Improving private drug sellers' practices for managing common health problems in Nepal.

BACKGROUND: In most Asian countries, 50 - 90% of pharmaceutical sales are made in private drug outlets, by personnel with some training in drugs but not for the treatment of common health problems. The objective of the study was to determine effects of focused training for private drug sellers to improve practices in treating acute respiratory infections and diarrhoea in children, and anaemia in pregnancy in Nepal. METHODS: Randomized controlled, four way nested design study incorporating four interventions for drug retailers in both hill and terai districts. One group received mailed printed educational materials followed by mailed feedback; a second received small group training followed by feedback; a third received small group training only; and a fourth, the control group, received no intervention. Surrogate customer method was used to assess practices. Outcomes were measured using multivariate linear regression. RESULTS: A significant increase in the asking of key history questions, recommendation ( prescribing by drug retailers) of cotrimoxazole, and advice-giving for pneumonia; a significant increase in ORS recommendation, and advice giving for diarrhoea including the avoidance of antidiarrhoeals; and a significant increase in asking key history questions and recommending appropriate products in pregnancy cases. CONCLUSIONS: Training intervention as well as training followed by practice feedback was effective in improving the management of common illnesses and pregnancy by private drug sellers.

Have we improved use of medicines in developing and transitional countries and do we know how to? Two decades of evidence.

OBJECTIVE: To assess progress in improving use of medicines in developing and transitional countries by reviewing empirical evidence, 1990-2009, concerning patterns of primary care medicine use and intervention effects. METHODS: We extracted data on medicines use, study setting, methodology and interventions from published and unpublished studies on primary care medicine use. We calculated the medians of six medicines use indicators by study year, country income level, geographic region, facility ownership and prescriber type. To estimate intervention impacts, we calculated greatest positive (GES) and median effect sizes (MES) from studies meeting accepted design criteria. RESULTS: Our review comprises 900 studies conducted in 104 countries, reporting data on 1033 study groups from public (62%), and private (mostly for profit) facilities (26%), and households. The proportion of treatment according to standard treatment guidelines was 40% in public and <30% in private-for-profit sector facilities. Most indicators showed suboptimal use and little progress over time: Average number of medicines prescribed per patient increased from 2.1 to 2.8 and the percentage of patients receiving antibiotics from 45% to 54%. Of 405 (39%) studies reporting on interventions, 110 (27%) used adequate study design and were further analysed. Multicomponent interventions had larger effects than single component ones. Median GES was 40% for provider and consumer education with supervision, 17% for provider education alone and 8% for distribution of printed education materials alone. Median MES showed more modest improvements. CONCLUSIONS: Inappropriate medicine use remains a serious global problem.

Predictors of antibiotic use in African communities: evidence from medicines household surveys in five countries.

OBJECTIVES: To investigate antibiotic use in five national household surveys conducted with the WHO methodology to identify key determinants of antibiotic use in the community. METHODS: Data from The Gambia, Ghana, Kenya, Nigeria and Uganda surveys were combined. We used logistic regression models that accounted for the clustered survey design to identify the determinants of care seeking outside the home and antibiotic use for 2914 cases of recent acute illness. RESULTS: Overall, 95% of individuals with acute illness took medicines, 90% sought care outside their homes and 36% took antibiotics. In multivariate analyses, illness severity was a strong predictor of seeking care outside the home. Among those who sought outside care, the strongest predictor of antibiotic use was the presence of upper respiratory symptoms (OR: 3.02, CI: 2.36-3.86, P<0.001), followed by gastrointestinal symptoms or difficulty breathing, and antibiotics use was less likely if they had fever. The odds of receiving antibiotics were higher when visiting a public hospital or more than one healthcare facility. CONCLUSIONS: The nature and severity of symptoms and patterns of care seeking had the greatest influence on decisions to take antibiotics. Antibiotics were widely available and inappropriately used in all settings. Policies to regulate antibiotics distribution as well as interventions to educate prescribers, dispensers and consumers are needed to improve antibiotic use.

