A retrospective survey of HIV drug resistance among patients 1 year after initiation of antiretroviral therapy at 4 clinics in Malawi.

In 2004, Malawi began scaling up its national antiretroviral therapy (ART) program. Because of limited treatment options, population-level surveillance of acquired human immunodeficiency virus drug resistance (HIVDR) is critical to ensuring long-term treatment success. The World Health Organization target for clinic-level HIVDR prevention at 12 months after ART initiation is ≥ 70%. In 2007, viral load and HIVDR genotyping was performed in a retrospective cohort of 596 patients at 4 ART clinics. Overall, HIVDR prevention (using viral load ≤ 400 copies/mL) was 72% (95% confidence interval [CI], 67%-77%; range by site, 60%-83%) and detected HIVDR was 3.4% (95% CI, 1.8%-5.8%; range by site, 2.5%-4.7%). Results demonstrate virological suppression and HIVDR consistent with previous reports from sub-Saharan Africa. High rates of attrition because of loss to follow-up were noted and merit attention.

The impact of preprinted prescription forms on medication prescribing errors in an ophthalmology clinic in northeast Thailand: a non-randomised interventional study.

OBJECTIVES: To understand the incidence and types of medication prescribing errors in a low resource setting ophthalmology clinic and to determine the impact of a preprinted prescription based on the hospital formulary (FormularyScript) on medication prescribing errors. DESIGN: Non-randomised interventional study. SETTING: Ophthalmology clinic in a teaching hospital in northeast Thailand. PARTICIPANTS: 4349 handwritten prescriptions collected from October 2009 to December 2009, and 4146 FormularyScripts collected from February 2010 to May 2010. PRIMARY AND SECONDARY OUTCOME MEASURES: All prescriptions from the handwritten and FormularyScript groups were analysed for medication error rates by types (legibility, ambiguous, incomplete, abbreviation and accuracy) and subtypes (drug name, strength, which eye, route and dispensed amount). RESULTS: Comparison of error rates in the two groups showed a 10-fold reduction in the overall error rate using FormularyScript (32.9%-3.5%, p<0.001). FormularyScripts were associated with statistically significant (p<0.001) decreases in the following error types: legibility (16.1%-0.1%), incomplete (16.1%-0.1%) and abbreviation (3.1%-0.3%). There was no statistically significant change in accuracy errors (0.8%-0.6%, p=0.21). Ambiguous errors increased with FormularyScripts (0.6%-2.5%, p<0.001), likely due to the introduction of new ways to make errors. Decreases were seen in all legibility, abbreviation and accuracy error subtypes, and four out of six incomplete error subtypes. There were statistically significant increases in both ambiguous error subtypes: which eye (0.3%-2.5%, p<0.001) and drug name (0.3%-0.6%, p=0.03). CONCLUSIONS: In our study population, outpatient medication prescribing errors were common and primarily due to legibility and incomplete error types. A preprinted prescription form has the potential to decrease medication prescribing errors related to legibility, incomplete prescribing information and use of unacceptable abbreviations without changing the overall rate of accuracy errors. However, new error types can occur.

Multidrug resistance among new tuberculosis cases: detecting local variation through lot quality-assurance sampling.

BACKGROUND: Current methodology for multidrug-resistant tuberculosis (MDR TB) surveys endorsed by the World Health Organization provides estimates of MDR TB prevalence among new cases at the national level. On the aggregate, local variation in the burden of MDR TB may be masked. This paper investigates the utility of applying lot quality-assurance sampling to identify geographic heterogeneity in the proportion of new cases with multidrug resistance. METHODS: We simulated the performance of lot quality-assurance sampling by applying these classification-based approaches to data collected in the most recent TB drug-resistance surveys in Ukraine, Vietnam, and Tanzania. We explored 3 classification systems- two-way static, three-way static, and three-way truncated sequential sampling-at 2 sets of thresholds: low MDR TB = 2%, high MDR TB = 10%, and low MDR TB = 5%, high MDR TB = 20%. RESULTS: The lot quality-assurance sampling systems identified local variability in the prevalence of multidrug resistance in both high-resistance (Ukraine) and low-resistance settings (Vietnam). In Tanzania, prevalence was uniformly low, and the lot quality-assurance sampling approach did not reveal variability. The three-way classification systems provide additional information, but sample sizes may not be obtainable in some settings. New rapid drug-sensitivity testing methods may allow truncated sequential sampling designs and early stopping within static designs, producing even greater efficiency gains. CONCLUSIONS: Lot quality-assurance sampling study designs may offer an efficient approach for collecting critical information on local variability in the burden of multidrug-resistant TB. Before this methodology is adopted, programs must determine appropriate classification thresholds, the most useful classification system, and appropriate weighting if unbiased national estimates are also desired.

