Motivational and cognitive predictors of apathy after subthalamic nucleus stimulation in Parkinson's disease.

Postoperative apathy is a frequent symptom in Parkinson's disease patients who have undergone bilateral deep brain stimulation of the subthalamic nucleus. Two main hypotheses for postoperative apathy have been suggested: (i) dopaminergic withdrawal syndrome relative to postoperative dopaminergic drug tapering; and (ii) direct effect of chronic stimulation of the subthalamic nucleus. The primary objective of our study was to describe preoperative and 1-year postoperative apathy in Parkinson's disease patients who underwent chronic bilateral deep brain stimulation of the subthalamic nucleus. We also aimed to identify factors associated with 1-year postoperative apathy considering: (i) preoperative clinical phenotype; (ii) dopaminergic drug management; and (iii) volume of tissue activated within the subthalamic nucleus and the surrounding structures. We investigated a prospective clinical cohort of 367 patients before and 1 year after chronic bilateral deep brain stimulation of the subthalamic nucleus. We assessed apathy using the Lille Apathy Rating Scale and carried out a systematic evaluation of motor, cognitive and behavioural signs. We modelled the volume of tissue activated in 161 patients using the Lead-DBS toolbox and analysed overlaps within motor, cognitive and limbic parts of the subthalamic nucleus. Of the 367 patients, 94 (25.6%) exhibited 1-year postoperative apathy: 67 (18.2%) with 'de novo apathy' and 27 (7.4%) with 'sustained apathy'. We observed disappearance of preoperative apathy in 22 (6.0%) patients, who were classified as having 'reversed apathy'. Lastly, 251 (68.4%) patients had neither preoperative nor postoperative apathy and were classified as having 'no apathy'. We identified preoperative apathy score [odds ratio (OR) 1.16; 95% confidence interval (CI) 1.10, 1.22; P < 0.001], preoperative episodic memory free recall score (OR 0.93; 95% CI 0.88, 0.97; P = 0.003) and 1-year postoperative motor responsiveness (OR 0.98; 95% CI 0.96, 0.99; P = 0.009) as the main factors associated with postoperative apathy. We showed that neither dopaminergic dose reduction nor subthalamic stimulation were associated with postoperative apathy. Patients with 'sustained apathy' had poorer preoperative fronto-striatal cognitive status and a higher preoperative action initiation apathy subscore. In these patients, apathy score and cognitive status worsened postoperatively despite significantly lower reduction in dopamine agonists (P = 0.023), suggesting cognitive dopa-resistant apathy. Patients with 'reversed apathy' benefited from the psychostimulant effect of chronic stimulation of the limbic part of the left subthalamic nucleus (P = 0.043), suggesting motivational apathy. Our results highlight the need for careful preoperative assessment of motivational and cognitive components of apathy as well as executive functions in order to better prevent or manage postoperative apathy.

Beneficial effects of citrulline enteral administration on sepsis-induced T cell mitochondrial dysfunction.

Severe sepsis induces a sustained immune dysfunction associated with poor clinical behavior. In particular, lymphopenia along with increased lymphocyte apoptosis and decreased lymphocyte proliferation, enhanced circulating regulatory T cells (Treg), and the emergence of myeloid-derived suppressor cells (MDSCs) have all been associated with persistent organ dysfunction, secondary infections, and late mortality. The mechanisms involved in MDSC-mediated T cell dysfunction during sepsis share some features with those described in malignancies such as arginine deprivation. We hypothesized that increasing arginine availability would restore T cell function and decrease sepsis-induced immunosuppression. Using a mouse model of sepsis based on cecal ligation and puncture and secondary pneumonia triggered by methicillin-resistant Staphylococcus aureus inoculation, we demonstrated that citrulline administration was more efficient than arginine in increasing arginine plasma levels and restoring T cell mitochondrial function and proliferation while reducing sepsis-induced Treg and MDSC expansion. Because there is no specific therapeutic strategy to restore immune function after sepsis, we believe that our study provides evidence for developing citrulline-based clinical studies in sepsis.

Citrulline enteral administration markedly reduces immunosuppressive extrafollicular plasma cell differentiation in a preclinical model of sepsis.

