63 research outputs found
The effects on public health of climate change adaptation responses: a systematic review of evidence from low- and middle-income countries
Climate change adaptation responses are being developed and delivered in many parts of the world in the absence of detailed knowledge of their effects on public health. Here we present the results of a systematic review of peer-reviewed literature reporting the effects on health of climate change adaptation responses in low- and middle-income countries (LMICs). The review used the 'Global Adaptation Mapping Initiative' database (comprising 1682 publications related to climate change adaptation responses) that was constructed through systematic literature searches in Scopus, Web of Science and Google Scholar (2013–2020). For this study, further screening was performed to identify studies from LMICs reporting the effects on human health of climate change adaptation responses. Studies were categorised by study design and data were extracted on geographic region, population under investigation, type of adaptation response and reported health effects. The review identified 99 studies (1117 reported outcomes), reporting evidence from 66 LMICs. Only two studies were ex ante formal evaluations of climate change adaptation responses. Papers reported adaptation responses related to flooding, rainfall, drought and extreme heat, predominantly through behaviour change, and infrastructural and technological improvements. Reported (direct and intermediate) health outcomes included reduction in infectious disease incidence, improved access to water/sanitation and improved food security. All-cause mortality was rarely reported, and no papers were identified reporting on maternal and child health. Reported maladaptations were predominantly related to widening of inequalities and unforeseen co-harms. Reporting and publication-bias seems likely with only 3.5% of all 1117 health outcomes reported to be negative. Our review identified some evidence that climate change adaptation responses may have benefits for human health but the overall paucity of evidence is concerning and represents a major missed opportunity for learning. There is an urgent need for greater focus on the funding, design, evaluation and standardised reporting of the effects on health of climate change adaptation responses to enable evidence-based policy action
Tavistock Adult Depression Study (TADS): a randomised controlled trial of psychoanalytic psychotherapy for treatment-resistant/treatment-refractory forms of depression
ABSTRACT: BACKGROUND: Long-term forms of depression represent a significant mental health problem for which there is a lack of effective evidence-based treatment. This study aims to produce findings about the effectiveness of psychoanalytic psychotherapy in patients with treatment-resistant/treatment-refractory depression and to deepen the understanding of this complex form of depression. METHODS: INDEX GROUP: Patients with treatment resistant/treatment refractory depression. DEFINITION & INCLUSION CRITERIA: Current major depressive disorder, 2 years history of depression, a minimum of two failed treatment attempts, [greater than or equal to]14 on the HRSD or [greater than or equal to]21 on the BDI, plus complex personality and/or psycho-social difficulties. EXCLUSION CRITERIA: Moderate or severe learning disability, psychotic illness, bipolar disorder, substance dependency or receipt of test intervention in the previous two years. DESIGN: Pragmatic, randomised controlled trial with qualitative and clinical components. TEST INTERVENTION: 18 months of weekly psychoanalytic psychotherapy, manualised and fidelity-assessed using the Psychotherapy Process Q-Sort. CONTROL CONDITION: Treatment as usual, managed by the referring practitioner. RECRUITMENT: GP referrals from primary care. RCT MAIN OUTCOME: HRSD (with [less than or equal to]14 as remission). SECONDARY OUTCOMES: depression severity (BDI-II), degree of co-morbid disorders Axis-I and Axis-II (SCID-I and SCID-II-PQ), quality of life and functioning (GAF, CORE, Q-les-Q), object relations (PROQ2a), Cost-effectiveness analysis (CSRI and GP medical records). FOLLOW-UP: 2 years. Plus: a). Qualitative study of participants' and therapists' problem formulation, experience of treatment and of participation in trial. (b) Narrative data from semi-structured pre/post psychodynamic interviews to produce prototypes of responders and non-responders. (c) Clinical case-studies of sub-types of TRD and of change. DISCUSSION: TRD needs complex, long-term intervention and extended research follow-up for the proper evaluation of treatment outcome. This pushes at the limits of the design of randomised therapeutic trials,. We discuss some of the consequent problems and suggest how they may be mitigated. Trial registration Current Controlled Trials ISRCTN40586372
