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A new modified-release oral formulation combines acarbose and orlistat (MR-OA) to enhance efficacy and reduce adverse effects through controlled drug release. This study aims to compare the pharmacodynamic properties of the orlistat component of MR-OA (MR-O) with a conventional orlistat product, Xenical (Conv-O), analyzing the percentage of fecal fat excretion. In addition, the pharmacokinetic properties of the complete formulation, MR-OA, were compared with Conv-O. In Part I of the study, 20 healthy volunteers were randomized in a single-blind, crossover trial to take MR-O or Conv-O (120-mg orlistat) 3 times daily for 9 days. Fecal fat was measured at baseline and after each treatment. MR-O and Conv-O similarly increased fecal fat percentage from 3.8% to 13.5%, confirming pharmacodynamic equivalence. Adverse events were few and generally rated as mild. In Part II, participants received MR-OA and then Conv-O, with blood samples collected for 12 hours to measure orlistat and acarbose levels. Orlistat's peak concentration stayed below 5 ng/mL, and acarbose plasma levels were mostly undetectable, indicating minimal systemic absorption. This shows that the new weight loss product MR-OA retains the dietary energy loss pathway used in Conv-O. Consistent with previous studies, minimal systemic absorption of orlistat and acarbose was observed for MR-OA, confirming that no significant alteration of the original substances occurs when modifying their release.

Background: Armed conflict and insecurity have been linked to deteriorations in reproductive health and rights globally. In Nigeria, armed violence has taken a significant toll on women's and girls' health and safety. However, knowledge is limited about how conflict shapes attitudes surrounding their ability to make autonomous decisions on relationships and childbearing. Drawing on a socioecological framework and terror management theory, we aimed to investigate the association between conflict, insecurity, and attitudes toward women's and girls' reproductive autonomy in Nigeria.

Methods: We conducted a cross-sectional study using data from two sources: the World Values Survey (WVS) and the Uppsala Conflict Data Program-Georeferenced Event Dataset (UCDP-GED). Nationally representative data on attitudes of 559 men and 534 women was collected by WVS in 2017-2018. Linear probability models estimated the association between attitudes toward five dimensions of women and girl's reproductive autonomy (contraception, safe abortion, marital decisionmaking, delayed childbearing, early marriage), respondents' perceptions of neighborhood insecurity using WVS data, and geospatial measures of conflict exposure drawn from UCDP-GED.

Results: Exposure to armed conflict and perceived neighborhood insecurity were associated with more supportive attitudes toward access to safe abortion among both men and women. Among women, conflict exposure was associated with higher support for contraception and the perception that early marriage can provide girls with security. Conflict -affected men were more likely to support a delay in girls' childbearing.

Conclusion: Our findings suggest that conflict and insecurity pose a threat to, but also facilitate opportunities for, women's and girls' reproductive autonomy. Contraception, abortion, early marriage, and postponement or childbearing may be perceived as risk -aversion strategies in response to mortality threats, livelihood losses, and conflict -driven sexual violence. Our findings foreshadow changes in fertility and relationship patterns in conflict -affected Nigeria and highlight the need for health programming to ensure access to contraception and safe abortion services.

