Evidence-informed health policy: are we beginning to get there at last

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The role of rapid diagnostics in managing Ebola epidemics

Ebola emerged in West Africa around December 2013 and swept through Guinea, Sierra Leone and Liberia, giving rise to 27,748 confirmed, probable and suspected cases reported by 29 July 2015. Case diagnoses during the epidemic have relied on polymerase chain reaction-based tests. Owing to limited laboratory capacity and local transport infrastructure, the delays from sample collection to test results being available have often been 2 days or more. Point-of-care rapid diagnostic tests offer the potential to substantially reduce these delays. We review Ebola rapid diagnostic tests approved by the World Health Organization and those currently in development. Such rapid diagnostic tests could allow early triaging of patients, thereby reducing the potential for nosocomial transmission. In addition, despite the lower test accuracy, rapid diagnostic test-based diagnosis may be beneficial in some contexts because of the reduced time spent by uninfected individuals in health-care settings where they may be at increased risk of infection; this also frees up hospital beds. We use mathematical modelling to explore the potential benefits of diagnostic testing strategies involving rapid diagnostic tests alone and in combination with polymerase chain reaction testing. Our analysis indicates that the use of rapid diagnostic tests with sensitivity and specificity comparable with those currently under development always enhances control, whether evaluated at a health-care-unit or population level. If such tests had been available throughout the recent epidemic, we estimate, for Sierra Leone, that their use in combination with confirmatory polymerase chain-reaction testing might have reduced the scale of the epidemic by over a third

Good on paper: the gap between programme theory and real-world context in Pakistan's Community Midwife programme

Objective To understand why skilled birth attendance—an acknowledged strategy for reducing maternal deaths—has been effective in some settings but is failing in Pakistan and to demonstrate the value of a theory-driven approach to evaluating implementation of maternal healthcare interventions. Design Implementation research was conducted using an institutional ethnographic approach. Setting and population National programme and local community levels in Pakistan. Methods Observations, focus group discussions, and in-depth interviews were conducted with 38 Community Midwives (CMWs), 20 policymakers, 45 healthcare providers and 136 community members. A critical policy document review was conducted. National and local level data were brought together. Main outcomes Alignment of programme theory with real-world practice. Results Data revealed gaps between programme theory, assumptions and reality on the ground. The design of the programme failed to take into account: (1) the incongruity between the role of a midwife and dominant class and gendered norms that devalue such a role; (2) market and consumer behaviour that prevented CMWs from establishing private practices; (3) the complexity of public–private sector cooperation. Uniform deployment policies failed to consider existing provider density and geography. Conclusions Greater attention to programme theory and the ‘real-world’ setting during design of maternal health strategies is needed to achieve consistent results in different contexts

Addressing disparities in maternal health care in Pakistan: gender, class and exclusion

Background: After more than two decades of the Safe Motherhood Initiative and Millennium Development Goals aimed at reducing maternal mortality, women continue to die in childbirth at unacceptably high rates in Pakistan. While an extensive literature describes various programmatic strategies, it neglects the rigorous analysis of the reasons these strategies have been unsuccessful, especially for women living at the economic and social margins of society. A critical gap in current knowledge is a detailed understanding of the root causes of disparities in maternal health care, and in particular, how gender and class influence policy formulation and the design and delivery of maternal health care services. Taking Pakistan as a case study, this research builds upon two distinct yet interlinked conceptual approaches to understanding the phenomenon of inequity in access to maternal health care: social exclusion and health systems as social institutions. Methods/Design: This four year project consists of two interrelated modules that focus on two distinct groups of participants: (1) poor, disadvantaged women and men and (2) policy makers, program managers and health service providers. Module one will employ critical ethnography to understand the key axes of social exclusion as related to gender, class and zaat and how they affect women’s experiences of using maternal health care. Through health care setting observations, interviews and document review, Module two will assess policy design and delivery of maternal health services. Discussion: This research will provide theoretical advances to enhance understanding of the power dynamics of gender and class that may underlie poor women’s marginalization from health care systems in Pakistan. It will also provide empirical evidence to support formulation of maternal health care policies and health care system practices aimed at reducing disparities in maternal health care in Pakistan. Lastly, it will enhance inter-disciplinary research capacity in the emerging field of social exclusion and maternal health and help reduce social inequities and achieve the Millennium Development Goal No. 5

Combined changes in Wnt signalling response and contact inhibition induce altered proliferation in radiation treated intestinal crypts

