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Opportunistic salpingectomy (OS), which is the removal of fallopian tubes during hysterectomy or instead of tubal ligation without removal of ovaries, is recommended to prevent ovarian cancer, particularly serous ovarian cancer. However, the effectiveness of OS is still undetermined. To examine observed vs expected rates of ovarian cancer among individuals who have undergone OS. This is a population-based, retrospective cohort study of all individuals in British Columbia, Canada, who underwent OS or a control surgery (hysterectomy alone or tubal ligation) between 2008 and 2017, with follow-up until December 31, 2017. Those with any gynecological cancer diagnosed before or within 6 months of their procedure were excluded. Data analysis was performed from April to August 2021. Removal of both fallopian tubes at the time of hysterectomy or instead of tubal ligation while leaving ovaries intact. An ovarian cancer diagnosis listed in the British Columbia Cancer Registry. Age-specific rates of epithelial and serous ovarian cancer in the control group were combined with the specific follow-up time in the OS group to calculate expected numbers (and 95% CIs) of ovarian cancers in the OS group. These were compared with observed numbers. Age-adjusted expected and observed numbers of breast and colorectal cancers were also examined in the OS group. There were 25 889 individuals who underwent OS (mean [SD] age, 40.2 [7.1] years; median [IQR] follow-up, 3.2 [1.6-5.1] years) and 32 080 who underwent hysterectomy alone or tubal ligation (mean [SD] age, 38.2 [7.9] years; median [IQR] follow-up, 7.3 [4.6-8.7] years). There were no serous ovarian cancers in the OS group and 5 or fewer epithelial ovarian cancers. The age-adjusted expected number was 5.27 (95% CI, 1.78-19.29) serous cancers and 8.68 (95% CI, 3.36-26.58) epithelial ovarian cancers. Age-adjusted expected vs observed numbers of breast cancers (22.1 expected vs 23 observed) and colorectal cancers (9.35 expected vs 8 observed) were not significantly different. In this cohort study, the OS group had significantly fewer serous and epithelial ovarian cancers than were expected according to the rate at which they arose in the control group. These findings suggest that OS is associated with reduced ovarian cancer risk.

Increasing demand for fecal microbiota transplantation (FMT) has created a need for stool banks sourced from long-term healthy donors. Here, we describe our experience in recruiting and screening fecal donors.MethodsMailbox, newspaper, and online advertisements were used. Potential donors were required to satisfy a prescreen telephone conversation, pass blood and stool investigations, then undertake a screening interview including medical history, physical examination, and evaluation of donor selection criteria.ResultsOne hundred sixteen potential donors were prescreened of whom 74 failed—47 declined based on study donation requirements (primarily related to frequency and duration of donations), 13 had medical comorbidities, 6 variant Creutzfeldt–Jakob disease risk factors, 8 for other reasons. Thirty-eight completed stool and blood testing—1 failed blood testing (indeterminate hepatitis C serology), whereas 15 failed stool investigations (5 Dientamoeba fragilis, 5 Blastocystis hominis, 1 B. hominis and D. fragilis, 1 Giardia intestinalis plus D. fragilis, 1 Norovirus plus Clostridium difficile toxin positive, and 2 leucocytes or erythrocytes on stool microscopy). Of the 18 potential donors proceeding to screening interview, 6 were excluded (3 body mass index >30, 1 illicit drug use, 1 uncontrolled anxiety and concerns regarding compliance, 1 irregular bowel movements after new medication commencement). In total, only 12 of 116 (10%) potential donors were enrolled as study donors.ConclusionsRecruitment of fecal donors for FMT is challenging with only a small percentage ultimately serving as donors. Many were unable or unwilling to meet the donor commitment requirements. A surprisingly large proportion of healthy asymptomatic donors failed stool testing, primarily due to gastrointestinal parasites.

