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.

Effectiveness of Continuous Dopaminergic Therapies in Parkinson's Disease: A Review of L-DOPA Pharmacokinetics/Pharmacodynamics.

Background: Parkinson's disease (PD) is characterized by striatal dopamine deficiency. Since dopamine cannot cross the digestive and blood-brain barriers, its precursor, levodopa (L-DOPA), remains the mainstay of treatment. However, the significant pharmacokinetic (Pk) and pharmacodynamic (Pd) limitations of L-DOPA, combined with the severity of PD, may trigger motor and non-motor complications, for which continuous dopaminergic delivery therapies have been developed. Objective: The aim of this study was to review the literature on the Pk/Pd limitations of L-DOPA and how current treatments of continuous dopaminergic administration ameliorate these problems, in order to identify the need for new therapeutic avenues. Methods: A comprehensive literature search was carried out using PubMed and 75 articles were initially extracted. Following independent screening by two reviewers and consideration of eligibility, 10 articles were chosen for further analysis. Information concerning the Pk/Pd of L-DOPA was classified for each article. Results: Pk/Pd problems notably include: (i) restricted digestive and cerebral absorption; (ii) unnecessary peripheral distribution; (iii) short half-life; (iv) age- and PD-induced decline of central aromatic L-amino acid decarboxylase; (v) misdistribution in many cells; and (vii) pulsatile stimulation of dopaminergic receptors. Current treatments only slightly ameliorate some of these problems. Conclusions: Many Pk/Pd constraints are not resolved by existing continuous dopaminergic delivery therapies. This highlights the significant gap between these treatments and the ideal of continuous dopaminergic stimulation.

Trends in Adolescent Sexual and Reproductive Health Outcomes Before and Into the COVID-19 Pandemic in Burkina Faso and Kenya: Evidence From Panel Data.

PURPOSE: Many predicted that COVID-19 would have a substantial impact on the sexual and reproductive health (SRH) trajectories of adolescents in sub-Saharan Africa. The lack of longitudinal data with information collected before and into the pandemic has limited investigation into this topic. METHODS: We performed a secondary analysis using nationally representative longitudinal data from Kenya and Burkina Faso, collected at three time points (pre-COVID-19 in late 2019, and during COVID-19 in 2020 and 2021), to determine the extent to which SRH outcomes and behaviors, including pregnancy, contraceptive use, partnership status, and sexual activity, changed during the pandemic among adolescent women. RESULTS: Among adolescents aged 15-19 years (Kenya n = 1,893, Burkina Faso n = 1,422), there was a reduction in both partnership and pregnancy in 2021 as compared to pre-COVID 2019. Contraception use significantly increased between 2019 and 2021 in Kenya only (adjusted odds ratio [aOR]: 1.42, 95% confidence interval [CI] 1.03-1.97). COVID-19-related household income loss was associated with a decline in sexual activity among unmarried Kenyan girls (aOR: 0.47, 95% CI 0.25-0.87) and lower odds of pregnancy in Burkina Faso (aOR: 0.13, 95% CI 0.02-0.91). We did not find a relationship between COVID-19 measures and initiation of partnership or marriage in either setting. DISCUSSION: Contrary to expectations, our results suggest that COVID-19 did not have a consistent or sustaining impact on adolescent SRH and behaviors in Burkina Faso and Kenya. Further research is needed to assess the longer-term implications of the pandemic on adolescent social and health outcomes.

Intersectionality, gender norms, and young adolescents in context: a review of longitudinal multicountry research programmes to shape future action.

