Tag: pubmed

Pharmacoeconomics. 2022 Oct 27. doi: 10.1007/s40273-022-01209-8. Online ahead of print.

ABSTRACT

Fenfluramine, tradename Fintepla^®, was appraised within the National Institute for Health and Care Excellence (NICE) single technology appraisal (STA) process as Technology Appraisal 808. Within the STA process, the company (Zogenix International) provided NICE with a written submission and a mathematical health economic model, summarising the company’s estimates of the clinical effectiveness and cost-effectiveness of fenfluramine for patients with Dravet syndrome (DS). This company submission (CS) was reviewed by an evidence review group (ERG) independent of NICE. The ERG, Kleijnen Systematic Reviews in collaboration with Maastricht University Medical Centre, produced an ERG report. This paper presents a summary of the ERG report and the development of the NICE guidance. The CS included a systematic review of the evidence for fenfluramine. From this review the company identified and presented evidence from two randomised trials (Study 1 and Study 1504), an open-label extension study (Study 1503) and ‘real world evidence’ from a prospective and retrospective study. Both randomised trials were conducted in patients up to 18 years of age with DS, whose seizures were incompletely controlled with previous anti-epileptic drugs. A Bayesian network meta-analysis was performed to compare fenfluramine with cannabidiol plus clobazam. There was no evidence of a difference between any doses of fenfluramine and cannabidiol in the mean convulsive seizure frequency (CSF) rate during treatment. However, fenfluramine increased the number of patients achieving ≥ 50% reduction in CSF frequency from baseline compared to cannabidiol. The company used an individual-patient state-transition model (R version 3.5.2) to model cost-effectiveness of fenfluramine. The CSF and convulsive seizure-free days were estimated using patient-level data from the placebo arm of the fenfluramine registration studies. Subsequently, a treatment effect of either fenfluramine or cannabidiol was applied. Utility values for the economic model were obtained by mapping Pediatric Quality of Life Inventory data from the registration studies to EuroQol-5D-3L Youth (EQ-5D-Y-3L). The company included caregiver utilities in their base-case, as the severe needs of patients with DS have a major impact on parents and caregivers. There were several key issues. First, the company included caregiver utilities in the model in a way that when patients in the economic model died, the corresponding caregiver utility was also set to zero. Second, the model was built in R statistical software, resulting in transparency issues. Third, the company assumed the same percentage reduction for convulsive seizure days as was estimated for CSF. Fourth, during the final appraisal committee meeting, influential changes were made to the model that were not in line with the ERG’s preferences (but were accepted by the appraisal committee). The company’s revised and final incremental cost effectiveness ratio (ICER) in line with committee preferences resulted in fenfluramine dominating cannabidiol. Fenfluramine was recommended as an add-on to other antiepileptic medicines for treating seizures associated with DS in people aged 2 years and older in the National Health Service (NHS).

PMID:36301414 | DOI:10.1007/s40273-022-01209-8

Obes Surg. 2022 Oct 27. doi: 10.1007/s11695-022-06328-x. Online ahead of print.

ABSTRACT

PURPOSE : Intestinal remodeling and adaptation of the alimentary limb after Roux-en-Y gastric bypass (RYGB) play an important role in the pathophysiological events that lead to type 2 diabetes mellitus (T2DM) improvement. Intestinal absorptive loop hypertrophy and growth following surgery have been related to GLP-2 secretion by ileal L-cells. The secretion of peptide tyrosine-tyrosine (PYY) enterohormone after a meal has been proposed as a trigger for ileal secretion of GLP-1. Our aim is to determine the role of PYY as a GLP-2 secretion modulator as an adaptation result in the alimentary limb after RYGB.

METHOD: We used a non-obese euglycemic rodent model. Circulating glucose, insulin, PYY, and GLP-2 were measured in the experimental and control groups. We used four groups: fasting control, Sham-operated, RYGB-operated (RYGB), and RYGB-operated and treated with BIIE0246 (RYGB + BII). BIIE0246 is a NPY2 receptor antagonist in L-cells. Intestinal glucose transporters and GLP-1 and PYY gut expression and hypertrophy were analyzed after 12 weeks of surgery.

RESULTS: RYGB increased PYY3-36 plasma levels in rats with or without BII treatment. A high-insulin response was observed in the RYGB group but not in the control or RYGB + BII groups. BIIE0246 treatment limited plasma GLP-2 levels. In the alimentary intestinal limb, hypertrophy and SGLT1 and GLUT1 expression appeared to be reduced after RYGB compared to controls.

CONCLUSION: The postprandial ileal PYY secretion is enhanced after RYGB. This increase mediates GLP-2 release through its binding to the Y2 receptor on L-cells. This mechanism plays a role in alimentary limb hypertrophy after surgery.

