Health-related quality of life (HRQoL) is a broad concept reflecting a patient's general subjective perception of the effect of an illness or intervention on physical, psychological and social aspects of their daily life. HRQoL among patients infected with HIV has become an important indicator of impact of disease and treatment outcomes. A cross-sectional survey was carried out at Chitungwiza Central Hospital, Zimbabwe, to assess HRQoL in patients with HIV/AIDS receiving antiretroviral therapy (ART), using two validated instruments. The HIV/AIDS-targeted quality of life (HAT-QoL) and EuroQoL Five-dimensions-Three-level (EQ-5D-3L) instruments were used to assess HRQoL. Internal consistency reliability and convergent validity of the two instruments were also evaluated. For construct validity, the relationships between HRQoL scores and socio-economic and HIV/AIDS-related characteristics were explored. The median scores for the HAT-QoL dimensions ranged from 33.3 (financial worries) to 100 (HIV mastery). A considerably low HAT-QoL dimension score of 50.0 was observed for sexual function. There were ceiling effects for all HAT-QoL dimension scores except for financial worries and disclosure worries. Floor effects were observed for financial worries and sexual function. The median of the EQ-5D-3L index and visual analogue scale (VAS) was 0.81 and 79.0, respectively. There were no floor or ceiling effects for both the EQ-5D-3L index and VAS. The overall scale Cronbach's alpha was 0.83 for HAT-Qol and 0.67 for EQ-5D-3L. HAT-QoL demonstrated good convergent validity with EQ-5D index (0.58) and VAS (0.40). A higher level of HRQoL was positively and significantly related to income, education and employment. The patients' self-reported HRQoL was generally satisfactory in all the HAT-QoL dimensions as well as the two components on the EQ-5D-3L instrument. The two instruments demonstrated good measurement properties in HIV/AIDS patients receiving ART and have potential for use, alongside biomarkers, in monitoring outcomes of interventions.

Background The WHO elimination strategy for hepatitis C virus advocates scaling up screening and treatment to reduce global hepatitis C incidence by 80% by 2030, but little is known about how this reduction could be achieved and the costs of doing so. We aimed to evaluate the effects and cost of different strategies to scale up screening and treatment of hepatitis C in Pakistan and determine what is required to meet WHO elimination targets for incidence. MethodsWe adapted a previous model of hepatitis C virus transmission, treatment, and disease progression for Pakistan, calibrating using available data to incorporate a detailed cascade of care for hepatitis C with cost data on diagnostics and hepatitis C treatment. We modelled the effect on various outcomes and costs of alternative scenarios for scaling up screening and hepatitis C treatment in 2018-30. We calibrated the model to country-level demographic data for 1960-2015 (including population growth) and to hepatitis C seroprevalence data from a national survey in 2007-08, surveys among people who inject drugs (PWID), and hepatitis C seroprevalence trends among blood donors. The cascade of care in our model begins with diagnosis of hepatitis C infection through antibody screening and RNA confirmation. Diagnosed individuals are then referred to care and started on treatment, which can result in a sustained virological response (effective cure). We report the median and 95% uncertainty interval (UI) from 1151 modelled runs.Findings One-time screening of 90% of the 2018 population by 2030, with 80% referral to treatment, was projected to lead to 13•8 million (95% UI 13•4-14•1) individuals being screened and 350 000 (315 000-385 000) treatments started annually, decreasing hepatitis C incidence by 26•5% (22•5-30•7) over 2018-30. Prioritised screening of high prevalence groups (PWID and adults aged ≥30 years) and rescreening (annually for PWID, otherwise every 10 years) are likely to increase the number screened and treated by 46•8% and decrease incidence by 50•8% (95% UI 46•1-55•0). Decreasing hepatitis C incidence by 80% is estimated to require a doubling of the primary screening rate, increasing referral to 90%, rescreening the general population every 5 years, and re-engaging those lost to follow-up every 5 years. This approach could cost US$8•1 billion, reducing to $3•9 billion with lowest costs for diagnostic tests and drugs, including health-care savings, and implementing a simplified treatment algorithm. Interpretation Pakistan will need to invest about 9•0% of its yearly health expenditure to enable sufficient scale up in screening and treatment to achieve the WHO hepatitis C elimination target of an 80% reduction in incidence by 2030.Funding UNITAID.

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The high unit cost of producing blood relative to the annual GDP per capita demonstrates that acquiring safe blood is a burden on the health care sector in Zimbabwe. Introducing additional safety measures, such as nucleic acid amplification testing and pathogen reduction technology, although desirable, will further increase this burden.