The sustained immunosuppression associated with severe sepsis favors an increased susceptibility to secondary infections and remains incompletely understood. Plasmablast and plasma cell subsets, whose primary function is to secrete antibodies, have emerged as important suppressive populations that expand during sepsis. In particular, sepsis supports CD39hi plasmablast metabolic reprogramming associated with adenosine-mediated suppressive activity. Arginine deficiency has been linked to an increased risk of secondary infections in sepsis. Overcoming arginine shortage by citrulline administration efficiently improves sepsis-induced immunosuppression and secondary infections in the cecal ligation and puncture murine model. Here, we aimed to determine the impact of citrulline administration on B cell suppressive responses in sepsis. We demonstrate that restoring arginine bioavailability through citrulline administration markedly reduces the dominant extrafollicular B cell response, decreasing the immunosuppressive LAG3+ and CD39+ plasma cell populations, and restoring splenic follicles. At the molecular level, the IRF4/MYC-mediated B cell reprogramming required for extrafollicular plasma cell differentiation is shunted in the splenic B cells of mice fed with citrulline. Our study reveals a prominent impact of nutrition on B cell responses and plasma cell differentiation and further supports the development of citrulline-based clinical studies to prevent sepsis-associated immune dysfunction.

ON/OFF non-motor evaluation: a new way to evaluate non-motor fluctuations in Parkinson's disease.

BACKGROUND: NMF are currently poorly evaluated in therapeutic decisions. A quantification of their severity would facilitate their integration. The objective of this study was to validate an autoquestionnaire evaluating the severity of non-motor fluctuations (NMF) in Parkinson's disease (PD). METHODS: Patients with PD were included in presurgical situation for deep brain stimulation of subthalamic nuclei. They participated in the PREDISTIM cohort (a study evaluating the predictive factors for therapeutic response of subthalamic stimulation in PD) in 17 centres in France. Our questionnaire, resulting from previous phases of development, included 11 non-motor symptoms (NMS). Their severity ranged from 0 to 10 and was assessed in OFF and then ON-Dopa to study their fluctuations. RESULTS: 310 patients were included, of whom 98.8% had NMS and 98.0% had NMF. Each NMS was significantly improved by L-Dopa (decrease in severity score ranging from 43.1% to 69.9%). Fatigue was the most frequent and most severe NMS. NMS were considered more bothersome than motor symptoms by 37.5% of patients in OFF-Dopa and 34.9% in ON-Dopa. CONCLUSIONS: This is the first questionnaire allowing a real-time quantification of the severity of NMS and their fluctuation with levodopa. It was able to confirm and measure the effect of L-dopa and show differences according to the patients and the NMS. It differs from other questionnaires by its measurement at a precise moment of the severity of the NMS, allowing its use during pretherapeutic assessments.Our questionnaire has been validated to measure the severity of NMF. It will be able to quantify the non-motor effect of anti-parkinsonian treatments and could facilitate the integration of NMF in therapeutic decisions.

Direct and indirect estimation of adolescent sexual intercourse and contraceptive use in Rajasthan India: an application of the best friend methodology.

BACKGROUND: Existing estimates of adolescent sexual and reproductive health (ASRH) behaviors may be a gross undercount given the sensitivity of this behavior in Indian culture. The objective of this study was to estimate ASRH behaviors in Rajasthan, India using direct questions and the best friend approach that seeks to reduce social desirability bias. METHODS: We used population-based data of adolescents aged 15-19 in Rajasthan collected between September and December 2022. Data include whether the respondent and her closest female friend ever had a partner, ever had sex, ever used contraception, and were currently using contraception. We estimated respondent and best friend ASRH outcomes separately, overall and among unmarried adolescents for whom we anticipate social desirability bias is greatest. RESULTS: The best friend approach performed well, with method assumptions largely met even before adjustments. Respondent and best friend estimates were similar among all adolescents except for current contraceptive use, which was higher for friends (though not significantly so). However, we observed large differences in ASRH behaviors between unmarried respondents and friends, with a significantly higher percentage of friends who ever had a partner (4.3% respondents, 11.6% friends), and a slightly higher percentage who ever had sex (2.4%, 3.8%) and who were currently using contraception (17.0%, 19.7% among those in need of contraception). CONCLUSIONS: We observed potential benefits of using the best friend methodology in estimating premarital sexual activity, but further work is needed to refine social network-based measures of sensitive adolescent behaviors in larger study samples to better understand ASRH needs.

Postabortion care service availability, readiness, and access in Burkina Faso: results from linked female-facility cross-sectional data.

