The German Development Bank as a policy entrepreneur for social health protection: a case study of the development and implementation of the ‘Sehat Sahulat Programme’ in Khyber Pakhtunkhwa, Pakistan

# Background The German Development Bank (KfW) supported the Government of Khyber Pakhtunkhwa (GoKP) to design and implement its first social health protection (SHP) scheme, named the Sehat Sahulat Programme (SSP). We described the role of KfW in the evolution of SSP with a view to identifying transferrable lessons for international development agencies working on similar initiatives in socioeconomically comparable contexts. # Methods We employed a qualitative instrumental case study design approach. First, we obtained and analysed key programme documents to describe the chronology of events and policy changes. We then undertook in-depth interviews to understand factors influencing policy changes. Finally, we carried out non-participant observations to understand how policy decisions were made and implemented. We employed maximum variation sampling to recruit participants and conducted a thematic analysis of data. # Results SSP was described by GoKP officials as an innovative financing strategy and a flagship project of the government formed by the Pakistan Tehreek-i-Insaf (PTI). First, programme officials reported that KfW was instrumental in both designing and financing SSP, which had plans to provide free health insurance to low-income families and raise revenue through paid enrollment of the wealthy (solidarity). Second, GoKP deviated from this model and covered the entire population of KP free of cost. Through SSP, GoKP envisaged service provision through private hospitals (subsidiarity). In the third year, GoKP included public sector hospitals in the programme. Although planned supplementary insurance products might result in inequitable utilisation, KfW continued supporting SSP and committed funding for piloting outpatient department services for two years, 2023 and 2024. # Conclusions This in-depth case study has highlighted the potentially positive role of international development assistance in introducing innovative financing strategies to promote universal health coverage. However, development partners might have limited control over how things evolve

The notion of access to health care in a large-scale social health protection initiative: a case study of 'Sehat Sahulat Programme' at Khyber Pakhtunkhwa, Pakistan

# Background Sehat Sahulat Programme (SSP), a health insurance initiative, was launched by the Government of Khyber Pakhtunkhwa (GoKP) in Pakistan to improve access to quality health services. In this paper, we describe the notion of access under SSP, present stakeholders' views on access-related challenges, and suggest ways forward to realise SSP's access-related objective in the broader context of its contribution towards Pakistan's drive to achieve Universal Health Coverage (UHC). # Methods We employed a case study design approach using three data sources. We used official GoKP programme documents to capture the chronology of events (policy interventions), in-depth interviews to explore the drivers behind the events and non-participant observations to understand the decision-making and implementation processes. We employed maximum variation sampling. Access to documents and observation sites was gained through the SSP director. We recruited interviewees through direct and indirect approaches and conducted thematic analysis. # Findings GoKP engaged the State Life Insurance Corporation (SLIC) of Pakistan as a purchaser. SLIC purchased services from public and private hospitals for SSP patients, up to 600,000 Pakistani Rupees (PKR) per family per year. Considering this insurance coverage, GoKP officials claimed SSP made health care accessible, which the development partners contested. Instead of the narrow finance-centric definition by GoKP, the development partners highlighted the broader dimensions of access, including the services’ acceptability and availability. Tensions existed between the interpretation of the stakeholders on different dimensions of access. For instance, GoKP and SLIC claimed that including private hospitals in SSP improved services’ availability, but development partners noted an under-supply of private providers in remote districts of the province. Bridging such an undersupply, SLIC made inter-district referrals, which the patient advocates noted led to travel costs and geographical barriers. Similarly, GoKP officials claimed SSP had good acceptability. The providers noted that SSP’s acceptability was damaged by limited patient choice, low package rates, and delayed claims payments. # Conclusions This analysis suggests that SSP had challenges with the acceptability and geographical dimensions of access which GoKP needed to address. A key transferrable lesson is that demand-side intervention (insurance) might not improve access with a weak supply side. Therefore, countries contemplating improving access to services enroute to achieving UHC need to address both supply and demand-side considerations

COVID-19 and diabetes in 2020: a systematic review

Attempts were made to review the literature on diabetic patients who experience complications when they contract COVID-19, and to determine whether ethnicity and other risk factors play an important role in the development of symptoms and their severity, as well as responding to medications. A literature search was performed using fve keywords, namely COVID-19, diabetes, ethnicity, medications, and risk factors between January 2019 and December 2020 using electronic databases such as PubMed, Science Direct, Google Scholar, Springer Link, and Scopus. Forty studies were included. The review indicated that diabetes was a signifcant risk factor for poorer outcomes and increased mortality associated with COVID-19. There were several risk factors for diabetic patients that increased their likelihood of poorer outcomes associated with COVID-19. These included black and Asian ethnicity, male sex with high BMI. In conclusion, patients with diabetes of black or Asian origin with high BMI, male sex, and older age had an increased risk of poorer outcomes associated with COVID-19. This highlights the importance of considering the history of the patient in prioritising care and treatment