Medicine prices, availability, and affordability in 36 developing and middle-income countries: a secondary analysis.

BACKGROUND: WHO and Health Action International (HAI) have developed a standardised method for surveying medicine prices, availability, affordability, and price components in low-income and middle-income countries. Here, we present a secondary analysis of medicine availability in 45 national and subnational surveys done using the WHO/HAI methodology. METHODS: Data from 45 WHO/HAI surveys in 36 countries were adjusted for inflation or deflation and purchasing power parity. International reference prices from open international procurements for generic products were used as comparators. Results are presented for 15 medicines included in at least 80% of surveys and four individual medicines. FINDINGS: Average public sector availability of generic medicines ranged from 29.4% to 54.4% across WHO regions. Median government procurement prices for 15 generic medicines were 1.11 times corresponding international reference prices, although purchasing efficiency ranged from 0.09 to 5.37 times international reference prices. Low procurement prices did not always translate into low patient prices. Private sector patients paid 9-25 times international reference prices for lowest-priced generic products and over 20 times international reference prices for originator products across WHO regions. Treatments for acute and chronic illness were largely unaffordable in many countries. In the private sector, wholesale mark-ups ranged from 2% to 380%, whereas retail mark-ups ranged from 10% to 552%. In countries where value added tax was applied to medicines, the amount charged varied from 4% to 15%. INTERPRETATION: Overall, public and private sector prices for originator and generic medicines were substantially higher than would be expected if purchasing and distribution were efficient and mark-ups were reasonable. Policy options such as promoting generic medicines and alternative financing mechanisms are needed to increase availability, reduce prices, and improve affordability.

Controlled trial of interventions to increase testing and treatment for Helicobacter pylori and reduce medication use in patients with chronic acid-related symptoms.

BACKGROUND: Many symptomatic patients take proton pump inhibitors or histamine-2 blockers for years and those without gastro-oesophageal reflux disease might benefit from Helicobacter pylori eradication. AIM: To increase testing and treatment of H. pylori and reduce chronic use of proton pump inhibitors and histamine-2 blockers. METHODS: We conducted a three-armed controlled trial in 14 managed care practices. We included adults who used proton pump inhibitors or histamine-2 blockers for >1 year and excluded those with gastro-oesophageal reflux disease or previous endoscopy. We compared usual care (n = 312 patients from 6 practices) to low-intensity (n = 147 from 3 practices) and high-intensity (n = 122 from 5 practices) interventions. Low-intensity intervention consisted of guidelines, patient-lists, and a "toolkit"; high-intensity intervention added academic group detailing by a gastroenterologist with reinforcement by pharmacists. RESULTS: Compared with usual care, the high-intensity intervention increased H. pylori test-ordering (29% versus 9% at 12 months, P = 0.02). About half (23 of 58) of patients tested positive and 22 received eradication treatments. The high-intensity intervention decreased proton pump inhibitor use by 9% per year (P = 0.028), but did not alter histamine-2 blocker use. The low intensity intervention was ineffective. CONCLUSIONS: Providing guidelines, patient-lists, and toolkits was no better than usual care. Adding group detailing and pharmacist reinforcements led to improvements in H. pylori management and decreases in proton pump inhibitor use.

Impact of decentralization on health services in Uganda: a look at facility utilization, prescribing and availability of essential drugs.