BACKGROUND: Little is known about postabortion care (PAC) services in Burkina Faso, despite PAC's importance as an essential and life-saving component of emergency obstetric care. This study aims to evaluate PAC service availability, readiness, and accessibility in Burkina Faso. METHODS: Data for this study come from the Performance Monitoring for Action (PMA) Burkina Faso project and the Harmonized Health Facility Assessment (HHFA) conducted by the Institut de Recherche en Sciences de la Santé and the Ministry of Health. PMA data from a representative sample of women aged 15-49 (n = 6,385) were linked via GPS coordinates to HHFA facility data (n = 2,757), which included all public and private health facilities in Burkina Faso. We assessed readiness to provide basic and comprehensive PAC using the signal functions framework. We then calculated distance to facilities and examined percent within 5 kms of a facility with any PAC, basic PAC, and comprehensive PAC overall and by women's background characteristics. RESULTS: PAC services were available in 46.4% of health facilities nationwide; only 38.3% and 35.0% of eligible facilities had all basic and comprehensive PAC signal functions, respectively. Removal of retained products of conception was the most common missing signal function for both basic and comprehensive PAC, followed by provision of any contraception (basic) or any LARC (comprehensive). Nearly 85% of women lived within 5 km of a facility providing any PAC services, while 50.5% and 17.4% lived within 5 km of a facility providing all basic PAC and all comprehensive PAC signal functions, respectively. Women with more education, greater wealth, and those living in urban areas had greater odds of living within 5 km of a facility with offering PAC, basic PAC, or comprehensive PAC. CONCLUSIONS: Results indicate a need for increased PAC availability and readiness, prioritizing basic PAC services at the primary level-the main source of care for many women-which would reduce structural disparities in access. The current deficiencies in PAC signal a need for broader strengthening of the primary healthcare services in Burkina Faso to reduce the burden of unsafe abortion-related morbidity and mortality while improving maternal health outcomes more broadly.

Diagnosis and Outcomes of Late-Onset Wilson's Disease: A National Registry-Based Study.

BACKGROUND: Wilson's disease (WD) is usually diagnosed in children and young adults; limited data exist on late-onset forms. OBJECTIVE: The aim was to characterize the clinical and paraclinical presentations, therapeutic management, and outcomes in patients with late-onset WD. METHODS: Patients diagnosed with WD after age 40 years were identified from the French Wilson's Disease Registry (FWDR). Clinical, laboratory, and imaging findings and treatment were reported at diagnosis and last follow-up. RESULTS: Forty-five patients were identified (median age: 49, range: 40-64) and placed in three groups according to their clinical presentation: neurological (n = 20, median diagnostic delay: 20 months), hepatic (n = 13, diagnostic delay: 12 months), and family screening (n = 12), all confirmed genetically. Six neurological patients had an atypical presentation (1 torticollis, 2 writer's cramps, 2 functional movement disorders, and 1 isolated dysarthria), without T2/fluid-attenuated inversion recovery brain magnetic resonance imaging (MRI) hyperintensities; 5 of 6 had no Kayser-Fleischer ring (KFR); 5 of 6 had liver involvement. In the neurological group, 84% of patients improved clinically, and 1 developed copper deficiency. In the hepatic group, 77% had cirrhosis; 6 patients required liver transplantation. In the screened group, 43% had mild liver involvement; 3 were not treated and remained stable; 24-h urinary copper excretion was normal in 33% of patients at diagnosis. CONCLUSIONS: In the FWDR, late-onset forms of WD affect 8% of patients, mostly with neurological presentations. Thirty percent of the neurological forms were atypical (isolated long-lasting symptoms, inconspicuous brain MRI, no KFR). With personalized treatment, prognosis was good. This study emphasized that WD should be suspected at any age and even in cases of atypical presentation. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Enteral citrulline supplementation versus placebo on SOFA score on day 7 in mechanically ventilated critically ill patients: the IMMUNOCITRE randomized clinical trial.

BACKGROUND: Restoring plasma arginine levels through enteral administration of L-citrulline in critically ill patients may improve outcomes. We aimed to evaluate whether enteral L-citrulline administration reduced organ dysfunction based on the Sequential Organ Failure Assessment (SOFA) score and affected selected immune parameters in mechanically ventilated medical intensive care unit (ICU) patients. METHODS: A randomized, double-blind, multicenter clinical trial of enteral administration of L-citrulline versus placebo for critically ill adult patients under invasive mechanical ventilation without sepsis or septic shock was conducted in four ICUs in France between September 2016 and February 2019. Patients were randomly assigned to receive enteral L-citrulline (5 g) every 12 h for 5 days or isonitrogenous, isocaloric placebo. The primary outcome was the SOFA score on day 7. Secondary outcomes included SOFA score improvement (defined as a decrease in total SOFA score by 2 points or more between day 1 and day 7), secondary infection acquisition, ICU length of stay, plasma amino acid levels, and immune biomarkers on day 3 and day 7 (HLA-DR expression on monocytes and interleukin-6). RESULTS: Of 120 randomized patients (mean age, 60 ± 17 years; 44 [36.7%] women; ICU stay 10 days [IQR, 7-16]; incidence of secondary infections 25 patients (20.8%)), 60 were allocated to L-citrulline and 60 were allocated to placebo. Overall, there was no significant difference in organ dysfunction as assessed by the SOFA score on day 7 after enrollment (4 [IQR, 2-6] in the L-citrulline group vs. 4 [IQR, 2-7] in the placebo group; Mann‒Whitney U test, p = 0.9). Plasma arginine was significantly increased on day 3 in the treatment group, while immune parameters remained unaffected. CONCLUSION: Among mechanically ventilated ICU patients without sepsis or septic shock, enteral L-citrulline administration did not result in a significant difference in SOFA score on day 7 compared to placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02864017 (date of registration: 11 August 2016).

