PLOS ONE: [sortOrder=DATE_NEWEST_FIRST, sort=Date, newest first, q=subject:"Biotechnology"]PLOShttps://journals.plos.org/plosone/webmaster@plos.orgaccelerating the publication of peer-reviewed sciencehttps://journals.plos.org/plosone/search/feed/atom?sortOrder=DATE_NEWEST_FIRST&unformattedQuery=subject:%22Biotechnology%22&sort=Date,+newest+firstAll PLOS articles are Open Access.https://journals.plos.org/plosone/resource/img/favicon.icohttps://journals.plos.org/plosone/resource/img/favicon.ico2024-03-29T02:04:43ZEtonogestrel-releasing subdermal contraceptive implant: Budget impact analysis based on the Brazilian private healthcare systemAgnaldo Lopes da Silva FilhoRicardo Luis Pereira BuenoYohanna RamiresLara Marina Cruz Lino10.1371/journal.pone.03012072024-03-28T14:00:00Z2024-03-28T14:00:00Z<p>by Agnaldo Lopes da Silva Filho, Ricardo Luis Pereira Bueno, Yohanna Ramires, Lara Marina Cruz Lino</p>
High rates of unplanned pregnancies persist despite pharmacological developments and advancements in contraceptive methods. Here, we demonstrate that the etonogestrel-releasing subdermal contraceptive implant (IMP-ETN) may be an appropriate and cost-effective alternative to levonorgestrel-releasing intrauterine systems (LNG-IUSs) for women in Brazil. For our pharmacoeconomic analysis, we reviewed the literature on IMP-ETN regarding its acceptance, eligibility criteria, choice, relations with age, adverse events and, finally, the unmet need in the fee-for-service private healthcare sector. We considered qualitative observations in combination with quantitative analysis and performed a deterministic sensitivity analysis to investigate whether this technology can be self-sustainable over a period of five years. The target population for this analysis comprised 158,696 women. Compared with the continued use of LNG-IUSs, adopting the IMP-ETN can result in a cost avoidance of $ 7.640.804,02 in the first year and $ 82,455,254.43 in five years. Disseminating information among physicians will promote this change and strengthen the potential cost avoided by private health system payers. These savings can be used to improve other healthcare programs and strategies. Moreover, the principles of care can be promoted by improving and adapting healthcare systems and expanding treatment and follow-up strategies. This would also provide support to women’s reproductive rights and improve their quality of life. Our results suggest that the IMP-ETN has a favorable cost-effectiveness profile. Given all its advantages and negative incremental cost impact over a period of five years, the IMP-ETN may be a more favorable alternative to LNG-IUSs. Therefore, it should be offered to beneficiaries with a private healthcare plan. This analysis overcomes previous barriers to the use of cost-benefit models, and our results may help balance decision-making by policymakers, technical consultants, and researchers.The VertiGO! Trial protocol: A prospective, single-center, patient-blinded study to evaluate efficacy and safety of prolonged daily stimulation with a multichannel vestibulocochlear implant prototype in bilateral vestibulopathy patientsBernd L. VermorkenBenjamin VolpeStan C. J. van BoxelJoost J. A. StultiensMarc van HoofRik MarcellisElke LoosAlexander van SoestChris McCrumKenneth MeijerNils GuinandAngélica Pérez FornosVincent van RompaeyElke DevochtRaymond van de Berg10.1371/journal.pone.03010322024-03-28T14:00:00Z2024-03-28T14:00:00Z<p>by Bernd L. Vermorken, Benjamin Volpe, Stan C. J. van Boxel, Joost J. A. Stultiens, Marc van Hoof, Rik Marcellis, Elke Loos, Alexander van Soest, Chris McCrum, Kenneth Meijer, Nils Guinand, Angélica Pérez Fornos, Vincent van Rompaey, Elke Devocht, Raymond van de Berg</p>
Background <p>A combined vestibular (VI) and cochlear implant (CI) device, also known as the vestibulocochlear implant (VCI), was previously developed to restore both vestibular and auditory function. A new refined prototype is currently being investigated. This prototype allows for concurrent multichannel vestibular and cochlear stimulation. Although recent studies showed that VCI stimulation enables compensatory eye, body and neck movements, the constraints in these acute study designs prevent them from creating more general statements over time. Moreover, the clinical relevance of potential VI and CI interactions is not yet studied. The VertiGO! Trial aims to investigate the safety and efficacy of prolonged daily motion modulated stimulation with a multichannel VCI prototype.