INTRODUCTION: Uganda began implementation of a structural adjustment programme (SAP) in July 1994 in order to improve social services. The decentralization of health services administration to district level was intended to improve the quality of health services and pharmaceutical supplies in the hospitals, with resultant increase in the level of utilization of health facilities. OBJECTIVE: This study evaluated the impact of the decentralization policy on health facility utilization; availability of essential drugs, and prescribing patterns for acute respiratory infections (ARI), diarrhoea, and malaria in two district hospitals in Uganda. DESIGN: Mixed method evaluation design, involving both quantitative and qualitative methods. Time series analyses of data from utilization, pharmacy stock, and prescription records before and after the policy change. Key informant interviews and focus group discussions to obtain information on perceptions and attitude of stakeholders on the process of the policy implementation. STUDY SETTING AND POPULATION: The study was conducted in two district hospitals in northern Uganda. A total of seven years of utilization and pharmacy stock data including 5040 patient records from the hospitals were analysed retrospectively. In-depth interviews were conducted among 11 politicians from each district; 100 open-ended questionnaires were administered to patients in each hospital; 86 health care workers were interviewed using semi-structured questionnaires; and focus group discussions were conducted with 23 health care providers. MAIN OUTCOME MEASURES: Facility utilization was evaluated by average monthly attendance in the outpatient department and paediatric ward admissions. Availability was assessed as average number of drugs per month. Prescribing indicator outcomes included: for malaria, percent chloroquine tablets and percent chloroquine injection; for ARI, percent receiving antibiotics or injections; for diarrhoea, use of oral rehydration salts (ORS), antidiarrhoeal mixtures, and antibiotics. The average number of drugs prescribed assessed polypharmacy. RESULTS: There was a general increase in patient attendance in both hospitals, although the initial increase later declined in Apac. Drug availability was erratic and not always adequate. The situation was better in Lira where funding for drug procurement was more accessible. Prescribing patterns varied, with improvement in some indicators, while others showed no change or even worsened. CONCLUSIONS: The decentralization policy led to increased utilization of health facilities. The perception was that the policy was good because it "empowered the community in terms of creating a sense of responsibility in the stakeholders, and a sense of ownership that facilitated sustainability" of public institutions. In spite of the views expressed by the stakeholders, the policy failed to improve drug shortages, inefficient utilization of resources, and low morale among hospital staff. Staff should be re-trained and better remunerated in order to cope with the implementation of the policy. Local politicians should clearly understand their roles and responsibility under the new policy. Efficient utilization of funds at all levels of the district administrative structures should be ensured.

Attitudes and perceptions of stakeholders on decentralization of health services in Uganda: the case of Lira and Apac districts.

BACKGROUND: In Uganda, the decentralization of administrative functions, management, and responsibility for health care to districts, which began in 1994, resulted in fundamental changes in health care delivery. Since the introduction of the policy in Uganda, little information has been available on stakeholders' perceptions about the benefits of the policy and how decentralization affected health care delivery. OBJECTIVES: To identify the perceptions and beliefs of key stakeholders on the impact and process of decentralization and on the operations of health services in two districts in Uganda, and to report their suggestions to improve future implementation of similar policies. DESIGN: We used qualitative research methods that included focus group discussions with 90 stakeholders from both study districts. SETTING: The sample population comprised of 12 health workers from the two hospitals, 11 district health administrators, and 67 Local Council Leaders. MAIN OUTCOME MEASURES: Perceptions and concerns of stakeholders on the impact of decentralization on district health services. RESULTS: There was a general consensus that decentralization empowered local administrative and political decision-making. Among stakeholders, the policy was perceived to have created a sense of ownership and responsibility. Major problems that were said to be associated with decentralization included political harassment of civil servants, increased nepotism, inadequate financial resources, and mismanagement of resources. CONCLUSIONS: This study elicited perceptions about critical factors upon which successful implementation of the decentralization policy depended. These included: appreciation of the role of all stakeholders by district politicians; adequate availability and efficient utilization of resources; reasonably developed infrastructure prior to the policy change; appropriate sensitisation and training of those implementing policies; and the good will and active involvement of the local community. In the absence of these factors, implementation of decentralization of services to districts may not immediately make economic and administrative sense.

Impact of an educational intervention to improve prescribing by private physicians in Uganda.