krawczyk
Recently the common adiponutrin (PNPLA3) polymorphism p.I148M has been identified as a genetic determinant of severe forms of non-alcoholic fatty liver disease and alcoholic liver disease. Additionally, insulin resistance -linked to the development of non-alcoholic steatohepatitis -increases the risk of developing gallstones. Here we assessed whether the PNPLA3 p.I148M (c.444 C>G) polymorphism affects glucose and lipid levels and increases gallstone risk. We analysed 229 individuals with gallstones from 108 families (age 24-80 years, BMI 17-55 kg/m 2 ) and 258 gallstone-free controls (age 20-70 years, BMI 14-43 kg/m 2 ). Fasting glucose, triglyceride and cholesterol serum levels were determined. The p.I148M polymorphism was genotyped using a PCR-based assay with 5'-nuclease and fluorescence detection. Case-control association tests and nonparametric linkage (NPL) analysis in sib-pairs were performed. Individuals carrying the [GG] genotype had significantly (P<0.0001) higher median fasting glucose levels as compared to [GC] and [CC] carriers. After adjustment for multiple testing, we detected a trend for an association between triglyceride levels and variant adiponutrin in gallstone patients (P=0.032), and gallstone cases carrying the genotype [CC] presented with significantly higher triglyceride levels than the corresponding controls (P<0.003). No significant effects on cholesterol metabolism were detected. Neither genotype distributions nor NPL scores provided evidence for association or linkage between the PNPLA3 variant and gallstones. In conclusion, homozygous carriers of the PNPLA3 risk allele display higher fasting glucose. Although this adiponutrin variant may affect triglyceride homeostasis, it does not increase the risk of cholelithiasis. K e y w o r d s : adiponutrin, insulin resistance, metabolic syndrome, PNPLA3, single nucleotide polymorphism, triglyceride 25) and hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus infection Taking into account the previously reported association between the adiponutrin variant and non-genetic risk factors for gallstones (e.g. hepatic fat accumulation, liver injury, distorted glucose metabolism), we now aimed to dissect the possible role of the PNPLA3 SNP in gallstone formation. In this respect we genotyped a cohort of sibs with gallstones and unrelated gallstone-free controls. To investigate the role of variant adiponutrin in other metabolic traits, we related PNPLA3 genotypes to serum lipid and glucose levels. MATERIAL AND METHODS Patients Only individuals with documented Caucasian ethnicity were included in the study. As shown in In all study participants glucose, TG and cholesterol levels in serum (mg/dL) were determined by standard assays after an overnight fasting period. The study was conducted according to a study design approved by the local ethical committee, and all participants signed an informed consent form. Genotyping Genomic DNA was isolated from EDTA anticoagulated blood according to the membrane-based QIAamp DNA extraction protocol (Qiagen, Hilden, Germany). The PNPLA3 coding SNP p.I148M (rs738409) was genotyped using solutionphase hybridization reactions with 5'-nuclease and fluorescence detection (TaqMan assays) in a 7300 real-time PCR system (Applera, Norwalk, CT). Primer and probe sequences were: forward primer 5'-AACTTCTCTCTCCTTTGCTTTCACA-3'; reverse primer 5'-TCTACAGTGGCCTTATCCCTCC-3'; VIC 5'-TTCCTGCTTCATGCC-3'; FAM 5'-CCTGCTTCATCCC-3'. To ensure genotyping quality, we included negative controls and DNA samples with known PNPLA3 genotypes as internal controls. PCR reactions contained 20 ng DNA, 900 nM of each primer, 1× TaqMan Universal Master Mix, and 200 nM of VIClabelled and FAM-labelled probes in 25 µL-reactions. Amplification conditions were 95°C for 10 min, 40 cycles of 92°C for 15 s, and 60°C for 1 min. Statistics Unless stated otherwise, statistical analysis was performed with SPSS 18.0 (SPSS, Munich, Germany). All phenotypic quantitative data were expressed as medians and ranges, unless stated specifically. Because we performed multiple tests (n=17), the significance threshold was corrected for multiple testing and two-sided P values <0.003 were considered as significant. The effects of the adiponutrin SNP and of other potential lithogenic factors (age, BMI, gender, serum glucose and lipid levels) Exact tests were performed to check the consistency of genotyping results with Hardy-Weinberg equilibrium (HWE) (http://ihg2.helmholtz-muenchen.de/cgi-bin/hw/hwa1.pl). We performed power calculations using PS: Power and Sample Size Calculation v.3.0 (http://biostat. mc.vanderbilt.edu/wiki/ Main/PowerSampleSize) (35). Association case-control analysis and non-parametric linkage (NPL) tests were performed to investigate the role of the