Assessing the relationship of patient reported outcome measures with functional status in dysferlinopathy: A Rasch analysis approach

Dysferlinopathy is a muscular dystrophy with a highly variable functional disease progression in which the relationship of function to some patient reported outcome measures (PROMs) has not been previously reported. This analysis aims to identify the suitability of PROMs and their association with motor performance.Two-hundred and four patients with dysferlinopathy were identified in the Jain Foundation\u27s Clinical Outcome Study in Dysferlinopathy from 14 sites in 8 countries. All patients completed the following PROMs: Individualized Neuromuscular Quality of Life Questionnaire (INQoL), International Physical Activity Questionnaire (IPAQ), and activity limitations for patients with upper and/or lower limb impairments (ACTIVLIMs). In addition, nonambulant patients completed the Egen Klassifikation Scale (EK). Assessments were conducted annually at baseline, years 1, 2, 3, and 4. Data were also collected on the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) and Performance of Upper Limb (PUL) at these time points from year 2. Data were analyzed using descriptive statistics and Rasch analysis was conducted on ACTIVLIM, EK, INQoL. For associations, graphs (NSAD with ACTIVLIM, IPAQ and INQoL and EK with PUL) were generated from generalized estimating equations (GEE). The ACTIVLIM appeared robust psychometrically and was strongly associated with the NSAD total score (Pseud

Quantifying Golgi structure using EM : combining volume-SEM and stereology for higher throughput

John Lucocq was supported by a Programme grant from the Wellcome Trust (Number 045404). Sophie Ferguson was a recipient of a 600th anniversary studentship from the University of St Andrews.Investigating organelles such as the Golgi complex depends increasingly on high-throughput quantitative morphological analyses from multiple experimental or genetic conditions. Light microscopy (LM) has been an effective tool for screening but fails to reveal fine details of Golgi structures such as vesicles, tubules and cisternae. Electron microscopy (EM) has sufficient resolution but traditional transmission EM (TEM) methods are slow and inefficient. Newer volume scanning EM (volume-SEM) methods now have the potential to speed up 3D analysis by automated sectioning and imaging. However, they produce large arrays of sections and/or images, which require labour-intensive 3D reconstruction for quantitation on limited cell numbers. Here, we show that the information storage, digital waste and workload involved in using volume-SEM can be reduced substantially using sampling-based stereology. Using the Golgi as an example, we describe how Golgi populations can be sensed quantitatively using single random slices and how accurate quantitative structural data on Golgi organelles of individual cells can be obtained using only 5–10 sections/images taken from a volume-SEM series (thereby sensing population parameters and cell–cell variability). The approach will be useful in techniques such as correlative LM and EM (CLEM) where small samples of cells are treated and where there may be variable responses. For Golgi study, we outline a series of stereological estimators that are suited to these analyses and suggest workflows, which have the potential to enhance the speed and relevance of data acquisition in volume-SEM.Publisher PDFPeer reviewe

Does integration of HIV and sexual and reproductive health services improve technical efficiency in Kenya and Swaziland? An application of a two-stage semi parametric approach incorporating quality measures.

Theoretically, integration of vertically organized services is seen as an important approach to improving the efficiency of health service delivery. However, there is a dearth of evidence on the effect of integration on the technical efficiency of health service delivery. Furthermore, where technical efficiency has been assessed, there have been few attempts to incorporate quality measures within efficiency measurement models particularly in sub-Saharan African settings. This paper investigates the technical efficiency and the determinants of technical efficiency of integrated HIV and sexual and reproductive health (SRH) services using data collected from 40 health facilities in Kenya and Swaziland for 2008/2009 and 2010/2011. Incorporating a measure of quality, we estimate the technical efficiency of health facilities and explore the effect of integration and other environmental factors on technical efficiency using a two-stage semi-parametric double bootstrap approach. The empirical results reveal a high degree of inefficiency in the health facilities studied. The mean bias corrected technical efficiency scores taking quality into consideration varied between 22% and 65% depending on the data envelopment analysis (DEA) model specification. The number of additional HIV services in the maternal and child health unit, public ownership and facility type, have a positive and significant effect on technical efficiency. However, number of additional HIV and STI services provided in the same clinical room, proportion of clinical staff to overall staff, proportion of HIV services provided, and rural location had a negative and significant effect on technical efficiency. The low estimates of technical efficiency and mixed effects of the measures of integration on efficiency challenge the notion that integration of HIV and SRH services may substantially improve the technical efficiency of health facilities. The analysis of quality and efficiency as separate dimensions of performance suggest that efficiency may be achieved without sacrificing quality

Impact of integration of sexual and reproductive health services on consultation duration times: results from the Integra Initiative.