Curative intervention is possible if colorectal cancer is identified early, underscoring the need to detect the earliest stages of malignant transformation. A candidate biomarker is the expanded proliferative zone observed in crypts before adenoma formation, also found in irradiated crypts. However, the underlying driving mechanism for this is not known. Wnt signaling is a key regulator of proliferation, and elevated Wnt signaling is implicated in cancer. Nonetheless, how cells differentiate Wnt signals of varying strengths is not understood. We use computational modeling to compare alternative hypotheses about how Wnt signaling and contact inhibition affect proliferation. Direct comparison of simulations with published experimental data revealed that the model that best reproduces proliferation patterns in normal crypts stipulates that proliferative fate and cell cycle duration are set by the Wnt stimulus experienced at birth. The model also showed that the broadened proliferation zone induced by tumorigenic radiation can be attributed to cells responding to lower Wnt concentrations and dividing at smaller volumes. Application of the model to data from irradiated crypts after an extended recovery period permitted deductions about the extent of the initial insult. Application of computational modeling to experimental data revealed how mechanisms that control cell dynamics are altered at the earliest stages of carcinogenesis

Cardiogenic shock in a patient with hypothyroid myopathy responsive only to thyroxin replacement: a case report

The effect of hypothyroidism on the cardiovascular system has been well documented. Cardiac dysfunction due to hypothyroidism manifests as both systolic and diastolic dysfunction of the heart leading to cardiac arrhythmia and congestive heart failure. Its presentation in the form of refractory hypotension is rare. We describe a 52 year old man on whom Hypothyroid Cardiomyopathy manifested as cardiogenic shock responsive only to thyroxin replacement

Toward trustworthy medical device in silico clinical trials: a hierarchical framework for establishing credibility and strategies for overcoming key challenges

Computational models of patients and medical devices can be combined to perform an in silico clinical trial (ISCT) to investigate questions related to device safety and/or effectiveness across the total product life cycle. ISCTs can potentially accelerate product development by more quickly informing device design and testing or they could be used to refine, reduce, or in some cases to completely replace human subjects in a clinical trial. There are numerous potential benefits of ISCTs. An important caveat, however, is that an ISCT is a virtual representation of the real world that has to be shown to be credible before being relied upon to make decisions that have the potential to cause patient harm. There are many challenges to establishing ISCT credibility. ISCTs can integrate many different submodels that potentially use different modeling types (e.g., physics-based, data-driven, rule-based) that necessitate different strategies and approaches for generating credibility evidence. ISCT submodels can include those for the medical device, the patient, the interaction of the device and patient, generating virtual patients, clinical decision making and simulating an intervention (e.g., device implantation), and translating acute physics-based simulation outputs to health-related clinical outcomes (e.g., device safety and/or effectiveness endpoints). Establishing the credibility of each ISCT submodel is challenging, but is nonetheless important because inaccurate output from a single submodel could potentially compromise the credibility of the entire ISCT. The objective of this study is to begin addressing some of these challenges and to identify general strategies for establishing ISCT credibility. Most notably, we propose a hierarchical approach for assessing the credibility of an ISCT that involves systematically gathering credibility evidence for each ISCT submodel in isolation before demonstrating credibility of the full ISCT. Also, following FDA Guidance for assessing computational model credibility, we provide suggestions for ways to clearly describe each of the ISCT submodels and the full ISCT, discuss considerations for performing an ISCT model risk assessment, identify common challenges to demonstrating ISCT credibility, and present strategies for addressing these challenges using our proposed hierarchical approach. Finally, in the Appendix we illustrate the many concepts described here using a hypothetical ISCT example

Efficacy of therapist-delivered transdiagnostic CBT for patients with persistent physical symptoms in secondary care: a randomised controlled trial

Background: Medically unexplained symptoms otherwise referred to as persistent physical symptoms (PPS) are debilitating to patients. As many specific PPS syndromes share common behavioural, cognitive, and affective influences, transdiagnostic treatments might be effective for this patient group. We evaluated the clinical efficacy and cost-effectiveness of a therapist-delivered, transdiagnostic cognitive behavioural intervention (TDT-CBT) plus (+) standard medical care (SMC) v. SMC alone for the treatment of patients with PPS in secondary medical care. Methods: A two-arm randomised controlled trial, with measurements taken at baseline and at 9, 20, 40- and 52-weeks post randomisation. The primary outcome measure was the Work and Social Adjustment Scale (WSAS) at 52 weeks. Secondary outcomes included mood (PHQ-9 and GAD-7), symptom severity (PHQ-15), global measure of change (CGI), and the Persistent Physical Symptoms Questionnaire (PPSQ). Results: We randomised 324 patients and 74% were followed up at 52 weeks. The difference between groups was not statistically significant for the primary outcome (WSAS at 52 weeks: estimated difference -1.48 points, 95% confidence interval from -3.44 to 0.48, p = 0.139). However, the results indicated that some secondary outcomes had a treatment effect in favour of TDT-CBT + SMC with three outcomes showing a statistically significant difference between groups. These were WSAS at 20 weeks (p = 0.016) at the end of treatment and the PHQ-15 (p = 0.013) and CGI at 52 weeks (p = 0.011). Conclusion: We have preliminary evidence that TDT-CBT + SMC may be helpful for people with a range of PPS. However, further study is required to maximise or maintain effects seen at end of treatment