</p> Methods <p>A single-center clinical trial will be carried out to evaluate prolonged VCI stimulation, assess general safety and explore interactions between the CI and VI. A single-blind randomized controlled crossover design will be implemented to evaluate the efficacy of three types of stimulation. Furthermore, this study will provide a proof-of-concept for a VI rehabilitation program. A total of minimum eight, with a maximum of 13, participants suffering from bilateral vestibulopathy and severe sensorineural hearing loss in the ear to implant will be included and followed over a five-year period. Efficacy will be evaluated by collecting functional (i.e. image stabilization) and more fundamental (i.e. vestibulo-ocular reflexes, self-motion perception) outcomes. Hearing performance with a VCI and patient-reported outcomes will be included as well.</p> Discussion <p>The proposed schedule of fitting, stimulation and outcome testing allows for a comprehensive evaluation of the feasibility and long-term safety of a multichannel VCI prototype. This design will give insights into vestibular and hearing performance during VCI stimulation. Results will also provide insights into the expected daily benefit of prolonged VCI stimulation, paving the way for cost-effectiveness analyses and a more comprehensive clinical implementation of vestibulocochlear stimulation in the future.</p> Trial registration <p>ClinicalTrials.gov: NCT04918745. Registered 28 April 2021.</p>Effects of the Momentum project on postpartum family planning norms and behaviors among married and unmarried adolescent and young first-time mothers in Kinshasa: A quasi-experimental studyAnastasia J. GageFrancine E. WoodRianne GayPierre Akilimali10.1371/journal.pone.03003422024-03-28T14:00:00Z2024-03-28T14:00:00Z<p>by Anastasia J. Gage, Francine E. Wood, Rianne Gay, Pierre Akilimali</p>
This study evaluated the effect of Momentum–an integrated family planning, maternal and newborn health, and nutrition intervention–on postpartum family planning norms and behaviors among ever married and never-married first-time mothers age 15–24 in Kinshasa, Democratic Republic of the Congo. Using data collected in 2018 and 2020, we conducted an intent-to-treat analysis among 1,927 first-time mothers who were about six-months pregnant at enrollment. Difference-in-differences models were run for panel data and treatment effects models with inverse-probability weighting for endline-only outcomes. Average treatment effects (ATE) were estimated. Momentum had positive effects on partner discussion of family planning in the early postpartum period (ever married 15–19: ATE = 0.179, 95% CI = 0.098, 0.261; never married 15–19: ATE = 0.131, 95% CI = 0.029, 0.232; ever married 20–24: ATE = 0.233, 95% CI = 0.164, 0.302; never married 20–24: ATE = 0.241, 95% CI = 0.121, 0.362) and discussion with a health worker, and on obtaining a contraceptive method in the early postpartum period, except among never married adolescents. Among adolescents, intervention effects on modern contraceptive use within 12 months of childbirth/pregnancy loss were larger for the never married (ATE = 0.251, 95% CI = 0.122, 0.380) than the ever married (ATE = 0.114, 95% CI = 0.020, 0.208). Full intervention exposure had consistently larger effects on contraceptive behaviors than partial exposure, except among ever married adolescents. Momentum had no effect on normative expectations about postpartum family planning use among adolescents, and on descriptive norms and personal agency among those who were never married. Results for normative outcomes and personal agency underscored the intersectionality between young maternal age and marital status. Future programs should improve personal agency and foster normative change in support of postpartum family planning uptake and tailor interventions to different age and marital status subsets of first-time mothers.Confirming the attainment of maximal oxygen uptake within special and clinical groups: A systematic review and meta-analysis of cardiopulmonary exercise test and verification phase protocolsVictor A. B. CostaAdrian W. MidgleyJulia K. BaumgartSean CarrollTodd A. AstorinoGustavo Z. SchaunGuilherme F. FonsecaFelipe A. Cunha10.1371/journal.pone.02995632024-03-28T14:00:00Z2024-03-28T14:00:00Z<p>by Victor A. B. Costa, Adrian W. Midgley, Julia K. Baumgart, Sean Carroll, Todd A. Astorino, Gustavo Z. Schaun, Guilherme F. Fonseca, Felipe A. Cunha</p>
Background and aim <p>A plateau in oxygen uptake (V˙O2) during an incremental cardiopulmonary exercise test (CPET) to volitional exhaustion appears less likely to occur in special and clinical populations. Secondary maximal oxygen uptake (V˙O2max) criteria have been shown to commonly underestimate the actual V˙O2max. The verification phase protocol might determine the occurrence of ‘true’ V˙O2max in these populations. The primary aim of the current study was to systematically review and provide a meta-analysis on the suitability of the verification phase for confirming ‘true’ V˙O2max in special and clinical groups. Secondary aims were to explore the applicability of the verification phase according to specific participant characteristics and investigate which test protocols and procedures minimise the differences between the highest V˙O2 values attained in the CPET and verification phase.