The lack of human resources is a key challenge in scaling up of HIV services in Africa's health care system. Integrating HIV services could potentially increase their effectiveness and optimize the use of limited resources and clinical staff time. We examined the impact of integration of provider initiated HIV counselling and testing (PITC) and family planning (FP counselling and FP provision) services on duration of consultation to assess the impact of PITC and FP integration on staff workload. This study was conducted in 24 health facilities in Kenya under the Integra Initiative, a non-randomized, pre/post intervention trial to evaluate the impact of integrated HIV and sexual and reproductive health services on health and service outcomes. We compared the time spent providing PITC-only services, FP-only services and integrated PITC/FP services. We used log-linear regression to assess the impact of plausible determinants on the duration of clients' consultation times. Median consultation duration times were highest for PITC-only services (30 min), followed by integrated services (10 min) and FP-only services (8 min). Times for PITC-only and FP-only services were 69.7% higher (95% Confidence Intervals (CIs) 35.8-112.0) and 43.9% lower (95% CIs -55.4 to - 29.6) than times spent on these services when delivered as an integrated service, respectively. The reduction in consultation times with integration suggests a potential reduction in workload. The higher consultation time for PITC-only could be because more pre- and post-counselling is provided at these stand-alone services. In integrated PITC/FP services, the duration of the visit fell below that required by HIV testing guidelines, and service mix between counselling and testing substantially changed. Integration of HIV with FP services may compromise the quality of services delivered and care must be taken to clearly specify and monitor appropriate consultation duration times and procedures during the process of integrating HIV and FP services

The Clinical Outcome Study for dysferlinopathy

Objective: To describe the baseline clinical and functional characteristics of an international cohort of 193 patients with dysferlinopathy. Methods: The Clinical Outcome Study for dysferlinopathy (COS) is an international multicenter study of this disease, evaluating patients with genetically confirmed dysferlinopathy over 3 years. We present a cross-sectional analysis of 193 patients derived from their baseline clinical and functional assessments. Results: There is a high degree of variability in disease onset, pattern of weakness, and rate of progression. No factor, such as mutation class, protein expression, or age at onset, accounted for this variability. Among patients with clinical diagnoses of Miyoshi myopathy or limb-girdle muscular dystrophy, clinical presentation and examination was not strikingly different. Respiratory impairment and cardiac dysfunction were observed in a minority of patients. A substantial delay in diagnosis was previously common but has been steadily reducing, suggesting increasing awareness of dysferlinopathies. Conclusions: These findings highlight crucial issues to be addressed for both optimizing clinical care and planning therapeutic trials in dysferlinopathy. This ongoing longitudinal study will provide an opportunity to further understand patterns and variability in disease progression and form the basis for trial design

Use of HIV counseling and testing and family planning services among postpartum women in Kenya: a multicentre, non-randomised trial.

BACKGROUND: Addressing the postnatal needs of new mothers is a neglected area of care throughout sub-Saharan Africa. The study compares the effectiveness of integrating HIV and family planning (FP) services into postnatal care (PNC) with stand-alone services on postpartum women's use of HIV counseling and testing and FP services in public health facilities in Kenya. METHODS: Data were derived from samples of women who had been assigned to intervention or comparison groups, had given birth within the previous 0-10 weeks and were receiving postnatal care, at baseline and 15 months later. Descriptive statistics describe the characteristics of the sample and multivariate logistic regression models assess the effect of the integrated model of care on use of provider-initiated testing and counseling (PITC) and FP services. RESULTS: At the 15-month follow-up interviews, more women in the intervention than comparison sites used implants (15 % vs. 3 %; p < 0.001), while injectables were the most used short-term method by women in both sites. Women who wanted to wait until later to have children (OR = 1.3; p < 0.01; 95 % CI: 1.1-1.5), women with secondary education (OR = 1.2; p < 0.05; 95 % CI: 1.0-1.4), women aged 25-34 years (OR = 1.2; p < 0.01; 95 % CI: 1.1-1.4) and women from poor households (OR = 1.6; p < 0.001; 95 % CI: 1.4-1.9) were associated with FP use. Nearly half (47 %) and about one-third (30 %) of mothers in the intervention and comparison sites, respectively, were offered PITC. Significant predictors of uptake of PITC were seeking care in a health center/dispensary relative to a hospital, having a partner who has tested for HIV and being poor. CONCLUSIONS: An integrated delivery approach of postnatal services is beneficial in increasing the uptake of PITC and long-acting FP services among postpartum women. Also, interventions aimed at increasing male partners HIV testing have a positive effect on the uptake of PITC and should be encouraged. TRIAL REGISTRATION: ClinicalTrials.gov NCT01694862

