Acceptability, feasibility, and likelihood of stakeholders implementing the novel BPaL regimen to treat extensively drug-resistant tuberculosis patients.

BACKGROUND: BPaL, a 6 month oral regimen composed of bedaquiline, pretomanid, and linezolid for treating extensively drug-resistant tuberculosis (XDR-TB) is a potential alternative for at least 20 months of individualized treatment regimens (ITR). The ITR has low tolerability, treatment adherence, and success rates, and hence to limit patient burden, loss to follow-up and the emergence of resistance it is essential to implement new DR-TB regimens. The objective of this study was to assess the acceptability, feasibility, and likelihood of implementing BPaL in Indonesia, Kyrgyzstan, and Nigeria. METHODS: We conducted a concurrent mixed-methods study among a cross-section of health care workers, programmatic and laboratory stakeholders between May 2018 and May 2019. We conducted semi-structured interviews and focus group discussions to assess perceptions on acceptability and feasibility of implementing BPaL. We determined the proportions of a recoded 3-point Likert scale (acceptable; neutral; unacceptable), as well as the overall likelihood of implementing BPaL (likely; neutral; unlikely) that participants graded per regimen, pre-defined aspect and country. We analysed the qualitative results using a deductive framework analysis. RESULTS: In total 188 stakeholders participated in this study: 63 from Kyrgyzstan, 51 from Indonesia, and 74 from Nigeria The majority were health care workers (110). Overall, 88% (146/166) of the stakeholders would likely implement BPaL once available. Overall acceptability for BPaL was high, especially patient friendliness was often rated as acceptable (93%, 124/133). In contrast, patient friendliness of the ITR was rated as acceptable by 45%. Stakeholders appreciated that BPaL would reduce workload and financial burden on the health care system. However, several stakeholders expressed concerns regarding BPaL safety (monitoring), long-term efficacy, and national regulatory requirements regarding introduction of the regimen. Stakeholders stressed the importance of addressing current health systems constraints as well, especially in treatment and safety monitoring systems. CONCLUSIONS: Acceptability and feasibility of the BPaL regimen is high among TB stakeholders in Indonesia, Kyrgyzstan, and Nigeria. The majority is willing to start using BPaL as the standard of care for eligible patients despite country-specific health system constraints.

Meta-analysis and systematic review of ADGRL3 (LPHN3) polymorphisms in ADHD susceptibility.

The gene encoding adhesion G protein-coupled receptor L3 (ADGRL3, also referred to as latrophilin 3 or LPHN3) has been associated with ADHD susceptibility in independent ADHD samples. We conducted a systematic review and a comprehensive meta-analysis to summarize the associations between the most studied ADGRL3 polymorphisms (rs6551665, rs1947274, rs1947275, and rs2345039) and both childhood and adulthood ADHD. Eight association studies (seven published and one unpublished) fulfilled criteria for inclusion in our meta-analysis. We also incorporated GWAS data for ADGRL3. In order to avoid overlapping samples, we started with summary statistics from GWAS samples and then added data from gene association studies. The results of our meta-analysis suggest an effect of ADGRL3 variants on ADHD susceptibility in children (n = 8724/14,644 cases/controls and 1893 families): rs6551665 A allele (Z score = -2.701; p = 0.0069); rs1947274 A allele (Z score = -2.033; p = 0.0421); rs1947275 T allele (Z score = 2.339; p = 0.0978); and rs2345039 C allele (Z score = 3.806; p = 0.0026). Heterogeneity was found in analyses for three SNPs (rs6551665, rs1947274, and rs2345039). In adults, results were not significant (n = 6532 cases/15,874 controls): rs6551665 A allele (Z score = 2.005; p = 0.0450); rs1947274 A allele (Z score = 2.179; p = 0.0293); rs1947275 T allele (Z score = -0.822; p = 0.4109); and rs2345039 C allele (Z score = -1.544; p = 0.1226). Heterogeneity was found just for rs6551665. In addition, funnel plots did not suggest publication biases. Consistent with ADGRL3's role in early neurodevelopment, our findings suggest that the gene is predominantly associated with childhood ADHD.

Thermal effects of a novel electrosurgical device for focused preparation in breast surgery tested in a specified porcine tissue ex vivo breast model using infrared measurement.