</p> Methods <p>Electronic databases (PubMed, Web of Science, SPORTDiscus, Scopus, and EMBASE) were searched using specific search strategies and relevant data were extracted from primary studies. Studies meeting inclusion criteria were systematically reviewed. Meta-analysis techniques were applied to quantify weighted mean differences (standard deviations) in peak V˙O2 from a CPET and a verification phase within study groups using random-effects models. Subgroup analyses investigated the differences in V˙O2max according to individual characteristics and test protocols. The methodological quality of the included primary studies was assessed using a modified Downs and Black checklist to obtain a level of evidence. Participant-level V˙O2 data were analysed according to the threshold criteria reported by the studies or the inherent measurement error of the metabolic analysers and displayed as Bland-Altman plots.</p> Results <p>Forty-three studies were included in the systematic review, whilst 30 presented quantitative information for meta-analysis. Within the 30 studies, the highest mean V˙O2 values attained in the CPET and verification phase protocols were similar (mean difference = -0.00 [95% confidence intervals, CI = -0.03 to 0.03] L·min<sup>-1</sup>, <i>p</i> = 0.87; level of evidence, LoE: strong). The specific clinical groups with sufficient primary studies to be meta-analysed showed a similar V˙O2max between the CPET and verification phase (<i>p</i> > 0.05, LoE: limited to strong). Across all 30 studies, V˙O2max was not affected by differences in test protocols (<i>p</i> > 0.05; LoE: moderate to strong). Only 23 (53.5%) of the 43 reviewed studies reported how many participants achieved a lower, equal, or higher V˙O2 value in the verification phase versus the CPET or reported or supplied participant-level V˙O2 data for this information to be obtained. The percentage of participants that achieved a lower, equal, or higher V˙O2 value in the verification phase was highly variable across studies (e.g. the percentage that achieved a higher V˙O2 in the verification phase ranged from 0% to 88.9%).</p> Conclusion <p>Group-level verification phase data appear useful for confirming a specific CPET protocol likely elicited V˙O2max, or a reproducible V˙O2peak, for a given special or clinical group. Participant-level data might be useful for confirming whether specific participants have likely elicited V˙O2max, or a reproducible V˙O2peak, however, more research reporting participant-level data is required before evidence-based guidelines can be given.</p> Trial registration <p>PROSPERO (CRD42021247658) https://www.crd.york.ac.uk/prospero.</p>From opt-out to opt-in consent for secondary use of medical data and residual biomaterial: An evaluation using the RE-AIM frameworkJennifer E. LutomskiPeggy Manders10.1371/journal.pone.02994302024-03-28T14:00:00Z2024-03-28T14:00:00Z<p>by Jennifer E. Lutomski, Peggy Manders</p>
Background <p>Patient records, imaging, and residual biomaterial from clinical procedures are crucial resources for medical research. In the Netherlands, consent for secondary research has historically relied on opt-out consent. For ethical-legal experts who purport passive consent undermines patient autonomy, opt-in consent (wherein affirmative action is required) is seen as the preferred standard. To date, there is little empirical research exploring patient feasibility, organizational consequences, and the potential risks for research based on secondary data. Thus, we applied the RE-AIM framework to evaluate the impact of migrating from an opt-out to an opt-in consent process.</p> Methods <p>This evaluation was carried out in Radboud University Medical Center, a large tertiary hospital located in the southeast of the Netherlands. All non-acute, mentally competent patients ≥16 years of age registered between January 13, 2020 and June 30, 2023 were targeted (N = 101,437). In line with the RE-AIM framework, individual and organizational consequences were evaluated across five domains: reach, efficacy, adoption, implementation, and maintenance.</p> Results <p>101,437 eligible patients were approached of whom 66,214 (65.3%) consented, 8,059 (7.9%) refused consent and 27,164 (26.8%) had no response. Of the 74,273 patients with a response, 89.1% consented to secondary use. The migration to an opt-in consent system was modestly successful; yet notably, differential response patterns by key sociodemographic characteristics were observed. Adaptions to the process flow improved its effectiveness and resulted in a reasonable response over time. Implementation was most affected by budgetary restraints, thus impeding the iterative approach which could have further improved domain outcomes.</p> Conclusion <p>This evaluation provides an overview of logistical and pragmatic issues encountered when migrating from opt-out to opt-in consent. Response bias remains a major concern. Though not always directly transferable, these lessons can be broadly used to inform other health care organizations of the potential advantages and pitfalls of an opt-in consent system.</p>Risk factors for catheter-associated bloodstream infection in hemodialysis patients: A meta-analysisHuajie GuoLing ZhangHua HeLili Wang10.1371/journal.pone.02997152024-03-27T14:00:00Z2024-03-27T14:00:00Z<p>by Huajie Guo, Ling Zhang, Hua He, Lili Wang</p>
