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Renal dysfunction in HIV positive patients on highly active antiretroviral therapy (HAART)
BACKGROUND: The use of HAART has turned HIV/AIDS into a chronic disease and people live longer. They now present with complications related to the treatment, ageing process and the virus itself. Renal dysfunction is a recognized complication in HIV infected patients on HAART and can present as acute kidney injury or chronic kidney disease.
METHODS: A cross sectional study was conducted at Parirenyatwa Hospital on patients receiving HAART. Inclusion criteria were age ≥ 18 years and provision of an informed consent. Clinical data was recorded. Body mass index, CD4 count, serum creatinine, urine for dipstick proteinuria and protein: creatinine ratio was collected. Creatinine was calculated using the Cockcroft-Gault formula. Renal dysfunction was defined as Creatinine clearance (CrCl)< 60mL/min.
RESULTS: A total of 122 patients with complete data were analysed. 69% were females. Mean age of patients was 37.7 ±11.3 years and Body mass index was26.0 ±5.2 kg/m². Renal dysfunction defined as CrCl< 60mL/min was found in 18.9 %,(n =23/122). Microalbuminuria was found to be a risk factor for renal dysfunction [OR 4.24 95% CI 1.00-17.04] p < 0.049.
CONCLUSION: Renal dysfunction is common among patients on HAART and micro albuminuria is a risk factor for developing renal dysfunction. For patients on HAART routine urine protein: creatinine ratio and calculation of creatinine clearance should be done at regular intervals to monitor if the patients are developing renal dysfunction
Prevalence and risk factors for diabetes chronic complications in Harare, Zimbabwe
Background: Diabetes is a chronic condition which often causes severe long term complications which compromise quality of life and burdens health care systems and can cause permanent disability and even death. The incidence of diabetes and the associated complications in Harare as reported through surveillance data has been on the increase. In order to reduce disease burden due to diabetes chronic complications, prevalence and risk factors for diabetes chronic complications must be determined through studies.
Methods: A total of 284 diabetics attending diabetic clinics at Parirenyatwa and Harare Central Hospitals were enrolled in this cross sectional analytic study. Interviewer administered questionnaires were used to collect data. The occurrence of diabetes chronic complications and their associated risk factors were analyzed. Written informed consent was sought and obtained from all the respondents.
Results: Overall, prevalence of diabetes chronic complications was high with 45% of respondents having at least one diabetes chronic complication. Significant risk factors associated with diabetes chronic complications were: age>50 years (OR=4.34, p10 years (OR=2.36, p10 years with diabetes (adjusted OR=5.34, p<0.001); high LDL-Cholesterol (adjusted OR=1.84, p=0.039) and type 2 diabetes (adjusted OR=6.48, p<0.001).
Conclusion: Overall prevalence of diabetes chronic complications was high but comparable to other studies. Several demographic, patho-physiologic and life-style related risk factors associated with diabetes chronic complications were identified. There is need to comprehensively address all risk factors in order to reduce diabetes chronic complications
Determinants of Post Natal Care Uptake in Bikita District, Masvingo Province, 2011
Postnatal care (PNC) gives an opportunity to detect medical problems of the
mother and neonate and reduce morbidity and mortality. In 2010 PNC uptake in Bikita was
43%. This study was conducted to determine factors associated with low PNC uptake in
Bikita.
Materials and methods: A 1:1 unmatched case control study was conducted. A case was
defined as a woman who attended at least one antennal care visit and did not attend first( 10
day) PNC visit. A control was a woman who attended both antenatal care and first (10 day)
PNC visit. Random sampling was used to select cases and controls from ANC and PNC
registers at health centres. An interviewer administered questionnaire using constructs of the
Health belief model was used. Focus group discussions were conducted with women who
were not study participants who had come for ANC and PNC. A check list was used to asses
availability of resources for use in PNC. Epi Info 3.5.1 was used to analyse data. Qualitative
data was coded , grouped and analysed manually.
