Effect of exercise interventions in the early phase to improve physical function after hip fracture – a systematic review and meta-analysis

Background: The efficacy of exercise interventions in the early recovery phase, i.e. started within the first three months after hip fracture, has been poorly studied compared to prolonged exercise interventions. Objective: To examine the effect of exercise interventions to improve physical function in the early phase after hip fracture. Data sources: Seven databases including MEDLINE via Ovid, The Cochrane Library, Embase, Cinahl, Pedro, AMED and Web of Science were comprehensively searched till December 2019. Eligibility criteria: Randomised controlled trials (RCTs) of exercise interventions initiated within the first three months after hip fracture to improve physical function, were eligible for inclusion. Primary outcome was physical function assessed using walking ability, walking speed, balance, muscle strength, mobility, and endurance. Data extraction and data synthesis: We conducted subgroup analyses specifically to investigate outcomes of these individual measurements. A meta-analysis was conducted to examine the overall effect of early exercise interventions. A meta-regression was conducted to examine the impact of study characteristic on exercise interventions. We used the PEDro score to determine quality of the included studies. Results: Nine studies (669 patients) were included. Despite high statistical heterogeneity, there was high to moderate quality evidence that exercise provided benefit in improving physical function (standardised mean difference (SMD) 1.07; 95% CI: 0.44 to 1.70; p 0.05). Meta-regression demonstrated no statistically significant association between study characteristics and exercise interventions (p > 0.05). Conclusion: Exercise in the early phase of hip fracture rehabilitation can improve physical function. It remains unclear what type of exercise is superior in the early phase after hip fracture. Limitations: This conclusion should be interpreted with caution given the high statistical heterogeneity reported and non-significant subgroup analyses of specific physical function measures, which were underpowered. Protocol Registration (PROSPERO): CRD42018091135

Recovery and prediction of physical function 1 year following hip fracture

Objectives: To investigate the recovery of physical function, health related quality of life (HRQoL), and pain for people following hip fracture for the initial 12 months, and to examine whether postoperative outcome measures of physical function, HRQoL, and pain can predict physical function at 3 and 12 months. Design: A prospective single-center observational study, as part of the HIPFRAC trial. Settings: One hospital with two associated municipalities in Norway. Subjects: 207 participants with hip fracture included in the study (140 participants transferred to a short-term nursing home placement and 67 transferred directly home at discharge from hospital). Method: Outcome measures were Short Physical Performance Battery (SPPB), Timed Up & Go (TUG), Stair climbing test (SC), Numeric Rating Scale (NRS) for pain at rest and in activity, and EQ-5D-5L index and health score. Data were analysed by repeated measures of variance and multivariate regression analyses. Results: There were statistically significant improvements in physical function (SPPB total score and TUG), NRS-pain in activity, and HRQoL (EQ-5D-5L) from hospital discharge to 3-month follow-up for the whole cohort and the two groups (p < 0.001). However, the largest improvements occurred within the first 3 months. Further statistically significant improvements occurred between 3 and 12 months (p < 0.05). The strongest predictors of physical function at 3 and 12 months post-fracture were physical function (SPPB) at hospital discharge and pre-fracture requirement of a walking aid. Conclusion: The recovery of physical function, HRQoL, and pain in participants after hip fracture indicates gradual improvements during the initial 12-month follow-up, with the largest improvements within the first 3 months

Effect of an additional health professional-led exercise programme on clinical health outcomes after hip fracture

Purpose: To examine the effect of an additional two-week health professional-led functional exercise programme compared to usual care for patients after hip fracture during a short-term nursing home stay directly after hospital discharge. Method: One hundred and forty participants, 65 years or older with hip fracture, admitted to a short-term nursing home stay were randomised to an intervention group or control group. Participants in the intervention group (n= 78) received the experimental programme consisted of functional exercises, performed by health care professionals up to four times a day, seven days a week, in addition to usual care during a two-week short-term nursing home stay. Participants in the control group (n= 62) received usual care alone. Primary outcome was Short Physical Performance Battery (SPPB). Secondary outcomes were Timed Up & Go (TUG), New Mobility Score (NMS), UCLA activity scale, Fall efficacy scale international (FES-I), The EuroQol five dimensionfive-level questionnaire (EQ-5D-5L), and numeric rating scale (NRS) for pain. Outcome measures were assessed after two weeks in a short-term nursing home stay and three months after hip fracture surgery. The activity monitor ActivPal registered activity during the two-week short-term nursing home stay.Results: No statistically significant differences between groups was found in any outcomes after two weeks or three months (p>0.05). There were statistically significant within-group improvements in primary outcome SPPB and in most secondary outcomes at all time points in both groups (p > 0.05). Conclusions: A two-week health professional-led functional exercise programme in addition to usual care demonstrated no difference in clinical outcomes compared to usual care alone up to three months after hip fracture. The patients with hip fracture are fragile and vulnerable in this early phase, and usual physiotherapy may be sufficient to improve their physical function. Trial registration: ClinicalTrials.gov NCT02780076