Discriminatory gender norms can intersect and interact with other dimensions of discrimination-such as age, race, ethnicity, disability, education status, and sexual orientation-to shape individuals' experiences and impact their health and wellbeing. This interaction is referred to as intersectionality. Although the theory has been in circulation since the late 1980s, only recently has it gained traction in low-income and middle-income settings, and it has yet to fully penetrate global research on adolescence. The social and structural intersectional drivers of adolescent health and wellbeing, particularly during early adolescence (age 10-14 years), are poorly understood. The evidence base for designing effective interventions for this formative period of life is therefore relatively small. In this Review, we examine how gender intersects with other forms of disadvantage in the early stages of adolescence. Analysing data from hybrid observation-intervention longitudinal studies with young adolescents in 16 countries, our aim is to inform the health and wellbeing of girls and boys from a range of social contexts, including in conflict settings. Adolescents' perceptions about gender norms vary by context, depend on individual opinion, and are shaped by socioecological drivers of gender inequalities in health. Shifting those perceptions is therefore challenging. We argue for the importance of applying an intersectionality lens to improve health and wellbeing outcomes for young adolescents and conclude with five practical recommendations for programme design and research.

A qualitative exploration of reproductive coercion experiences and perceptions in four geo-culturally diverse sub-Saharan African settings.

Reproductive coercion (RC) is any intentional behavior that interferes with another's reproductive decision-making or pregnancy outcome. This study aims to qualitatively examine RC experiences and perceptions among women and men in Ethiopia, Nigeria (Kano and Anambra States), and Uganda. This is a secondary analysis utilizing qualitative data from the Women's and Girls' Empowerment in Sexual and Reproductive Health study. Across sites, focus group discussions (38 groups; n=320 participants) and in-depth interviews (n=120) were conducted, recorded, and transcribed. Transcripts were loaded into Atlas.ti, and quotes describing experiences of reproductive control or abuse were coded as "reproductive coercion." RC quotes were input into a matrix for thematic analysis. Emergent RC themes included indirect reproductive pressures, direct family planning interference, concurrent experiences of violence, and responses to RC. Indirect reproductive pressures included tactics to both promote and prevent pregnancy, while direct interference centered on pregnancy promotion. Women who were not compliant with their partners' reproductive demands were often subjected to violence from multiple actors (i.e., parents, in-laws, community members) in addition to their partners. Despite concurrent forms of violence, women across sites resisted RC by using contraceptives covertly, choosing to abort, or leaving their abusive partnerships. Women and men across sites indicated that men were highly influential in fertility. RC behaviors were a mechanism of control over desired reproductive outcomes, which were often rooted in perceptions of childbearing as social status. Findings indicate a need for more nuanced community interventions targeting social norms, as well as improved RC screening and response within health services.

The impact of subthalamic deep-brain stimulation in restoring motor symmetry in Parkinson's disease patients: a prospective study.

BACKGROUND AND OBJECTIVES: The impact of subthalamic deep-brain stimulation (STN-DBS) on motor asymmetry and its influence on both motor and non-motor outcomes remain unclear. The present study aims at assessing the role of STN-DBS on motor asymmetry and how its modulation translates into benefits in motor function, activities of daily living (ADLs) and quality of life (QoL). METHODS: Postoperative motor asymmetry has been assessed on the multicentric, prospective Predictive Factors and Subthalamic Stimulation in Parkinson's Disease cohort. Asymmetry was evaluated at both baseline (pre-DBS) and 1 year after STN-DBS. A patient was considered asymmetric when the right-to-left MDS-UPDRS part III difference was ≥ 5. In parallel, analyses have been carried out using the absolute right-to-left difference. The proportion of asymmetric patients at baseline was compared to that in the post-surgery evaluation across different medication/stimulation conditions. RESULTS: 537 PD patients have been included. The proportion of asymmetric patients was significantly reduced after both STN-DBS and medication administration (asymmetric patients: 50% in pre-DBS MedOFF, 35% in MedOFF/StimON, 26% in MedON/StimOFF, and 12% in MedON/StimON state). Older patients at surgery and with higher baseline UPDRS II scores were significantly less likely to benefit from STN-DBS at the level of motor asymmetry. No significant correlation between motor asymmetry and ADLs (UPDRS II) or overall QoL (PDQ-39) score was observed. Asymmetric patients had significantly higher mobility, communication, and daily living PDQ-39 sub-scores. CONCLUSIONS: Both STN-DBS and levodopa lead to a reduction in motor asymmetry. Motor symmetry is associated with improvements in certain QoL sub-scores.

