Ultrasensitive Detection of Cancer Biomarkers in the Clinic by Use of a Nanostructured Microfluidic Array

Multiplexed biomarker protein detection holds unrealized promise for clinical cancer diagnostics due to lack of suitable measurement devices and lack of rigorously validated protein panels. Here we report an ultrasensitive electrochemical microfluidic array optimized to measure a four-protein panel of biomarker proteins, and we validate the protein panel for accurate oral cancer diagnostics. Unprecedented ultralow detection into the 5-50 fg.mL(-1) range was achieved for simultaneous measurement of proteins interleukin 6 (IL-6), IL-8, vascular endothelial growth factor (VEGF), and VEGF-C in diluted serum. The immunoarray achieves high sensitivity in 50 min assays by using off-line protein capture by magnetic beads carrying 400 000 enzyme labels and similar to 100 000 antibodies. After capture of the proteins and washing to inhibit nonspecific binding, the beads are magnetically separated and injected into the array for selective capture by antibodies on eight nanostructured sensors. Good correlations with enzyme-linked immunosorbent assays (ELISA) for protein determinations in conditioned cancer cell media confirmed the accuracy of this approach. Normalized means of the four protein levels in 78 oral cancer patient serum samples and 49 controls gave clinical sensitivity of 89 and specificity of 98 for oral cancer detection, demonstrating high diagnostic utility. The low-cost, easily fabricated immunoarray provides a rapid Serum test for diagnosis and personalized therapy of oral cancer. The device is readily adaptable to clinical diagnostics of other cancers. This record was migrated from the OpenDepot repository service in June, 2017 before shutting down

Burden of disease in adults admitted to hospital in a rural region of coastal Kenya: an analysis of data from linked clinical and demographic surveillance systems

Background Estimates of the burden of disease in adults in sub-Saharan Africa largely rely on models of sparse data. We aimed to measure the burden of disease in adults living in a rural area of coastal Kenya with use of linked clinical and demographic surveillance data. Methods We used data from 18 712 adults admitted to Kilifi District Hospital (Kilifi , Kenya) between Jan 1, 2007, and Dec 31, 2012, linked to 790 635 person-years of observation within the Kilifi Health and Demographic Surveillance System, to establish the rates and major causes of admission to hospital. These data were also used to model diseasespecifi c disability-adjusted life-years lost in the population. We used geographical mapping software to calculate admission rates stratifi ed by distance from the hospital. Findings The main causes of admission to hospital in women living within 5 km of the hospital were infectious and parasitic diseases (303 per 100 000 person-years of observation), pregnancy-related disorders (239 per 100 000 personyears of observation), and circulatory illnesses (105 per 100 000 person-years of observation). Leading causes of hospital admission in men living within 5 km of the hospital were infectious and parasitic diseases (169 per 100 000 personyears of observation), injuries (135 per 100 000 person-years of observation), and digestive system disorders (112 per 100 000 person-years of observation). HIV-related diseases were the leading cause of disability-adjusted lifeyears lost (2050 per 100 000 person-years of observation), followed by non-communicable diseases (741 per 100 000 personyears of observation). For every 5 km increase in distance from the hospital, all-cause admission rates decreased by 11% (95% CI 7–14) in men and 20% (17–23) in women. The magnitude of this decline was highest for endocrine disorders in women (35%; 95% CI 22–46) and neoplasms in men (30%; 9–45). Interpretation Adults in rural Kenya face a combined burden of infectious diseases, pregnancy-related disorders, cardiovascular illnesses, and injuries. Disease burden estimates based on hospital data are aff ected by distance from the hospital, and the amount of underestimation of disease burden diff ers by both disease and sex

Risk of Injection-Site Abscess among Infants Receiving a Preservative-Free, Two-Dose Vial Formulation of Pneumococcal Conjugate Vaccine in Kenya.

There is a theoretical risk of adverse events following immunization with a preservative-free, 2-dose vial formulation of 10-valent-pneumococcal conjugate vaccine (PCV10). We set out to measure this risk. Four population-based surveillance sites in Kenya (total annual birth cohort of 11,500 infants) were used to conduct a 2-year post-introduction vaccine safety study of PCV10. Injection-site abscesses occurring within 7 days following vaccine administration were clinically diagnosed in all study sites (passive facility-based surveillance) and, also, detected by caregiver-reported symptoms of swelling plus discharge in two sites (active household-based surveillance). Abscess risk was expressed as the number of abscesses per 100,000 injections and was compared for the second vs first vial dose of PCV10 and for PCV10 vs pentavalent vaccine (comparator). A total of 58,288 PCV10 injections were recorded, including 24,054 and 19,702 identified as first and second vial doses, respectively (14,532 unknown vial dose). The risk ratio for abscess following injection with the second (41 per 100,000) vs first (33 per 100,000) vial dose of PCV10 was 1.22 (95% confidence interval [CI] 0.37-4.06). The comparator vaccine was changed from a 2-dose to 10-dose presentation midway through the study. The matched odds ratios for abscess following PCV10 were 1.00 (95% CI 0.12-8.56) and 0.27 (95% CI 0.14-0.54) when compared to the 2-dose and 10-dose pentavalent vaccine presentations, respectively. In Kenya immunization with PCV10 was not associated with an increased risk of injection site abscess, providing confidence that the vaccine may be safely used in Africa. The relatively higher risk of abscess following the 10-dose presentation of pentavalent vaccine merits further study