PURPOSE: This article investigates the qualities and thermal effects of a novel electrosurgical device (PT) which has been designed by ERBE Elektromedizin GmbH, Germany, for the preparation of critical locations such as in skin-sparing or nipple-sparing techniques and compares it to a standard device (SD) in a porcine ex vivo breast model using an heat map generated by infrared thermography. METHODS: In total, 42 abdominal wall specimens of porcine tissue consisting of the skin and the underlying subcutaneous and muscle layer were alternately dissected using one of the devices and pre-settings. During the preparation with the two devices, the epicutaneous temperature was measured by an infrared camera (VarioCam, Jenoptik, Germany) and the maximum temperature as well as the slope of the temperature rise was analysed. RESULTS: The use of PT shows significantly lower values for [Formula: see text] compared to SD. This effect was independent from the chosen mode. Using the same instrument in different modes, the use of AutoCut mode showed a significant reduction of [Formula: see text] at all indicated time points (SD: p < 0.0001 and PT: p < 0.0001). In summary, the combination of AutoCut + PT showed the lowest rise in temperature, whereas the combination of DryCut + SD led to the highest rise in temperature. The temperature difference between these two settings was 13.84 °C, which means a possible temperature reduction of 67% can be achieved by the right choice of device and its tailored mode. CONCLUSIONS: The novel PT shows a significant reduction in epicutaneous temperature and a significant reduction of the slope of temperature rise most probably by a more focused application of energy compared to SD.

Exocytosis-related genes and response to methylphenidate treatment in adults with ADHD.

Experimental studies have demonstrated that methylphenidate (MPH) modulates the synaptic vesicle trafficking and synaptotagmin-1 (SytI) mRNA levels. SytI is a regulatory protein of the SNARE complex, a neurotransmitter exocytosis mediator. Despite this evidence, most SNARE complex-related genes have never been evaluated in attention-deficit/hyperactivity disorder (ADHD) pharmacogenetics. This study evaluates, for we believe the first time, polymorphisms on the SNARE complex-related genes STX1A (rs2228607), VAMP2 (26bp Ins/Del) and SYT1 (rs1880867 and rs2251214) on the response to immediate-release methylphenidate (IR-MPH) in a naturalistic sample of adults with ADHD. The sample comprised 433 subjects, of which 272 (62.8%) have completed the short-term IR-MPH treatment (at least 30 days). The main outcome measure was the categorical variable of short-term response to IR-MPH based on the Swanson, Nolan and Pelham Rating Scale version 4 (SNAP-IV), and on the clinical global impression-improvement scale. Additional analyses evaluated the percentage of SNAP-IV symptom reduction for each dimension as well as short- and long- (7 years) term treatment persistence. SYT1-rs2251214 was associated with the categorical short-term response to IR-MPH (P=0.006, PFDR=0.028), and with the percentage of inattention and oppositional defiant disorder symptoms reduction (P=0.007, PFDR=0.028 and P=0.017, PFDR=0.048, respectively). SYT1-rs2251214 was also associated with short-term treatment persistence (P=0.018, PFDR=0.048), and with months of treatment (P=0.002, PFDR=0.016) in the long-term protocol. Our findings suggest that SYT1-rs2251214 presents a broad influence in IR-MPH response variability in adults with ADHD, being involved with both symptom response and treatment persistence. If such findings are replicated, SytI could represent a key element in MPH pharmacodynamics in adults with ADHD.

A novel organ donor facility: a decade of experience with liver donors.

Transplant surgeons have historically traveled to donor hospitals, performing complex, time-sensitive procedures with unfamiliar personnel. This often involves air travel, significant delays, and frequently occurs overnight.In 2001, we established the nation's first organ recovery center. The goal was to increase efficiency,reduce costs and reduce surgeon travel. Liver donors and recipients, donor costs, surgeon hours and travel time, from April 1,2001 through December 31,2011 were analyzed. Nine hundred and fifteen liver transplants performed at our center were analyzed based on procurement location (living donors and donation after cardiac death donors were excluded). In year 1, 36% (9/25) of donor procurements occurred at the organ procurement organization (OPO) facility, rising to 93%(56/60) in the last year of analysis. Travel time was reduced from 8 to 2.7 h (p<0.0001), with a reduction of surgeon fly outs by 93% (14/15) in 2011. Liver organ donor charges generated by the donor were reduced by37% overall for donors recovered at the OPO facility versus acute care hospital. Organs recovered in this novel facility resulted in significantly reduced surgeon hours, air travel and cost. This practice has major implications for cost containment and OPO national policy and could become the standard of care.

Altruistic living donors: evaluation for nondirected kidney or liver donation.