Objective <p>This meta-analysis aimed to elucidate the risk factors contributing to catheter-associated bloodstream infection in hemodialysis patients.</p> Methods <p>Comprehensive literature searches were conducted in both English and Chinese databases, which encompassed PubMed, Cochrane Library, Embase, CNKI, Wanfang Data, VIP Database and China Biomedical Literature Database. The search timeframe extended from each database’s inception to March 8, 2023. Two independent researchers executed literature screening, data extraction, and quality assessment using the Newcastle-Ottawa Scale. Statistical analysis of the data was performed using RevMan 5.3 software, facilitating the identification of significant risk factors associated with catheter-related bloodstream infections in hemodialysis patients. This meta-analysis is registered with PROSPERO under the registration number CRD42023406223.</p> Results <p>Forty-nine studies were incorporated into this meta-analysis, from which 22 risk factors were examined. Through the analysis, 17 risk factors exhibited statistical significance (<i>P</i> < 0.05): age (OR = 1.52, 95% CI [0.49, 4.68]), diabetes (OR = 2.52, 95% CI [1.95, 3.25]), kidney disease (OR = 3.45, 95% CI [1.71, 6.96]), history of catheter-associated infection (OR = 2.79, 95% CI [1.96, 3.98]), hypertension (OR = 1.43, 95% CI [1.08, 1.91]), dialysis duration (OR = 3.06, 95% CI [1.70, 5.50]), catheter placement site (OR = 1.91, 95%CI [1.35, 2.70]), catheter duration (OR = 2.06, 95% CI [1.17, 3.60]), number of catheterizations (OR = 4.22, 95% CI [3.32, 5.37]), catheter types (OR = 3.83, 95% CI [2.13, 6.87]), CD4<sup>+</sup> cells (OR = 0.33, 95% CI [0.18, 0.63]), albumin (ALB, OR = 2.12, 95% CI [1.15, 3.91]), C-reactive protein (CRP, OR = 1.73, 95% CI [1.47, 2.03]), hemoglobin (Hb, OR = 1.48, 95% CI [0.54, 4.07]), procalcitonin (PCT, OR = 1.05, 95% CI [1.03, 1.06]), inadequate hand hygiene (OR = 5.32, 95% CI [1.07, 26.37]), and APACHE II scores (OR = 2.41, 95% CI [1.33, 4.37]).</p> Conclusion <p>This meta-analysis suggests that age, diabetes, kidney disease, history of catheter-associated infection, hypertension, dialysis duration, catheter placement site, catheter duration, number of catheterizations, catheter type, CD4<sup>+</sup> cells, albumin, C-reactive protein, hemoglobin, procalcitonin, inadequate hand hygiene, and APACHE II scores significantly influence the incidence of catheter-associated bloodstream infection in hemodialysis patients.</p>Exploring the drivers of agricultural wages growth in China: A comprehensive framework utilizing input-output and structural decomposition methodsPeijiang ZhengYang LiYingying Qi10.1371/journal.pone.02990672024-03-27T14:00:00Z2024-03-27T14:00:00Z<p>by Peijiang Zheng, Yang Li, Yingying Qi</p>
This study explores the factors driving agricultural wages growth in China from 1981 to 2020. We propose a comprehensive framework that combines input-output analysis and structural decomposition analysis to investigate the drivers of agricultural wages growth from four perspectives: supply, demand, industrial linkages, and agricultural support policies. The findings indicate that changes in consumer demand, investment demand, and labor mobility play significant roles in driving the growth of agricultural wages in China. Additionally, agricultural support policies have contributed to an increase in agricultural wages to some extent. However, changes in industrial linkages negatively affect agricultural wages growth. A notable strength of this study lies in the methodology employed, which ensures a comprehensive and systematic analysis encompassing diverse factors rather than a restricted perspective.The motivations and experiences of specialists who provide outreach services in rural operating rooms: A survey study from British ColumbiaAnshu ParajuleeKathrin StollNancy HumberSean EbertKim WilliamsJude Kornelsen10.1371/journal.pone.02987572024-03-27T14:00:00Z2024-03-27T14:00:00Z<p>by Anshu Parajulee, Kathrin Stoll, Nancy Humber, Sean Ebert, Kim Williams, Jude Kornelsen</p>