Assessing the Relationship of Patient Reported Outcome Measures With Functional Status in Dysferlinopathy: A Rasch Analysis Approach

Dysferlinopathy is a muscular dystrophy with a highly variable functional disease progression in which the relationship of function to some patient reported outcome measures (PROMs) has not been previously reported. This analysis aims to identify the suitability of PROMs and their association with motor performance.Two-hundred and four patients with dysferlinopathy were identified in the Jain Foundation's Clinical Outcome Study in Dysferlinopathy from 14 sites in 8 countries. All patients completed the following PROMs: Individualized Neuromuscular Quality of Life Questionnaire (INQoL), International Physical Activity Questionnaire (IPAQ), and activity limitations for patients with upper and/or lower limb impairments (ACTIVLIMs). In addition, nonambulant patients completed the Egen Klassifikation Scale (EK). Assessments were conducted annually at baseline, years 1, 2, 3, and 4. Data were also collected on the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) and Performance of Upper Limb (PUL) at these time points from year 2. Data were analyzed using descriptive statistics and Rasch analysis was conducted on ACTIVLIM, EK, INQoL. For associations, graphs (NSAD with ACTIVLIM, IPAQ and INQoL and EK with PUL) were generated from generalized estimating equations (GEE). The ACTIVLIM appeared robust psychometrically and was strongly associated with the NSAD total score (Pseudo R2 0.68). The INQoL performed less well and was poorly associated with the NSAD total score (Pseudo R2 0.18). EK scores were strongly associated with PUL (Pseudo R2 0.69). IPAQ was poorly associated with NSAD scores (Pseudo R2 0.09). This study showed that several of the chosen PROMs demonstrated change over time and a good association with functional outcomes. An alternative quality of life measure and method of collecting data on physical activity may need to be selected for assessing dysferlinopathy

Numbers, systems, people: how interactions influence integration. Insights from case studies of HIV and reproductive health services delivery in Kenya.

Drawing on rich data from the Integra evaluation of integrated HIV and reproductive-health services, we explored the interaction of systems hardware and software factors to explain why some facilities were able to implement and sustain integrated service delivery while others were not. This article draws on detailed mixed-methods data for four case-study facilities offering reproductive-health and HIV services between 2009 and 2013 in Kenya: (i) time-series client flow, tracking service uptake for 8841 clients; (ii) structured questionnaires with 24 providers; (iii) in-depth interviews with 17 providers; (iv) workload and facility data using a periodic activity review and cost-instruments; and (v) contextual data on external activities related to integration in study sites. Overall, our findings suggested that although structural factors like stock-outs, distribution of staffing and workload, rotation of staff can affect how integrated care is provided, all these factors can be influenced by staff themselves: both frontline and management. Facilities where staff displayed agency of decision making, worked as a team to share workload and had management that supported this, showed better integration delivery and staff were able to overcome some structural deficiencies to enable integrated care. Poor-performing facilities had good structural integration, but staff were unable to utilize this because they were poorly organized, unsupported or teams were dysfunctional. Conscientious objection and moralistic attitudes were also barriers.Integra has demonstrated that structural integration is not sufficient for integrated service delivery. Rather, our case studies show that in some cases excellent leadership and peer-teamwork enabled facilities to perform well despite resource shortages. The ability to provide support for staff to work flexibly to deliver integrated services and build resilient health systems to meet changing needs is particularly relevant as health systems face challenges of changing burdens of disease, climate change, epidemic outbreaks and more