INTRODUCTION: Private physicians in urban Uganda treat a large percentage of common adult illnesses. Improving their prescribing would not only encourage more rational drug use, but also reduce costs to patients. Interventions to improve drug use are generally more successful when face-to-face educational methods are included. OBJECTIVES: To determine the effectiveness of a face-to-face educational intervention on the treatment of acute respiratory infections (ARI), malaria, and non-dysenteric diarrhoea by private physicians in three urban areas of Uganda. METHODS: The study used an intervention with comparison group design to evaluate the impact of the educational intervention. A total of 108 private physicians was divided into intervention (n = 30) and control (n = 78) groups. Surrogate patients, trained to simulate presenting symptoms and signs of the target conditions, were used to collect data on the medical practices and prescribing behaviours of the physicians. Intervention physicians were invited to a one-day interactive educational seminar facilitated by local opinion leaders that covered principles of rational drug use and the National Standard Treatment Guidelines for treating the target conditions. Physicians were also provided with data about baseline practices. RESULTS: Baseline data indicated high rates of inappropriate treatment practices by both intervention and control groups. There was nearly universal antibiotic use for ARI (over 90%), high rates of injections recommended for malaria (over 30%), and high rates of polypharmacy (over thee drugs per patient). After the intervention, some significant improvements in key practices were observed in the intervention group. Compared to control physicians, antibiotic prescribing for ARI decreased by 23% in the intervention group, use of combination products for malaria declined by 28%, there were trends towards better adherence to guidelines for ARI and malaria, and marginal decreases in drug costs. However, the overall impacts of the intervention were limited, especially on quality indicators concerning history taking, adequate examination, and advice to patients. CONCLUSION: The face-to-face educational intervention resulted in some small improvements in key prescribing practices of private physicians. However, an intervention that involved repeated contacts with prescribers and which addressed economic considerations would be needed to obtain larger improvements. Private physicians need to be sensitized to and encouraged to use the National Standard Treatment Guidelines, and attempts to improve their prescribing should be supported by community education.

A comparison of prescribing practices between public and private sector physicians in Uganda.

INTRODUCTION: Previous studies in the public sector in Uganda have demonstrated major prescribing problems due to polypharmacy and irrational use of antibiotics and injections. Little is known about prescribing in the private sector although there is little government regulation influencing practice in this sector. The introduction of policies such as the Uganda National Standard Treatment Guidelines (UNSTG) was expected to improve prescribing practices in the public and private sectors. This paper measures appropriateness of prescribing practices in the public and private sectors in Uganda for the treatment of Acute Respiratory Infections (ARI) and malaria in adult patients. DESIGN AND SAMPLING: We combined a prospective survey of treatment for simulated patients presenting with symptoms of malaria and ARI in 119 randomly selected private clinics and a retrospective survey of 600 prescription records for malaria and ARI (300 for each condition) randomly selected from 10 public health units in the Kampala, Masaka, and Jinja urban areas. OUTCOME MEASURES: Percentage of drug appropriately prescribed in each condition, % injection prescription, percentage antibiotic prescription, average number of drugs per case, average standardized cost per prescription, distribution of types of drugs prescribed. RESULTS: The overall appropriateness of prescribing for ARI and malaria was poor in both public and private sectors. Treatment of malaria was significantly less appropriate in the public sector compared to the private sector (14% vs. 27%, p = 0.002), with injectable chloroquine much more commonly prescribed. Prescribing of antibiotics for ARI was nearly universal in both sectors, with some prescriptions containing up to three antibiotics; newer, more expensive antibiotics were more commonly prescribed in the private sector. Polypharmacy and unnecessary prescribing of vitamins were common in both conditions and both sectors. CONCLUSIONS: Prescribing for adult malaria and ARI by both private and public practitioners did not conform to the UNSTGs. Although practitioners were largely the same in both sectors, prescribing practices often differed dramatically. The extent of inappropriate prescribing in both sectors calls for in-depth investigation of the system factors and motivations that underlie problem practices, and the development of interventions that target these causative factors.

Segmented regression analysis of interrupted time series studies in medication use research.

Interrupted time series design is the strongest, quasi-experimental approach for evaluating longitudinal effects of interventions. Segmented regression analysis is a powerful statistical method for estimating intervention effects in interrupted time series studies. In this paper, we show how segmented regression analysis can be used to evaluate policy and educational interventions intended to improve the quality of medication use and/or contain costs.