Menstrual regulation: examining the incidence, methods, and sources of care of this understudied health practice in three settings using cross-sectional population-based surveys.

BACKGROUND: Menstrual regulation is a practice that may exist within the ambiguity surrounding one's pregnancy status and has been the subject of limited research. The aim of this study is to measure the annual rate of menstrual regulation in Nigeria, Cote d'Ivoire, and Rajasthan, India, overall and by background characteristics and to describe the methods and sources women use to bring back their period. METHODS: Data come from population-based surveys of women aged 15-49 in each setting. In addition to questions on women's background characteristics, reproductive history, and contraceptive experiences, interviewers asked women whether they had ever done something to bring back their period at a time when they were worried they were pregnant, and if so, when it occurred and what methods and source they used. A total of 11,106 reproductive-aged women completed the survey in Nigeria, 2,738 in Cote d'Ivoire, and 5,832 in Rajasthan. We calculated one-year incidence of menstrual regulation overall and by women's background characteristics separately for each context using adjusted Wald tests to assess significant. We then examined the distribution of menstrual regulation methods and sources using univariate analyses. Method categories included surgery, medication abortion pills, other pills (including unknown pills), and traditional or "other" methods. Source categories included public facilities or public mobile outreach, private or non-governmental facilities or doctors, pharmacy or chemist shops, and traditional or "other" sources. RESULTS: Results indicate substantial levels of menstrual regulation in West Africa with a one-year incidence rate of 22.6 per 1,000 women age 15-49 in Nigeria and 20.6 per 1,000 in Cote d'Ivoire; women in Rajasthan reported only 3.3 per 1,000. Menstrual regulations primarily involved traditional or "other" methods in Nigeria (47.8%), Cote d'Ivoire (70.0%), and Rajasthan (37.6%) and traditional or "other" sources (49.4%, 77.2%, and 40.1%, respectively). CONCLUSION: These findings suggest menstrual regulation is not uncommon in these settings and may put women's health at risk given the reported methods and sources used. Results have implications for abortion research and our understanding of how women manage their fertility.

Menstrual regulation, or bringing back a late period, is an understudied practice that women may use when they are worried they are pregnant but that may be viewed as distinct from abortion. This study seeks to measure the frequency of menstrual regulation in Nigeria, Cote d'Ivoire, and Rajasthan, India, overall and by women's characteristics and to describe the methods and sources women use. We used data from representative surveys of women aged 15­49 years old in each study setting. We asked women whether they had ever done something to bring back a late period at a time when they were worried they were pregnant, and if so, what methods and sources they used. Results indicate that menstrual regulation may be a common practice, particularly in West Africa; the observed one-year rates were 22.6 menstrual regulations per 1,000 women aged 15­49 in Nigeria and 20.6 menstrual regulations per 1000 women in Cote d'Ivoire; women in Rajasthan only reported 3.3 menstrual regulations per 1000 women per year. Menstrual regulations primarily involved traditional or "other" methods in Nigeria (47.8%), Cote d'Ivoire (70.0%), and Rajasthan (37.6%) and traditional or "other" sources (49.4%, 77.2%, and 40.1%, respectively). These findings suggest menstrual regulation is not uncommon and may put women's health at risk given the reported methods and sources used. Results have implications for abortion research and our understanding of how women manage their fertility.

Postabortion care availability, readiness, and accessibility in Niger in 2022: results from linked facility-female cross-sectional data.