Although the introduction of NAT could further improve the safety of the blood supply, current evidence suggests that it cannot be considered cost effective. Reducing the test costs for NAT through efficient donor recruitment, negotiating the price of reagents, and the efficient use of technology will improve cost effectiveness.

The aim of this study was to develop a pharmacokineticpharmacodynamic (PKPD) model that quantifies the efficacy of haloperidol, accounting for the placebo effect, the variability in exposure-response, and the dropouts. Subsequently, the developed model was utilized to characterize an effective dosing strategy for using haloperidol as a comparator drug in future antipsychotic drug trials. The time course of plasma haloperidol concentrations from 122 subjects and the Positive and Negative Syndrome Scale (PANSS) scores from 473 subjects were used in this analysis. A nonlinear mixed-effects modeling approach was utilized to describe the time course of PK and PANSS scores. Bootstrapping and simulationbased methods were used for the model evaluation. A 2-compartment model adequately described the haloperidol PK profiles. The Weibull and E max models were able to describe the time course of the placebo and the drug effects, respectively. An exponential model was used to account for dropouts. Joint modeling of the PKPD model with dropout model indicated that the probability of patients dropping out is associated with the observed high PANSS score. The model evaluation results confirmed that the precision and accuracy of parameter estimates are acceptable. Based on the PKPD analysis, the recommended oral dose of haloperidol to achieve a 30% reduction in PANSS score from baseline is 5.6 mg/d, and the corresponding steady-state effective plasma haloperidol exposure is 2.7 ng/mL.In conclusion, the developed model describes the time course of PANSS scores adequately, and a recommendation of haloperidol dose was derived for future antipsychotic drug trials.Key Words: haloperidol, population pharmacokinetics-pharmacodynamics, PANSS total, schizophrenia, dropout model (J Clin Psychopharmacol 2013;33: 731Y739) H aloperidol, a typical antipsychotic, was the most widely used drug for many years in the treatment of patients with schizophrenia and other psychotic disorders.1 Haloperidol is still widely used as the prototypical comparator antipsychotic for randomized controlled trials. The effective dose of haloperidol is still not known, which is a problem when it is used as a comparator drug. 5 for the acute and the maintenance treatment of schizophrenia symptoms. In addition, in many clinical trials, higher doses of haloperidol are used as a comparator. This may be linked to higher incidence of adverse effects such as extrapyramidal side effects, and therefore comparison between drugs could be biased. 6 Recently, Giegling et al 7 discussed a statistical strategy for choosing an appropriate dose and the corresponding exposure of haloperidol for clinical studies based on the observed response. However, the observed interindividual variability (IIV) in the pharmacokinetics (PK) and pharmacodynamics (PD) of haloperidol was not fully characterized because of the small sample size of patients. To our knowledge, there is no literature available on population-based pharmacokinetic-pharmacodynamic (PKPD) modeling of haloperidol u...

ObjectivesThe WHO currently recommends stool testing using GeneXpert MTB/Rif (Xpert) for the diagnosis of paediatric tuberculosis (TB). The simple one-step (SOS) stool method enables processing for Xpert testing at the primary healthcare (PHC) level. We modelled the impact and cost-effectiveness of implementing the SOS stool method at PHC for the diagnosis of paediatric TB in Ethiopia and Indonesia, compared with the standard of care.SettingAll children (age <15 years) presenting with presumptive TB at primary healthcare or hospital level in Ethiopia and Indonesia.Primary outcomeCost-effectiveness estimated as incremental costs compared with incremental disability-adjusted life-years (DALYs) saved.MethodsDecision tree modelling was used to represent pathways of patient care and referral. We based model parameters on ongoing studies and surveillance, systematic literature review, and expert opinion. We estimated costs using data available publicly and obtained through in-country expert consultations. Health outcomes were based on modelled mortality and discounted life-years lost.ResultsThe intervention increased the sensitivity of TB diagnosis by 19–25% in both countries leading to a 14–20% relative reduction in mortality. Under the intervention, fewer children seeking care at PHC were referred (or self-referred) to higher levels of care; the number of children initiating anti-TB treatment (ATT) increased by 18–25%; and more children (85%) initiated ATT at PHC level. Costs increased under the intervention compared with a base case using smear microscopy in the standard of care resulting in incremental cost-effectiveness ratios of US$132 and US$94 per DALY averted in Ethiopia and Indonesia, respectively. At a cost-effectiveness threshold of 0.5×gross domestic product per capita, the projected probability of the intervention being cost-effective in Ethiopia and Indonesia was 87% and 96%, respectively. The intervention remained cost-effective under sensitivity analyses.ConclusionsThe addition of the SOS stool method to national algorithms for diagnosing TB in children is likely to be cost-effective in both Ethiopia and Indonesia.

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