PMID:36301409 | DOI:10.1007/s11695-022-06328-x

Prev Sci. 2022 Oct 27. doi: 10.1007/s11121-022-01449-2. Online ahead of print.

ABSTRACT

Suicide is the fourth leading cause of death among adolescents, globally. Though post-primary, school-based suicide prevention (PSSP) has the potential to be a key strategy for preventing adolescent suicidal thoughts and behaviours (STBs), there are persisting challenges to translating PSSP research to practice. Intervention and contextual factors relevant to PSSP are likely key to both PSSP effectiveness and implementation. As such, this systematic review aimed to summarise the effectiveness of PSSP for adolescent STBs and highlight important intervention and contextual factors with respect to PSSP. PsycINFO, Medline, Education Source, ERIC, Web of Science, and the Cochrane Central Register of Controlled Trials were searched to identify randomised and non-randomised studies evaluating the effectiveness of interventions located in post-primary, school-based settings targeting adolescent STBs. PSSP effectiveness and intervention and contextual factors were synthesised narratively. Twenty-eight studies were retained, containing nearly 47,000 participants. Twelve out of twenty-nine trials comparing intervention and independent control comparators reported statistically significant reductions in STBs postintervention, and 5/7 trials comparing preintervention and postintervention scores demonstrated significant reductions in STBs over time. Reporting and analysis of intervention and contextual factors were lacking across studies, but PSSP effectiveness and intervention acceptability varied across type of school. Although school personnel commonly delivered PSSP interventions, their input and perspectives on PSSP interventions were lacking. Notably, adolescents had little involvement in designing, inputting on, delivering and sharing their perspectives on PSSP interventions. Twenty out of twenty-eight studies were rated as moderate/high risk of bias, with non-randomised trials demonstrating greater risks of bias and trial effectiveness, in comparison to cluster randomised trials. Future research should prioritise complete reporting and analysis of intervention and contextual factors with respect to PSSP, involving key stakeholders (including adolescents and school personnel) in PSSP, and investigating key stakeholders’ perspectives on PSSP. Given the inverse associations between both study quality and study design with PSSP effectiveness, particular consideration to study quality and design in PSSP research is needed. Future practice should consider PSSP interventions with universal components and PSSP which supports and involves key stakeholders in engaging with PSSP.

PMID:36301381 | DOI:10.1007/s11121-022-01449-2

Wien Klin Wochenschr. 2022 Oct 27. doi: 10.1007/s00508-022-02098-9. Online ahead of print.

ABSTRACT

BACKGROUND: Remdesivir is the only antiviral agent approved for the treatment of hospitalized coronavirus disease 2019 (COVID-19) patients requiring supplemental oxygen. Studies show conflicting results regarding its effect on mortality.

METHODS: In this single center observational study, we included adult hospitalized COVID-19 patients. Patients who were treated with remdesivir were compared to controls. Remdesivir was administered for 5 days. To adjust for any imbalances in our cohort, a propensity score matched analysis was performed. The aim of our study was to analyze the effect of remdesivir on in-hospital mortality and length of stay (LOS).

RESULTS: After propensity score matching, 350 patients (175 remdesivir, 175 controls) were included in our analysis. Overall, in-hospital mortality was not significantly different between groups remdesivir 5.7% [10/175] vs. control 8.6% [15/175], hazard ratio 0.50, 95% confidence interval (CI) 0.22-1.12, p = 0.091. Subgroup analysis showed a significant reduction of in-hospital mortality in patients who were treated with remdesivir ≤ 7 days of symptom onset remdesivir 4.2% [5/121] vs. control 10.4% [13/125], hazard ratio 0.26, 95% CI 0.09 to 0.75, p = 0.012 and in female patients remdesivir 2.9% [2/69] vs. control 12.2% [9/74], hazard ratio 0.18 95%CI 0.04 to 0.85, p = 0.03. Patients in the remdesivir group had a significantly longer LOS (11 days vs. 9 days, p = 0.046).

CONCLUSION: Remdesivir did not reduce in-hospital mortality in our whole propensity score matched cohort, but subgroup analysis showed a significant mortality reduction in female patients and in patients treated within ≤ 7 days of symptom onset. Remdesivir may reduce mortality in patients who are treated in the early stages of illness.

PMID:36301355 | DOI:10.1007/s00508-022-02098-9

Environ Monit Assess. 2022 Oct 27;195(1):39. doi: 10.1007/s10661-022-10642-3.