Introduction <p>Outreach care has long been used in Canada to address the lack of access to specialist care in rural settings, but research on the experiences of specialists providing these services is lacking. This descriptive survey study aimed to understand 1) specialists’ motivation for engaging in outreach work, (2) their perceptions of the quality of care at their rural outreach hospital, and (3) the supports they receive for their outreach work, in order to create a supportive framework to encourage specialist outreach contributions.</p> Methods <p>In July 2022, specialist physicians who provide outreach operating room services at rural hospitals participating in the Rural Surgical and Obstetrical Networks initiative in the province of British Columbia were invited to complete an anonymous survey.</p> Results <p>21 of 45 invited outreach specialists completed the survey (47% response rate). Three-quarters of respondents had a surgical specialty. The opportunity to deliver care to underserved patients was the most common motivator for outreach work. Rural hospitals received high ratings from respondents on overall safety and various aspects of communication and teamwork. Postoperative care was a concern for a minority (one-fifth) of respondents, and about half had experienced unnecessary delays between procedures some or most of the time. Generally, respondents felt integrated into rural teams and reported receiving adequate nursing and anesthetic support. The two most common desired additional supports were better/more equipment and space and additional staffing. All 19 respondents not planning to retire soon intended to provide outreach services for at least three more years.</p> Conclusion <p>Specialists providing outreach OR services in small volume rural hospitals in BC usually have altruistic motives for outreach work. For the most part, these specialists have positive experiences in rural hospitals, but they can be better supported through investment in infrastructure and health human resources. Specialists intend to provide outreach services long-term, indicating a stable outreach workforce. More research on the facilitators and barriers of specialist outreach work is needed.</p>Socio-economic disparities and predictors of fertility among adolescents aged 15 to 19 in Zambia: Evidence from the Zambia Demographic and Health Survey (2018)Samson ShumbaVanessa MoongaThomas Osman MiyobaStephen JereJessy Mutale NkondePeter Mumba10.1371/journal.pgph.00027392024-03-27T14:00:00Z2024-03-27T14:00:00Z<p>by Samson Shumba, Vanessa Moonga, Thomas Osman Miyoba, Stephen Jere, Jessy Mutale Nkonde, Peter Mumba</p>
Globally, 12 million girls aged 15–19 give birth each year, and Africa hosts 19% of youth aged 15–24. In Zambia, 29% of adolescents experience childbirth, with variations by age. Projections suggest a continued rise in these trends by 2030. Zambia came up with Adolescent Health Strategic Plan 2011–2015 among the specific policies being advocated for was Adolescent-Friendly Health Services (ADFHS) in order to mitigate among others adolescent fertility. The study aims to investigate socio-economic disparities and predictors of fertility in Zambian adolescents aged 15 to 19. The study used a cross-sectional study design utilized the 2018 Zambia Demographic Health Survey (ZDHS). The variable of interest in this study is “total number of children ever born” among adolescents aged 15 to 19 years. The explanatory variables that were used in the study were demographic, socio-economic, behavioral and community level factors. The Rao–Scott Chi-square test was used to test for association between categorical variables. Determinants of adolescent fertility were identified through a multilevel ordinal logistic regression conducted at a significance level of 5%. Analysis in the study was carried out using Stata version 14.2. A total of 3,000 adolescents were involved in the study, revealing that 75.88% had not given birth, 21.14% had one child, and 2.98% had at least two children. The findings revealed that education played a protective role, with adjusted odds ratios (AOR) of 0.47 (95% CI, 0.23–0.97), 0.21 (95% CI, 0.10–0.47), and 0.03 (95% CI, 0.00–0.54) for primary, secondary, and tertiary education, respectively. On the other hand, certain factors were associated with an elevated risk of fertility. These included the age of adolescents, educational attainment, marital status, wealth index, contraceptive use, exposure to family planning (FP) messages, being educated about FP at health facilities, and age at first sexual encounter. Among contextual factors, only community age at first birth was identified as a predictor of fertility, AOR, 1.59 (95% CI, 1.01–2.52). The study highlights sociodemographic disparities in adolescent fertility, emphasizing the need for targeted sexual reproductive health policies. Education protects against having more than one child, while marital status significantly influences fertility, particularly for married adolescents. The research provides valuable insights into the complex factors shaping adolescent fertility in Zambia, offering guidance for interventions and policies to support this vulnerable demographic.Cost-effectiveness of a pediatric operating room installation in Sub-Saharan AfricaAva YapSalamatu I. HalidNancy UkwuRuth LaverdePaul ParkGreg KlazuraEmma BryceMaija CheungElliot MarseilleDoruk OzgedizEmmanuel A. Ameh10.1371/journal.pgph.00017482024-03-27T14:00:00Z2024-03-27T14:00:00Z<p>by Ava Yap, Salamatu I. Halid, Nancy Ukwu, Ruth Laverde, Paul Park, Greg Klazura, Emma Bryce, Maija Cheung, Elliot Marseille, Doruk Ozgediz, Emmanuel A. Ameh</p>