PNPLA3 p.I148M variant in the development of gallstones. For the association analysis, all gallstone-free controls and a single randomly selected member (these individuals are denoted cases throughout this report) of each sib-pair family were included. The association between the adiponutrin variant and cholelithiasis was tested in contingency tables (genotypes: Armitrage's trend test; alleles: chi 2 test). NPL scores were calculated using GENEHUNTER-MODSCORE v2.0.1 (www.staff.uni-marburg.de/_strauch/software.html) (36) both for the risk (minor) allele frequencies (MAF) in our ASP cohort and for alleles frequencies provided in the Entrez SNP database (http://www.ncbi.nlm.nih.gov/snp). In short, the NPL score allows estimation of the significance of a given allele shared among the family members in the development of the disease; for this the allele frequencies at the analysed genetic locus are compared with the null hypothesis of no linkage (4). Thus, if gallstone disease is linked to the PNPLA3 polymorphism, affected sibs are more likely to share the same allele. RESULTS Obesity enhances gallstone risk PNPLA3 p.I148M variant and gallstone risk: case-control association and sib-pairs analyses The adiponutrin p.I148M variant was successfully genotyped in all individuals with gallstones (n=229, Association between variant adiponutrin and metabolic traits For this analysis we included only unrelated cases (n=108) and all controls (n=258). DISCUSSION This study demonstrates that the adiponutrin p.I148M variant influences glucose and triglyceride levels in our study population. On the other hand, although it has been previously shown that fatty liver disease and enhanced liver fibrosis are both risk factors for cholelithiasis, the variant does not increase gallstone risk per se. Since our case-control study investigating the effect of the adiponutrin variant on gallstone formation is underpowered, we also performed a non-parametric linkage analysis. Indeed, the study cohort let us previously identify the ABCG8 p.D19H variant as the first genetic risk factor for gallstone formation in humans (4). In this study the analysis of sib-pairs showed that this variant was strongly associated with cholelithiasis (NPL score =7.1, P=4.6 x 10 -13 ), which was in line with results of a large GWAS in gallstone patients (3). Hence, the cohort of sib-pairs can be regarded as robust framework for identifying genes associated with gallstone formation. Additionally, sib-pair analysis omits the bias that is encountered in case-control analysis as controls could develop gallbladder stones later in life. Hence, the present analysis of sib-pairs, which did not reveal an association between gallstones and the PNPLA3 variant p.I148M, excludes this SNP as a major risk factor for cholelithiasis. BMI and serum glucose levels are known risk factors for gallstone formation (11). Our results show that each of these factors increases the disease risk, which is in line with the notion that cholelithiasis is a complex multifactorial disorder. Interestingly, we observed that increased serum cholesterol levels lowered the chance of developing gallstones. In contrast, previous studies have demonstrated that patients carrying the ABCG8 (35) and SLC10A2 (7) cholelithiasis risk variants present with lower total serum cholesterol concentrations. It can be hypothesised that the lower risk of developing gallstones in patients with increased serum cholesterol levels might be primarily due to decreased transport of cholesterol into bile. This might lead to increased serum cholesterol but lower biliary cholesterol concentrations. On the other hand, the use of cholesterol lowering drugs (e.g. statins) may significantly lower the risk of developing gallstones (37-39). Hence a functional link between cholesterol levels, hepatobiliary transporters and gallstone formation has not yet been thoroughly investigated and future studies are warranted. It has been previously shown that the PNPLA3 risk allele is associated with severe forms of hepatic fat accumulation In summary, our current study underscores the possible metabolic role of the adiponutrin p.I148M polymorphism. Nevertheless, given the negative results from the previous large studies this effect might be apparent only in selected individuals, for example in those who have gallstones as an additional phenotype. Although the variant does not increase the risk of developing gallstones per se, additional functional studies are warranted to define the molecular link between adiponutrin and metabolic traits
The Vagaries of Psychoanalytic Interpretation: An Investigation into the Causes of the Consensus Problem in Psychoanalysis
A comparative study of the frictional properties of emollient bath additives using porcine skin
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