We investigated the association between values and attitudes toward sexual and reproductive health and rights (SRHR) and gender equality, with reproductive agency in Ethiopia, Kenya, and Zimbabwe. Using 2020-21 World Values Survey (WVS) data (n = 3096), we utilised the SRHR Support Index including five subindices to gauge SRHR attitudes, the WVS Equality Index for gender equality values, and the perceived level of freedom of choice and control over whether, when, and how many children to have as a proxy for reproductive agency. Descriptive statistics, bivariate, and multivariable logistic regressions were used to analyse how values and attitudes differed between respondents of high vs low reproductive agency using the median as cut-off, stratified by country and sex. Country, education, subjective social class, and religion were associated with reproductive agency. Adjusted analyses indicated associations between supportive values and attitudes towards equitable masculinity norms, SRHR interventions and gender equality, with high reproductive agency. Associations varied more between countries than by sex. Findings suggest an association between SRHR and gender equality values and attitudes and the level of reproductive agency, and underscore the importance of addressing values and attitudes in context-specific interventions. Measures of SRHR progress should be critically reviewed and complemented with self-assessed - as opposed to researcher-ascribed - items to support the successful implementation of global SRHR agendas. Nous avons & eacute;tudi & eacute; l'association entre les valeurs et les attitudes & agrave; l'& eacute;gard de la sant & eacute; et des droits sexuels et reproductifs et de l'& eacute;galit & eacute; de genre, avec la capacit & eacute; d'action en mati & egrave;re de procr & eacute;ation en & Eacute;thiopie, au Kenya et au Zimbabwe. & Agrave; l'aide des donn & eacute;es de l'Enqu & ecirc;te mondiale sur les valeurs (WVS) 2020-2021 (n = 3096), nous avons utilis & eacute; l'indice de soutien & agrave; la sant & eacute; et aux droits sexuels et reproductifs comprenant cinq sous-indices pour & eacute;valuer les attitudes en mati & egrave;re de sant & eacute; et de droits sexuels et reproductifs, l'indice d'& eacute;galit & eacute; de la WVS pour les valeurs d'& eacute;galit & eacute; des sexes et le niveau per & ccedil;u de libert & eacute; de choix et de contr & ocirc;le sur le fait d'avoir des enfants, le moment et le nombre des naissances comme indicateur de la capacit & eacute; d'action en mati & egrave;re de procr & eacute;ation. Des statistiques descriptives, des r & eacute;gressions logistiques bivari & eacute;es et multivari & eacute;es ont & eacute;t & eacute; utilis & eacute;es pour analyser la mani & egrave;re dont les valeurs et les attitudes diff & eacute;raient entre les r & eacute;pondants ayant une capacit & eacute; d'action reproductive & eacute;lev & eacute;e et faible, au moyen de la m & eacute;diane comme seuil, stratifi & eacute;e par pays et par sexe. Le pays, l'& eacute;ducation, la classe sociale subjective et la religion & eacute;taient associ & eacute;s & agrave; la capacit & eacute; d'action en mati & egrave;re de procr & eacute;ation. Les analyses ajust & eacute;es ont indiqu & eacute; des associations entre les valeurs et les attitudes de soutien & agrave; l'& eacute;gard des normes de masculinit & eacute; & eacute;quitables, les interventions de sant & eacute; et de droits sexuels et reproductifs et l'& eacute;galit & eacute; des sexes, avec une capacit & eacute; d'action reproductive & eacute;lev & eacute;e. Les associations variaient davantage entre les pays que selon le sexe. Les r & eacute;sultats sugg & egrave;rent une association entre les valeurs et attitudes en mati & egrave;re de sant & eacute; et droits sexuels et reproductifs et d'& eacute;galit & eacute; des sexes et le niveau de capacit & eacute; d'action en mati & egrave;re de procr & eacute;ation, et soulignent combien il est important d'aborder les valeurs et attitudes dans des interventions sp & eacute;cifiques au contexte. Les mesures des progr & egrave;s en mati & egrave;re de sant & eacute; et de droits sexuels et reproductifs doivent & ecirc;tre examin & eacute;es de mani & egrave;re critique et compl & eacute;t & eacute;es par des & eacute;l & eacute;ments d'auto-& eacute;valuation - par opposition & agrave; des & eacute;l & eacute;ments attribu & eacute;s par les chercheurs - pour soutenir une mise en oe uvre r & eacute;ussie des programmes mondiaux de sant & eacute; et de droits sexuels et reproductifs. Investigamos la asociaci & oacute;n entre valores y actitudes relacionados con la salud y los derechos sexuales y reproductivos (SDSR) y la igualdad de g & eacute;nero con la agencia reproductiva en Etiop & iacute;a, Kenia y Zimbabue. Utilizando datos de la Encuesta Mundial de Valores (EMV) de 2020-21 (n = 3096), utilizamos el & Iacute;ndice de Apoyo para SDSR, incluidos cinco sub & iacute;ndices para medir las actitudes sobre SDSR, el & Iacute;ndice de Igualdad de la EMV para los valores de igualdad de g & eacute;nero y el nivel percibido de libertad de elecci & oacute;n y control de si tener o no hijos, cu & aacute;ndo tenerlos y cu & aacute;ntos tener como un indicador de la agencia reproductiva. Se utilizaron estad & iacute;sticas descriptivas y regresiones log & iacute;sticas bivariadas y multivariables para analizar las diferencias entre los valores y las actitudes de las encuestadas con mucha agencia reproductiva y aqu & eacute;llas con poca agencia reproductiva, utilizando la mediana como punto de corte, estratificadas por pa & iacute;s y sexo. El pa & iacute;s, el nivel de escolaridad, la clase social subjetiva y la religi & oacute;n de las participantes estaban asociados con su agencia reproductiva. Los an & aacute;lisis ajustados indicaron asociaciones entre los valores y las actitudes que apoyaban las normas de masculinidad equitativas, las intervenciones de SDSR y la igualdad de g & eacute;nero, con mucha agencia reproductiva. Las asociaciones variaron m & aacute;s entre pa & iacute;ses que por sexo. Los hallazgos indican una asociaci & oacute;n entre los valores y las actitudes relacionados con SDSR e igualdad de g & eacute;nero y el nivel de agencia reproductiva, y subrayan la importancia de abordar los valores y las actitudes en intervenciones realizadas en contextos espec & iacute;ficos. Las medidas de los avances en SDSR deben revisarse de manera cr & iacute;tica y suplementarse con elementos autoevaluados, y no adscritos por investigadores, para respaldar la ejecuci & oacute;n exitosa de las agendas mundiales de SDSR.

