three with their family members. We conducted a series of meetings and workshops with key stakeholders to design the intervention, working closely with the NTP to enable government ownership. Our findings highlight the negative impacts of MDR-TB treatment on mental health, with greater impacts felt among those with limited social and financial support, predominantly married women. Michie et al's (2011) framework for behaviour change proved helpful in identifying corresponding practice- and policy-level changes. The findings from this study emphasise the need for tailored psycho-social support. Recent work on simple psychological support packages for the general population can usefully be adapted for use with people with MDR-TB

Identifying unmet clinical need in hypertrophic cardiomyopathy using national electronic health records

Introduction: To evaluate unmet clinical need in unselected hypertrophic cardiomyopathy (HCM) patients to determine the risk of a wide range of subsequent cardiovascular disease endpoints and safety endpoints relevant for trial design. Methods: Population based cohort (CALIBER, linked primary care, hospital and mortality records in England, period 1997–2010), all people diagnosed with HCM were identified and matched by age, sex and general practice with ten randomly selected people without HCM. Random-effects Poisson models were used to assess the associations between HCM and cardiovascular diseases and bleeding. Results: Among 3,290,455 eligible people a diagnosis of hypertrophic cardiomyopathy was found in 4 per 10,000. Forty-one percent of the 1,160 individuals with hypertrophic cardiomyopathy were women and the median age was 57 years. The median follow-up was 4.0 years. Compared to general population controls, people with HCM had higher risk of ventricular arrhythmia (incidence rate ratio = 23.53, [95% confidence interval 12.67–43.72]), cardiac arrest or sudden cardiac death (6.33 [3.69–10.85]), heart failure (4.31, [3.30–5.62]), and atrial fibrillation (3.80 [3.04–4.75]). HCM was also associated with a higher incidence of myocardial infarction ([MI] 1.90 [1.27–2.84]) and coronary revascularisation (2.32 [1.46–3.69]).The absolute Kaplan-Meier risks at 3 years were 8.8% for the composite endpoint of cardiovascular death or heart failure, 8.4% for the composite of cardiovascular death, stroke or myocardial infarction, and 1.5% for major bleeding. Conclusions: Our study identified major unmet need in HCM and highlighted the importance of implementing improved cardiovascular prevention strategies to increase life-expectancy of the contemporary HCM population. They also show that national electronic health records provide an effective method for identifying outcomes and clinically relevant estimates of composite efficacy and safety endpoints essential for trial design in rare diseases

Selection and Validation of Reference Genes for Quantitative Real-Time PCR in Buckwheat (Fagopyrum esculentum) Based on Transcriptome Sequence Data

Quantitative reverse transcription PCR (qRT-PCR) is one of the most precise and widely used methods of gene expression analysis. A necessary prerequisite of exact and reliable data is the accurate choice of reference genes. We studied the expression stability of potential reference genes in common buckwheat (Fagopyrum esculentum) in order to find the optimal reference for gene expression analysis in this economically important crop. Recently sequenced buckwheat floral transcriptome was used as source of sequence information. Expression stability of eight candidate reference genes was assessed in different plant structures (leaves and inflorescences at two stages of development and fruits). These genes are the orthologs of Arabidopsis genes identified as stable in a genome-wide survey gene of expression stability and a traditionally used housekeeping gene GAPDH. Three software applications – geNorm, NormFinder and BestKeeper - were used to estimate expression stability and provided congruent results. The orthologs of AT4G33380 (expressed protein of unknown function, Expressed1), AT2G28390 (SAND family protein, SAND) and AT5G46630 (clathrin adapter complex subunit family protein, CACS) are revealed as the most stable. We recommend using the combination of Expressed1, SAND and CACS for the normalization of gene expression data in studies on buckwheat using qRT-PCR. These genes are listed among five the most stably expressed in Arabidopsis that emphasizes utility of the studies on model plants as a framework for other species

Community-based directly observed therapy (DOT) versus clinic DOT for tuberculosis: a systematic review and meta-analysis of comparative effectiveness.

Background: Directly observed therapy (DOT), as recommended by the World Health Organization, is used in many countries to deliver tuberculosis (TB) treatment. The effectiveness of community-based (CB DOT) versus clinic DOT has not been adequately assessed to date. We compared TB treatment outcomes of CB DOT (delivered by community health workers or community volunteers), with those achieved through conventional clinic DOT. Methods: We performed a systematic review and meta-analysis of studies before 9 July 2014 comparing treatment outcomes of CB DOT and clinic DOT. The primary outcome was treatment success; the secondary outcome was loss to follow-up. Results: Eight studies were included comparing CB DOT to clinic DOT, one a randomised controlled trial. CB DOT outperformed clinic DOT treatment success (pooled odds ratio (OR) of 1.54, 95% confidence interval (CI) 1.01 – 2.36, p = 0.046, I2 heterogeneity 84%). No statistically significant difference was found between the two DOT modalities for loss to follow-up (pooled OR 0.86, 95% CI 0.48 to 1.55, p = 0.62, I2 83%). Conclusions: Based on this systematic review, CB DOT has a higher treatment success compared to clinic DOT. However, as only one study was a randomised controlled trial, the findings have to be interpreted with caution

Equivalence and noninferiority trials – are they viable alternatives for registration of new drugs? (III)

The scientific community's reliance on active-controlled trials is steadily increasing, as widespread agreement emerges concerning the role of these trials as viable alternatives to placebo trials. These trials present substantial challenges with regard to design and interpretation as their complexity increases, and the potential need for larger sample sizes impacts the cost and time variables of the drug development process. The potential efficacy and safety benefits derived from these trials may never be demonstrated by other methods. Active-controlled trials can develop valuable data to inform both prescribers and patients about the dose- and time-dependent actions of any new drug and can contribute to the management and communication of risks associated with the relevant therapeutic products

Translating evidence into policy for cardiovascular disease control in India

Cardiovascular diseases (CVD) are leading causes of premature mortality in India. Evidence from developed countries shows that mortality from these can be substantially prevented using population-wide and individual-based strategies. Policy initiatives for control of CVD in India have been suggested but evidence of efficacy has emerged only recently. These initiatives can have immediate impact in reducing morbidity and mortality. Of the prevention strategies, primordial involve improvement in socioeconomic status and literacy, adequate healthcare financing and public health insurance, effective national CVD control programme, smoking control policies, legislative control of saturated fats, trans fats, salt and alcohol, and development of facilities for increasing physical activity through better urban planning and school-based and worksite interventions. Primary prevention entails change in medical educational curriculum and improved healthcare delivery for control of CVD risk factors-smoking, hypertension, dyslipidemia and diabetes. Secondary prevention involves creation of facilities and human resources for optimum acute CVD care and secondary prevention. There is need to integrate various policy makers, develop effective policies and modify healthcare systems for effective delivery of CVD preventive care