Results: One hundred and fifty cases and 150 controls were recruited. Independent factors
associated with non-uptake of PNC were; practicing seclusion until umbilical cord fell off,
[AOR 3.43,( 95%CI: 1.73-6.81)], residing in village/resettlement [AOR 3.71(95%Cl: 1.30-
9.90)],delivering at home [AOR 6.0(95%CI: 3.50-12.71)], staying more than 5km from
health centre [AOR 1.73(95%CI: 1.03:2.89)],. Factors associated with PNC uptake were
secondary/tertiary level of education [AOR 0.25 (95%CI: 0.11-0.73)] and ability of mother
to attend PNC within 48 hours after at home delivery [AOR 0.60(95%CI: 0.21:0.96)].
Discussion and Conclusion : Delivering at home may lead to transmission of HIV from
mother to child if the mother is HIV positive due to non swallowing of Nevirapine during
delivery. Death of mother and neonate may occur due to lack of medically skilled assistance.
Construction of more waiting mothers shelters may increase the number of institutional
deliveries and prevent maternal and neonatal deaths. As a result of the findings of this study
Save the Children UK has been approached to assist in the construction of waiting mothers’
shelters at Chikuku and Bikita rural hospital.Introduction: Postnatal care (PNC) gives an opportunity to detect medical problems of the
mother and neonate and reduce morbidity and mortality. In 2010 PNC uptake in Bikita was
43%. This study was conducted to determine factors associated with low PNC uptake in
Bikita.
Materials and methods: A 1:1 unmatched case control study was conducted. A case was
defined as a woman who attended at least one antennal care visit and did not attend first( 10
day) PNC visit. A control was a woman who attended both antenatal care and first (10 day)
PNC visit. Random sampling was used to select cases and controls from ANC and PNC
registers at health centres. An interviewer administered questionnaire using constructs of the
Health belief model was used. Focus group discussions were conducted with women who
were not study participants who had come for ANC and PNC. A check list was used to asses
availability of resources for use in PNC. Epi Info 3.5.1 was used to analyse data. Qualitative
data was coded , grouped and analysed manually.
Results: One hundred and fifty cases and 150 controls were recruited. Independent factors
associated with non-uptake of PNC were; practicing seclusion until umbilical cord fell off,
[AOR 3.43,( 95%CI: 1.73-6.81)], residing in village/resettlement [AOR 3.71(95%Cl: 1.30-
9.90)],delivering at home [AOR 6.0(95%CI: 3.50-12.71)], staying more than 5km from
health centre [AOR 1.73(95%CI: 1.03:2.89)],. Factors associated with PNC uptake were
secondary/tertiary level of education [AOR 0.25 (95%CI: 0.11-0.73)] and ability of mother
to attend PNC within 48 hours after at home delivery [AOR 0.60(95%CI: 0.21:0.96)].
Discussion and Conclusion : Delivering at home may lead to transmission of HIV from
mother to child if the mother is HIV positive due to non swallowing of Nevirapine during
delivery. Death of mother and neonate may occur due to lack of medically skilled assistance.
Construction of more waiting mothers shelters may increase the number of institutional
deliveries and prevent maternal and neonatal deaths. As a result of the findings of this study
Save the Children UK has been approached to assist in the construction of waiting mothers’
shelters at Chikuku and Bikita rural hospital.Ministry of Health and Child Welfare Centre for Disease Control, Atlant
PREDICTING POTENTIAL CYP450 ENZYME INHIBITION BASED DRUG-DRUG INTERACTION DURING DRUGS PRESCRIPTION USING A COMPUTER AID
Introduction: The increase in the number of drugs on the market and concomitant
treatment of co-infections has increased the potential for drug interactions making it
difficult for healthcare professionals to minimize the potential adverse effects of every
drug. Fortunately, Medical Informatics has been evolving to match this increase in
complexity in medical delivery. Pharmacoinformatics has become particularly relevant in
addressing some of the undesirable effects associated with the increased practice of
polypharmacy. Therefore, the major aim of this study was to develop a computer based
pharmacoinformatic tool for use by clinicians and pharmacists in the prediction of in vivo
drug-drug interactions (DDIs) using in vitro data.