Maturation trajectories of cortical resting-state networks depend on the mediating frequency band

The functional significance of resting state networks and their abnormal manifestations in psychiatric disorders are firmly established, as is the importance of the cortical rhythms in mediating these networks. Resting state networks are known to undergo substantial reorganization from childhood to adulthood, but whether distinct cortical rhythms, which are generated by separable neural mechanisms and are often manifested abnormally in psychiatric conditions, mediate maturation differentially, remains unknown. Using magnetoencephalography (MEG) to map frequency band specific maturation of resting state networks from age 7 to 29 in 162 participants (31 independent), we found significant changes with age in networks mediated by the beta (13–30 Hz) and gamma (31–80 Hz) bands. More specifically, gamma band mediated networks followed an expected asymptotic trajectory, but beta band mediated networks followed a linear trajectory. Network integration increased with age in gamma band mediated networks, while local segregation increased with age in beta band mediated networks. Spatially, the hubs that changed in importance with age in the beta band mediated networks had relatively little overlap with those that showed the greatest changes in the gamma band mediated networks. These findings are relevant for our understanding of the neural mechanisms of cortical maturation, in both typical and atypical development.This work was supported by grants from the Nancy Lurie Marks Family Foundation (TK, SK, MGK), Autism Speaks (TK), The Simons Foundation (SFARI 239395, TK), The National Institute of Child Health and Development (R01HD073254, TK), National Institute for Biomedical Imaging and Bioengineering (P41EB015896, 5R01EB009048, MSH), and the Cognitive Rhythms Collaborative: A Discovery Network (NFS 1042134, MSH). (Nancy Lurie Marks Family Foundation; Autism Speaks; SFARI 239395 - Simons Foundation; R01HD073254 - National Institute of Child Health and Development; P41EB015896 - National Institute for Biomedical Imaging and Bioengineering; 5R01EB009048 - National Institute for Biomedical Imaging and Bioengineering; NFS 1042134 - Cognitive Rhythms Collaborative: A Discovery Network

Study of environmental enteropathy and malnutrition (SEEM) in Pakistan: protocols for biopsy based biomarker discovery and validation

Background: Environmental Enteropathy (EE), characterized by alterations in intestinal structure, function, and immune activation, is believed to be an important contributor to childhood undernutrition and its associated morbidities, including stunting. Half of all global deaths in children \u3c 5 years are attributable to under-nutrition, making the study of EE an area of critical priority. Methods: Community based intervention study, divided into two sub-studies, 1) Longitudinal analyses and 2) Biopsy studies for identification of EE features via omics analyses. Birth cohorts in Matiari, Pakistan established: moderately or severely malnourished (weight for height Z score (WHZ) \u3c − 2) children, and well-nourished (WHZ \u3e 0) children. Blood, urine, and fecal samples, for evaluation of potential biomarkers, will be collected at various time points from all participants (longitudinal analyses). Participants will receive appropriate educational and nutritional interventions; non-responders will undergo further evaluation to determine eligibility for further workup, including upper gastrointestinal endoscopy. Histopathological changes in duodenal biopsies will be compared with duodenal biopsies obtained from USA controls who have celiac disease, Crohn’s disease, or who were found to have normal histopathology. RNA-Seq will be employed to characterize mucosal gene expression across groups. Duodenal biopsies, luminal aspirates from the duodenum, and fecal samples will be analyzed to define microbial community composition (omic analyses). The relationship between histopathology, mucosal gene expression, and community configuration will be assessed using a variety of bioinformatic tools to gain better understanding of disease pathogenesis and to identify mechanism-based biomarkers. Ethical review committees at all collaborating institutions have approved this study. All results will be made available to the scientific community. Discussion: Operational and ethical constraints for safely obtaining intestinal biopsies from children in resource-poor settings have led to a paucity of human tissue-based investigations to understand and reverse EE in vulnerable populations. Furthermore, EE biomarkers have rarely been correlated with gold standard histopathological confirmation. The Study of Environmental Enteropathy and Malnutrition (SEEM) is designed to better understand the pathophysiology, predictors, biomarkers, and potential management strategies of EE to inform strategies to eradicate this debilitating pathology and accelerate progress towards the 2030 Sustainable Development Goals. Trial registration: Retrospectively registered; clinicaltrials.gov ID NCT03588013

Maturation trajectories of cortical resting-state networks depend on the mediating frequency band.