Electronic decision protocols for ART patient triaging to expand access to HIV treatment in South Africa: a cross sectional study for development and validation.

BACKGROUND: The shortage of doctors and nurses, along with future expansion into rural clinics, will require that the majority of clinic visits by HIV infected patients on antiretroviral therapy (ART) are managed by non-doctors. The goal of this study was to develop and evaluate a screening protocol to determine which patients needed a full clinical assessment and which patients were stable enough to receive their medications without a doctor's consultation. For this study, we developed an electronic, handheld tool to guide non-physician counselors through screening questions. METHODS: Patients visiting two ART clinics in South Africa for routine follow-up visits between March 2007 and April 2008 were included in our study. Each patient was screened by non-physician counselors using the handheld device and then received a full clinical assessment. Clinicians' report on whether full clinical assessment had been necessary was used as the gold standard for determining "required referral". Observations were randomly divided into two datasets--989 for developing a referral protocol and 200 for validating protocol performance. RESULTS: A third of patients had at least one physical complaint, and 16% had five or more physical complaints. 38% of patients required referral for full clinical assessment. We identify a subset of questions which are 87% sensitive and 47% specific for recommended patient referral. CONCLUSIONS: The final screening protocol is highly sensitive and could reduce burden on ART clinicians by 30%. The uptake and acceptance of the handheld tool to support implementation of the protocol was high. Further examination of the data reveals several important questions to include in future referral algorithms to improve sensitivity and specificity. Based on these results, we identify a refined algorithm to explore in future evaluations.

Drug resistance surveillance in resource-poor settings: current methods and considerations for TB, HIV, and malaria.

In resource-constrained environments, monitoring the occurrence of tuberculosis (TB), human immunodeficiency virus (HIV), or malaria resistant to the limited number of available drugs is essential for national treatment program success. Countries with limited resources and technical capacity rely on survey designs and methods that are simple and easily integrated into routine clinical activities to minimize the impact on overburdened clinics. This paper reviews the most commonly used methods for drug-resistance surveillance of TB, HIV, and malaria and discusses the strengths and limitations of these different strategies.

Health indicators: eliminating bias from convenience sampling estimators.

Public health practitioners are often called upon to make inference about a health indicator for a population at large when the sole available information are data gathered from a convenience sample, such as data gathered on visitors to a clinic. These data may be of the highest quality and quite extensive, but the biases inherent in a convenience sample preclude the legitimate use of powerful inferential tools that are usually associated with a random sample. In general, we know nothing about those who do not visit the clinic beyond the fact that they do not visit the clinic. An alternative is to take a random sample of the population. However, we show that this solution would be wasteful if it excluded the use of available information. Hence, we present a simple annealing methodology that combines a relatively small, and presumably far less expensive, random sample with the convenience sample. This allows us to not only take advantage of powerful inferential tools, but also provides more accurate information than that available from just using data from the random sample alone.

Estimating the magnitude and direction of bias in tuberculosis drug resistance surveys conducted only in the public sector: a simulation study.

BACKGROUND: Accurate assessment of the burden of drug-resistant TB requires systematic efforts to quantify its magnitude and trend. In approximately half the countries where resistance has been reported, estimates are based on surveys conducted in public sector facilities. However, in locations where a substantial fraction of TB cases seek care with private providers, these surveys may not accurately measure resistance in the entire population. METHODS: We describe a mathematical model to investigate biases associated with sampling only from public sector cases in India, where TB treatment is offered in both public and private sectors. We then propose and demonstrate a weighted estimator as an efficient method for including small numbers of cases from the private sector as a way to recover valid estimates of resistance in the population under study. RESULTS: We find that public sector surveys rarely provide valid estimates of drug-resistance among new and retreatment cases. Further, the magnitude and direction of the bias are sensitive to many parameters describing the health-seeking behaviours and treatment outcomes of tuberculosis patients, disallowing simple adjustments to recover accurate estimates. CONCLUSIONS: In locations where large numbers of tuberculosis patients are diagnosed and treated by private sector practitioners who are not typically included in drug resistance surveys, targeted surveys for assessing drug resistance are required to validly estimate resistance.

An assessment of Lot Quality Assurance Sampling to evaluate malaria outcome indicators: extending malaria indicator surveys.