ObjectiveThe aim of the study was to explore the factors that contributed to the adoption of opportunistic salpingectomies (removal of fallopian at the time of hysterectomy or in lieu of tubal ligation) by gynecologic surgeons in British Columbia (where a knowledge translation initiative took place) and in Ontario (a comparator where no knowledge translation initiative took place). We aimed to understand why the knowledge translation initiative undertaken by OVCARE in British Columbia resulted in such a dramatic uptake in opportunistic salpingectomy.MethodsWe undertook a qualitative evaluation of clinicians' decisions about whether or not they should adopt the practice of opportunistic salpingectomy based on interviews with gynecologic surgeons in British Columbia and Ontario (n = 28). The analysis draws from the Consolidated Framework for Implementation Research.ResultsRegional cohesion combined with practice change information exposure and thought leader support were important in explaining differences in adoption levels between participants. The British Columbian knowledge translation campaign was successful because provincial thought leaders exposed gynecologic surgeons to recommendations through multiple sources within a highly socially cohesive environment wherein clinicians felt pressure to adopt the recommendations. In both provinces, high adopters often believed that the workload and surgical risk associated with the adoption was low and the potential benefit—because of limited ovarian cancer detection and treatment options—was high.ConclusionThis research points to the important role that local professional networks can play in encouraging clinicians to change their practice by creating a cohesive regional environment where clinicians are repeatedly exposed to important information and supported in their practice change by local thought leaders.

In this multicenter trial comparing immediate (≤10 seconds) with delayed (≥60 seconds) clamping of the umbilical cord after preterm birth, there was no significant difference between groups in the primary composite outcome of death or major morbidity by 36 weeks of postmenstrual age.

Aims: The aim of this study was to evaluate the influence of case management on family member or other care giver involvement in residential aged care settings; staff family relationships and family satisfaction with residential care. Method: This was a controlled before and after study involving pre and post intervention testing and comparison between intervention and control groups from two 30 bed rural high care residential aged care facilities. Staff from the intervention facility underwent case management training and resources were allocated to implement case management. General demographic information was collected about the family member and the residents. The Family Involvement Questionnaire and the Family Perception of Care Tool was used pre and post intervention to determine the level of family involvement and their perception of care provided. Results: Visiting levels increased in the intervention site but not the control site. No significant differences were found for the two sites over the two phases but increases were seen in correspondence, attendance at social activities, overseeing staff interactions, attendance at case conferences and rate of family member decision making about treatments or care for the intervention site. The overall satisfaction with care and the relationships increased at the intervention site but the changes were not significant. Conclusion: Although there were no statistically significant results due to the sample size, there were positive changes at the intervention site. Case management is a potentially suitable model of care in the aged care setting.

ObjectiveLarge-scale mortality trials require reliable secondary assessments of impairment. We compared the Ages and Stages Questionnaire (ASQ-3), a screening tool self-administered by parents, in classifying impairment using the ‘gold standard’ Bayley Scales of Infant Development (Bayley-III), a diagnostic tool administered by trained assessors.DesignAnalysis of 405 children around 2 years corrected age from the Australian Placental Transfusion Study, a trial conducted over 8 years.SettingSecondary analysis of international, open-label, multicentre randomised trial.PatientsChildren born <30 weeks gestation.InterventionsImmediate (<10 s) versus delayed (60 s+) cord clamping.Main outcomesASQ-3 and Bayley-III assessments around 2 years corrected age. Impairment (or developmental delay) was defined as <2 SD below the mean (<70) for Bayley-III domains.ResultsThe area under the receiver operating curve for ASQ-3 domains predicting delay was 0.75–0.99. Sensitivity for predicting delay was 57%–100%, while specificity was 88%–90%.We modelled the cost and sample size using a less expensive, though less precise, screening assessment for impairment compared with a more costly diagnostic assessment. For detecting a 25% reduction in the relative risk of delay, using ASQ-3 rather than Bayley-III could require double the sample size (15 000 to 30 000), but outcome assessment cost savings would be US$13M (EUR$12M). However, assessment cost savings may be outweighed by upscaling.ConclusionsWhen measuring developmental outcomes in a large-scale clinical trial, using a more precise diagnostic tool may be financially prohibitive, so increasing the sample size and using a less precise but appropriately calibrated tool may be more affordable.Trial registration numberACTRN12610000633088.

