Epidemiological trends and future care needs for pelvic floor disorders

We sought to provide a review of the recent literature regarding the prevalence and epidemiological trends in pelvic floor disorders (PFDs) including pelvic organ prolapse (POP), urinary incontinence (UI) and fecal incontinence (FI). We also examined the current trends in surgical treatment for these disorders and discuss future care needs

Characterizing the Bladderʼs Response to Onabotulinum Toxin Type A Using a Rat Model

To characterize the response of the rat bladder neuromuscular system to intramural injection of onabotulinum toxin type A (BoNT/A) over 9 weeks using in vivo cystometry (CMG) and in vitro contractility (IVC)

Comparison of Vaginal Hysterectomy Techniques and Interventions for Benign Indications: A Systematic Review

OBJECTIVE: To create evidence-based clinical practice guidelines based on a systematic review of published literature regarding the risks and benefits of available preoperative, intraoperative, and postoperative technical steps and interventions at the time of vaginal hysterectomy for benign indications. DATA SOURCES: We systematically searched the literature to identify studies that compared technical steps or interventions during the preoperative, intraoperative, and postoperative periods surrounding vaginal hysterectomy. We searched MEDLINE, Cochrane Central Register of Controlled Trials, Health Technology Assessments, and ClinicalTrials.gov from their inception until April 10, 2016, using the MeSH term "Hysterectomy, Vaginal" and associated text words. We included comparative studies, single-group studies, and systematic reviews published in English. METHODS OF STUDY SELECTION: We double-screened 4,250 abstracts, identifying 60 eligible studies. Discrepancies were adjudicated by a third reviewer. We followed standard systematic review methodology and the Grades for Recommendation, Assessment, Development and Evaluation approach to evaluate the evidence and generate guideline recommendations. TABULATION, INTEGRATION, AND RESULTS: Because of limited literature, only 16 perioperative risks, technical steps, and interventions were identified: obesity, large uteri, prior surgery, gonadotropin-releasing hormone agonists, vaginal antisepsis, bilateral salpingo-oophorectomy, morcellation, apical closure, uterine sealers, hemostatic injectants, hot cone, retractor, cystoscopy, vaginal packing, bladder management, and accustimulation. We organized and reported these as four domains: patient selection, preoperative, intraoperative, and postoperative. We did not identify any patient characteristics precluding a vaginal approach; chlorhexidine or povidone is appropriate for vaginal antisepsis; vasopressin decreases blood loss by 130 cc; tissue-sealing devices decrease blood loss by 44 cc and operative time by 15 minutes with uncertain complication implications; vertical cuff closure results in 1-cm increased vaginal length; either peritoneum or epithelium can be used for colpotomy closure; and routine vaginal packing is not advised. CONCLUSION: Minimal data exist to guide surgeons with respect to planning and performing a vaginal hysterectomy. This study identifies available information and future areas for investigation

HIV prevention in high-risk women in South Africa: condom use and the need for change.

Introduction: Young women are at disproportionate risk of HIV infection in South Africa. Understanding risk behaviors and factors associated with ability to negotiate safe sex and condom use is likely to be key in curbing the spread of HIV. Traditionally prevention efforts have focused on creating behavioral changes by increasing knowledge about HIV/AIDS. Methods: This was a cross-sectional analysis from a prospective observational cohort study of 245 women at a high-risk of HIV infection in KwaZulu-Natal, South Africa. Results: Participants demonstrated a high level of HIV/AIDS knowledge. Overall, 60.3% of participants reported condom use. Reported condom use at last sexual encounter varied slightly by partner type (57.0% with steady versus 64.4% with casual partners), and self-perceived ability to choose to use a condom was significantly lower with steady partners compared to casual partners (p<0.01). In multivariate analysis, women who had high school education were more likely to use condoms at their last sex encounter compared to those with only primary school education (RR of 1.36 (95% Confidence Interval (CI) 1.06–1.75) and 1.46 (95% CI 1.13–1.88) for grades 8–10 and 11–12, respectively). Those who used condoms as a contraceptive method were twice as likely to use condoms compared to women who did not report using them as a contraceptive method. Greater perceived ability to choose to use condoms was associated with higher self-reported condom use at last encounter, irrespective of partner type (RR = 2.65 (95% CI 2.15–32.5). Discussion: Self-perceived ability to use condoms, level of formal education and condom use as a contraceptive were all significantly associated with self-reported condom use at last sexual encounter. These findings suggest that that gender inequality and access to formal education, as opposed to lack of HIV/AIDS knowledge, prevent safer sexual practices in South Africa

HIV Prevention in High-Risk Women in South Africa: Condom Use and the Need for Change