ABSTRACT

Groundwater contamination becomes an alarming threat to the provision of ecosystem services and natural resources. A very high level of groundwater contamination has been observed in the northeastern states particularly in North Tripura district. Therefore, the present study considered the region as a case study to evaluate the hydrogeochemical facies, heavy metal pollution and irrigation indices, and their impact on human health. For the investigation, we have collected a total of 35 groundwater samples from North Tripura district. Hydrogeochemical facies through Piper plot reflect Ca²⁺-Mg²⁺-HCO₃^– and Na⁺-HCO₃^– as dominant water types. Gibbs plot identifies the dominance of rock-water interaction process in groundwater hydrochemistry. Geochemical plots indicate the dominance of silicate weathering, ion exchange and carbonate dissolution processes in groundwater mineralisation. The order of trace metal contaminations follows Fe > As > Zn > Mn > Cu > Pb. Results of heavy metal indices suggest above 80% samples are at high risk due to high Fe contamination. The risk of the heavy metal indices is associated with rising elevation in southern part of North Tripura. Findings of health risk assessment study imply that children face much carcinogenic and non-carcinogenic risks than adults because of unsafe levels of Fe and As. Multivariate statistical tools are applied to unravel interrelationships among all ions and trace metals as well as probable hydrogeochemical processes in groundwater. Results of Wilcox and USSL plots suggest 77% samples meet irrigation suitability criteria. Besides, the analysis suggests a better insight to identify hydrogeochemical processes controlling groundwater chemistry and the suitability of groundwater for irrigation and drinking purposes. The study also suggests treatment and sustainable management of groundwater resources is compulsory to reduce trace metal contaminations before public use.

PMID:36301348 | DOI:10.1007/s10661-022-10642-3

Arch Gynecol Obstet. 2022 Oct 27. doi: 10.1007/s00404-022-06778-9. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study was to evaluate the postoperative course after different methods of hysterectomy for benign diseases with special emphasis on time to recovery and patient-centred aspects such as postoperative quality of life and satisfaction.

METHODS: A collective of 242 women who had undergone vaginal hysterectomy (VH), laparoscopic supracervical hysterectomy (LASH) or total laparoscopic hysterectomy (TLH) for various benign conditions was studied in this retrospective investigation. Patients completed a standardised questionnaire addressing quality of life, recovery and sick leave as well as general questions on their postoperative course after hysterectomy.

RESULTS: A total of 242 cases were analysed (82 VH, 92 LASH and 68 TLH). The data demonstrate significant differences in regard to age between groups. The present study shows shorter hospitalisation with laparoscopy, with LASH patients returning to work at least one week earlier on average. There were no relevant differences in the overall postoperative course during the index hospital stay. In the long run, laparoscopic patients were not more satisfied with their choice than VH patients.

CONCLUSION: No significant long-term differences could be observed in terms of quality of life and overall postoperative satisfaction between VH and LH groups. In regard to socioeconomic aspects, laparoscopic approaches were associated with shorter hospitalisation and LASH patients returning to work at least one week earlier on average. Contrary to these data on objective recovery; however, a laparoscopic approach did not lead to patient-perceived, i.e. subjective improvement of time to full recovery.

PMID:36301347 | DOI:10.1007/s00404-022-06778-9

J Womens Health (Larchmt). 2022 Oct 25. doi: 10.1089/jwh.2022.0065. Online ahead of print.

ABSTRACT

Background: The U.S. Preventive Services Task Force recommends biennial screening mammography for average-risk women aged 50-74 years. We aim to generate county-level prevalence estimates for mammography use to examine disparities among counties. Materials and Methods: We used data from the 2018 Behavioral Risk Factor Surveillance System (BRFSS) (n = 111,902 women) and linked them to county-level data from the American Community Survey. We defined two outcomes: mammography within the past 2 years (current); and mammography 5 or more years ago or never (rarely or never). We poststratified the data with U.S. Census estimated county population counts, ran Monte Carlo simulations, and generated county-level estimates. We aggregated estimates to state and national levels. We validated internal consistency between our model-based and BRFSS state estimates using Spearman and Pearson correlation coefficients. Results: Nationally, more than three in four women [78.7% (95% confidence interval {CI}: 78.2%-79.2%)] were current with mammography, although with large variations among counties. Also, nationally, about one in nine women [11% (95% CI: 10.8%-11.3%)] rarely or never had a mammogram. County estimates for being current ranged from 60.4% in New Mexico to 86.9% in Hawaii. Rarely or never having a mammogram ranged from 6% in Connecticut to 23.0% in Alaska, and on average, almost one in eight women in all the counties. Internal consistency correlation coefficient tests were ≥0.94. Conclusions: Our analyses identified marked county variations in mammography use across the country among women aged 50-74 years. We generated estimates for all counties, which may be helpful for targeted outreach to increase mammography uptake.

PMID:36301186 | DOI:10.1089/jwh.2022.0065

Soc Stud Sci. 2022 Oct 27:3063127221127666. doi: 10.1177/03063127221127666. Online ahead of print.