Reducing infections among women undergoing cesarean section in Colombia by means of continuous quality improvement methods.

BACKGROUND: Improving obstetric care in resource-limited countries is a major international health priority. OBJECTIVE: To reduce infection rates after cesarean section by optimizing systems of obstetric care for low-income women in Colombia by means of quality improvement methods. METHODS: Multidisciplinary teams in 2 hospitals used simple methods to improve their systems for prescribing and administering perioperative antibiotic prophylaxis. Process indicators were the percentage of women in whom prophylaxis was administered and the percentage of these women in whom it was administered in a timely fashion. The outcome indicator was the surgical site infection rate. RESULTS: Before improvement, prophylaxis was administered to 71% of women in hospital A; 24% received prophylaxis in a timely fashion. Corresponding figures in hospital B were 36% and 50%. Systems improvements included implementing protocols to administer prophylaxis to all women and increasing the availability of the antibiotic in the operating room. These improvements were associated with increases in overall and timely administration of prophylaxis (P<.001) in both hospitals by time series analysis, with adjustment for volume and case mix. After improvement, overall and timely administration of prophylaxis was 95% and 96% in hospital A and 89% and 96% in hospital B. In hospital A, the surgical site infection rate decreased immediately after the improvements (P<.001). In hospital B, the infection rate began a downward trend before the improvements that continued after their implementation (P =.04). CONCLUSION: Simple quality improvement methods can be used to optimize obstetric services and improve outcomes of care in resource-limited settings.

Supplemental insurance and use of effective cardiovascular drugs among elderly medicare beneficiaries with coronary heart disease.

CONTEXT: Cost-sharing in US prescription drug coverage plans for elderly persons varies widely. Evaluation of prescription drug use among elderly persons by type of health insurance could provide useful information for designing a Medicare drug program. OBJECTIVE: To determine use of effective cardiovascular drugs among elderly persons with coronary heart disease (CHD) by type of health insurance. DESIGN, SETTING, AND PATIENTS: Cross-sectional evaluation of 1908 community-dwelling adults, aged 66 years or older, with a history of CHD or myocardial infarction from the 1997 Medicare Current Beneficiary Survey, a nationally representative sample of Medicare beneficiaries. MAIN OUTCOME MEASURES: Use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), beta-blockers, and nitrates, and out-of-pocket expenditures for prescription drugs, stratified by type of health insurance: Medicare without drug coverage (Medicare only or self-purchased supplemental insurance) or with drug coverage (Medicaid, other public program, Medigap, health maintenance organization, or employer-sponsored plan). RESULTS: Statin use ranged from 4.1% in Medicare patients with no drug coverage to 27.4% in patients with employer-sponsored drug coverage (P<.001). Less variation between these 2 types occurred for beta-blockers (20.7% vs 36.1%; P =.003) and nitrates (20.4% vs 38.0%; P =.005). In multivariate analyses, statin use remained significantly lower for patients with Medicare only (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.05-0.49) and beta-blocker use was lower for Medicaid patients (OR, 0.55; 95% CI, 0.34-0.88) vs those with employer-sponsored coverage. Nitrate use occurred less frequently in persons lacking drug coverage (patients with Medicare only, P =.049; patients with supplemental insurance without drug coverage, P =.03). Patients with Medicare only spent a much larger fraction of income on prescription drugs compared with those with employer-sponsored drug coverage (7.9% vs 1.7%; adjusted P<.001). CONCLUSION: Elderly Medicare beneficiaries with CHD who lack drug coverage have disproportionately large drug expenditures and lower use rates of statins, a class of relatively expensive drugs that improve survival.

Designing an intervention to improve the management of Helicobacter pylori infection.