BACKGROUND: Large investments and increased global prioritization of malaria prevention and treatment have resulted in greater emphasis on programme monitoring and evaluation (M&E) in many countries. Many countries currently use large multistage cluster sample surveys to monitor malaria outcome indicators on a regional and national level. However, these surveys often mask local-level variability important to programme management. Lot Quality Assurance Sampling (LQAS) has played a valuable role for local-level programme M&E. If incorporated into these larger surveys, it would provide a comprehensive M&E plan at little, if any, extra cost. METHODS: The Mozambique Ministry of Health conducted a Malaria Indicator Survey (MIS) in June and July 2007. We applied LQAS classification rules to the 345 sampled enumeration areas to demonstrate identifying high- and low-performing areas with respect to two malaria program indicators-'household possession of any bednet' and 'household possession of any insecticide-treated bednet (ITN)'. RESULTS: As shown by the MIS, no province in Mozambique achieved the 70% coverage target for household possession of bednets or ITNs. By applying LQAS classification rules to the data, we identify 266 of the 345 enumeration areas as having bednet coverage severely below the 70% target. An additional 73 were identified with low ITN coverage. CONCLUSIONS: This article demonstrates the feasibility of integrating LQAS into multistage cluster sampling surveys and using these results to support a comprehensive national, regional and local programme M&E system. Furthermore, in the recommendations we outlined how to integrate the Large Country-LQAS design into macro-surveys while still obtaining results available through current sampling practices.

National implementation of Integrated Management of Childhood Illness (IMCI): policy constraints and strategies.

Integrated Management of Childhood Illness (IMCI) is a pediatric care management strategy that has been shown to improve health care service quality and increase health care cost savings in multi-country evaluations. However, many countries have faced significant training, health system, political, and financial constraints to national implementation and, as a result, have not been able to observe sustained benefits of IMCI. This article reviews the literature for evidence of IMCI health impacts, common implementation constraints, and policy strategies for health system strengthening and successful implementation.

Cluster designs to assess the prevalence of acute malnutrition by lot quality assurance sampling: a validation study by computer simulation.

Traditional lot quality assurance sampling (LQAS) methods require simple random sampling to guarantee valid results. However, cluster sampling has been proposed to reduce the number of random starting points. This study uses simulations to examine the classification error of two such designs, a 67x3 (67 clusters of three observations) and a 33x6 (33 clusters of six observations) sampling scheme to assess the prevalence of global acute malnutrition (GAM). Further, we explore the use of a 67x3 sequential sampling scheme for LQAS classification of GAM prevalence. Results indicate that, for independent clusters with moderate intracluster correlation for the GAM outcome, the three sampling designs maintain approximate validity for LQAS analysis. Sequential sampling can substantially reduce the average sample size that is required for data collection. The presence of intercluster correlation can impact dramatically the classification error that is associated with LQAS analysis.

A national survey of prisoners on antiretroviral therapy in Malawi: access to treatment and outcomes on therapy.

BACKGROUND: Malawi is making good progress scaling up antiretroviral therapy (ART), but we do not know the levels of access of high-risk, disadvantaged groups such as prisoners. The aim of this study was to measure access and treatment outcomes of prisoners on ART at the national level. METHODOLOGY: A retrospective cohort study was conducted examining patient follow-up records from all 103 public sector ART clinics in Malawi, and observations were censored on 31 December, 2006. RESULTS: By 31 December, 2006, a total of 81,821 patients had been started on ART. Of these, 103 (0.13%) were prisoners. At ART initiation, 93% of prisoners were in World Health Organization (WHO) clinical stage 3 or 4 while 7% started in stage 1 or 2 with a CD4-lymphocyte count of < or =250/mm3. Treatment outcomes by the end of December 2006 were as follows: 66 (64%) alive and on ART at their registration facility; 9 (9%) dead; 8 (8%) lost to follow-up; and 20 (19%) transferred out to another facility. The probability of being alive and on ART at 6 and 12 months was 82.5% and 77.7%. CONCLUSIONS: In spite of the rapid scale-up of ART, only a small number of HIV-positive prisoners had accessed ART by the end of 2006. Treatment outcomes were good. Initiatives are now needed to improve access to HIV testing and ART in Malawi's prisons.

Early warning indicators for HIV drug resistance in Malawi.

BACKGROUND: Malawi started rapid scale-up of antiretroviral therapy (ART) in 2004 and by December 2006 had initiated over 85,000 patients on treatment. Early warning indicator (EWI) reports can help to minimize the risk of emerging drug resistance. METHODS: Data collected during the routine quarterly supervision of 103 public sector sites was used to compile the first EWI report for HIV drug resistance (HIVDR) in Malawi, reflecting outcomes for October to December 2006. RESULTS: All sites reach the World Health Organization (WHO) targets for prescribing practices and drug supply continuity. The target for adherence was achieved by 85% of sites and 84% achieved the target for minimizing treatment defaults; however, less than half of all sites reach the WHO target for patient retention. CONCLUSIONS: These results emphasize the importance of defaulter tracing and initiating treatment earlier in the course of HIV infection. As part of a comprehensive HIVDR monitoring programme, the Ministry of Health plans for on-going tracking of these indicators, as well as special data collection from the private sector. Plans are also underway to gather information on other recommended indicators that are not collected during routine supervision.

