Adverse drug reactions in patients admitted on internal medicine wards in a district and regional hospital in Uganda.

INTRODUCTION: The burden of both community and hospital acquired adverse drug reactions (ADRs) are some of the important issues in pharmacotherapy. At the time of this study there was very scanty literature in this area from Africa. OBJECTIVE: This study was done to determine the frequency and characteristics of ADRs in patients admitted on medical wards in public hospitals. METHODS: This was a longitudinal observational study on 728 adult patients on medical wards in one regional and one district hospitals. Community and hospital acquired ADRs were assessed. RESULTS: Thirty three patients (4.5%) were admitted with suspected ADR, and an ADR was the reason for hospitalization in 1.5%. Most ADRs were due to antiparasitic products, mainly quinine (61%). Community acquired ADRs prolonged hospital stay, 5.6 days vs 4.0 days (p-value < 0.001). During hospitalization ADRs occurred in 49.5% of the patients. Antiparasitic products, predominantly quinine, were the commonest drugs class associated with ADRs (85.9%). Hospital acquired ADRs did not affect hospital stay, 4.2 days vs 3.9 (p-value 0.129). CONCLUSION: ADRs are an important cause of morbidity in patients, both in the community and in hospitals, and the majority are associated with the commonly used drugs.

Use of a pilot drug information centre.

INTRODUCTION: Provision of access to drug information by prescribers and other health care professionals is important in pharmacotherapy. At the time of this study there was very scanty literature in this area from Africa. OBJECTIVE: To assess use of a pilot drug information centre (DIC) which was set up in a department of Pharmacology and Therapeutics in a university teaching hospital in Uganda. METHODS: This was a situational analysis with a prospective study design. The pilot DIC was established and its use over an eleven-month period was assessed. The received queries were evaluated for source of the query, reason for the query and type of query. RESULTS: During the 11 months 297 queries were received, 72.3% of which were from public hospitals. Most were from prescribing doctors (54.2%). Majority were on drug-drug interaction (41.2%), followed by therapy (23.2%). Out of 197 specific drug requests, 65.5% were on antiretroviral. CONCLUSION: We found that healthcare professionals were enthusiastically using the drug information centre. It is, therefore, necessary and feasible to establish a DIC in Uganda that will enable these professionals to readily access drug information.

Improved efficacy with amodiaquine instead of chloroquine in sulfadoxine/pyrimethamine combination treatment of falciparum malaria in Uganda: experience with fixed-dose formulation.

Amodiaquine (AQ) is an affordable compound, chemically related to chloroquine (CQ) but often effective against CQ resistant Plasmodium falciparum. In Uganda, a pre-packed fixed-dose combination of CQ plus sulfadoxine/pyrimethamine (CQ+SP) called Homapak is used in the home based management of fever program (HBM). We performed a single blind randomized trial to determine the efficacy of AQ+SP in comparison with the fixed-dose CQ+SP (Homapak) in the treatment of uncomplicated falciparum malaria in Ugandan children aged 6 months to 5 years. The study was done in 2004 at Walkuba Health Center, a sub-urban area in Jinja district, Uganda. Primary outcome was the day 14 per protocol clinical and parasitological response according to the WHO. A total of 183 children were included (mean age 28 months) and 90% completed 28 days of follow up. The day 14 adequate clinical and parasitological response was 70.9% for CQ+SP and 97.4% for AQ+SP (p<0.001). In those given CQ+SP, treatment failure rates for the 6 months to 2 years age group were much higher (48.2%) than in the older children (18.2%, p=0.004). The day 28 PCR adjusted parasitological failure rates were also higher in the CQ+SP (31.3%) than in the AQ+SP group (13.1%) (p=0.003), with a higher gametocyte carriage among the CQ+SP group. We conclude that the efficacy of AQ+SP was significantly superior to the fixed-dose CQ+SP (Homapak), particularly among the youngest children. Thus, AQ could be used instead of CQ in combination with SP to improve the effectiveness against falciparum malaria in Uganda.