BACKGROUND: An intervention to improve the testing and treatment of Helicobacter pylori (HP) in patients receiving chronic acid suppression (AS) therapy was developed at Harvard Pilgrim Health Care (HPHC), a mixed-model not-for-profit health maintenance organization. METHODS: Ten full-time primary care physicians (4 staff model and 6 group practice) were interviewed in 1999 about their knowledge, attitudes, and practice regarding dyspepsia, the use of chronic AS drugs, and approaches to HP infection, as well as about the feasibility and acceptability of various potential interventions that might be used in a quality improvement program. RESULTS: Self-reported practice regarding dyspepsia and HP infection were relatively uniform, and physicians were generally aware of current recommendations. Three common misperceptions acted as barriers to optimal HP management: Untreated HP was not considered an important problem; patients who used drugs for chronic AS rarely had HP infection; and chronic use of AS drugs was considered effective and without adverse consequence. All physicians wanted brief educational materials with explicit guidelines, preferably locally adapted and endorsed by local experts. All informants agreed that the main barrier to successful QI interventions was the requirement for any extra time or effort, particularly when directed at populations of patients who do not have symptomatic complaints. DISCUSSION: The interviews revealed the many barriers to improving the management of HP infection and to targeting educational messages and tailoring different methods for facilitating practice change across different managed care settings. Evidence-based components of the intervention program include physician education, a notification/reminder system, and practice-based tools to facilitate change and minimize workload.

Utilization of essential medications by vulnerable older people after a drug benefit cap: importance of mental disorders, chronic pain, and practice setting.

OBJECTIVE: To identify specific characteristics of patients, physicians, and treatment settings associated with decreased receipt of essential medications in a chronically ill, older population following a Medicaid three-prescription monthly reimbursement limit (cap). DESIGN: Quasi-experiment with bivariate and multivariate regression. SETTING: Patients in the New Hampshire Medicaid program and their regular prescribing physicians. PARTICIPANTS: Three hundred and forty-three chronically ill Medicaid enrollees with regular use of essential medications for heart disease, asthma/chronic obstructive pulmonary disease, diabetes mellitus, seizure, or coagulation disorders who received an average of three or more prescriptions per month during the baseline year. MEASUREMENTS: Postcap patient-level change in standard monthly dose of essential medications compared with the baseline period, presence of 11 comorbidities (defined by regular use of specific indicator drugs), practice setting, and location of regular prescribing physician. RESULTS: The mean percentage change in standard doses of essential medications following the cap was -34.4%. Larger changes were significantly associated with several baseline measures: greater numbers of precap medications, greater numbers of comorbidities, longer hospitalizations, and greater use of ambulatory services. The three comorbidities associated with the largest relative reduction in essential drug use were psychoses/bipolar disorders, anxiety/sleep problems, and chronic pain. Patients of physicians in group practices, clinics, or hospitals tended to have smaller dose reductions than those whose physicians were in solo or small-group practice. CONCLUSIONS: Patients most at risk of reduced access to essential medications because of a reimbursement cap include those with multiple chronic illnesses requiring drug therapy, especially illnesses with a mental health component. Physicians in clinics or large group practices may have maintained patient medication regimens more effectively.

The case for a medicare drug coverage benefit: a critical review of the empirical evidence.

The lack of an outpatient prescription drug benefit under Medicare has become a conspicuous omission in the face of accelerated growth in prescription drug expenditures and increased availability of highly effective medications. This article provides a critical review of the empirical evidence on the effect of drug coverage on the use of prescription drugs, health care outcomes, and health care costs among Medicare beneficiaries. The existing literature provides considerable evidence that drug coverage is associated with greater use of all drugs and clinically essential medications and that not all forms of coverage provide the same protection. Longitudinal evidence from elderly and disabled persons in Medicaid indicates that restricting coverage has serious adverse health outcomes for sick and low-income beneficiaries that actually lead to increased health care costs.

Ten recommendations to improve use of medicines in developing countries.