OBJECTIVES: To evaluate the feasibility of using the NeuroMotion smartphone application for remote General Movements Assessment for screening of infants for cerebral palsy in Kathmandu, Nepal. 

METHOD: Thirty-one term born infants at risk of cerebral palsy due to birth asphyxia or neonatal seizures were recruited for the follow-up at Paropakar Maternity and Women’s Hospital, 1st October 2021 to 7th January 2022. Parents filmed their children at home using the app at 3 months’ age and the videos were assessed for technical quality using a standardized form and for fidgety movements by Prechtl’s General Movements Assessment. Usability of the app was evaluated through a parental survey. 

RESULTS: Twenty families sent in altogether 46 videos out of which 35 had approved technical quality. Sixteen children had at least one video with approved technical quality. Three infants lacked fidgety movements. The level of agreement between assessors was acceptable (Krippendorf alpha 0.781). Parental answers to the usability survey were in general positive. 

INTERPRETATION: Engaging parents in screening of cerebral palsy with the help of a smartphone-aided remote General Movements Assessment is possible in the urban area of a South Asian lower middle-income country.

Background

In development of inhaled drugs- and formulations the measured concentration in the systemic circulation is often used as a surrogate for local dosimetry in the lungs. To further elucidate regional differences in the fate of drugs in the lungs, different aerodynamic sizes of aerosols have been used to target major airway regions. An alternative approach to achieve regional targeting of aerosols, is to use a defined aerosol bolus together with a bolus breath hold strategy. A small volume of test aerosol is intercalated and stopped at different penetration depths, to achieve increased drug deposition at chosen lung locations. Drug permeation from the lung regions is then investigated by repeatedly sampling venous blood from the systemic circulation.

The PreciseInhale® (PI) exposure platform was developed to allow generation of aerosols from different sources, including clinical inhalers, into a holding chamber, for subsequent use with alternative exposure modules in vitro and in vivo. In the current first-in-human study was investigated the feasibility of a new clinical exposure module added to the PI system. By extracting aerosol puffs from a medical inhaler for subsequent delivery to volunteers, it was possible to administer whole lung exposures, as well as regional targeting exposures.

Methods

Aerosols containing 250 µg/25 µg fluticasone propionate (FP)/salmeterol xinafoate (SMX) were automatically actuated and extracted from the pressurized Metered Dose Inhaler (pMDI) Evohaler Seretide forte into the PI system's holding chamber, then administered to the healthy volunteers using controlled flowrate and volume exposure cycles.

Two main comparisons were made by measuring the systemic PK response: I. One label dose directly from the inhaler to the subject was compared to the same dose extracted from the pMDI into the PI system and then administered to the subject. II A small aerosol bolus at a penetration level in the central airways was compared to a small aerosol bolus at a penetration level in the peripheral lung.