Sights and insights: Vocational outdoor students’ learning

Outdoor leader and adventure sport education in the United Kingdom has been characterized by an over-emphasis on technical skills at the expense of equally important, but often marginalized intra- and inter-personal skills necessary for contemporary outdoor employment. This study examined the lived experience of vocational outdoor students in order, firstly, to identify what was learned about the workplace through using reflective practice and, secondly, what was learned about reflective practice through this experience. The study used a purposive sample of students (n=15) who were invited to maintain reflective journals during summer work experience, and this was followed up with semi-structured interviews. Manual Interpretative Phenomenological Analysis (IPA) revealed that in the workplace setting students used reflective practice to understand and develop technical proficiency, support awareness of the value of theory, and acted as a platform to express emergent concepts of ‘professionalism’. Lessons about reflective practice emphasized its value in social settings, acknowledging different ways of reflection, and understanding and managing professional life beyond graduation

Using an equity-based framework for evaluating publicly funded health insurance programmes as an instrument of UHC in Chhattisgarh State, India

Universal health coverage (UHC) has provided the impetus for the introduction of publicly funded health insurance (PFHI) schemes in the mixed health systems of India and many other low- and middle-income countries. There is a need for a holistic understanding of the pathways of impact of PFHI schemes, including their role in promoting equity of access. Methods: This paper applies an equity-oriented evaluation framework to assess the impacts of PFHI schemes in Chhattisgarh State by synthesising literature from various sources and highlighting knowledge gaps. Data were collected from an extensive review of publications on PFHI schemes in Chhattisgarh since 2009, including empirical studies from the first author's PhD and grey literature such as programme evaluation reports, media articles and civil society campaign documents. The framework was constructed using concepts and frameworks from the health policy and systems research literature on UHC, access and health system building blocks, and is underpinned by the values of equity, human rights and the right to health

A critical analysis of purchasing arrangements in Kenya: the case of micro health insurance

BACKGROUND:Strategic purchasing can ensure that financial resources are used in a way that optimally enhances the attainment of health system goals. A number of low- and middle-income countries, including Kenya, have experimented with micro health insurance (MHIs) as a means to purchase health services for the informal sector. This study aimed to examine the purchasing practices of MHIs in Kenya. METHODS:The study was guided by an analytical framework that compared purchasing practices of MHIs with the ideal actions for strategic purchasing along three pairs of principal-agent relationships (government-purchaser, purchaser-provider and citizen-purchaser). The study adopted a qualitative descriptive case study design with 2 MHIs as cases. Data were collected through document reviews (regulation, marketing materials, websites) and semi-structured interviews with key informants (n = 27). RESULTS:The regulatory framework for MHIs did not adequately support strategic purchasing practice and was exacerbated by poor coordination between health and financial sectors. The MHIs strategically contracted health providers over whom they could exercise bargaining power, sometimes at the expense of quality. There were no clear channels for beneficiaries to provide timely feedback to the purchaser. MHIs premium payments were family-based, low-cost and offered limited benefits. Coverage was based on ability to pay, which may have excluded low-income households from membership. CONCLUSIONS:Adequate policy, legal and regulatory frameworks that integrate MHIs into the broader health financing system and support strategic purchasing practices are required. The state departments responsible for finance and health should form coordinating structures that ensure that MHI's role in universal health coverage is owned across all relevant sectors, and that actors, such as regulators, perform in a coordinated manner. The frameworks should also seek to align purchasers' relationships with providers so that clear and consistent signals are received by providers from all purchasing mechanisms present within the health system

A critical analysis of purchasing arrangements in Kenya: the case of the national hospital insurance fund