BACKGROUND: Postabortion care (PAC), which is an essential element of emergency obstetric care, is underresearched in Niger. The study aims to assess the availability, readiness, and accessibility of facility-based PAC services in Niger. METHODS: This study uses female and facility data from Performance Monitoring for Action Niger. The female data include a nationally representative sample of women aged 15-49 (n = 3,696). Using GPS coordinates, these female data were linked to a sample of public and private facilities (n = 258) that are expected to provide PAC. We assessed PAC availability and facility readiness to provide basic and comprehensive PAC using the signal functions framework, overall and by facility type. We then calculated the distance between women and their closest facility and estimated the proportion of women living within five kilometers (5 km) of a facility providing any PAC, basic PAC, and comprehensive PAC, overall and by women's background characteristics. RESULTS: Only 36.4% and 14% of eligible facilities had all basic and comprehensive PAC signal functions, respectively. Oxytocics and laparotomy were the most missing signal function for basic and comprehensive PAC, respectively. Private facilities were the least ready to provide the full range of PAC services. While 47% of women lived within 5 km of a facility providing any PAC services, only 33.4% and 7.9% lived within 5 km of a facility providing all basic and all comprehensive PAC signal functions, respectively. Women who were divorced/widowed, had higher levels of education, and were living in urban areas had increased odds of living within 5 km of a facility with any or basic PAC. Women who were never married had increased odds of living within 5 km of a facility with comprehensive PAC, while urban residence was fully predictive of living within 5 km of a facility with comprehensive PAC. CONCLUSIONS: This study found PAC availability and readiness to be insufficient in Niger, with inadequate and disparate accessibility to facilities providing PAC services. We recommended stakeholders ensure stock of essential commodities and availability of PAC services at primary facilities in order to mitigate the negative maternal health repercussions of unsafe abortion in this setting.

Abortion care availability, readiness, and access: linking population and health facility data in Kinshasa and Kongo Central, DRC.

BACKGROUND: The Democratic Republic of Congo (DRC) legalized abortion in 2018 to preserve health and pledged to provide quality postabortion care (PAC), yet little is known about the availability of abortion care services and if facilities are prepared to provide them; even less is known about the accessibility of these services. Using facility and population-based data in Kinshasa and Kongo Central, this study examined the availability of abortion services, readiness of facilities to provide them, and inequities in access. METHODS: Data on 153 facilities from the 2017-2018 DRC Demographic and Health Survey Service Provision Assessment (SPA) were used to examine signal functions and readiness of facilities to provide services across three abortion care domains (termination of pregnancy, basic treatment of abortion complications, and comprehensive treatment of abortion complications). To examine PAC and medication abortion provision before and after abortion decriminalization, we compared estimates from the 2017-2018 SPA facilities to estimates from the Performance Monitoring for Action (PMA) data collected in 2021 (n = 388). Lastly, we assessed proximity to PAC and medication abortion using PMA by geospatially linking facilities to representative samples of 2,326 and 1,856 women in Kinshasa and Kongo Central, respectively. RESULTS: Few facilities had all the signal functions under each abortion care domain, but most facilities had many of the signal functions: overall readiness scores were > 60% for each domain. In general, readiness was higher among referral facilities compared to primary facilities. The main barriers to facility readiness were stock shortages of misoprostol, injectable antibiotics, and contraception. Overall, provision of services was higher post-decriminalization. Access to facilities providing PAC and medication abortion was almost universal in urban Kinshasa, but patterns in rural Kongo Central showed a positive association with education attainment and wealth. CONCLUSION: Most facilities had many of the necessary signal functions to provide abortion services, but the majority experienced challenges with commodity availability. Inequities in accessibility of services also existed. Interventions that address supply chain challenges may improve facility readiness to provide abortion care services, and further efforts are needed to narrow the gap in accessibility, especially among poor women from rural settings.

The International Sexual Health And REproductive Health during COVID-19 (I-SHARE) Study: A Multicountry Analysis of Adults from 30 Countries Prior to and During the Initial Coronavirus Disease 2019 Wave.

BACKGROUND: There is limited evidence to date about changes to sexual and reproductive health (SRH) during the initial wave of coronavirus disease 2019 (COVID-19). To address this gap, our team organized a multicountry, cross-sectional online survey as part of a global consortium. METHODS: Consortium research teams conducted online surveys in 30 countries. Sampling methods included convenience, online panels, and population-representative. Primary outcomes included sexual behaviors, partner violence, and SRH service use, and we compared 3 months prior to and during policy measures to mitigate COVID-19. We conducted meta-analyses for primary outcomes and graded the certainty of the evidence. RESULTS: Among 4546 respondents with casual partners, condom use stayed the same for 3374 (74.4%), and 640 (14.1%) reported a decline. Fewer respondents reported physical or sexual partner violence during COVID-19 measures (1063 of 15 144, 7.0%) compared to before COVID-19 measures (1469 of 15 887, 9.3%). COVID-19 measures impeded access to condoms (933 of 10 790, 8.7%), contraceptives (610 of 8175, 7.5%), and human immunodeficiency virus/sexually transmitted infection (HIV/STI) testing (750 of 1965, 30.7%). Pooled estimates from meta-analysis indicate that during COVID-19 measures, 32.3% (95% confidence interval [CI], 23.9%-42.1%) of people needing HIV/STI testing had hindered access, 4.4% (95% CI, 3.4%-5.4%) experienced partner violence, and 5.8% (95% CI, 5.4%-8.2%) decreased casual partner condom use (moderate certainty of evidence for each outcome). Meta-analysis findings were robust in sensitivity analyses that examined country income level, sample size, and sampling strategy. CONCLUSIONS: Open science methods are feasible to organize research studies as part of emergency responses. The initial COVID-19 wave impacted SRH behaviors and access to services across diverse global settings.