Abortion information-seeking experiences among women who obtained abortions in Kinshasa, DRC: Results from a qualitative study.

Little is known about the process of seeking information related to abortion care options among women in the Democratic Republic of Congo (DRC). Understanding how women obtain information can help identify opportunities for intervention to increase awareness and use of safe pregnancy termination options. Using qualitative data collected from women in Kinshasa, DRC who reported having an abortion in the last 10 years, this study aims to determine how women navigate obtaining information about their options for abortion and the role of their social network in their information-seeking processes. Data for this analysis come from a mixed-method study of abortion in Kinshasa conducted from December 2021 to April 2022. Fifty-two qualitative interviews followed a structured interview guide, including open-ended questions and probes, developed by a multidisciplinary team of researchers in Kinshasa and the United States. Inductive thematic analysis was conducted using Atlas.ti, and a thematic analysis matrix was used to describe the major themes and subthemes. Thematic analysis revealed two main themes with nested subthemes. The first and most salient theme highlighted the highly selective and narrow information search process women engaged in, involving no others or very few individuals (e.g., partners, women in one's community, or providers) that the pregnant woman chose strategically. The second theme revealed the heterogeneous and often stigmatizing nature of these interactions, including attempts at deterrence from many sources and information of varying completeness and accuracy. While the recent liberalization of the abortion law in the DRC is essential to improve access to safe abortion, public health gains will not materialize unless they are accompanied by community-level actions to raise awareness about the legality and availability of safe abortions services, including medication abortion pills for safe self-managed abortion.

The Use of Image Guided Programming to Improve Deep Brain Stimulation Workflows with Directional Leads in Parkinson's Disease.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a preferred treatment for parkinsonian patients with severe motor fluctuations. Proper targeting of the STN sensorimotor segment appears to be a crucial factor for success of the procedure. The recent introduction of directional leads theoretically increases stimulation specificity in this challenging area but also requires more precise stimulation parameters. OBJECTIVE: We investigated whether commercially available software for image guided programming (IGP) could maximize the benefits of DBS by informing the clinical standard care (CSC) and improving programming workflows. METHODS: We prospectively analyzed 32 consecutive parkinsonian patients implanted with bilateral directional leads in the STN. Double blind stimulation parameters determined by CSC and IGP were assessed and compared at three months post-surgery. IGP was used to adjust stimulation parameters if further clinical refinement was required. Overall clinical efficacy was evaluated one-year post-surgery. RESULTS: We observed 78% concordance between the two electrode levels selected by the blinded IGP prediction and CSC assessments. In 64% of cases requiring refinement, IGP improved clinical efficacy or reduced mild side effects, predominantly by facilitating the use of directional stimulation (93% of refinements). CONCLUSIONS: The use of image guided programming saves time and assists clinical refinement, which may be beneficial to the clinical standard care for STN-DBS and further improve the outcomes of DBS for PD patients.

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.

Family planning service disruptions in the first two years of the COVID-19 pandemic: Evidence from health facilities in seven low- and middle-income countries.

Many speculated that COVID-19 would severely restrict the delivery of essential health services, including family planning (FP), but evidence of this impact is limited, partly due to data limitations. We use cross-sectional data collected from regional and national samples of health facilities (n = 2,610) offering FP across seven low- and middle-income countries (LMICs) between 2019 and 2021, with longitudinal data from four geographies, to examine reported disruptions to the FP service environment during COVID-19, assess how these disruptions varied according to health system characteristics, and evaluate how disruptions evolved throughout the first two years of the pandemic, relative to a pre-pandemic period. Findings show significant variation in the impact of COVID-19 on facility-based FP services across LMICs, with the largest disruptions to services occurring in Rajasthan, India, where COVID-19 cases were highest among geographies sampled, while in most sub-Saharan African settings there were limited disruptions impacting FP service availability, method provision, and contraceptive supplies. Facility-reported disruptions to care were not reflected in observed changes to the number of FP clients or types of stockouts experienced in the first two years of the pandemic. Public and higher-level facilities were generally less likely to experience COVID-19-related disruptions to FP services, suggesting policy mitigation measures-particularly those implemented among government-operated health facilities-may have been critical to ensuring sustained delivery of reproductive healthcare during the pandemic.

