Investigation of laparoscopic therapy in 56 cases of duodenal ulcer perforation

We report six patients with adult congenital biliary dilatation treated by surgery. Of the six cases, five were female and the patients' age at diagnosis ranged from 19 to 51 years old. By Todani's classification for bile duct dilatation, three were categorized as Ⅰa, one as Ⅰb, and two as Ⅳa. All six cases had anomalous arrangement of the pancreatobiliary duct. Resection of the cystic portion and hepaticojejunostomy (Roux-Y) were performed in all. After surgery, one patient classified as Ⅰa and one as Ⅳa had complications of cholangitis and intrahepatic stones. We removed the stones by the percutaneous transhepatic route with dilatation of the stenotic anastomosis, but cholangitis recurred in the Ⅳa patient. Although surgical resection of the cystic portion and reconstruction of biliary tract is considered to be a standard treatment for adult congenital biliary dilatation, this Ⅳa case had complications after surgical treatment. Thus short-term follow-up is necessary to prevent or diagnose stenotic anastomosis following the operation

Costs of fragility hip fractures globally:a systematic review and meta-regression analysis

Purpose – To systematically review the costs of hip fractures globally and identify drivers of differences in costs. Methods – A systematic review was conducted to identify studies reporting patient level fragility hip fracture costs between 1990 and 2015. We extracted data on the participants and costs from these studies. Cost data concerning the index hospitalisation were pooled and a meta-regression was used to examine its potential drivers. We also pooled data on the first year costs following hip fracture and considered healthcare, social care as well as other cost categories if reported by studies. Results – 113 studies reported costs of hip fracture based on patient level data. Patients developing complications as well as patients enrolled in intervention arms of comparative studies were found to have significantly higher costs compared to the controls. The pooled estimate of the cost for the index hospitalisation was $10,075. Health and social care costs at 12 months were$43,669 with inpatient costs being their major driver. Meta-regression analysis identified age, gender and geographic region as being significantly associated with the differences in costs for the index hospitalisation. Conclusions – Hip fracture poses a significant economic burden and variation exists in their costs across different regions. We found that there was a considerable variation across studies in terms of study design, methodology, follow up period, costs considered and results reported that highlights the need for more standardisation in this area of research. </p

Socio-economic status and the risk of developing hand, hip or knee osteoarthritis: a region-wide ecological study

SummaryObjectiveTo determine the association between socio-economic status (SES) and risk of hand, hip or knee osteoarthritis (OA) at a population level.DesignRetrospective ecological study using the System for the Development of Research in Primary Care (SIDIAP) database (primary care anonymized records for >5 million people in Catalonia (Spain)). Urban residents >15 years old (2009–2012) were eligible. Outcomes: Validated area-based SES deprivation index MEDEA (proportion of unemployed, temporary workers, manual workers, low educational attainment and low educational attainment among youngsters) was estimated for each area based on census data as well as incident diagnoses (ICD-10 codes) of hand, hip or knee OA (2009–2012). Zero-inflated Poisson models were fitted to study the association between MEDEA quintiles and the outcomes.ResultsCompared to the least deprived, the most deprived areas were younger (43.29 (17.59) vs 46.83 (18.49), years (Mean SD), had fewer women (49.1% vs 54.8%), a higher percentage of obese (16.2% vs 8.4%), smokers (16.9% vs 11.9%) and high-risk alcohol consumption subjects (1.5% vs 1.3%). Compared to the least deprived, the most deprived areas had an excess risk of OA: age-sex-adjusted Incidence Rate Ratio (IRR) 1.26 (1.11–1.42) for hand, 1.23 (1.17–1.29) hip, and 1.51 (1.45–1.57) knee. Adjustment for obesity attenuated this association: 1.06 (0.93–1.20), 1.04 (0.99–1.09), and 1.23 (1.19–1.28) respectively.ConclusionsDeprived areas have higher rates OA (hand, hip, knee). Their increased prevalence of obesity accounts for a 50% of the excess risk of knee OA observed. Public health interventions to reduce the prevalence of obesity in this population could reduce health inequalities

Anti-Osteoporosis Medication Prescriptions and Incidence of Subsequent Fracture Among Primary Hip Fracture Patients in England and Wales:An Interrupted Time-Series Analysis