Materials and methods: The prototypic tool was developed using Standard Query
Language (SQL) database and Delphi 6.0 as the programming language. Literature
sources were assembled, both as databases and symposia abstracts, original publications
of drug-enzyme or drug-drug interactions for competitive and mechanism-based
inhibition. Sources with validated in vitro methods and having the following parameters:
inhibition constant (Ki); maximum enzyme velocity (Vmax); substrate concentration
needed to reach half maximal velocity (Km); fraction metabolized by cytochrome P450
(fm) and fraction cleared by cytochrome P450 (fh), were considered. Different plasma
concentrations of the inhibitor available to the enzyme site for interaction were tested
with and without taking into account protein binding. The concentrations included the
average maximum plasma concentration (Cmax) and the estimated of maximum
concentration of the inhibitor at entrance to the liver (Iin.max), both bound and unbound. A
pilot study was carried out among 10 doctors and 10 pharmacists to test the medical
relevance of the tool using a questionnaire with scores ranging from 1 (best) to 6 (worst).
Results and discussion: Various drug combinations were tested. The best predictions of
in vivo drug-drug interactions were achieved when the concentration of inhibitor was set
at the unbound maximum concentration at entrance to the liver enzymes with better
overall geometric mean fold error (GMFE) values of 0.68 and overall root mean square
error (RMSE) of 3.13 without considering mechanism-based inhibition (MBI). There was
improvement in overall GMFE (0.49) and RMSE (1.71) for steady-state unbound Cmax
when MBI was incorporated. A preliminary evaluation of the tool by medical
professionals has highly recommended application in private practice and in academia as
a teaching tool, and with mixed reactions in public sector. The survey recommended that
modifications be made on details captured under product composition.
Conclusion: The pharmacoinformatic tool developed during this work is likely to be well
received by the medical community starting as a teaching tool. More drugs used routinely
need to be added, and a high sample size evaluation of relevance and acceptability
conducted. The predictive capacity of the tool had low levels of bias when the
concentration of inhibitor was set at the unbound maximum concentration at entrance to
the liver enzymes. However more work needs to be done to include Drug-Drug
Interactions (DDIs) due to induction and irreversible enzyme inhibition or through
inhibition of other enzymes not considered in this study
Development, safety and efficacy evaluation of actinic damage retarding nano-pharmaceutical treatments in oculocutaneous albinism
Introduction: There are at least 17 000 Persons living with albinism (PLWA) in Zimbabwe. Oculocutaneous albinism (OCA) is a congenital amelanistic pigmentation disorder that affects all known vertebrates and has no known cure. Melanogenesis is the body’s primary protection from actinic damage, which summarizes all the acute and chronic solar induced adverse dermatological conditions. This impairment therefore makes PLWA highly susceptible to all forms of this damage.
Problem statement: Commercial products for actinic damage in PLWA are not readily available. Chemical sunscreens used by PLWA are ineffective and do not treat symptoms of actinic damage. The possible use of promising broad spectrum physical sunscreens in albinistic treatments is hindered by their opaque and un-aesthetic nature.
Research hypothesis: A treatment based on nanometric TiO2 and ZnO incorporating the active extracts of A. excelsa, T. emetica and M. flabellifolia will be aesthetic, efficacious and safe in retarding and alleviating all forms of actinic damage in PLWA.
Research aims: To develop albinistic actinic damage treatments, using nano TiO2 and ZnO as sun-blocks and incorporating selected herbs. The dermato-pharmacokinetics, stability, efficacy, toxicity and aesthetics of the resultant formulation on albinistic skin types were also investigated in this study.
Materials and methods: Emulsion formulation was done according to FDA-CFSAN, COLIPA, and OECD mandated technical guidelines and testing methods. Formulation skin sensitivity were evaluated through Draize ocular and skin sensitivity tests as well as in-vivo patch tests guided by OECD 428/404 technical guidelines and opinion SCCNFP 0750/03. Percutaneous absorption and albinistic skin dermato-pharmacokinetics were evaluated ex-vivo using Franz diffusion tests and sequential adhesive tape stripping respectively according to OECD guidelines 428 and SCCNFP opinions as well as related work done by A O Gamer and Diembeck et al as guides. Analysis for Ti and Zn were done by ICP-AES and Flame AAS respectively. Efficacy and SPF testing was done as per FDA–CFSAN, Colipa and OECD M389/EN mandated test methods.