The functional significance of resting state networks and their abnormal manifestations in psychiatric disorders are firmly established, as is the importance of the cortical rhythms in mediating these networks. Resting state networks are known to undergo substantial reorganization from childhood to adulthood, but whether distinct cortical rhythms, which are generated by separable neural mechanisms and are often manifested abnormally in psychiatric conditions, mediate maturation differentially, remains unknown. Using magnetoencephalography (MEG) to map frequency band specific maturation of resting state networks from age 7 to 29 in 162 participants (31 independent), we found significant changes with age in networks mediated by the beta (13-30 Hz) and gamma (31-80 Hz) bands. More specifically, gamma band mediated networks followed an expected asymptotic trajectory, but beta band mediated networks followed a linear trajectory. Network integration increased with age in gamma band mediated networks, while local segregation increased with age in beta band mediated networks. Spatially, the hubs that changed in importance with age in the beta band mediated networks had relatively little overlap with those that showed the greatest changes in the gamma band mediated networks. These findings are relevant for our understanding of the neural mechanisms of cortical maturation, in both typical and atypical development

Somatosensory cortex functional connectivity abnormalities in autism show opposite trends, depending on direction and spatial scale

Functional connectivity is abnormal in autism, but the nature of these abnormalities remains elusive. Different studies, mostly using functional magnetic resonance imaging, have found increased, decreased, or even mixed pattern functional connectivity abnormalities in autism, but no unifying framework has emerged to date. We measured functional connectivity in individuals with autism and in controls using magnetoencephalography, which allowed us to resolve both the directionality (feedforward versus feedback) and spatial scale (local or long-range) of functional connectivity. Specifically, we measured the cortical response and functional connectivity during a passive 25-Hz vibrotactile stimulation in the somatosensory cortex of 20 typically developing individuals and 15 individuals with autism, all males and right-handed, aged 8-18, and the mu-rhythm during resting state in a subset of these participants (12 per group, same age range). Two major significant group differences emerged in the response to the vibrotactile stimulus. First, the 50-Hz phase locking component of the cortical response, generated locally in the primary (S1) and secondary (S2) somatosensory cortex, was reduced in the autism group (P < 0.003, corrected). Second, feedforward functional connectivity between S1 and S2 was increased in the autism group (P < 0.004, corrected). During resting state, there was no group difference in the mu-α rhythm. In contrast, the mu-β rhythm, which has been associated with feedback connectivity, was significantly reduced in the autism group (P < 0.04, corrected). Furthermore, the strength of the mu-β was correlated to the relative strength of 50 Hz component of the response to the vibrotactile stimulus (r = 0.78, P < 0.00005), indicating a shared aetiology for these seemingly unrelated abnormalities. These magnetoencephalography-derived measures were correlated with two different behavioural sensory processing scores (P < 0.01 and P < 0.02 for the autism group, P < 0.01 and P < 0.0001 for the typical group), with autism severity (P < 0.03), and with diagnosis (89% accuracy). A biophysically realistic computational model using data driven feedforward and feedback parameters replicated the magnetoencephalography data faithfully. The direct observation of both abnormally increased and abnormally decreased functional connectivity in autism occurring simultaneously in different functional connectivity streams, offers a potential unifying framework for the unexplained discrepancies in current findings. Given that cortical feedback, whether local or long-range, is intrinsically non-linear, while cortical feedforward is generally linear relative to the stimulus, the present results suggest decreased non-linearity alongside an increased veridical component of the cortical response in autism

Altered Onset Response Dynamics in Somatosensory Processing in Autism Spectrum Disorder.

Abnormalities in cortical connectivity and evoked responses have been extensively documented in autism spectrum disorder (ASD). However, specific signatures of these cortical abnormalities remain elusive, with data pointing toward abnormal patterns of both increased and reduced response amplitudes and functional connectivity. We have previously proposed, using magnetoencephalography (MEG) data, that apparent inconsistencies in prior studies could be reconciled if functional connectivity in ASD was reduced in the feedback (top-down) direction, but increased in the feedforward (bottom-up) direction. Here, we continue this line of investigation by assessing abnormalities restricted to the onset, feedforward inputs driven, component of the response to vibrotactile stimuli in somatosensory cortex in ASD. Using a novel method that measures the spatio-temporal divergence of cortical activation, we found that relative to typically developing participants, the ASD group was characterized by an increase in the initial onset component of the cortical response, and a faster spread of local activity. Given the early time window, the results could be interpreted as increased thalamocortical feedforward connectivity in ASD, and offer a plausible mechanism for the previously observed increased response variability in ASD, as well as for the commonly observed behaviorally measured tactile processing abnormalities associated with the disorder