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.

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.

Differential discontinuation by covert use status in Kenya.

Objectives: Qualitative research suggests that covert users may be more likely to discontinue contraception due to the logistics of discretion and fear of disclosure. This study sought to quantify whether covert users are more likely to discontinue contraception than overt users. Study design: We used a national longitudinal survey from Kenya conducted from November 2019/February 2020 to November 2020/April 2021 to test whether the time to discontinuation between covert and overt users still in need of contraception differed using survival analyses over a period of 5 years since method initiation. Results: Multivariate Cox regression results showed there was an interaction with time and covert use on the risk of discontinuation; for every additional month of use, there was an increased risk of discontinuation of covert users compared to overt users (3% increased hazard, p = 0.02). At 1 and 2 years, there were no differences in the hazard of discontinuation (adjusted hazard ratio [aHR]1 year 0.95, 95% CI 0.54-1.65 and aHR2 years 1.37, 95% CI 0.85-2.21), yet at 3, 4, and 5 years, the hazard of discontinuation was higher for covert compared to overt users (aHR3 years 1.99, 95% 1.11-3.56; aHR4 years 2.89, 95% CI 2.0-6.40; aHR5 years 4.18, 95% CI 1.45-12.0). Conclusions: These results suggest efforts are needed to support covert users in managing their contraceptive use and for improving contraceptive counseling surrounding covert use. Our findings shed light on the increasing challenge covert users face after approximately the first 2 years of use; covert users require additional follow-up in both research and care provision. Implications: Covert users are at a higher risk of discontinuation of contraception while still trying to avoid pregnancy, particularly after the first 2 years of use. Family planning providers and programs must protect access to and maintain the privacy of reproductive services to this population, focusing on follow-up care provision and counseling.

Overview on wearable sensors for the management of Parkinson's disease.

Parkinson's disease (PD) is affecting about 1.2 million patients in Europe with a prevalence that is expected to have an exponential increment, in the next decades. This epidemiological evolution will be challenged by the low number of neurologists able to deliver expert care for PD. As PD is better recognized, there is an increasing demand from patients for rigorous control of their symptoms and for therapeutic education. In addition, the highly variable nature of symtoms between patients and the fluctuations within the same patient requires innovative tools to help doctors and patients monitor the disease in their usual living environment and adapt treatment in a more relevant way. Nowadays, there are various body-worn sensors (BWS) proposed to monitor parkinsonian clinical features, such as motor fluctuations, dyskinesia, tremor, bradykinesia, freezing of gait (FoG) or gait disturbances. BWS have been used as add-on tool for patients' management or research purpose. Here, we propose a practical anthology, summarizing the characteristics of the most used BWS for PD patients in Europe, focusing on their role as tools to improve treatment management. Consideration regarding the use of technology to monitor non-motor features is also included. BWS obviously offer new opportunities for improving management strategy in PD but their precise scope of use in daily routine care should be clarified.

Predictors and Pathophysiology of Axial Postural Abnormalities in Parkinsonism: A Scoping Review.