The unmet need for pediatric surgery imposes enormous health and economic consequences globally, predominantly shouldered by Sub-Saharan Africa (SSA) where children comprise almost half of the population. Lack of knowledge about the economic impact of improving pediatric surgical infrastructure in SSA inhibits the informed allocation of limited resources towards the most cost-effective interventions to bolster global surgery for children. We assessed the cost-effectiveness of installing and running two dedicated pediatric operating rooms (ORs) in a hospital in Nigeria with a pre-existing pediatric surgical service by constructing a decision tree model of pediatric surgical delivery at this facility over a year, comparing scenarios before and after the installation of the ORs, which were funded philanthropically. Health outcomes measured in disability-adjusted life years (DALYs) averted were informed by the hospital’s operative registry and prior literature. We adopted an all healthcare payor’s perspective including costs incurred by the local healthcare system, the installation (funded by the charity), and patients’ families. Costs were annualized and reported in 2021 United States dollars ($). The incremental cost-effectiveness ratios (ICERs) of the annualized OR installation and operation were presented. One-way and probabilistic sensitivity analyses were performed. We found that installing and operating two dedicated pediatric ORs averted 538 DALYs and cost $177,527 annually. The ICER of the ORs’ installation and operation was $330 per DALY averted (95% uncertainty interval [UI] 315–336) from the all healthcare payor’s perspective. This ICER was well under the cost-effectiveness threshold of the country’s half-GDP per capita in 2020 ($1043) and remained cost-effective in one-way and probabilistic sensitivity analyses. Installation of additional dedicated pediatric operating rooms in Nigeria with pre-existing pediatric surgical capacity is therefore very cost-effective, supporting investment in children’s global surgical infrastructure as an economically sound intervention.Effects of injectable contraception with depot medroxyprogesterone acetate or norethisterone enanthate on estradiol levels and menstrual, psychological and behavioral measures relevant to HIV risk: The WHICH randomized trialMandisa Singata-MadlikiJenni SmitMags BeksinskaYusentha BalakrishnaChanel AvenantIvana BeeshamIshen SeocharanJoanne BattingJanet P. HapgoodG. Justus Hofmeyr10.1371/journal.pone.02957642024-03-26T14:00:00Z2024-03-26T14:00:00Z<p>by Mandisa Singata-Madliki, Jenni Smit, Mags Beksinska, Yusentha Balakrishna, Chanel Avenant, Ivana Beesham, Ishen Seocharan, Joanne Batting, Janet P. Hapgood, G. Justus Hofmeyr</p>
Background <p>Observational data suggest lower HIV risk with norethisterone enanthate (NET-EN) than with depo-medroxyprogesterone acetate intramuscular (DMPA-IM) injectable contraceptives. If confirmed, a switch between these similar injectable methods would be programmatically feasible and could impact the trajectory of the HIV epidemic. We aimed in this paper to investigate the effects of DMPA-IM and NET-EN on estradiol levels, measures of depression and sexual activity and menstrual effects, relevant to HIV risk; and to ascertain whether these measures are associated with estradiol levels.</p> Methods <p>This open-label trial conducted at two sites in South Africa from 5 November 2018 to 30 November 2019, randomized HIV-negative women aged 18–40 to DMPA-IM 150 mg intramuscular 12-weekly (n = 262) or NET-EN 200 mg intramuscular 8-weekly (n = 259). Data were collected on hormonal, behavioral and menstrual effects at baseline and at 25 weeks (25W).</p> Results <p>At 25W, median 17β estradiol levels were substantially lower than at baseline (p<0.001) for both methods: 76.5 pmol/L (interquartile range (IQR) 54.1 to 104.2) in the DMPA-IM group (n = 222), and 69.8 pmol/L (IQR: 55.1 to 89.3) in the NET-EN group (n = 225), with no statistical difference between the two methods (p = 0.450). Compared with DMPA-IM, NET-EN users reported significantly less amenorrhoea, fewer sexual acts, fewer users reporting at least one act of unprotected sex, more condom use with steady partner, more days with urge for sexual intercourse, more days feeling partner does not love her, and more days feeling sad for no reason. We did not find a clear association between estradiol levels and sexual behavior, depression and menstrual effects. Behavioral outcomes suggest less sexual exposure with NET-EN than DMPA-IM. The strength of this evidence is high due to the randomized study design and the consistency of results across the outcomes measured.