Pharmacokinetic interactions between chloroquine, sulfadoxine and pyrimethamine and their bioequivalence in a generic fixed-dose combination in healthy volunteers in Uganda.

BACKGROUND: A pre-packaged fixed-dose formulation of chloroquine (CQ) and sulfadoxine/pyrimethamine (S/P) combination (Homapak) is widely used for the treatment of falciparum malaria in Ugandan children. It is however a product whose pharmacokinetics and interactions have not been studied. OBJECTIVES: To explore possible pharmacokinetic interactions between CQ and S/P during co-administration, and to determine their bioavailability in the locally made Homapak compared to the Good Manufacturing Practice (GMP) made formulations. METHODS: Thirty-two adult healthy volunteers were randomized into four groups and given single oral doses of fixed-dose CQ+S/P combination (Homapak), or GMP formulations of S/P (Fansidar), CQ (Pharco), or their combination. Plasma samples were followed for 21 days, analysed by HPLC-UV methods, with pharmacokinetic modeling using the WinNonlin software. RESULTS: Sulfadoxine in Homapak was more rapidly absorbed (ka = 0.55 h(-1)) than in Fansidar + CQ (ka = 0.27 h(-1), p=0.004), but not more than S in Fansidar alone group (ka = 0.32 h(-1), p=0.03). No significant differences were observed in the other pharmacokinetic parameters of S, P and CQ when given together or separately. The relative bioavailability of CQ and S in Homapak showed bioequivalence to reference formulations. CONCLUSIONS: There were no pharmacokinetic interactions between CQ, S and P when the compounds were given together, however, more investigations would be needed to explore this further. Compared with GMP made drugs, both S and CQ are bioequivalent in Homapak, the Ugandan made fixed-dose formulation. Furthermore, the absorption of S was more rapid which could be advantageous in malaria treatment.

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.

Review of five paradigm papers on economic, biomedical, community, sociocultural and political perspectives in improving use of medicines.

This paper presents a review of five paradigm presentations at the first International Conference on Improving Use of Medicines (ICIUM) in Chiang Mai, Thailand, April 1-4, 1997. The paradigm papers covered economic, biomedical, community, socio-cultural and political approaches in improving the use of medicines. Salient points on problems examined by each of the paradigms, limitations of each paradigm, and challenges to be tackled are highlighted in the review from the view point of a health care provider. Some common features of the five paradigms relating to problems in medicine use have been reviewed. These features could provide bases for reaching consensus in finding solutions to some of the burning issues in the area of medicine use. It is becoming increasingly clear that there is growing concern about the way medicines are used: is it rational and in the best interest of the patients?

Relative reactivity of the V3 loop PND of HIV-1 subtypes A, B, C, D, and F with sera from selected Ugandan localities.

Synthetic peptides comprising the predicted principal neutralizing determinant (PND) in new African and North American HIV-1 clones were tested in ELISA for reactivity with ninety six serum samples from asymptomatic donors in six selected localities in Uganda. Irrespective of the geographical origin of the samples, the majority of the test sera cross-reacted at high intensities with the peptides derived from the North American clone, BRT3.6 (Group B), the Ugandan clone, CUG045, (Group C), and the Romanian clone, FRMA (Group F). The frequency of reactivity of the peptides from BRT3.6, CUG045, and FRMA were within the ranges of 57-100%, 50-100%, and 57-100%, respectively, for the sera collected from these disparate localities. In contrast to these findings, the V3 peptides derived from the other Ugandan isolates showed a more restricted pattern of reactivity with the same serum samples: AUG06c (1-63%), DUG23c (2%), and DUG044 (38-87%). The results from ELISA inhibition assay indicated that the V3 peptide from BRT 3.6, CUG045, and FRMA express closely related antigenic specificities quite distinct from those in AUG06c and DUG044. The residues comprising the PND in BRT 3.6, CUG045, and FRMA appear to be well conserved in the HIV-1 subtypes prevalent in the selected Ugandan locales.