Assessing the quality of data aggregated by antiretroviral treatment clinics in Malawi.

PROBLEM: As national antiretroviral treatment (ART) programmes scale-up, it is essential that information is complete, timely and accurate for site monitoring and national planning. The accuracy and completeness of reports independently compiled by ART facilities, however, is often not known. APPROACH: This study assessed the quality of quarterly aggregate summary data for April to June 2006 compiled and reported by ART facilities ("site report") as compared to the "gold standard" facility summary data compiled independently by the Ministry of Health supervision team ("supervision report"). Completeness and accuracy of key case registration and outcome variables were compared. Data were considered inaccurate if variables from the site reports were missing or differed by more than 5% from the supervision reports. Additionally, we compared the national summaries obtained from the two data sources. LOCAL SETTING: Monitoring and evaluation of Malawi's national ART programme is based on WHO's recommended tools for ART monitoring. It includes one master card for each ART patient and one patient register at each ART facility. Each quarter, sites complete cumulative cohort analyses and teams from the Ministry of Health conduct supervisory visits to all public sector ART sites to ensure the quality of reported data. RELEVANT CHANGES: Most sites had complete case registration and outcome data; however many sites did not report accurate data for several critical data fields, including reason for starting, outcome and regimen. The national summary using the site reports resulted in a 12% undercount in the national total number of persons on first-line treatment. Several facility-level characteristics were associated with data quality. LESSONS LEARNED: While many sites are able to generate complete data summaries, the accuracy of facility reports is not yet adequate for national monitoring. The Ministry of Health and its partners should continue to identify and support interventions such as supportive supervision to build sites' capacity to maintain and compile quality data to ensure that accurate information is available for site monitoring and national planning.

Antiretroviral therapy in the Malawi defence force: access, treatment outcomes and impact on mortality.

BACKGROUND: HIV/AIDS affects all sectors of the population and the defence forces are not exempt. A national survey was conducted in all public and private sectors in Malawi that provide antiretroviral therapy (ART) to determine the uptake of ART by army personnel, their outcomes while on treatment, and the impact of ART on mortality in the Malawi Defence Force. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort analysis was carried out, collecting data on access and retention on treatment from all 103 public and 38 private sector ART clinics in Malawi, using standardised patient master cards and clinic registers. Observations were censored on December 31(st) 2006. Independent data on mortality trends in army personnel from all causes between 2002 and 2006 were available from army records. By December 31(st) 2006, there were 85,168 patients ever started on ART in both public and private sectors, of whom 547 (0.7%) were army personnel. Of these, 22% started ART in WHO clinical stage 1 or 2 with a CD4-lymphocyte count of

Antiretroviral therapy in the Malawi police force: access to therapy and treatment outcomes.

A national survey was carried out in all the 103 public sector and 38 private sector facilities in Malawi providing antiretroviral therapy (ART) to determine uptake of ART and subsequent treatment outcomes in police force personnel. All patients registered for ART and their subsequent treatment outcomes were censored on December 31st 2006. There were 85168 patients started on ART in both public and private sectors, of whom 463 (0.6%) were police force personnel. Of police force personnel starting ART, 17% were in WHO clinical stage 1 or 2 with a CD4-lymphocyte count of < or = 250 cells/microL and 83% were in stage 3 or 4. Treatment outcomes of police force personnel by the end of December 2006 were 302 (65%) alive and on ART at their registration facility, 59 (13%) dead, 30 (7%) lost to follow-up, 1 stopped treatment and 71 (15%) transferred to another facility. Their probability of being alive on ART at 6-, 12- and 18-months was 83.2%, 78.6% and 76.7% respectively. There has been a good access of police force personnel to ART since national scale up commenced with good treatment outcomes, and this should serve as an example for other police forces in the region.

A national survey of prisoners on antiretroviral therapy in Malawi: access to treatment and outcomes on therapy.

BACKGROUND: Malawi is making good progress scaling up antiretroviral therapy (ART), but we do not know the levels of access of high-risk, disadvantaged groups such as prisoners. The aim of this study was to measure access and treatment outcomes of prisoners on ART at the national level. METHODOLOGY: A retrospective cohort study was conducted examining patient follow-up records from all 103 public sector ART clinics in Malawi, and observations were censored on December 31, 2006. RESULTS: By December 31, 2006, a total of 81,821 patients had been started on ART. Of these, 103 (0.13%) were prisoners. At ART initiation, 93% of prisoners were in World Health Organization (WHO) clinical stage 3 or 4 while 7% started in stage 1 or 2 with a CD4-lymphocyte count of