Inappropriate prescribing reduces the quality of medical care and leads to a waste of resources. To address these problems, a variety of educational and administrative approaches to improve prescribing have been tried. This article reviews the experiences of the last decade in order to identify which interventions have proven effective in developing countries, and suggests a range of policy options for health planners and managers. Considering the magnitude of resources that are wasted on inappropriately used drugs, many promising interventions are relatively inexpensive. Simple methods are available to monitor drug use in a standardized way and to identify inefficiencies. Intervention approaches that have proved effective in some settings are: standard treatment guidelines; essential drugs lists; pharmacy and therapeutics committees; problem-based basic professional training; and targeted in-service training of health workers. Some other interventions, such as training of drug sellers, education based on group processes and public education, need further testing, but should be supported. Several simplistic approaches have proven ineffective, such as disseminating prescribing information or clinical guidelines in written form only. Two issues that will require a long-term strategic approach are improving prescribing in the private sector and monitoring the impacts of health sector reform. Sufficient evidence is now available to persuade policy-makers that it is possible to promote rational drug use. If such effective strategies are followed, the quality of health care can be improved and drug expenditures reduced.

Plasma 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) levels and immune response.

For determination of whether plasma 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) pesticide levels (< or =1-32 ppb) are associated with immune suppression or DNA damage in lymphocytes, 302 individuals residing in Moore County, North Carolina, in 1994-1996 provided a blood specimen, underwent a skin test, and answered a questionnaire concerning factors affecting plasma organochlorine pesticide levels and the immune system. The blood specimens were analyzed for levels of plasma DDE (a metabolite of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane), numbers and types of blood cells, immunoglobulin levels, mitogen-induced lymphoproliferative activity, and lymphocyte micronuclei. When DDE levels were categorized as 1 or less, more than 1 to 2, more than 2 to 4.3, more than 4.3 to 7.6, and more than 7.6 ppb, individuals with higher plasma DDE levels had lowered mitogen-induced lymphoproliferative activity (concanavalin A, range: 74,218 dropping to 55,880 counts per minute, p = 0.03) and modestly increased total lymphocytes (range: 2.0-2.3 x 10(3)/microl, p = 0.05) and immunoglobulin A levels (range: 210-252 mg/dl, p = 0.04). There were no consistent differences in response to the skin tests by plasma DDE levels. Plasma DDE levels were not associated with a higher frequency of micronuclei. The authors conclude that relatively low levels of plasma DDE are associated with statistically significant changes in immune markers, although the magnitude of the effects are of uncertain clinical importance.

Use of antihypertensive drugs by Medicare enrollees: does type of drug coverage matter?

Research has demonstrated that Medicare beneficiaries with drug coverage consume more clinically essential drugs. However, generosity of coverage varies considerably across beneficiaries. This study examines the association between types of drug coverage and the consumption and cost per tablet of essential antihypertensive medications among beneficiaries with hypertension. The findings indicate that while both state- and employer-sponsored drug coverage are associated with greater consumption of antihypertensive drugs and lower out-of-pocket costs per tablet, private supplemental coverage is not associated with greater use and is associated with only slightly lower out-of-pocket costs than among noncovered beneficiaries.

Multicenter epidemiologic and health services research on therapeutics in the HMO Research Network Center for Education and Research on Therapeutics.

Research and education programs in therapeutics that combine the data, organizational capabilities, and expertise of several managed care organizations working in concert can serve an important role when a single organization is not large enough to address a question of interest, when diversity in populations or delivery systems is required, and when it is necessary to establish consistency of results in different settings. Nine members of the HMO Research Network, a consortium of health maintenance organizations (HMOs) that perform public domain research, have formed a Center for Education and Research on Therapeutics (CERT), sponsored by the Agency for Healthcare Research and Quality, to conduct multicenter research in therapeutics. The CERT uses a distributed organizational model with shared leadership, in which data reside at the originating organization until they are needed to support a specific study. Extraction of data from the host computer systems, and some manipulation of data, is typically accomplished through computer programs that are developed centrally, then modified for use at each site. For complex studies, pooled analysis files are created by a coordinating center, and then analysed by investigators throughout the HMOs. It is also possible to contact HMO members when necessary. This multicenter environment has several benefits, addressing: (1) a wide array of questions about the safety and effectiveness of therapeutics, (2) the impact of efforts to change clinicians' and patients' behavior, and (3) pharmacoeconomic and pharmacogenetic questions.