Optimal Contract Design for Co-development of Companion Diagnostics

As the number of new drugs requiring companion diagnostics rises, more and more partnerships are formed between drug and diagnostics manufacturers to develop the necessary companion diagnostic. An increasingly significant issue is that of the optimal revenue/profit sharing or compensation schemes for such partnerships. We investigate the structure of an optimal compensation scheme under a scenario where a large pharmaceutical firm that is developing a drug intends to partner with a smaller diagnostics firm to develop a companion diagnostic test for the drug. We describe an optimal contract as one that maximizes the pharmaceutical firm\u27s expected profits while offering enough incentives for the diagnostics firm to accept the contract and then work at an effort level that is preferred by the pharmaceutical firm. We formulate the problem of determining the optimal contract as an instance of the Principal-Agent problem. We then present a numerical approach for solving the problem

Quiet Time for Mechanically Ventilated Patients in The Medical Intensive Care Unit

Objective: Sleep disruption occurs frequently in critically ill patients. The primary aim of this study was to examine the effect of quiet time (QT) on patient sedation frequency, sedation and delirium scores; and to determine if consecutive QTs influenced physiologic measures (heart rate, mean arterial blood pressure and respiratory rate). Method: A prospective study of a quiet time protocol was conducted with 72 adult patients on mechanical ventilation. Setting: A Medical Intensive Care Unit (MICU) in the Midwest region of the United States. Results: Sedation was given less frequently after QT (p = 0.045). Those who were agitated prior to QT were more likely to be at goal sedation after QT (p \u3c 0.001). Although not statistically significant, the majority of patients who were negative on the Confusion Assessment Method (CAM-ICU) prior to QT remained delirium free after QT. Repeated measures analysis of variance (ANOVA) for three consecutive QTs showed a significant difference for respiratory rate (p = 0.035). Conclusion: QT may influence sedation administration and promote patient rest. Future studies are required to further understand the influence of QT on mechanically ventilated patients in the intensive care unit

Womens experiences of HIV testing and counselling in the labour ward: A case of Bwaila hospital

Introduction: HIV counseling and testing during labour can be emotional, but is important because it allows mothers and babies to receive PMTCT prophylaxis if previous identification of HIV infection has not occurred. The study explores how HIV testing and counseling during early labour affects women.Methodology: This was a qualitative exploratory study to understand women’s experiences during early labor. From September to October 2009, we conducted 10 indepth interviews with women who tested for HIV during early labour. We recruited women who tested > 3 months previously and those who had never tested for HIV from the postpartum ward of Bwaila Hospital. Data were analyzed manually using the life story approach in order to examine and analyse subjective experiences of women and their constructions of the social world. Transcripts were read multiple times to understand meanings which participants attached to their experiences. We coded data according to emerging themes and subthemes.Results: Ten women 20-35 years were interviewed. Eight women had unknown HIV status while two had known HIV results but re-tested to update their status. Four women were found HIV-positive while 6 were  HIVnegative. The primary theme was that women appreciated and accepted HIV testing and counseling. Testing was accepted as a necessary step to protect the infant from HIV infection. Counseling was viewed as helpful for acceptance of HIV status. One key subtheme was that HIV positive women experienced disappointment about their HIV diagnosis, though this was outweighed by the knowledge that one could protect her infant. All women viewed the short time to complete the counseling and testing procedures as favourable.Conclusion: Labour testing is acceptable and should be promoted to enhance PMTCT services by identifying HIV positive women with unknown status. Counseling helps women to accept being found with HIV and seek appropriate services

Enabling Small-Scale Maize Marketing and Processing to Assure Supplies of Low-Cost Staples

Crop Production/Industries, Downloads December 2008 - July 2009: 6,

Improving primary care antimicrobial stewardship by implementing a peer audit and feedback intervention in Cape Town community healthcare centres

Background. The increasing prevalence of antibiotic resistance is a major threat to public health. Primary care, where 80% of antibiotics are consumed, is a pivotal setting to direct antimicrobial stewardship (AMS) efforts. However, the ideal model to improve antibiotic prescribing in primary care in low-resource settings is not known.Objective. To implement a multidisciplinary audit and feedback AMS intervention with the aim to improve appropriate antibiotic prescribing at primary care level.Methods. The intervention was implemented and monitored in 10 primary care centres of the Cape Town metropole between July 2017 and June 2019. The primary and secondary outcome measures were monthly adherence to a bundle of antibiotic quality process measures and monthly antibiotic consumption, respectively. Multidisciplinary audit and feedback meetings were initiated and integrated into facility clinical meetings. Two Excel tools were utilised to automatically calculate facility audit scores and consumption. Once a month, 10 antibiotic prescriptions were randomly selected for a peer review audit by the team. The prescriptions were audited for adherence to a bundle of seven antibiotic process measures using the standard treatment guidelines (STG) and Essential Medicines List (EML) as standard. Concurrently, primary care pharmacists monitored monthly antibiotic consumption by calculating defined daily doses (DDDs) per 100 prescriptions dispensed. Adherence and consumption feedback were regularly provided to the facilities. Learning collaboratives involving representative multidisciplinary teams were held twice-yearly. Pre-, baseline and post-intervention periods were defined as 6 months before, first 6 months and last 6 months of the study, respectively.Results. The mean overall adherence increased from 19% (baseline) to 47% (post intervention) (p<0.001). Of the 2 077 prescriptions analysed, 33.7% had an antibiotic prescribed inappropriately. No diagnosis had been captured in patient notes, and the antibiotic chosen was not according to the STG and EML in 30.1% and 31.7% of cases, respectively. Seasonal variation was observed in prescribing adherence, with significantly lower adherence in winter and spring months (adjusted odds ratio 0.60). A reduction of 12.9 DDDs between the pre- and post-intervention periods (p=0.0084) was documented, which represented a 19.3% decrease in antibiotic consumption.Conclusion. The study demonstrated that peer reviewed audit and feedback is an effective AMS intervention to improve antibiotic prescribing in primary care in a low-resource setting. The intervention, utilising existing resources and involving multidisciplinary engagement, may be incorporated into existing quality improvement processes at facility level, to ensure sustainable change