BACKGROUND:Purchasing refers to the process by which pooled funds are paid to providers in order to deliver a set of health care interventions. Very little is known about purchasing arrangements in low- and middle-income countries (LMICs), and certainly not in Kenya. This study aimed to critically analyse purchasing arrangements in Kenya, using the National Hospital Insurance Fund (NHIF) as a case study. METHODS:We applied a principal-agent relationship framework, which identifies three pairs of principal-agent relationships (government-purchaser, purchaser-provider, and citizen-purchaser) and specific actions required within them to achieve strategic purchasing. A qualitative case study approach was applied. Data were collected through document reviews (statutes, policy and regulatory documents) and in-depth interviews (n=62) with key informants including NHIF officials, Ministry of Health (MoH) officials, insurance industry actors, and health service providers. Documents were summarised using standardised forms. Interviews were recorded, transcribed verbatim, and analysed using a thematic framework approach. RESULTS:The regulatory and policy framework for strategic purchasing in Kenya was weak and there was no clear accountability mechanism between the NHIF and the MoH. Accountability mechanisms within the NHIF have developed over time, but these emphasized financial performance over other aspects of purchasing. The processes for contracting, monitoring, and paying providers do not promote equity, quality, and efficiency. This was partly due to geographical distribution of providers, but also due to limited capacity within the NHIF. There are some mechanisms for assessing needs, preferences, and values to inform design of the benefit package, and while channels to engage beneficiaries exist, they do not always function appropriately and awareness of these channels to the beneficiaries is limited. CONCLUSION:Addressing the gaps in the NHIF's purchasing performance requires a number of approaches. Critically, there is a need for the government through the MoH to embrace its stewardship role in health, while recognizing the multiplicity of actors given Kenya's devolved context. Relatively recent decentralisation reforms present an opportunity that should be grasped to rewrite the contract between the government, the NHIF and Kenyans in the pursuit of universal health coverage (UHC)

A critical analysis of health care purchasing arrangements in Kenya: A case study of the county departments of health

BACKGROUND:Purchasing in health care financing refers to the transfer of pooled funds to health care providers for the provision of health care services. There is limited empirical work on purchasing arrangements and what is required for strategic purchasing in low- and middle-income countries. We conducted this study to critically assess the purchasing arrangements of the county departments of health (CDOH) who are the largest purchasers of health care in Kenya. METHODS:We used a qualitative case study approach to assess the extent to which the purchasing actions of the CDOH in Kenya were strategic. We purposively sampled 10 counties and collected data using in-depth interviews (n = 81), focus group discussions (n = 4), and documents review. We analyzed data using a framework approach. RESULTS:County departments of health did not practice strategic purchasing. The government's (national and county) role as a steward for the purchasing function was characterized by poor accountability and inadequate budgetary allocations for service delivery. The absence of a purchaser-provider split between the CDOH and public health care providers undermined provider selection based on performance and quality. Poor public participation and ineffective complaints and feedback mechanisms limited public accountability and responsiveness to the needs of the people. CONCLUSION:Our findings show that while there are frameworks that could promote strategic purchasing of the CDOH, strategic purchasing is impaired by poor implementation of these frameworks and the inherent weaknesses of a public integrated purchasing system that lacks purchaser-provider split

[PP.01.13] Marked BP distribution shift from casual to ambulatory measurement in Kenya

Objective: Few studies have used ambulatory blood pressure monitoring (ABPM) to describe blood pressure (BP) patterns in sub-Saharan Africa (sSA). We conducted a population-based study in Kilifi, Kenya to determine the usefulness of ABPM in this setting. Methods: Design and method: An age-stratified sample of 1248 individuals were randomly selected from our Demographic Surveillance Area. Of these, 986 underwent casual BP measurement at their homes using an automated Omron™ M10-IT monitor. All individuals with casual BP above 140/90mmHg (mean of 2 out of 3 readings) and a random subset with BP below 140/90mmHg were invited to undergo 24-hour ABPM within one week of screening. ESH defined cutoffs were used to define hypertensive status. Results: Of 415 individuals who underwent both casual and ABPM measurement, 162 (39%) had sustained hypertension, 161 (39%) were normotensive, 58 (14%) had whitecoat hypertension and 34 (8%) had masked hypertension. Population BP was markedly higher when using casual BP compared to ABPM (11mmHg 95% CI [9–13] systolic and 9mmHg [7–11] diastolic). If casual BP measurement only had been used, age standardized population prevalence of hypertension would have been 26.5% (19.3–35.6). ‘True’ prevalence by ABPM was 17.1% (11.0–24.4), masked hypertension 7.6 (2.8–13.7)% and white coat hypertension 3.8% (1.7–6.1) of the population. The sensitivity and specificity of casual BP measurement for ‘diagnosing’ hypertension were 80% (73–86) and 84% (79–88) respectively. The positive and negative predictive values were 80% (74–85) and 84% (79–89). BP indices and validity measures showed strong age related trends; for example sensitivity of casual BP was 9.7% (2.5–24.9) in 30–39 year olds but 91% (83–97) in 60–69 year olds. Non-dipping was present in 9% (3–15) of the population and was strongly associated with masked hypertension (OR 10, [4–27]). Conclusions: Casual BP measurement methods substantially overestimated hypertension prevalence, while failing to identify a significant proportion who were hypertensive on ABPM. Whether ABPM identifies those at risk of future vascular events better than casual methods and is justified on cost effectiveness in sSA are key research questions.</p