We assessed the landscape of diagnostic pathology practice and how molecular classification could potentially impact management of patients with endometrial cancer by collecting patient samples, clinicopathologic data, and patient outcomes from EC patients diagnosed in 2016 at 10 Canadian tertiary cancer centers and 19 community hospitals. ProMisE molecular subtype (POLEmut, MMRd, p53abn, No Specific Molecular Profile (NSMP)) was assigned retrospectively. 1357 patients were fully evaluable including 85 POLEmut (6.3%), 380 MMRd (28.0%), 643 NSMP (47.4%), and 249 p53abn ECs (18.3%). Immunohistochemistry (IHC) for MMR proteins was undertaken at the time of primary diagnosis in 2016 in only 42% of the cohort (570/1357; range 3.5–95.4%/center). p53 IHC had only been performed in 21.1% of the cohort (286/1357; range 10.1–41.9%/center). Thus, based on the retrospective molecular subtype assignment, 54.7% (208/380) of MMRd EC had not been tested with MMR IHC (or MSI) and 48.2% (120/249) of p53abn ECs were not tested with p53 IHC in 2016. Molecular subtype diversity within histotypes was profound; most serous carcinomas were p53abn (91.4%), but only 129/249 (51.8%) p53abn EC were serous. Low-grade (Gr1-2) endometrioid carcinomas were mostly NSMP (589/954, 61.7%) but included all molecular subtypes, including p53abn (19/954, 2.0%). Molecular subtype was significantly associated with clinical outcomes (p < 0.001) even in patients with stage I disease (OS p = 0.006, DSS p < 0.001, PFS p < 0.001). Assessment of national pathologic practice in 2016 shows highly variable use of MMR and p53 IHC and demonstrates significant opportunities to improve and standardize biomarker reporting. Inconsistent, non-reflexive IHC resulted in missed opportunities for Hereditary Cancer Program referral and Lynch Syndrome diagnosis, and missed potential therapeutic implications (e.g., chemotherapy in p53abn EC, immune blockade for MMRd EC). Routine integration of molecular subtyping into practice can improve the consistency of EC pathology assessment and classification.

Background A newly defined congenital myasthenic syndrome (CMS) caused by DPAGT1 mutations has recently been reported. While many other CMS-associated proteins have discrete roles localised to the neuromuscular junction, DPAGT1 is ubiquitously expressed, modifying many proteins, and as such is an unexpected cause of isolated neuromuscular involvement. Methods We present detailed clinical characteristics of five patients with CMS caused by DPAGT1 mutations. Results Patients have prominent limb girdle weakness and minimal craniobulbar symptoms. Tubular aggregates on muscle biopsy are characteristic but may not be apparent on early biopsies. Typical myasthenic features such as pyridostigmine and 3, 4- diaminopyridine responsiveness, and decrement on repetitive nerve stimulation are present. Conclusions These patients mimic myopathic disorders and are likely to be under-diagnosed. The descriptions here should facilitate recognition of this disorder. In particular minimal craniobulbar involvement and tubular aggregates on muscle biopsy help to distinguish DPAGT1 CMS from the majority of other forms of CMS. Patients with DPAGT1 CMS share similar clinical features with patients who have CMS caused by mutations in GFPT1, another recently identified CMS subtype.