Principal Results: SPF 16, aesthetic and stable emulsions were formulated. Negligible irritation indices for the treatment were recorded for Draize and human patch testing. No percutaneous absorption was observed for ex-vivo diffusion tests and sequential tape stripping tests. Different skin reservoir properties were observed at different skin sites
Conclusions: The studies demonstrate, direct evidence that neither Zn nor Ti can penetrate actinic damaged skin regardless of anatomical site and that albinistic dermato-pharmacokinetics are depended on anatomical region and extent of UVR exposure. The high extraction yields and the phyto-constituents of the selected herbs show a correlation with the traditional uses of the plants in traditional medicine. All sensitivity tests showed negligible irritation potential. Based on the foregoing, it is concluded that, incorporation of nanometric TiO2, ZnO and herbs in treatments to retard actinic damage in PLWA is feasible, aesthetic, efficacious, and commercializable and does not pose any health risk.Harare Institute of Technology.
University of Zimbabwe Research Grant.
ICF Grant from the Government of Zimbabwe
Epidemiology of oral Kaposi’s sarcoma in Zimbabwe 1988-1997: A population-based study
Objective: Sub-Saharan Africa has the highest number of HIV/AIDS cases globally which contrasts with the lack of population-based studies of oral Kaposi's sarcoma (OKS); one of the clinical cardinal signs of HIV/AIDS. To date, no study has investigated the incidence of OKS in African populations affected by the HIV/AIDS epidemic. It is, therefore, the purpose of this study to assess the burden of OKS in the Zimbabwean population over a 10 year period. Design: A descriptive epidemiological study was undertaken to assess the burden of OKS by determining the frequencies, incidence and cumulative rates, the lifetime risk and chances of developing OKS according to site (topography), gender, age, race/ethnic origin of the Zimbabwean population. A total of 445 incident cases of OKS from the upper and lower lips, oral vestibule, retromolar area, floor of mouth, tongue, cheek, mucosa, gums, hard and soft palate were accessed from the Zimbabwe National Cancer Registry (ZNCR). Cases from the skin, pharynx, larynx and the major salivary glands were excluded from the study. Setting: This comprised the population of Zimbabwe during the 10 year period 1988-1997. The population figures used for this study were fro the 1992 Census Zimbabwe National Report. The study population was standardized by the direct method against the world standard population to calculate the age standardized incidence rate (ASIR). The SPSS statistical software programme (SPSS Inc. 2001, USA) was used for the statistical analysis. Results: OKS comprised 0.92% of total body malignancies and 51 % of oral malignancies with a mean age of study cases of 37.6 years and median age of 32 years. Histology of the primary (64.5%) and clinical diagnosis (34.6%) were the predominant methods of diagnosis. OKS affected nearly only blacks and males more than females, with a male to female ratio of 1.9:1. The most affected age groups by OKS were the 30 to 34 years for male and 25 to 29 years for both females and the whole population. Other notable peaks in OKS rates were in the 0 to 4 year and the 75+ age groups. OKS mostly affected the palate (70.2%) followed by, in descending order, the tongue (13.3%) and mouth (8.3%). The age adjusted age standardized incidence rate (ASIR) of OKS exponentially increased the entire study period bypassing oral squamous cell carcinoma (OSCC) as the predominant oral malignancy in 1994. Among AIDS-associated malignancies, OKS accounted for 98% while the balance comprised Burkitt’s lymphoma, Hodgkin's and Non-Hodgkin's lymphomas,
haemangiosarcoma and lymphoma not specified. Conclusion: OKS was the commonest malignancy of young adults affecting males more than females. OKS steady increased for the entire study period overtaking SCC in 1994 to become the commonest oral malignancy for the remainder of the study period. The palate was the most affected intra-oral site by OKS
Investigation into the pharmacodynamics of ethanol as a nerve blocking agent
Ethanol is a known nerve-blocking agent, yet its clinical use is minimal. This is partly due to
unclear dosage levels and not enough knowledge of its pharmacodynamics and overwhelming
dominance of its psychomotor properties. This research intended to investigate into the
pharmacodynamics of ethanol as a nerve blocking agent, try and establish an effective dose that
can be used clinically, as well as comparing its effects on various parts of the motor unit.