Effect of thermal treatment and storage on bioactive compounds, organic acids and antioxidant activity of baobab fruit (Adansonia digitata) pulp from Malawi

Bioactive compounds of baobab (Adansonia digitata) pulp from Malawi were investigated. The effect of thermal treatment and storage on selected quality attributes of the juice was also evaluated. Organic compounds were analysed by HPLC; total phenol content (TPC) and total antioxidant activity (FRAP, ABTS and DPPH) were measured by spectrophotometry. Malawi baobab pulp contains high levels of procyanidin B2 (533 ± 22.6 mg/100 g FW), vitamin C (AA + DHA) (466 ± 2.5 mg/100 g FW), gallic acid (68.5 ± 12.4 mg/100 g FW) and (−)-epicatechin (43.0 ± 3.0 mg/100 g FW) and showed a maximum TPC of 1.89 × 103 ± 1.61 mg GAE/100 g FW. The maximum antioxidant activity was 2.81 × 103 ± 92.8 mg TEAC/100 g FW for FRAP, 1.52 × 103 ± 17.1 mg TEAC/100 g FW for ABTS and 50.9 ± 0.43% DPPH for DPPH. Thermal pasteurisation (72 °C, 15 s) retained vitamin C which further showed extended half-life under refrigeration temperature (6 °C). Procyanidin B2, (−)-epicatechin, TPC and antioxidant activity fluctuated during storage. Antioxidant activity was significantly correlated (p ≤ 0.05) with bioactive compounds and TPC

Womens experiences of HIV testing and counselling in the labour ward: A case of Bwaila hospital

Introduction: HIV counseling and testing during labour can be emotional, but is important because it allows mothers and babies to receive PMTCT prophylaxis if previous identification of HIV infection has not occurred. The study explores how HIV testing and counseling during early labour affects women. Methodology: This was a qualitative exploratory study to understand women’s experiences during early labor. From September to October 2009, we conducted 10 indepth interviews with women who tested for HIV during early labour. We recruited women who tested > 3 months previously and those who had never tested for HIV from the postpartum ward of Bwaila Hospital. Data were analyzed manually using the life story approach in order to examine and analyse subjective experiences of women and their constructions of the social world. Transcripts were read multiple times to understand meanings which participants attached to their experiences. We coded data according to emerging themes and subthemes. Results: Ten women 20-35 years were interviewed. Eight women had unknown HIV status while two had known HIV results but re-tested to update their status. Four women were found HIV-positive while 6 were HIVnegative. The primary theme was that women appreciated and accepted HIV testing and counseling. Testing was accepted as a necessary step to protect the infant from HIV infection. Counseling was viewed as helpful for acceptance of HIV status. One key subtheme was that HIV positive women experienced disappointment about their HIV diagnosis, though this was outweighed by the knowledge that one could protect her infant. All women viewed the short time to complete the counseling and testing procedures as favourable. Conclusion: Labour testing is acceptable and should be promoted to enhance PMTCT services by identifying HIV positive women with unknown status. Counseling helps women to accept being found with HIV and seek appropriate services

Loss of Humoral and Cellular Immunity to Invasive Nontyphoidal Salmonella During Current or Convalescent Plasmodium falciparum Infection in Malawian Children.

Invasive nontyphoidal Salmonella (iNTS) infections are commonly associated with Plasmodium falciparum infections, but the immunologic basis for this linkage is poorly understood. We hypothesized that P. falciparum infection compromises the hosts' humoral and cellular immunity to NTS which increases their susceptibility to iNTS infection. We prospectively recruited children aged between 6 and 60 months at a Community Health Centre in Blantyre, Malawi and allocated them to the following groups; febrile with uncomplicated malaria, febrile malaria-negative, non-febrile malaria-negative. S Typhimurium (STm)-specific; serum bactericidal activity (SBA) and blood bactericidal activity (WBBA), complement C3 deposition and neutrophil respiratory burst activity (NRBA) were measured. SBA to STm was reduced in febrile P. falciparum infected (Median -0.201og10, IQR [-1.85, 0.32]) compared to non-febrile malaria-negative (Median -1.42log10, IQR [-2.0, -0.47], p=0.052). In relation to SBA, C3 deposition on STm was significantly reduced in febrile P. falciparum infected (Median 7.5%, IQR [4.1, 15.0]) compared to non-febrile malaria-negative (Median 29%, IQR [11.8, 48.0], p=0.048). WBBA to STm was significantly reduced in febrile P. falciparum infected (Median 0.25log10, IQR [-0.73, 1.13], p=0.0001) compared to non-febrile malaria-negative (Median -1.0log10, IQR [-1.68, -0.16]). In relation to WBBA, STm-specific NRBA was reduced in febrile P. falciparum infected (Median 8.8% IQR [3.7, 20], p=0.0001) compared to non-febrile malaria-negative (Median 40.5% IQR [33, 65.8]). P. falciparum infection impairs humoral and cellular immunity to STm in children during malaria episodes, which may explain the increased risk of iNTS observed in children from malaria endemic settings. The mechanisms underlying humoral immunity impairment are incompletely understood and should be explored further