INTRODUCTION: Young women are at disproportionate risk of HIV infection in South Africa. Understanding risk behaviors and factors associated with ability to negotiate safe sex and condom use is likely to be key in curbing the spread of HIV. Traditionally prevention efforts have focused on creating behavioral changes by increasing knowledge about HIV/AIDS. METHODS: This was a cross-sectional analysis from a prospective observational cohort study of 245 women at a high-risk of HIV infection in KwaZulu-Natal, South Africa. RESULTS: Participants demonstrated a high level of HIV/AIDS knowledge. Overall, 60.3% of participants reported condom use. Reported condom use at last sexual encounter varied slightly by partner type (57.0% with steady versus 64.4% with casual partners), and self-perceived ability to choose to use a condom was significantly lower with steady partners compared to casual partners (p<0.01). In multivariate analysis, women who had high school education were more likely to use condoms at their last sex encounter compared to those with only primary school education (RR of 1.36 (95% Confidence Interval (CI) 1.06-1.75) and 1.46 (95% CI 1.13-1.88) for grades 8-10 and 11-12, respectively). Those who used condoms as a contraceptive method were twice as likely to use condoms compared to women who did not report using them as a contraceptive method. Greater perceived ability to choose to use condoms was associated with higher self-reported condom use at last encounter, irrespective of partner type (RR = 2.65 (95% CI 2.15-32.5). DISCUSSION: Self-perceived ability to use condoms, level of formal education and condom use as a contraceptive were all significantly associated with self-reported condom use at last sexual encounter. These findings suggest that that gender inequality and access to formal education, as opposed to lack of HIV/AIDS knowledge, prevent safer sexual practices in South Africa

Training curriculum in minimally invasive emergency digestive surgery : 2022 WSES position paper

Background Minimally invasive surgery (MIS), including laparoscopic and robotic approaches, is widely adopted in elective digestive surgery, but selectively used for surgical emergencies. The present position paper summarizes the available evidence concerning the learning curve to achieve proficiency in emergency MIS and provides five expert opinion statements, which may form the basis for developing standardized curricula and training programs in emergency MIS. Methods This position paper was conducted according to the World Society of Emergency Surgery methodology. A steering committee and an international expert panel were involved in the critical appraisal of the literature and the development of the consensus statements. Results Thirteen studies regarding the learning curve in emergency MIS were selected. All but one study considered laparoscopic appendectomy. Only one study reported on emergency robotic surgery. In most of the studies, proficiency was achieved after an average of 30 procedures (range: 20-107) depending on the initial surgeon's experience. High heterogeneity was noted in the way the learning curve was assessed. The experts claim that further studies investigating learning curve processes in emergency MIS are needed. The emergency surgeon curriculum should include a progressive and adequate training based on simulation, supervised clinical practice (proctoring), and surgical fellowships. The results should be evaluated by adopting a credentialing system to ensure quality standards. Surgical proficiency should be maintained with a minimum caseload and constantly evaluated. Moreover, the training process should involve the entire surgical team to facilitate the surgeon's proficiency. Conclusions Limited evidence exists concerning the learning process in laparoscopic and robotic emergency surgery. The proposed statements should be seen as a preliminary guide for the surgical community while stressing the need for further research.Peer reviewe

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

Post-Operative Functional Outcomes in Early Age Onset Rectal Cancer

Background: Impairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (&lt;50 years) is rising, there is little data on functional outcomes in this group. Methods: The REACCT international collaborative database was reviewed and data on eligible patients analysed. Inclusion criteria comprised patients with a histologically confirmed rectal cancer, &lt;50 years of age at time of diagnosis and with documented follow-up including functional outcomes. Results: A total of 1428 (n=1428) patients met the eligibility criteria and were included in the final analysis. Metastatic disease was present at diagnosis in 13%. Of these, 40% received neoadjuvant therapy and 50% adjuvant chemotherapy. The incidence of post-operative major morbidity was 10%. A defunctioning stoma was placed for 621 patients (43%); 534 of these proceeded to elective restoration of bowel continuity. The median follow-up time was 42 months. Of this cohort, a total of 415 (29%) reported persistent impairment of functional outcomes, the most frequent of which was bowel dysfunction (16%), followed by bladder dysfunction (7%), sexual dysfunction (4.5%) and infertility (1%). Conclusion: A substantial proportion of patients with early-onset rectal cancer who undergo surgery report persistent impairment of functional status. Patients should be involved in the discussion regarding their treatment options and potential impact on quality of life. Functional outcomes should be routinely recorded as part of follow up alongside oncological parameters

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe