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BackgroundO’Donnell-Luria-Rodan syndrome (ODLURO) is an autosomal-dominant neurodevelopmental disorder caused by pathogenic, mostly truncating variants in KMT2E. It was first described by O’Donnell-Luria et al in 2019 in a cohort of 38 patients. Clinical features encompass macrocephaly, mild intellectual disability (ID), autism spectrum disorder (ASD) susceptibility and seizure susceptibility.MethodsAffected individuals were ascertained at paediatric and genetic centres in various countries by diagnostic chromosome microarray or exome/genome sequencing. Patients were collected into a case cohort and were systematically phenotyped where possible.ResultsWe report 18 additional patients from 17 families with genetically confirmed ODLURO. We identified 15 different heterozygous likely pathogenic or pathogenic sequence variants (14 novel) and two partial microdeletions of KMT2E. We confirm and refine the phenotypic spectrum of the KMT2E-related neurodevelopmental disorder, especially concerning cognitive development, with rather mild ID and macrocephaly with subtle facial features in most patients. We observe a high prevalence of ASD in our cohort (41%), while seizures are present in only two patients. We extend the phenotypic spectrum by sleep disturbances.ConclusionOur study, bringing the total of known patients with ODLURO to more than 60 within 2 years of the first publication, suggests an unexpectedly high relative frequency of this syndrome worldwide. It seems likely that ODLURO, although just recently described, is among the more common single-gene aetiologies of neurodevelopmental delay and ASD. We present the second systematic case series of patients with ODLURO, further refining the mutational and phenotypic spectrum of this not-so-rare syndrome.

Objectives Sepsis is a life-threatening medical emergency. There is a paucity of information on whether quality improvement approaches reduce the in-hospital sepsis caseload or save lives and decrease the healthcare system and society's cost at the provincial/national levels. This study aimed to assess the outcomes and economic impact of a province-wide quality improvement initiative in Canada. Design Retrospective population-based study with interrupted time series and return on investment analyses. Setting The sepsis cases and deaths averted over time for British Columbia were calculated and compared with the rest of Canada (excluding Quebec and three territories). Patients Aggregate data were obtained from the Canadian Institute for Health Information on risk-adjusted in-hospital sepsis rates and sepsis mortality in acute care sites across Canada. Interventions In 2012, the British Columbia Sepsis Network was formed to reduce sepsis occurrence and mortality through education, knowledge translation, and quality improvement. Measurements and main results A return on investment analysis compared the financial investment for the British Columbia Sepsis Network with the savings from averted sepsis occurrence and mortality. An estimated 981 sepsis cases and 172 deaths were averted in the post-British Columbia Sepsis Network period (2014-2018). The total cost, including the development and implementation of British Columbia Sepsis Network, was $449,962. Net savings due to cases averted after program costs were considered were $50.6 million in 2018. This translates into a return of $112.5 for every dollar invested. Conclusions British Columbia Sepsis Network appears to have averted a greater number of sepsis cases and deaths in British Columbia than the national average and yielded a positive return on investment. Our findings strengthen the policy argument for targeted quality improvement initiatives for sepsis care and provide a model of care for other provinces in Canada and elsewhere globally.

Background: Quality improvement (QI) has received much wider attention in public policy, given the ever-increasing aging population and growing demand of long-term care (LTC). In the policy context, health system planners and administrators need to know the evidence on cost-effectiveness for resource allocation decisions. The objectives of this study were to: identify costs and benefits of the QI strategies in the economic literature; and synthesize the methodological approaches used in the economic studies and reported evidence around the cost-effectiveness of QI strategies in LTC. Methods: A scoping review of three online databases, including PubMed, EconLit, and Google Scholar, was conducted to identify economic studies focusing on elderly population published from September 2010 to August 2020. A combination of search expressions was used to identify the original research articles. Study titles and abstracts were screened, and only full-text articles meeting the inclusion criteria were retained in the review. A standard data extraction template was used capturing patient population, intervention, comparator, the outcome of interest, and study design (PICOS). Results: The search identified 657 records, of which 16 were included in the review. The financial costs were categorized into three groups: (i) developmental, (ii) operational, and (iii) health resource utilization. The terms ‘Quality of life,’ ‘Health-related Quality of Life’, and ‘Quality of Care’ were interchangeably used to express the health outcomes. This study showed mixed results suggesting a substantial variability around cost-effectiveness of QI interventions targeting elderly population in LTC. Almost all studies reported a public payer perspective and a discount rate ranged from 0 to 7%. A poorly defined baseline, the complex nature of the intervention, a lack of appropriate comparator, and varying duration of implementation were key methodological limitations. Conclusions: This review highlights important knowledge gaps regarding societal costs and inconsistencies in reporting of the outcome measures. More research is needed to analyze long-term costs and consequences to better inform decisions on resource allocation in LTC.

Commissioned research was undertaken to explore the role of networks in supporting large-scale change and improvement. Participatory action research and social network analysis were used to study the BC Sepsis Network. Findings of this research include insights into distributed leadership, enablers and barriers within a network approach; the importance of relationships and trust; and the need for meaningful and timely data. Recommendations are made for health leaders who are considering utilizing networks for improving patient quality and safety.

Laparoscopic Roux-en-Y gastric bypass (RYGBP) has been used increasingly more often in the past 10 years. The authors summarize their experience and safety/complications data based on 849 laparoscopic RYGBP procedures. They also evaluate the use of the Endopath trocar in terms of trocar-site hernias, bowel obstruction, and elimination of time-consuming fascial closure. From July 2000 to December 2003, 849 laparoscopic RYGBP procedures were performed using a bladeless, 12-mm, visual entry trocar. The patients’ average body mass index (BMI) was 53.2 kg/m2. The trocar ports (n = 3,744) were not closed. Perioperative and postoperative assessments were performed. In this study, 74% of the patients were retained for follow-up evaluation (mean, 10 months). Among these patients, no intraoperative bowel or vascular injuries, no mortality, and two trocar-site hernias (0.2%) were found. At 1 year, the mean excess weight loss was 73.4%. The Endopath trocar system shows a trend toward reducing trocar-site hernias, decreasing bowel obstruction, and eliminating the need for time-consuming fascial closure, although further studies are needed to confirm these findings.

There is experimental evidence but very few human studies that suggest a role for obesity in the formation and progression of some glomerular lesions. We report the case of a morbidly obese male with hematuria and proteinuria that was subsequently diagnosed with renal failure which required dialysis. Histological findings of the renal biopsy performed during a laparoscopic gastric bypass are presented. His renal failure resolved with the weight loss.

A 1991 National Institutes of Health Consensus Conference concluded that severely obese adults could be eligible for bariatric surgery if they had a body mass index (BMI) > or =35 kg/m(2) with or > or =40 kg/m(2) without obesity comorbidity. It was thought at that time that there were inadequate data to support bariatric surgery in severely obese adolescents. An estimated 25% of children in the United States are obese, a number that has doubled over a 30-year period. Very little information has been published on the subject of obesity surgery in adolescents. Therefore we reviewed our 20-year database on bariatric surgery in adolescents. Severely obese adolescents, ranging from 12 to less than 18 years of age, were considered eligible for bariatric surgery according to the National Institutes of Health adult criteria. Gastroplasty was the procedure of choice in the initial 3 years of the study followed by gastric bypass, which was found to be significantly more effective for weight loss in adults. Distal gastric bypass (D-GBP) was used in extremely obese patients (BMI > or =60 kg/m(2)) before 1992 and long-limb gastric bypass (LL-GBP) was used for superobese patients (BMI > or =50 kg/m(2)) after 1992. Laparoscopic gastric bypass was used after 2000. Thirty-three adolescents (27 white, 6 black; 19 females, 14 males) underwent the following bariatric operations between 1981 and June 2001: horizontal gastroplasty in one, vertical banded gastroplasty in two, standard gastric bypass in 17 (2 laparoscopic), LL-GBP in 10, and D-GBP in three. Mean BMI was 52 +/- 11 kg/m(2) (range 38 to 91 kg/m(2)), and mean age was 16 +/- 1 years (range 12.4 to 17.9 years). Preoperative comorbid conditions included the following: type II diabetes mellitus in two patients, hypertension in 11, pseudotumor cerebri in three, gastroesophageal reflux in five, sleep apnea in six, urinary incontinence in two, polycystic ovary syndrome in one, asthma in one, and degenerative joint disease in 11. There were no operative deaths or anastomotic leaks. Early complications included pulmonary embolism in one patient, major wound infection in one, minor wound infections in four, stomal stenoses (endoscopically dilated) in three, and marginal ulcers (medically treated) in four. Late complications included small bowel obstruction in one and incisional hernias in six patients. There were two late sudden deaths (2 years and 6 years postoperatively), but these were unlikely to have been caused by the bariatric surgical procedure. Revision procedures included one D-GBP to gastric bypass for malnutrition and one gastric bypass to LL-GBP for inadequate weight loss. Regain of most or all of the lost weight was seen in five patients at 5 to 10 years after surgery; however, significant weight loss was maintained in the remaining patients for up to 14 years after surgery. Comorbid conditions resolved at 1 year with the exception of hypertension in two patients, gastroesophageal reflux in two, and degenerative joint disease in seven. Self-image was greatly enhanced; eight patients have married and have children, five patients have completed college, and one patient is currently in college. Severe obesity is increasing rapidly in adolescents and is associated with significant comorbidity and social stigmatization. Bariatric surgery in adolescents is safe and is associated with significant weight loss, correction of obesity comorbidity, and improved self-image and socialization. These data strongly support obesity surgery for those unfortunate individuals who may have difficulty obtaining insurance coverage based on the 1991 National Institutes of Health Consensus Conference statement.

Cholesterol-rich microdomains present on the plasma membrane appear to play an important role in spatio-temporal regulation of cell signaling and cell adhesion processes. Compositional heterogeneity of these microdomains and their coalescence during cell-cell interactions may provide one mechanism for triggering and/or regulating signaling cascades from the plasma membrane to the cell interior. Biochemical analyses of distinct lipid microdomain subpopulations and single-rafts obtained from unstimulated and ligand-stimulated cells are critical for deciphering functional role of lipid rafts. We have designed a cell-free assay that captures detergent-resistant lipid rafts with an antibody against a raft-resident molecule and detects the presence of another lipid raft molecule. Moreover, this cell-free assay provides a simple and quick way to examine the simultaneous presence of two proteins in the lipid rafts, and has the potential to estimate trafficking of molecules in and out of the lipid microdomains during cell signaling on a single lipid raft-basis.

The purpose of this study was to measure the reliability of a classification system for pelvic girdle pain (PGP) and diagnostic accuracy of selected examination and clinical special findings for diagnosis of PGP.The design involved a prospective epidemiological study of pregnancy-related PGP. Consecutive subjects were recruited and classified using criteria defined by previous studies. Two clinicians examined the subjects and classified each patient into 1 of 5 classification groups. Clinical examination and clinical special tests were performed on the patients with PGP. Statistical analysis involved interobserver agreement using a kappa statistic and sensitivity and specificity values for the examination and clinical special testing.Twenty-one subjects were included in the analyses. Aggregated percentage of agreement for the classification system was 84.6%. The Cohen kappa was 0.78 (CI, 0.64-0.92; P.0001), which indicated substantial agreement during selection of the classification system. Most clinical examination and clinical special-test findings demonstrated low sensitivity and high specificity, whereas clusters of findings including the lunge, manual muscle testing of the hip (lower extremities), and passive range of motion of the hip demonstrated the strongest diagnostic value.Selected tests and measures are moderately discriminatory in diagnosing PGP. A classification system for diagnosing PGP demonstrates strong agreement and may be useful for clinicians.

Background: Morbid obesity is an epidemic in America. This series evaluates the safety and efficacy in the first 1,001 laparoscopic bariatric operations performed at The Bariatric Institute, Cleveland Clinic Florida. Methods: A retrospective review was conducted examining all patients undergoing a primary bariatric procedure (either laparoscopic gastric bypass or laparoscopic gastric banding) from July 2000 to December 2003. Results: 2 surgeons performed 1,001 laparoscopic bariatric operatons. Average age was 47 (19-75) years, average BMI was 55.6 (35-97) kg/m2, and average ASA class was III. Excess weight loss was 51% at 6 months, 73.4% at 1 year for the gastric bypass group and 54% at 1 year for the laparoscopic banding group. The overall complication rate was 31.8% (12.4% major and 19.4% minor) in the gastric bypass group and 13% in the laparoscopic banding group. There was no postoperative mortality. Conclusion: Laparoscopic bariatric surgery is feasible and safe for weight loss. Results obtained have been comparable to those reported for the open approach for weight loss, with a similar major morbidity rate and an improved mortality rate.

Many diseases in the obese population have been found to improve after weight loss. A 56-year-old female with a long history of myasthenia gravis (MG) and morbid obesity is reported. Preoperatively, she presented with a BMI of 46.5 kg/m2, and was on three medications and IV immunoglobulin every 5 weeks. After the surgical procedure, she improved and required less medication. Because MG and morbid obesity require careful perioperative management in order to avoid complications, a multidisciplinary approach is recommended.

Background: The authors reviewed the benefits of routine placement of closed drains in the peritoneal cavity following laparoscopic Roux-en-Y gastric bypass (LRYGBP). The purpose of the study was to determine whether routine closed abdominal drainage provides diagnostic and therapeutic advantages in the presence of complications such as bleeding and leaks. Materials and Methods: The medical records of 593 consecutive patients who had undergone LRYGBP from July 2001 through May 2003 were retrospectively reviewed. In all cases, antecolic antegastric LRYGBP was performed. Two 19-Fr Blake closed suction drains were left in place, one at the gastrojejunostomy and the other at the jejunojejunostomy. The incidence of bleeding and leaks was reviewed, and the utility of the drains relative to diagnosis and management was evaluated. Results: Bleeding presented in 24 patients (4.4%); in 8, the diagnosis was based on increased sanguinous output from the drain and decreased hematocrit. None of the patients with intraabdominal bleeding required reoperation. Of the 10 patients (1.68%) who presented with leaks, the diagnosis was made within 48 hours postoperatively in 5 patients (50%), based on the characteristics of the drain output. Nonoperative management with drainage and total parenteral nutrition was accomplished in 5 (50%) of the 10 patients with leaks. There was no mortality in the series. Conclusion: The routine use of abdominal drains after LRYGBP appears to be beneficial. Drains allowed early diagnosis of complications and in most cases, the successful treatment of leaks. When bleeding is suspected or documented, appropriate volume replacement therapy is mandatory to maintain adequate hemodynamic parameters. Drain output may orient the surgeon to take preventive measures such as discontinuing anticoagulation and early fluid resuscitation. In this series, in most cases the bleeding spontaneously stopped and no further surgical management was required.

The association between post-traumatic stress disorder (PTSD) and health-related quality of life (QOL) in female victims of intimate partner violence (IPV) was examined. The Short-Form Health Survey (SF-36) was used to evaluate health-related QOL. IPV victims with PTSD (IPV/PTSD+; n = 18), IPV victims without PTSD (IPV/PTSD-; n = 22), and a non-abused control group (NA; n = 30) were compared. Multiple Analyses of Covariance (covarying for socioeconomic status and age) indicated that the three groups scored significantly differently on health-related QOL, and the IPV/PTSD- group was significantly more impaired than the NA group. IPV/PTSD+ subjects were significantly more impaired than IPV/PTSD- subjects on physical functioning, mental health, vitality, role limitations due to emotional health, and social functioning. Multiple regression analyses indicated that PTSD severity was a significant statistical predictor of SF-36 mental health composite scores (but not of physical health composite scores), after controlling for depressive symptomatology and extent of physical and psychological abuse.

Background Lipid rafts present on the plasma membrane play an important role in spatiotemporal regulation of cell signaling. Physical and chemical characterization of lipid raft size and assessment of their composition before, and after cell stimulation will aid in developing a clear understanding of their regulatory role in cell signaling. We have used visual and biochemical methods and approaches for examining individual and lipid raft sub-populations isolated from a mouse CD4+ T cell line in the absence of detergents. Results Detergent-free rafts were analyzed before and after their interaction with antigen presenting cells. We provide evidence that the average diameter of lipid rafts isolated from un-stimulated T cells, in the absence of detergents, is less than 100 nm. Lipid rafts on CD4+ T cell membranes coalesce to form larger structures, after interacting with antigen presenting cells even in the absence of a foreign antigen. Conclusions Findings presented here indicate that lipid raft coalescence occurs during cellular interactions prior to sensing a foreign antigen.

Although visuoconstructive impairment has been reported in both Alzheimer's (DAT) and Huntington's (HD) disease, there is little knowledge concerning how this cognitive deficit differs quantitatively and qualitatively in these two progressive dementias. To address this issue, the present study compared performances on the Clock Drawing Test (CDT: command and copy) of 25 DAT patients, 25 equally demented HD patients, and 25 elderly normal controls (NC). In the command condition, both patients groups were significantly impaired compared to the NC group. Although there was no significant difference between DAT and HD patients' total quantitative scores, a qualitative error analysis revealed a number of dissociations between the two patient groups. Graphic difficulties, very common in HD patients, were virtually absent in DAT patients; in contrast, conceptual errors were almost exclusively seen in DAT patients and were related to the severity of their dementia. Perseveration and "stimulus-bound" responses were also more frequent in DAT patients, and both groups made visuospatial errors. In the copy condition, the DAT, but not the HD, patients evidenced a marked improvement in performance. These results indicate that while both DAT and HD patients have significant visuoconstructive difficulties even in the early stages of their disorders, the specific cognitive processes underlying their quantitative impairments are quite different. It is possible that the DAT patients' conceptual errors are yet another indicator of the deterioration of their semantic knowledge.