A program was established within our regional procurement organization to permit evaluation of altruistic living donors (LD) interested in nondirected kidney or liver segment donation prior to transplant center referral. During the initial 30 months of program operations, 731 donor inquiries were received of which 131 individuals called back after review of mailed information materials. Forty-seven candidates initiated and 19 completed the evaluation process. Seven underwent donation to include six kidneys and one liver segment, five are actively pending donation, five were excluded from donation following transplant center evaluation and two took no further action after their intended liver recipients received deceased donor (DD) transplants. Psychological evaluation of these 19 candidates found them to be free of psychopathology, highly cooperative and self-directed. They did not exhibit attention-seeking or religious motivations for their actions. All seven donors and recipients continue to do well postoperatively. This evaluation program has made possible large-scale screening and education of prospective altruistic LD within the general population and also provides a unique opportunity to further our understanding of those individuals interested in living-nondirected donation.

The stability of family decisions to consent or refuse organ donation: would you do it again?

OBJECTIVE: Past organ donation research has studied attitudes toward donation, predictors of signing donor cards, and distinguishing characteristics of donors vs. nondonors. The current study is the first to examine predictors of family members' satisfaction with the decision to consent or refuse donation of a dying loved one's organs or tissue. METHOD: This study surveyed 225 family members who had been approached to donate the organs or tissue of a dying loved one. Participants were surveyed about demographic characteristics, medical/hospital factors, previous knowledge of transplantation, the request process, religion, and characteristics of the deceased and of the recipient. Discriminant analyses were conducted to characterise four specific groups: a) donors who would donate again; b) donors who would not donate again; c) nondonors who would now donate; and d) nondonors who still would not donate. RESULTS: Three significant discriminant functions emerged discriminating donors from nondonors, those who were satisfied with their decision from those who were not, and people who would now donate from those who would not. Donation was predicated by formal education, being married, volunteerism, signing donor cards, and having personal conversations about donation. Subsequent satisfaction was predicted by comfort and confidence during the decision-making process, familiarity with medical center, and understanding of brain death. A willingness to now donate was predicted by personal discussions about donation. CONCLUSIONS: People should be encouraged not only to sign donor cards, but to have discussions with family about wishes. Individuals should be encouraged to seek the help of family and friends during the decision, and be aware of the need of social support from family and friends during and after the decision.

Strategies for success among OPOs: a study of three organ procurement organizations.

Productivity among organ procurement organizations varies widely in the US, and the pressure to determine critical success factors increases as the organ pool shrinks and managed care expands. This study compared three successful organ procurement organizations, identified commonalities among them in cost of doing business, and examined direct and indirect expenses, staffing, specialized requestor programs, and professional and public education programs. The three organ procurement organizations were chosen because of their performance in terms of donors per million population, complexity, and size. The following key indicators were compared and analyzed: annual operating budget, size and composition of staff, funds and resources invested in professional education versus public education, tissue recovery operations, results of minority initiatives, and employee compensation programs.

[The avidin-biotin system. Its application in virology]. / Le système avidine-biotine. Applications en virologie.

The report briefly reviews the strategies of utilisation of the avidin-biotin system and its variants, as well as the applications of this system in different fields, especially those linked to the diagnosis and the treatment of some viral and bacterial infections. Some of the techniques using the system are presented, as well as its advantages and the perspectives to ameliorate the methodologies and to enlarge the field of its applications.

A comparison of inpatient and outpatient Medicare allowable charges for continuous ambulatory peritoneal and center hemodialysis patients: a single-center study.

Medicare allowable charges were compared between 21 continuous ambulatory peritoneal dialysis (CAPD) and 25 center hemodialysis (CHD) patients for the 12-month period from Sept 1982 through Aug 1983 to determine if savings from CAPD therapy were offset by higher hospitalization charges. All adult patients on a single therapy for the 12-month period who were not dialyzed or hospitalized at other institutions were included. The CAPD and CHD patient groups did not differ significantly by age, sex, or incidence of systemic disease. However, the CHD group had significantly more black patients. The primary renal disease, the incidence of diabetes mellitus, and other systemic diseases did not differ between the groups. The number of hospital admissions was similar between the two groups. However, the CHD patients tended to have a higher number of hospital days than the CAPD group (17.5 v 12.4). Although the total hospital charges tended to be higher for CHD ($16,145) than CAPD patients ($9,872), this difference was not significant. Outpatient dialysis charges were significantly less expensive for CAPD ($16,470) than CHD ($28,233). Emergency department charges were also significantly less for the CAPD group. Charges for patients with and without systemic disease were analyzed separately. In both subgroups, all charges were less for CAPD therapy; however, this difference was significant only for outpatient dialysis charges. Total charges for the 12-month period were significantly less for the CAPD group ($26,453) than for CHD ($45,586). This demonstrates that hospitalization charges did not offset the savings of home dialysis in these patients.