</p> Conclusions <p>Estradiol levels were reduced to postmenopausal levels by both methods. Secondary outcomes suggesting less sexual exposure with NET-EN are consistent with reported observational evidence of less HIV risk with NET-EN. A randomized trial powered for HIV acquisition is feasible and needed to answer this important question.</p> Trial registration <p>PACTR 202009758229976.</p>Impact of extracorporeal membrane oxygenation-related complications on in-hospital mortalityEunae ByunPil Je KangSung Ho JungSeo Young ParkSang Ah LeeTae-Won KwonYong-Pil Cho10.1371/journal.pone.03007132024-03-25T14:00:00Z2024-03-25T14:00:00Z<p>by Eunae Byun, Pil Je Kang, Sung Ho Jung, Seo Young Park, Sang Ah Lee, Tae-Won Kwon, Yong-Pil Cho</p>
Introduction <p>Although extracorporeal membrane oxygenation (ECMO) is a well-established treatment for supporting severe cardiopulmonary failure, the morbidity and mortality of patients requiring ECMO support remain high. Evaluating and correcting potential risk factors associated with any ECMO-related complications may improve care and decrease mortality. This study aimed to assess the predictors of ECMO-related vascular and cerebrovascular complications among adult patients and to test the hypothesis that ECMO-related complications are associated with higher in-hospital mortality rates.</p> Methods <p>This single-center, retrospective study included 856 ECMO runs administered via cannulation of the femoral vessels of 769 patients: venoarterial (VA) ECMO (<i>n</i> = 709, 82.8%) and venovenous (VV) ECMO (<i>n</i> = 147, 17.2%). The study outcomes included the occurrence of ECMO-related vascular and cerebrovascular complications and in-hospital death. The association of ECMO-related complications with the risk of in-hospital death was analyzed.</p> Results <p>The incidences of ECMO-related vascular and cerebrovascular complications were 20.2% and 13.6%, respectively. The overall in-hospital mortality rate was 48.7%: 52.8% among VA ECMO runs and 29.3% among VV ECMO runs. Multivariable analysis indicated that age (<i>P</i> < 0.01), cardiopulmonary cerebral resuscitation (<i>P</i> < 0.01), continuous renal replacement therapy (<i>P</i> < 0.01), and initial platelet count [<50×10<sup>3</sup>/μL (<i>P</i> = 0.02) and 50–100(×10<sup>3</sup>)/μL (<i>P</i> < 0.01)] were associated with an increased risk of in-hospital death. ECMO-related vascular and cerebrovascular complications were not independently associated with higher in-hospital mortality rates for VA or VV ECMO runs.</p> Conclusion <p>ECMO-related vascular and cerebrovascular complications were not associated with an increased risk of in-hospital death among adult patients.</p>Clinical challenges of biomechanical performance of narrow-diameter implants in maxillary posterior teeth in aging patients: A finite element analysisSaranyoo PrasitwuttisakNattapon ChantarapanichKomsan ApinyauppathamKopchai PoomparnichSamroeng Inglam10.1371/journal.pone.02998162024-03-25T14:00:00Z2024-03-25T14:00:00Z<p>by Saranyoo Prasitwuttisak, Nattapon Chantarapanich, Komsan Apinyauppatham, Kopchai Poomparnich, Samroeng Inglam</p>
This study evaluated the biomechanical performance of narrow-diameter implant (NDI) treatment in atrophic maxillary posterior teeth in aging patients by finite element analysis. The upper left posterior bone segment with first and second premolar teeth missing obtained from a patient’s cone beam computed tomography data was simulated with cortical bone thicknesses of 0.5 and 1.0 mm. Three model groups were analyzed. The Regimen group had NDIs of 3.3 × 10 mm in length with non-splinted crowns. Experimental-1 group had NDIs of 3.0 × 10 mm in length with non-splinted crowns and Experimental-2 group had NDIs of 3.0 × 10 mm in length with splinted crowns. The applied load was 56.9 N in three directions: axial (along the implant axis), oblique at 30° (30° to the bucco-palatal plane compared to the vertical axis of the tooth), and lateral load at 90° (90° in the bucco-palatal plane compared to the vertical axis of the tooth). The results of the von Mises stress on the implant fixture, the elastic strain, and principal value of stress on the crestal marginal bone were analyzed. The axial load direction was comparable in the von Mises stress values in all groups, which indicated it was not necessary to use splinted crowns. The elastic strain values in the axial and oblique directions were within the limits of Frost’s mechanostat theory. The principal value of stress in all groups were under the threshold of the