PIP: In Uganda, health workers collected serum samples from 96 asymptomatic HIV-1 infected blood donors in Ishaka and Mbarara (southwest), Kisenyi and Kampala (central), and Lugazi and Jinja (east) so researchers working in a biochemistry laboratory at The City University of New York could describe the relative reactivity of the V3 loop from HIV-1 subtypes A, B, C, D, and F, as well as study the antigenic relationships within the PND encoded in the divergent HIV-1 subtypes. Regardless of geographic origin, the V3 peptides from most of the sera (at least 50%) collected in Uganda cross-reacted at high frequencies with the peptides derived from the novel North American clone (BRT3.6), the Ugandan clone (CUG045), and the Romanian clone (FRMA). The frequency of reactivity of these peptides with the test sera ranged from 57% to 100% for BRT3.6, from 50% to 100% for CUG045, and from 57% to 100% for FRMA. The V3 peptides from other Ugandan isolates (AUG06c, DUG044, and DUG23c) were less reactive with the same serum samples than BRT3.6, CUG045, and FRMA: 1-63%, 38-87%, and 2%, respectively. This finding suggests that the antigenic determinants expressed in AUG06c, DUG044, and DUG23c may not represent the PND encoded in most HIV-1 strains afflicting the Ugandan communities. The V3 peptides from BRT3.6, CUG045, and FRMA express closely related antigenic specificities altogether different from those in AUG06c and DUG044. The HIV-1 subtypes present in the selected Ugandan sites appear to effectively conserve the residues making up the PND in BRT3.6, CUG045, and FRMA.

Prescribing in hospital outpatient departments and rural health facilities in Uganda: some clinical and educational implications.

A comparison of prescribing patterns in hospital outpatient departments (OPD) and rural health units (RHU) in Uganda revealed an average of 2.45 and 1.66 drugs prescribed per treatment episode in OPD and RHU respectively. 40.1% of the OPD and 57.3% of the RHU prescriptions included antibacterials. It is argued that in view of the relevant morbidity pattern, an average of 1.4-1.5 drug/treatment episodes, as well as 15-20% receiving antibacterials would seem appropriate, thus leaving scope for considerable cost reductions. A successful strategy for achieving rational prescribing is likely to include a variety of educational approaches aimed at all present and future prescribers.

Traditional methods in management of diarrhoeal diseases in Uganda.

A total of 292 traditional healers were interviewed in five districts of Uganda to discover how diarrhoeal diseases were treated by them. At least two healers were present in every village visited, and over 42% of their case-load was concerned with diarrhoeal treatment. The investigation showed that a great variety of herbs/plants are used by traditional healers in the treatment of diarrhoeal diseases. All those interviewed used water as the main vehicle for their herbal preparations, the amount prescribed daily ranging from 20 ml to over 100 ml for children (in the case of 54.5% of healers) and 100 ml to over 500 ml for adults (56.6%); 26.4% of healers considered fluid supplements as mandatory and 70.5% advised patients to take as much fluid as possible. Only 3.1% of healers either limited or did not advise fluid intake. These findings indicate that traditional healers could play an important role in interventions to control diarrhoeal diseases using modern oral rehydration therapy if they are assisted to improve their techniques.

Cardiovascular reactivity to noradrenaline and angiotensin in normotensive, hypertensive and 6-hydroxydopamine treated rats.

Blood pressure responses to intravenous noradrenaline and angiotensin in the pithed rat preparations from normotensive, chronically hypertensive and 6-hydroxydopamine (6-OHDA) treated groups were found to follow different patterns. 6-OHDA treated rats were very sensitive to the effects of the two pressor agents and repeated administration of the two drugs invariably led to cardiovascular collapse.