Results and Conclusions

When one inhaler dose was administered via the PI system, the absorbed dose, expressed as AUC24, was approximately twice as high and the CV was less than half, compared to direct inhalation from the same pMDI. Bolus breath hold targeting of drugs from the same aerosol mixture to the peripheral lung and the central airways showed a difference in their appearance in the systemic circulation. Normalized to the same deposited dose, SMX had a 57 % higher C_max in the peripheral lung compared to the central airways. However, from 6 to 24 h after dosing the systemic concentrations of SMX from both regions were quite similar. FP had parallel concentrations curves with a 23 % higher AUC24 in the peripheral lung with no noticeable elevation around C_max. The permeability of these two substances from similar sized aerosols was indeed higher in the thinner air/blood barriers of the peripheral lung compared to the central airways, but differences as measured on the venous side of the circulation were not dramatic. In conclusion, the PI system provided better control of actuation, aspiration, and dispensation of aerosols from the clinical inhaler and thereby delivered higher quality read outs of pharmacokinetic parameters such as t_max, C_max, and AUC. Improved performance, using PI system, can likely also be employed for studying regional selectivity of other responses in the lungs, for use in drug development.

Background: Addressing attitudes is central to achieving sexual and reproductive health and rights (SRHR) and Agenda 2030. We aimed to develop a comprehensive index to measure attitudinal support for SRHR, expanding opportunities for global trend analyses and tailored interventions.

Methods: We designed a new module capturing attitudes towards different dimensions of SRHR, collected via the nationally representative World Values Survey in Ethiopia, Kenya, and Zimbabwe during 2020-2021 (n = 3,711). We used exploratory factor analysis of 58 items to identify sub-scales and an overall index. Adjusted regression models were used to evaluate the index according to sociodemographic characteristics, stratified by country and sex.

Results: A 23-item, five-factor solution was identified and used to construct sub-indices reflecting support for: (1) sexual and reproductive rights, (2) neighborhood sexual safety, (3) gender-equitable relationships, (4) equitable masculinity norms, and (5) SRHR interventions. These five sub-indices performed well across countries and socioeconomic subgroups and were combined into a comprehensive "SRHR Support Index", standardized on a 1-100 scale (mean = 39.19, SD = 15.27, Cronbach's alpha = 0.80) with higher values indicating more support for SRHR. Mean values were highest in Kenya (45.48, SD = 16.78) followed by Ethiopia (40.2, SD = 13.63), and lowest in Zimbabwe (32.65, SD = 13.77), with no differences by sex. Higher education and being single were associated with more support, except in Ethiopia. Younger age and urban residence correlated with more support among males only.

Conclusion: The SRHR Support Index has the potential to broaden SRHR attitude research from a comprehensive perspective - addressing the need for a common measure to track progress over time.

BACKGROUND: International guidelines recommend early intervention to all children at risk of cerebral palsy, but targeted screening programs are often lacking in low- and middle-income settings with the highest burden of disease. Smartphone applications have the potential to improve access to early diagnostics by empowering parents to film their children at home followed by centralized evaluation of videos with General Movements Assessment. We explored mothers’ perceptions about participating in a smartphone aided cerebral palsy screening program in Kathmandu, Nepal.

METHODS: This is an explorative qualitative study that used focus group discussions (n=2) and individual interviews (n=4) with mothers of term-born infants surviving birth asphyxia or neonatal seizures. Parents used the NeuroMotion™ smartphone app to film their children at home and the videos were analysed using General Movements Assessment. Sekhon et al.’s framework on the acceptability of health care interventions guided the design of the interviews and the deductive qualitative content analysis.

RESULTS: Mothers were interested in engaging with the programme and expressed hope it would benefit their children. Most felt use of the app was intuitive. They were, however, unclear about the way the analysis was performed. Support from the research team was often needed to overcome an initial lack of self-confidence in using the technology and to reduce anxiety related to the follow-up. The intervention was overall perceived as recommendable but should be supplemented by a face-to-face consultation.

CONCLUSION: Smartphone aided remote screening of cerebral palsy is acceptable in a lower middle-income population but requires additional technical support.