compressive stress and tensile strength of cortical bone. In the oblique and lateral directions, the splinted crown showed better results for both the von Mises stress, elastic strain, and principal value of stress than the non-splinted crown. In conclusion, category 2 NDIs can be used in the upper premolar region of aging patients in the case of insufficient bone for category 3 NDI restorations.Radiographic assessment of maxillary sinus membrane and lateral wall thickness using cone-beam CT in different facial types in southwestern Saudi ArabiaShahabe Saquib AbullaisSaad M. AlQahtaniSalman AlqahtaniAbdulrahman AlaamriAli Azhar DawasazAbdulelah AlqahtaniPrasad V. Dhadse10.1371/journal.pone.02984032024-03-25T14:00:00Z2024-03-25T14:00:00Z<p>by Shahabe Saquib Abullais, Saad M. AlQahtani, Salman Alqahtani, Abdulrahman Alaamri, Ali Azhar Dawasaz, Abdulelah Alqahtani, Prasad V. Dhadse</p>
The anatomy of the edentulous posterior maxilla and maxillary sinus possess unique challenges in implant dentistry. The purpose of this study was to assess maxillary sinus membrane thickness (MT) and lateral wall thickness (LWT) in different facial index profiles and to describe the clinical implications. A retrospective image analysis of 75 CBCT scans was done, which yielded a total of 150 sinus images. The facial index was calculated as per the formula given in the text and grouped as euryprosopic, mesoprosopic and leptoprosopic. The images obtained were of 36 women (48%) and 39 men (52%), with maximum subjects in 30–39 years age group. MT and LWT were measured at three different points on the radiograph at every 3mm from the base of the sinus floor in premolar and molar regions of each image. Results showed females had significant differences from males in LWT in both premolar and molar regions (p = 0.018 and 0.032 respectively). Subjects in 40–49 years of age had significant differences (p = 0.021) in MT in premolar region only. Also, difference in MT in premolar and molar regions were also statistically significant. Lastly, the present study did not find any statistically significant difference in MT and LWT in all three facial indices groups. It can be concluded that different facial indices have no positive correlation with maxillary sinus membrane thickness and lateral wall thickness. Hence, surgical complications are avoidable with proper detailed knowledge and appropriate identification of the anatomic structures characteristic to the maxillary sinus.The proton-sensing receptors TDAG8 and GPR4 are differentially expressed in human and mouse oligodendrocytes: Exploring their role in neuroinflammation and multiple sclerosisFionä CaratisMikołaj OpiełkaMartin HausmannMaria Velasco-EstevezBartłomiej RojekCheryl de VallièreKlaus SeuwenGerhard RoglerBartosz KaraszewskiAleksandra Rutkowska10.1371/journal.pone.02830602024-03-25T14:00:00Z2024-03-25T14:00:00Z<p>by Fionä Caratis, Mikołaj Opiełka, Martin Hausmann, Maria Velasco-Estevez, Bartłomiej Rojek, Cheryl de Vallière, Klaus Seuwen, Gerhard Rogler, Bartosz Karaszewski, Aleksandra Rutkowska</p>
Acidosis is one of the hallmarks of demyelinating central nervous system (CNS) lesions in multiple sclerosis (MS). The response to acidic pH is primarily mediated by a family of G protein-coupled proton-sensing receptors: OGR1, GPR4 and TDAG8. These receptors are inactive at alkaline pH, reaching maximal activation at acidic pH. Genome-wide association studies have identified a locus within the TDAG8 gene associated with several autoimmune diseases, including MS. Accordingly, we here found that expression of <i>TDAG8</i>, as opposed to <i>GPR4</i> or <i>OGR1</i>, is upregulated in MS plaques. This led us to investigate the expression of TDAG8 in oligodendrocytes using mouse and human <i>in vitro</i> and <i>in vivo</i> models. We observed significant upregulation of TDAG8 in human MO3.13 oligodendrocytes during maturation and in response to acidic conditions. However, its deficiency did not impact normal myelination in the mouse CNS, and its expression remained unaltered under demyelinating conditions in mouse organotypic cerebellar slices. Notably, our data revealed no expression of TDAG8 in primary mouse oligodendrocyte progenitor cells (OPCs), in contrast to its expression in primary human OPCs. Our investigations have revealed substantial species differences in the expression of proton-sensing receptors in oligodendrocytes, highlighting the limitations of the employed experimental models in fully elucidating the role of TDAG8 in myelination and oligodendrocyte biology. Consequently, the study does not furnish robust evidence for the role of TDAG8 in such processes. Nonetheless, our findings tentatively point towards a potential association between TDAG8 and myelination processes in humans, hinting at a potential link between TDAG8 and the pathophysiology of MS and warrants further research.