ABSTRACT

Principal component analysis (PCA) is a common statistical procedure. In forensics, it is used in facial recognition technologies and composite sketching systems. PCA is especially helpful in contexts with high facial diversity, which is often translated as racial diversity. In these settings, researchers use PCA to define a ‘normal face’ and organize the rest of the available facial diversity based on their resemblance to or difference from that norm. In this way, the use of PCA introduces an ‘ontology of the normal’ in which expectations about how a normal face should look are corroborated by statistical calculations of normality. I argue that the use of PCA can lead to a statistical reification of racial stereotypes that informs recognition practices. I discuss current and historical cases in which PCA is used: one of face perception theorization (‘face space theory’) and two of technology development (the ‘eigenfaces’ facial recognition algorithm and the ‘EvoFIT’ composite sketching system). In each, PCA aligns facial normality with racial expectations, and instrumentalizes race in specific ways: as a type, physical attribute, or genealogy. This analysis of PCA does two things. First, it opens the black box of facial recognition to uncover how stereotypes and intuitions about normality become part of theories and technologies of facial recognition. Second, it explains why racial categorizations remain central in contemporary identification technologies and other forensic practices.

PMID:36301181 | DOI:10.1177/03063127221127666

Stud Health Technol Inform. 2022 Oct 26;300:1-11. doi: 10.3233/SHTI220936.

ABSTRACT

Biomedical and Health Informatics (BMHI) have been essential catalysts for achievements in medical research and healthcare applications over the past 50 years. These include increasingly sophisticated information systems and data bases for documentation and processing, standardization of biomedical data, nomenclatures, and vocabularies to assist with large scale literature indexing and text analysis for information retrieval, and methods for computationally modeling and analyzing research and clinical data. Statistical and AI techniques for decision support, instrumentation integration, and workflow aids with improved data/information management tools are critical for scientific discoveries in the – omics revolutions with their related drug and vaccine breakthroughs and their translation to clinical and preventive healthcare. Early work on biomedical image and pattern recognition, knowledge-based expert systems, innovative database, software and simulation techniques, natural language processing and computational ontologies have all been invaluable for basic research and education. However, these methods are still in their infancy and many fundamental open scientific problems abound. Scientifically this is due to persistent limitations in understanding biological processes within complex living environments and ecologies. In clinical practice the modeling of fluid practitioner roles and methods as they adjust to novel cybernetic technologies present great opportunities but also the potential of unintended e-iatrogenic harms which must be constrained in order to adhere to ethical Hippocratic norms of responsible behavior. Balancing the art, science, and technologies of BMHI has been a hallmark of debates about the field’s historical evolution. The present article reviews selected milestones, achievements, and challenges in BMHI education mainly, from a historical perspective, including some commentaries from leaders and pioneers in the field, a selection of which have been published online recently by the International Medical Informatics Association (IMIA) as the first volume of an IMIA History WG eBook. The focus of this chapter is primarily on the development of BMHI in terms of those of its educational activities which have been most significant during the first half century of IMIA, and it concentrates mainly on the leadership and contributions of John Mantas who is being honored on his retirement by the Symposia in Athens for which this chapter has been written.

PMID:36300397 | DOI:10.3233/SHTI220936

Cell Transplant. 2022 Jan-Dec;31:9636897221129174. doi: 10.1177/09636897221129174.

ABSTRACT

In the Taihang Mountain areas, known as the “esophageal cancer zone” in China, the incidence of esophageal cancer (ESCA) ranks the first in the country and shows a familial and regional clustering trend. Taihang Mountain areas are located in a mountainous area, with inconvenient transportation, limited living conditions, unbalanced diet, and poor nutrition. Ninety percent of the pathological types of ESCA in Taihang Mountain areas are squamous cell carcinoma, among which the risk factors have not been well understood. These areas are usually remote villages and mountains with low population mobility, large family members, similar environmental factors, and a clear and stable genetic background. Therefore, according to the current situation, second-generation sequencing and multigroup analysis technology are used to analyze the familial ESCA patients; disease-related genetic variation are located; and then disease-related susceptibility genes associated with ESCA are screened and analyzed. Health education, tobacco control, endoscopic screening, and other health management projects for suspected and high-risk patients in areas with a high incidence of ESCA can be carried out for screening and early diagnosis, and the incidence of ESCA in Taihang Mountain areas can be reduced. A comprehensive continuous care pattern based on traditional medical nursing to track, monitor, evaluate, and intervene with patients diagnosed with ESCA to facilitate them with medications guidance, dietary guidance, and timely health problem-solving is established. Furthermore, statistical analysis of epidemiology, gene sequencing, and family genetics information can be performed on patients with ESCA in the Taihang Mountains areas to clarify the relationship between genetic phenotype and genotype during the occurrence of ESCA.

PMID:36300368 | DOI:10.1177/09636897221129174