Background In a critical obstetric situation, the time interval between the decision of performing a caesarean section (CS) and delivery can influence maternal and newborn outcomes. In Somaliland, consent for surgical procedures, such as CS needs to be sought from family members. Objective To determine the association between a delay in performing a CS and severe maternal and newborn outcomes in a national referral hospital in Somaliland. The type of barriers leading to delayed performance of CS after a doctor's decision were also explored. Methods Women were followed from the time of decision to perform CS until discharge from the hospital between 15 April 2019 and 30 March 2020. No delay was defined as < 1 hour and delayed CS was defined as 1-3 hours and >3 hours from decision of CS to delivery. Information was collected on barriers leading to delayed CS and maternal and newborn outcomes. Data was analysed using binary and multivariate logistic regression. Results Overall, 1255 women were recruited from a larger cohort of 6658 women. A delay in CS >3 hours was associated with higher odds of severe maternal outcomes (aOR 1.58, 95% CI [1.13-2.21]). On the contrary, delay in performing a CS >3 hours was associated with lower odds of stillbirth (aOR 0.48, 95% CI [0.32-0.71]) compared to women without delay. Further, family decision-making for consent was the most important barrier leading to delays of >3 hours as compared to financial factors and barriers related to healthcare providers (48% vs 26% and 15%, respectively, p < 0.001). Conclusions In this setting, delay in performing CS >3 hours was associated with higher risk of severe maternal outcomes. A standardised system of performing a CS by primarily addressing the barriers associated with family decision-making, financial aspects and healthcare providers is needed.

Background: We assessed the change in obstetric management after implementation of a quality improvement intervention, the Nepal Perinatal Quality Improvement Package (NePeriQIP).

Methods: The Nepal Perinatal Quality Improvement Package was a stepped-wedge cluster-randomized controlled trial conducted in 12 public hospitals in Nepal between April 2017 and October 2018. In this study, three hospitals allocated at different time points to the intervention were selected for a nested before-after analysis. We used bivariate and multivariate analyses to compare obstetric management in the control vs intervention group.

Results: There were 25 977 deliveries in the three hospitals during the study period: 10 207 (39%) in the control and 15 770 (61%) in the intervention group. After adjusting for maternal age, ethnicity, education, gestational age, stage of labor at admission, complications during labor, and birthweight, the intervention group had a higher proportion of fetal heart rate monitoring performed as per protocol (adjusted odds ratio [aOR] 1.19, 95% confidence interval [CI] 1.12-1.27), shorter time intervals between each fetal heart rate monitoring (aOR 2.09, 95% CI 1.96-2.23), a higher likelihood of abnormal fetal heart rate being detected (aOR 1.53, 95% CI 1.25-1.68), progress of labor more often being recorded immediately after per vaginal examination (aOR 2.73, 95% CI 2.55-2.93), and partograph filled as per standards (aOR 3.18, 95% CI 2.98-3.50). The cesarean birth rate was 2.5% in the control group and 8.2% in the intervention group (aOR 3.12, 95% CI 2.64-3.68).

Conclusions: The NePeriQIP intervention has potential to improve obstetric care, especially intrapartum fetal surveillance, in similar low-resource settings.

Objective The aim of this study was to evaluate the effect of a novel, oral, modified-release formulation of the lipase inhibitor orlistat and the glucosidase/amylase inhibitor acarbose (denoted EMP16) on relative body weight after 26 weeks compared with placebo. Methods The randomized, double-blind, placebo-controlled trial had a 26-week treatment period, with dose escalation up to 6 weeks. Participants, adults between ages 18 and 75 years, with BMI >= 30 kg/m(2) or >= 28 kg/m(2) with risk factors, were randomly assigned to EMP16 120-mg orlistat/40-mg acarbose (EMP16-120/40), EMP16-150/50, or placebo. The primary end point was relative weight loss from baseline to week 26 assessed in participants with at least one post-baseline weight measurement. Results Of 156 randomized participants, 149 constituted the intention-to-treat population. The mean (95% CI) estimated treatment difference to placebo in relative weight loss after 26 weeks in the intention-to-treat population was -4.70% (-6.16% to -3.24%; p < 0.0001) with EMP16-120/40 and -5.42% (-6.60% to -4.24%; p < 0.0001) with EMP16-150/50. Conclusions This trial indicates that orlistat and acarbose can be successfully combined in a modified-release formulation to provide efficacious weight loss with no unexpected safety issues. EMP16 may be a promising candidate among other medications for improved weight management.