Background: Postural abnormalities involving the trunk are referred to as axial postural abnormalities and can be observed in over 20% of patients with Parkinson's disease (PD) and in atypical parkinsonism. These symptoms are highly disabling and frequently associated with back pain and a worse quality of life in PD. Despite their frequency, little is known about the pathophysiology of these symptoms and scant data are reported about their clinical predictors, making it difficult to prompt prevention strategies. Objectives: We conducted a scoping literature review of clinical predictors and pathophysiology of axial postural abnormalities in patients with parkinsonism to identify key concepts, theories and evidence on this topic. Methods: We applied a systematic approach to identify studies, appraise quality of evidence, summarize main findings, and highlight knowledge gaps. Results: Ninety-two articles were reviewed: 25% reported on clinical predictors and 75% on pathophysiology. Most studies identified advanced disease stage and greater motor symptoms severity as independent clinical predictors in both PD and multiple system atrophy. Discrepant pathophysiology data suggested different potential central and peripheral pathogenic mechanisms. Conclusions: The recognition of clinical predictors and pathophysiology of axial postural abnormalities in parkinsonism is far from being elucidated due to literature bias, encompassing different inclusion criteria and measurement tools and heterogeneity of patient samples. Most studies identified advanced disease stage and higher burden of motor symptoms as possible clinical predictors. Pathophysiology data point toward many different (possibly non-mutually exclusive) mechanisms, including dystonia, rigidity, proprioceptive and vestibular impairment, and higher cognitive deficits.

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).

[Molecular basis of hyperammonemia secondary to asparaginase: from therapeutic efficacity to toxicity]. / Bases moléculaires de l'hyperammoniémie sous asparaginase : de l'efficacité thérapeutique à la toxicité.

Asparaginase is a key molecule in the treatment of acute lymphoblastic leukemia. It has improved response rates to chemotherapy. However, this is not without consequences. Therapeutic efficacy is sometimes achieved at the expense of toxicities that can lead to treatment discontinuation. Among them, patients can develop hyperammonemia which can sometimes be symptomatic leading to neurological disorders that can go as far as hyperammonemic coma or even death. Through a review of the current state of the literature, the objective is to understand the disparity of ammonia values as well as the clinical heterogeneity for a given ammonia concentration. A review of the literature including more than eighty publications was performed. The glutaminase activity of asparaginase seems to play an important role in the development of hyperammonia. At present, no risk factors have been identified for the development of hyperammonemia. On the other hand, the question of the impact of pre-analysis phase arises. Indeed, asparaginase continues to exert its activity in vitro, which leads to an artefactual increase in ammonia.

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 incidence and safety in Niger in 2021: Findings from a nationally representative cross-sectional survey of reproductive-aged women using direct and indirect measurement approaches.

Niger is a country in which legal restrictions and a dearth of research has long limited our understanding of the extent and safety of induced abortion. The current study is the first national study of induced abortion in Niger. It uses direct (self-report) and indirect (best friend method) to provide nationally representative estimates of induced abortion incidence and safety and evaluates the performance of the indirect measurement approach. We used cross-sectional, representative survey data on women aged 15-49 in Niger collected between January and May 2022; final sample included 3,696 women. The survey included questions on respondents' and their closest female friends' experience with abortion, including methods and sources used. We calculated one-year abortion incidence and the proportion of abortions involving non-recommended methods and/or sources to determine safety separately for respondents and friends, overall and by background characteristics. The fully adjusted one-year friend abortion rate was 6.7 abortions per 1,000 women in 2021, which was substantially higher than the corresponding respondent rate of 0.4 per 1,000 women. Confidence intervals were wide, but friend estimates suggest higher abortion rates among women in their 20s, those with secondary or higher education, and those with no children. Nearly all abortions were unsafe (97% respondents, 100% friends), involving non-recommended methods and/or sources. While abortion numbers were small, unsafe abortion appeared more common among older women, married women, those with children, and those residing in rural areas. Our findings indicate that, despite legal restrictions, some women undergo abortions in Niger at great risk to their physical safety. Ensuring adequate access to quality voluntary family planning services to prevent unintended pregnancy and postabortion care to treat complications is essential to reducing the risk of unsafe abortion in the country.