Conservative Iron Chelation for Neuroferritinopathy.

BACKGROUND: Neuroferritinopathy is a rare inherited neurodegenerative disease with brain iron accumulation characterized by brain iron overload resulting in progressive movement disorders. No treatment is currently available. OBJECTIVE: We assessed conservative iron chelation with deferiprone at 30 mg/kg/day on the disease progression with controlled periods of discontinuation. METHODS: Four patients with confirmed molecular diagnosis of neuroferritinopathy were given deferiprone at different stages of disease progression and with clinical and biological monitoring to control benefit and risk. RESULTS: The four patients showed slight to high improvement. In one case, we managed to stabilize disease progression for more than 11 years. In another case, we were able to reverse symptoms after a few months of treatment. The earliest the treatment was started, the most efficient it was on disease progression. CONCLUSIONS: Conservative iron chelation should be further assessed in neuroferritinopathy. © 2022 International Parkinson and Movement Disorder Society.

Factors impacting performance on the 6-minute walk test by people with late-onset Pompe disease.

INTRODUCTION/AIMS: Pompe disease is a progressive myopathy that combines motor, respiratory, and cardiac impairments. The 6-min walk test is the gold standard for assessing disease severity at the motor level. The objective of this study was to better determine the parameters that influence the total distance covered in patients with Pompe disease. METHODS: We performed a retrospective review of 15 patients with late-onset Pompe disease who were followed regularly at a single referral center. Logistic regression was used to investigate the links between motor, respiratory and cardiac variables and 6-min walk test performance. RESULTS: When considering baseline clinical and demographic variables, a seven-step backward elimination regression analysis yielded a model with two predictors (age and the use of an assistive device) that explained 85.5% of the variance. When considering the cardiorespiratory variables monitored during gait, a three-step backward elimination regression analysis showed that two predictors (heart rate recovery and the baseline partial pressure of carbon dioxide) explained 42.2% of the variance. DISCUSSION: Our results highlighted the importance of respiratory and cardiac adaptation during exercise (along with motor ability) during the 6-min walk test in patients with Pompe disease. Further studies of larger cohorts are necessary to validate the model, which might enable investigators to determine whether intra-individual fluctuations in 6-min walk test performance are related to physiological parameters and/or to other variables such as the patient's level of motivation during the test.

Influence of early identification and therapy on long-term outcomes in early-onset MTHFR deficiency.

MTHFR deficiency is a severe inborn error of metabolism leading to impairment of the remethylation of homocysteine to methionine. Neonatal and early-onset patients mostly exhibit a life-threatening acute neurologic deterioration. Furthermore, data on early-onset patients' long-term outcomes are scarce. The aims of this study were (1) to study and describe the clinical and laboratory parameters of early-onset MTHFR-deficient patients (i.e., ≤3 months of age) and (2) to identify predictive factors for severe neurodevelopmental outcomes in a cohort with early and late onset MTHFR-deficient patients. To this end, we conducted a retrospective, multicentric, international cohort study on 72 patients with MTHFR deficiency from 32 international metabolic centres. Characteristics of the 32 patients with early-onset MTHFR deficiency were described at time of diagnosis and at the last follow-up visit. Logistic regression analysis was used to identify predictive factors of severe neurodevelopmental outcome in a broader set of patients with early and non-early-onset MTHFR deficiency. The majority of early-onset MTHFR-deficient patients (n = 32) exhibited neurologic symptoms (76%) and feeding difficulties (70%) at time of diagnosis. At the last follow-up visit (median follow-up time of 8.1 years), 76% of treated early-onset patients (n = 29) exhibited a severe neurodevelopmental outcome. Among the whole study population of 64 patients, pre-symptomatic diagnosis was independently associated with a significantly better neurodevelopmental outcome (adjusted OR 0.004, [0.002-0.232]; p = 0.003). This study provides evidence for benefits of pre-symptomatic diagnosis and appropriate therapeutic management, highlighting the need for systematic newborn screening for MTHFR deficiency and pre-symptomatic treatment that may improve outcome.