Background Ovarian cancer is now recognized as a number of distinct diseases primarily defined by histological subtype. Both clear cell ovarian carcinomas (CCC) and ovarian endometrioid carcinomas (EC) may arise from endometriosis and frequently harbor mutations in the ARID1A tumor suppressor gene. We studied the influence of histological subtype on protein expression with reverse phase protein array (RPPA) and assessed proteomic changes associated with ARID1A mutation/BAF250a expression in EC and CCC. Methods Immunohistochemistry (IHC) for BAF250a expression was performed on 127 chemotherapy-naive ovarian carcinomas (33 CCC, 29 EC, and 65 high-grade serous ovarian carcinomas (HGSC)). Whole tumor lysates were prepared from frozen banked tumor samples and profiled by RPPA using 116 antibodies. ARID1A mutations were identified by exome sequencing, and PIK3CA mutations were characterized by MALDI-TOF mass spectrometry. SAM (Significance Analysis of Microarrays) was performed to determine differential protein expression by histological subtype and ARID1A mutation status. Multivariate logistic regression was used to assess the impact of ARID1A mutation status/BAF250a expression on AKT phosphorylation (pAKT). PIK3CA mutation type and PTEN expression were included in the model. BAF250a knockdown was performed in 3 clear cell lines using siRNA to ARID1A . Results Marked differences in protein expression were observed that are driven by histotype. Compared to HGSC, SAM identified over 50 proteins that are differentially expressed in CCC and EC. These included PI3K/AKT pathway proteins, those regulating the cell cycle, apoptosis, transcription, and other signaling pathways including steroid hormone signaling. Multivariate models showed that tumors with loss of BAF250a expression showed significantly higher levels of AKT-Thr 308 and AKT-Ser 473 phosphorylation (p < 0.05). In 31 CCC cases, pAKT was similarly significantly increased in tumors with BAF250a loss on IHC. Knockdown of BAF250a by siRNA in three CCC cell lines wild type for ARID1A showed no increase in either pAKT-Thr 308 or pAKT-S 473 suggesting that pAKT in tumor tissues is indirectly regulated by BAF250a expression. Conclusions Proteomic assessment of CCC and EC demonstrates remarkable differences in protein expression that are dependent on histotype, thereby further characterizing these cancers. AKT phosphorylation is associated with ARID1A /BAF250a deficient tumors, however in ovarian cancers the mechanism remains to be elucidated.

IntroductionDelayed cord clamping (DCC) is an evidence-based intervention that reduces mortality, anaemia and disability in infants born <37 weeks’ gestation who do not require immediate resuscitation. However, it is neither reliably recorded nor routinely implemented in Australia. The Wait a Minute or More (WAMM) study aims to reduce this gap between the evidence and practice by integrating timely sharing of cord clamping data with Evidence-based Practice for Improving Quality methods to increase the proportion of preterm infants receiving DCC for 60 s or longer (DCC60).MethodsThe WAMM study is a pragmatic stepped wedge cluster randomised trial (SW-CRT), informed by the Integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) framework. Up to 20 Australian maternity hospitals will participate in this pragmatic SW-CRT to evaluate if in (Population) infants <37 weeks’ gestation who do not need resuscitation, does (Intervention) the WAMM intervention (sharing of anonymised data on DCC60, together with a locally adapted quality improvement (QI) programme), compared with (Control) sharing of anonymised data on DCC60 alone, increase (primary Outcome) the proportion of infants receiving DCC60? At the end of 72 weeks, all sites will complete an 8-week period without the WAMM intervention to evaluate if implementation of DCC is sustained. Alongside the SW-CRT, an embedded process evaluation will assess the fidelity, acceptability, mechanisms of action and contextual barriers and enablers of the WAMM intervention.DiscussionUsing the stepped wedged design and guided by an explicit implementation framework (i-PARIHS), WAMM will provide information on the effectiveness and transferability of a locally adapted QI method to improve DCC60. If proven effective, ultimately scaling up the WAMM intervention globally will greatly improve childhood anaemia, death, disability and long-term costs.Trial registration numberACTRN12624000035527.