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Functional Mechanisms Underlying Pleiotropic Risk Alleles at the 19p13.1 Breast–Ovarian Cancer Susceptibility Locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P = 9.2 X 10-20), ER-negative BC (P = 1.1 X 10-13), BRCA1 -associated BC (P = 7.7 X 10-16) and triple negative BC (P-diff = 2 X 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P = 2 X 10-3) and ABHD8 (P \u3c 2 X 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8 , and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3\u27-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

[En]gendering the norms of customary inheritance in Botswana and South Africa

The article responds to the article by Weinberg in this issue. She traces the trajectory of court hearings concerning the contested inheritance of land in Botswana, which, after several prior judgements eventually resulted in a positive outcome for the woman litigants. I acknowledge the author’s key argument, which concerns the impact of power relations on the construction of customary law and the reproduction of knowledge in the courts. Certain versions of “custom” were promoted and others stilled to the disadvantage of women. I argue that the normative patterns of landholding are indeed gendered, but do not result in a binary structure of men and women. “Gender” should be disaggregated to take into account a range of status criteria within and across the categories of male and female in order to understand the differential impact of social relations on the outcomes of property struggles. The normative lines of property transmission frequently follow a logic of “family property” that allows for qualifying women to rights of property. Family property has vastly different social and legal consequences to private, individualised property rights. The corollary is that it is misleading to speak of the processes of succession to rights of access to, and control of customary property in terms of one-to-one “inheritance” of land. The concept of “living law” inadequately reflects these social dynamics.IBS

Evidence that the 5p12 Variant rs10941679 Confers Susceptibility to Estrogen Receptor-Positive Breast Cancer through FGF10 and MRPS30 Regulation

Genome-wide association studies (GWASs) have revealed increased breast cancer risk associated with multiple genetic variants at 5p12. Here, we report the fine mapping of this locus using data from 104,660 subjects from 50 case-control studies in the Breast Cancer Association Consortium (BCAC). With data for 3,365 genotyped and imputed SNPs across a 1 Mb region (positions 44,394,495–45,364,167; NCBI build 37), we found evidence for at least three independent signals: the strongest signal, consisting of a single SNP rs10941679, was associated with risk of estrogen receptor-positive (ER+) breast cancer (per-g allele OR ER+ = 1.15; 95% CI 1.13–1.18; p = 8.35 × 10−30). After adjustment for rs10941679, we detected signal 2, consisting of 38 SNPs more strongly associated with ER-negative (ER−) breast cancer (lead SNP rs6864776: per-a allele OR ER− = 1.10; 95% CI 1.05–1.14; p conditional = 1.44 × 10−12), and a single signal 3 SNP (rs200229088: per-t allele OR ER+ = 1.12; 95% CI 1.09–1.15; p conditional = 1.12 × 10−05). Expression quantitative trait locus analysis in normal breast tissues and breast tumors showed that the g (risk) allele of rs10941679 was associated with increased expression of FGF10 and MRPS30. Functional assays demonstrated that SNP rs10941679 maps to an enhancer element that physically interacts with the FGF10 and MRPS30 promoter regions in breast cancer cell lines. FGF10 is an oncogene that binds to FGFR2 and is overexpressed in ∼10% of human breast cancers, whereas MRPS30 plays a key role in apoptosis. These data suggest that the strongest signal of association at 5p12 is mediated through coordinated activation of FGF10 and MRPS30, two candidate genes for breast cancer pathogenesis