Contraceptive Use Before and After Abortion: A Cross-Sectional Study from Nigeria and Côte d'Ivoire.

Post-abortion contraception enables women to effectively manage their fertility to prevent unintended pregnancies. Using data from population-based surveys of women aged 15-49 in Nigeria and Côte d'Ivoire, we examined contraceptive dynamics immediately before and after an abortion and examined factors associated with these changes using multivariable logistic regressions. Covariates included sociodemographic characteristics, abortion source, post-abortion contraceptive communication (wanting to and actually talking to someone about contraception after abortion), and perceived contraceptive autonomy. We observed higher contraceptive use after abortion than before abortion. In Nigeria, wanting to talk to someone about contraception post-abortion was associated with increased adoption and decreased discontinuation, whereas talking to someone about contraception post-abortion was associated with increased adoption. Obtaining care from a clinical abortion source was associated with increased adoption and decreased discontinuation. Both post-abortion contraceptive communication variables were associated with post-abortion contraceptive use in both countries, whereas clinical source was only associated with post-abortion contraceptive use in Nigeria. Our findings suggest that ensuring that women have access to safe abortion as part of the formal health care system and receive comprehensive, high-quality post-abortion care services that include contraceptive counseling enables them to make informed decisions about their fertility that align with their reproductive goals.

Social Network-Based Induced Abortion Incidence Estimation in Burkina Faso: Examining the Impact of the Network Generating Question.

Social network-based methods are increasingly used to estimate induced abortion incidence and investigate correlates. Approaches differ in the social tie definitions used to identify which social network members' abortion experiences respondents will report. This study compares the effect of using the "best friend" (closest female friend) versus "confidante" (specifying mutual sharing of personal information) definition on abortion incidence estimation. We use data from a nationally representative survey of women aged 15-49 in Burkina Faso (conducted in 2020-2021) where respondents were randomized into two versions of an abortion module, using different friend definitions. We computed abortion rate estimates by friend definition and adjusted for assumption violations (transmission bias, surrogate sample selection bias). Unadjusted incidence rates varied from 11.7 [4.1-19.2] abortions per 1,000 women to 15.6 [9.7-21.4], depending on friend definition. The confidante definition yielded higher adjusted estimates (36.2 [25.1-47.2]) than the best friend definition (17.0 [8.7-25.3]) due to greater transmission bias adjustment. Both estimates exceeded the respondent self-reported abortion incidence (4.0 [2.2-5.9]). Our results indicate that either friend definition produces higher incidence estimates than self-report but suggest a potential advantage for the "best friend" over the "confidante" definition given lower transmission bias. Further research should assess generalizability of these findings in other contexts.

Pregnancy planning and acceptance and maternal psychological distress during pregnancy: results from the National Perinatal Survey, France, 2016.

BACKGROUND: Studies report heightened risks of mental health problems among women who experience an unintended pregnancy, but few consider the complexity of pregnancy intentions. In this study, we evaluate how different dimensions of pregnancy intentions (pregnancy planning and pregnancy acceptance) relate to two maternal depressive symptoms and perceived psychological distress. METHODS: This study draws from a cross-sectional national survey conducted in all maternities in France over a one-week period in 2016. All mothers 18 years and older who had a live birth during the study period were invited to participate. After excluding women who underwent infertility treatment, our analytical sample included 10,339 women. We first described levels and correlates of pregnancy planning and acceptance, defined in four categories; planned/welcomed, unplanned/welcomed, planned/unwelcomed, unplanned/unwelcomed. We then assessed the bivariate and multivariate associations between pregnancy planning and acceptance and two outcomes: women's self-perceived psychological health and the presence of two depressive symptoms during pregnancy. We used multivariate logistic regressions to evaluate these associations, after adjusting for socio-demographic and medical factors. RESULTS: Altogether 7.5 to 24.1% of mothers perceived their psychological health during pregnancy was poor, according to pregnancy planning and acceptance categories and 10.3 to 22.4% indicated feelings of sadness and loss of interest during pregnancy, according to pregnancy planning and acceptance categories. As compared to women with planned/welcomed pregnancies, the odds of perceived poor psychological health and depressive symptoms were 2.55 times (CI 2.20-2.95) and 1.75 times higher (CI 1.51-2.02), respectively, among unplanned/unwelcomed pregnancies and 2.02 (CI 1.61-2.53) and 2.07 (CI 1.7-2.5) higher, among planned/unwelcomed pregnancies. Among women with unplanned pregnancies, we also found higher odds of perceived poor psychological health among women whose pregnancy was unwelcomed while the odds of depressive symptoms were not different by pregnancy planning status among women with unwelcomed pregnancies. CONCLUSIONS: These findings consolidate previous reports of the association between pregnancy intentions and maternal psychological distress, while further specifying the relationship, which mostly depends on the acceptance of pregnancy timing rather than on pregnancy planning. Identifying women with low pregnancy acceptance can potentially enhance current medical practice by improving early detection of maternal depression.