In January 2005 the National Institute for Health and Care Excellence (NICE) in England and Wales provided new guidance on the use of anti-osteoporosis therapies for the secondary prevention of osteoporotic fractures. This was shortly followed in the same year by market authorisation of a generic form of alendronic acid. We here set out to estimate the actual practice impact of these events among hip fracture patients in terms of anti-osteoporosis medicationprescribing and subsequent fracture incidence using primary care data (Clinical Practice Research Datalink) from 1999-2013. Changes in level and trend of prescribing and subsequent fracture following publication of NICE guidance and availability of generic alendronic acid were estimated using an interrupted time series analysis. Both events were considered in combination within a 1-year ‘intervention period’. We identified 10,873 primary hip fracture patients between April 1999 and Sept 2012. Taking into account prior trend, the intervention period was associated with an immediate absolute increase of 14.9% (95% C.I. 10.9 – 18.9) for incident anti-osteoporosis prescriptions and a significant and clinically important reduction in subsequent major and subsequent hip fracture: -0.19% (95% C.I.-0.28 to -0.09) and -0.17% (95% C.I. -0.26 to -0.09) per six months, respectively. This equated to an approximate 14% (major) and 22% (hip) reduction at three years post-intervention relative to expected values based solely on pre-intervention level and trend. We conclude that among hip fracture patients, publication of NICE guidance and availability of generic alendronic acid was temporally associated with increased prescribing and a significant decline in subsequent fractures

Geographic variation in secondary fracture prevention after a hip fracture during 1999-2013:a UK study

Purpose To describe the geographic variation in anti-osteoporosis drug therapy prescriptions before and after a hip fracture during 1999-2013 in the UK. Methods We used primary care data (Clinical Practice Research Datalink) to identify patients with a hip fracture and primary care prescriptions of any anti-osteoporosis drugs prior to the index hip fracture and up to five years after. Geographic variations in prescribing before and after availability of generic oral bisphosphonates were analysed. Multivariable logistic regression models were adjusted for gender, age and body mass index (BMI). Results 13,069 patients (76% female) diagnosed with a hip fracture during 1999-2013 were identified. 11% had any anti-osteoporosis drug prescription in the six months prior to the index hip fracture. In the 0-4 months following a hip fracture 5% of patients were prescribed anti-osteoporosis drugs in 1999, increasing to 51% in 2011 to then decrease to 39% in 2013. The independent predictors (OR (95%CI)) of treatment initiation included gender (male:0.42 (0.36-0.49)), BMI (0.98 per kg/m2 increase (0.97-1.00)) and geographic region (1.29 (0.89-1.87) North East vs. 0.56(0.43-0.73) South Central region). Geographic differences in prescribing persisted over the 5-year follow-up. If all patients were treated at the rate of the highest performing region, then nationally an additional 3,214 hip fracture patients would be initiated on therapy every year. Conclusions Significant geographic differences exist in prescribing of anti-osteoporosis drugs after hip fracture despite adjustment for potential confounders. Further work examining differences in health care provision may inform strategies to improve secondary fracture prevention after hip fracture. </p

Protocol of a randomised trial of teriparatide followed by zoledronic acid to reduce fracture risk in adults with osteogenesis imperfecta

Introduction: Osteogenesis imperfecta (OI) is a rare genetic disease associated with multiple fractures throughout life. It is often treated with osteoporosis medications but their effectiveness at preventing fractures is unknown. The Treatment of Osteogenesis Imperfecta with Parathyroid Hormone and Zoledronic Acid trial will determine if therapy with teriparatide (TPTD) followed by zoledronic acid (ZA) can reduce the risk of clinical fractures in OI. Methods and analysis: Individuals aged ≥18 years with a clinical diagnosis of OI are eligible to take part. At baseline, participants will undergo a spine X-ray, and have bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at the spine and hip. Information on previous fractures and previous bone targeted treatments will be collected. Questionnaires will be completed to assess pain and other aspects of health-related quality of life (HRQoL). Participants will be randomised to receive a 2-year course of TPTD injections 20 µg daily followed by a single intravenous infusion of 5 mg ZA, or to receive standard care, which will exclude the use of bone anabolic drugs. Participants will be followed up annually, have a repeat DXA at 2 years and at the end of study. Spine X-rays will be repeated at the end of study. The duration of follow-up will range between 2 and 8 years. The primary endpoint will be new clinical fractures confirmed by X-ray or other imaging. Secondary endpoints will include participant reported fractures, BMD and changes in pain and HRQoL. Ethics and dissemination: The study received ethical approval in December 2016. Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results will inform clinical practice by determining if TPTD/ZA can reduce the risk of fractures in OI compared with standard care. Trial registration number: ISRCTN15313991