A total of 105 sciatic nerve – gastrocnemius muscle specimens were isolated from frogs, Xenopus
laevis. Ethanol at concentrations of 40%, 55% and 70%, each at doses of 1.5g/kg, 2.0g/kg and
2.5g/kg body weight (BW) was administered intraperitoneally, intramuscularly (into the
gastrocnemius) and topically (onto the sciatic nerve). Using EPIC system to monitor muscle
contractions, action potential and/or electromyogram the nerve block effects of each dose /
concentration combination were assessed. The effects on the nerve, neuromuscular junction and
muscle were assessed separately and compared, then as a single unit.
Results showed that intraperitoneally administered ethanol had no effect on neuromuscular
function. Intramuscular injections took 2.5 to 9.0 minutes to attain complete paralysis, and lasted
for 29.5 to 61.0 minutes, depending on concentration and dose (>/= 55%; >/= 2.0g/kg BW).
Topically applied ethanol took 15 to 30 seconds to block the nerve completely, depending on the
concentration (>/= 40%). The blockade lasted for 5 to 10 minutes. Intramuscularly injected
ethanol reduced the amplitude of indirectly elicited electromyography more than the directly
evoked one.
It was concluded that to achieve a complete and sustained ethanol nerve block, at least 55%
concentration, 2.0g/kg BW dose and intramuscular route are required. The duration of blockade
depends on concentration and dose administered. Ethanol affects both nerve and muscle. The
effect is more pronounced and instant on the nerve than on muscle
Diagnosis of neurological infections in AIDS patients: Possibilities for Zimbabwe
Routine cerebrospinal fluid (CSF) examination and culture was performed on CSF obtained from 23 HIV infected adults presenting with neurological symptoms at Parirenyatwa Hospital. Bacterial growth was obtained in CSF from two patients. Cryptococcal meningitis (CM) was the predominant cause of adult meningitis with 10 patients being diagnosed with CM based on the detection of C. neoformans (positive culture or India ink stain) or a positive CSF cryptococcal antigen test. In three of the 10 patients (33%) C. neoformans had been missed on India ink staining and culture. The cryptococcal antigen latex test offers a rapid and reliable test and its use must be advocated in the routine laborator
Carcinoma of the Thyroid at Harare Histopathology Laboratory (Zimbabwe)
The carcinoma of the thyroid gland seen at Harare Histopathology Laboratory (Zimbabwe) has been reviewed and analysed. There was a male to female ratio of 1:4. The commonest histological type of tumour was follicular carcinoma (70%). There were equal numbers of papillary and anaplastic types (14% each). Only two cases of medullary carcinoma were found, one of these being in a twelve-year-old female patient. The finding of a high occurance of follicular carcinoma is consistent with Zimbabwe being a country where endemic goitre is common
The rate of and indications for enucleations at Sekuru Kaguvi Eye Unit in Harare: a comparative analysis.
Objectives: To determine the rate of and indications for enucleation at Sekuru Kaguvi Eye Unit (SKEU) in Zimbabwe and compare the findings with those from other tertiary eye care centres in the developing world. Design: Descriptive retrospective cross sectional study.
Setting: Sekuru Kaguvi Eye Unit, Parirenyatwa Hospital, Harare, Zimbabwe.
Subjects: Records of patients who had undergone enucleation at Sekuru Kaguvi Eye Unit, between January 1988 to December 2000.
Main Outcome Measures: Rate and indications of enucleations done at SKEU during the study period. Results: Ocular tumours (64.2%) and ocular infections (26.4%>) were the leading indications for enucleation and the crude incidence rate for enucleation at SKEU was 0.17%
Conclusion: Indications for enucleation at the SKEU in Harare are similar to those experienced by other developing countrie