Partner involvement in abortion trajectories and subsequent abortion safety in Nigeria and Côte d'Ivoire.

BACKGROUND: Unsafe abortions contribute to maternal mortality and morbidity worldwide, with disproportionate impacts in lower-income countries. Identifying factors associated with an elevated risk of experiencing an abortion under the most unsafe conditions is an important component of addressing this burden. The partner's role in obtaining a safe or unsafe abortion is not well understood. This study provides a quantitative assessment of the relationship between partner involvement and subsequent abortion safety. METHODS: The data are drawn from the PMA2020 female surveys and abortion follow-up surveys, fielded in Nigeria and Côte d'Ivoire between 2018 and 2020. The sample includes 1144 women in Nigeria and 347 women in Côte d'Ivoire who reported having ever experienced an abortion. We assess partner involvement in discussing the abortion decision and/or in selecting the method or source and evaluate the relationship between partner involvement and most unsafe abortion (using non-recommended methods from a non-clinical source) versus safe or less safe abortion, adjusting for sociodemographic characteristics. RESULTS: We find a strong association between experiencing any partner involvement and decreased odds of experiencing a most unsafe abortion (Nigeria: aOR = 0.34, 95% CI 0.26-0.45; Côte d'Ivoire: aOR = 0.27, 95% CI 0.16-0.47). Analyzing the two types of partner involvement separately, we find that partner involvement in the decision is associated with lower odds of most unsafe abortion in both countries (Nigeria: aOR = 0.48, 95% CI 0.39-0.72; Côte d'Ivoire: aOR = 0.34, 95% CI 0.19-0.60); partner involvement in selecting the method and/or source was only significantly associated with lower odds of most unsafe abortion in Nigeria (Nigeria: aOR = 0.53, 95% CI 0.39-0.72; Côte d'Ivoire: aOR = 0.65, 95% CI 0.32-1.32). CONCLUSION: In Nigeria and in Côte d'Ivoire, respondents whose partners were involved in their abortion trajectory experienced safer abortions than those whose partners were not involved. These findings suggest the potential importance of including men in education on safe abortion care and persistent need to make safe abortion accessible to all, regardless of partner support.

Mental health consequences of military sexual trauma: results from a national survey in the French military.

BACKGROUND: Military sexual trauma (MST) is a major public health concern, given its prevalence and mental health sequelae. This phenomenon is particularly prevalent among women in the US military, although more cases involve men given their overrepresentation. Little is known about MST and its consequences in other military settings, including in Europe. METHODS: This study draws from a national survey in the French military, including 1268 servicemen and 232 servicewomen. We conducted bivariate and multivariate analysis, using simple and multinomial logistic regressions to evaluate the associations between different forms of MST (repeated sexual comments alone/one form of sexual oppression (coercion, repeated verbal unwanted attention or assault)/ several sexual stressors) and symptoms of depression and of positive post-traumatic stress disorder (PTSD) screening scores. RESULTS: Women were both more likely to experience MST and to experience more severe forms of MST than men. Women were also more likely than men to report mental health symptoms (31% versus 18% for symptoms of depression and 4.0% versus 1.8% for positive PTSD screening scores). Different forms of MST were associated with different levels of psychological distress. Women reporting repeated sexual comments alone had higher odds of depressive symptoms (OR=3.1 [1.7, 5.5]) relative to women with no MST. Likewise, the odds of depressive symptoms were 6.5 times higher among women and 8.0 times higher among men who experienced several sexual stressors relative to those who reported no MST. We also found higher relative risk of subthreshold PTSD screening scores among women reporting any form of sexual stressor, including sexual comments alone (RRR = 4.5 [2.8, 7.4]) and an elevenfold increase in the relative risk of positive PTSD screen scores (RRR = 11.3 [2.3, 55.6]) among women who experienced several sexual stressors relative to women with no MST. CONCLUSION: MST is associated with mental health distress among service members in the French military, especially for women. The heightened risk of MST coupled with psychological sequelae call for preventive programs to reduce MST and for screening programs to provide adequate psychological support.