Conclusion of diagnostic odysseys due to inversions disrupting GLI3 and FBN1

Many genetic testing methodologies are biased towards picking up structural variants (SVs) that alter copy number. Copy-neutral rearrangements such as inversions are therefore likely to suffer from underascertainment. In this study, manual review prompted by a virtual multidisciplinary team meeting and subsequent bioinformatic prioritisation of data from the 100K Genomes Project was performed across 43 genes linked to well-characterised skeletal disorders. Ten individuals from three independent families were found to harbour diagnostic inversions. In two families, inverted segments of 1.2/14.8 Mb unequivocally disrupted GLI3 and segregated with skeletal features consistent with Greig cephalopolysyndactyly syndrome. For one family, phenotypic blending was due to the opposing breakpoint lying ~45 kb from HOXA13. In the third family, long suspected to have Marfan syndrome, a 2.0 Mb inversion disrupting FBN1 was identified. These findings resolved lengthy diagnostic odysseys of 9–20 years and highlight the importance of direct interaction between clinicians and data-analysts. These exemplars of a rare mutational class inform future SV prioritisation strategies within the NHS Genomic Medicine Service and similar genome sequencing initiatives. In over 30 years since these two disease-gene associations were identified, large inversions have yet to be described and so our results extend the mutational spectra linked to these conditions

Determinants of the maternal 25-hydroxyvitamin D response to vitamin D supplementation during pregnancy

Context: Current approaches to antenatal vitamin D supplementation do not account for interindividual differences in 25-hydroxyvitamin D (25(OH)D) response.Objective: We assessed which maternal and environmental characteristics were associated with 25(OH)D after supplementation with cholecalciferol.Design: Within-randomization-group analysis of participants in the Maternal Vitamin D Osteoporosis Study trial of vitamin D supplementation in pregnancy.Setting: Hospital antenatal clinics.Participants: A total of 829 pregnant women (422 placebo, 407 cholecalciferol). At 14 and 34 weeks of gestation, maternal anthropometry, health, and lifestyle were assessed and 25(OH)D measured. Compliance was determined using pill counts at 19 and 34 weeks.Interventions: 1000 IU/d of cholecalciferol or matched placebo from 14 weeks of gestation until delivery.Main Outcome Measure: 25(OH)D at 34 weeks, measured in a single batch (Diasorin Liaison).Results: 25(OH)D at 34 weeks of gestation was higher in the women randomized to vitamin D (mean [SD], 67.7 [21.3] nmol/L) compared with placebo (43.1 [22.5] nmol/L; P &lt; .001). In women randomized to cholecalciferol, higher pregnancy weight gain from 14 to 34 weeks of gestation (kg) (? = ?0.81 [95% confidence interval ?1.39, ?0.22]), lower compliance with study medication (%) (? = ?0.28 [?0.072, ?0.48]), lower early pregnancy 25(OH)D (nmol/L) (? = 0.28 [0.16, 0.40]), and delivery in the winter vs the summer (? = ?10.5 [?6.4, ?14.6]) were independently associated with lower 25(OH)D at 34 weeks of gestation.Conclusions: Women who gained more weight during pregnancy had lower 25(OH)D in early pregnancy and delivered in winter achieved a lower 25(OH)D in late pregnancy when supplemented with 1000 IU/d cholecalciferol. Future studies should aim to determine appropriate doses to enable consistent repletion of 25(OH)D during pregnancy.<br/

Does antenatal cholecalciferol supplementation affect the mode or timing of delivery? Post hoc analyses of the MAVIDOS randomized controlled trial

Background Observational studies relating maternal 25-hydroxyvitamin D status to timing and mode of delivery have reported inconsistent results. We assessed the effect of antenatal cholecalciferol supplementation on the incidence of preterm birth, delivery mode and post-partum haemorrhage (PPH). Methods MAVIDOS was a randomized, double-blind, placebo-controlled trial of 1000 IU/day cholecalciferol from 14 weeks’ gestation until delivery. Gestational age, mode of delivery [categorized as spontaneous vaginal delivery (SVD), instrumental (including forceps and vacuum extraction) or Caesarean section] and PPH (>500 ml estimated blood loss) were determined from medical records. Results A total of 965 women participated in the study until delivery. Gestation at birth and incidence of preterm birth (cholecalciferol 5.7%, placebo 4.5%, P = 0.43) were similar between the two treatment groups. SVD (versus instrumental or Caesarean delivery) was more likely in women randomized to cholecalciferol [Relative Risk (RR) 1.13, 95% confidence interval (CI) 1.02,1.25] due to lower instrumental (RR 0.68, 95%CI 0.51,0.91) but similar risk of Caesarean delivery (RR 0.94, 95%CI 0.74,1.19). PPH was less common in women randomized to cholecalciferol [32.1% compared with placebo (38.1%, P = 0.054) overall], but similar when stratified by delivery mode. Conclusions Antenatal cholecalciferol supplementation did not alter timing of birth or prevalence of preterm birth but demonstrated a possible effect on the likelihood of SVD