Showing papers by "Mulago Hospital published in 2013"

Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial

Abstract: Early rapid fluid resuscitation (boluses) in African children with severe febrileillnesses increases the 48-hour mortality by 3.3% compared with controls (nobolus). We explored the effect of boluses on 48-hour all-cause mortality byclinical presentation at enrolment, hemodynamic changes over the first hour, andon different modes of death, according to terminal clinical events. We hypothesizethat boluses may cause excess deaths from neurological or respiratory eventsrelating to fluid overload. Pre-defined presentation syndromes (PS; severe acidosis or severe shock,respiratory, neurological) and predominant terminal clinical events(cardiovascular collapse, respiratory, neurological) were described by randomizedarm (bolus versus control) in 3,141 severely ill febrile children with shockenrolled in the Fluid Expansion as Supportive Therapy (FEAST) trial. Landmarkanalyses were used to compare early mortality in treatment groups, conditional onchanges in shock and hypoxia parameters. Competing risks methods were used toestimate cumulative incidence curves and sub-hazard ratios to compare treatmentgroups in terms of terminal clinical events. Of 2,396 out of 3,141 (76%) classifiable participants, 1,647 (69%) had a severemetabolic acidosis or severe shock PS, 625 (26%) had a respiratory PS and 976(41%) had a neurological PS, either alone or in combination. Mortality wasgreatest among children fulfilling criteria for all three PS (28% bolus, 21%control) and lowest for lone respiratory (2% bolus, 5% control) or neurological(3% bolus, 0% control) presentations. Excess mortality in bolus arms versuscontrol was apparent for all three PS, including all their component features. Byone hour, shock had resolved (responders) more frequently in bolus versus controlgroups (43% versus 32%, P <0.001), but excess mortality with boluseswas evident in responders (relative risk 1.98, 95% confidence interval 0.94 to4.17, P = 0.06) and 'non-responders' (relative risk 1.67, 95% confidenceinterval 1.23 to 2.28, P = 0.001), with no evidence of heterogeneity(P = 0.68). The major difference between bolus and control arms wasthe higher proportion of cardiogenic or shock terminal clinical events in bolusarms (n = 123; 4.6% versus 2.6%, P = 0.008) rather than respiratory (n =61; 2.2% versus 1.3%, P = 0.09) or neurological (n = 63, 2.1% versus1.8%, P = 0.6) terminal clinical events. Excess mortality from boluses occurred in all subgroups of children. Contrary toexpectation, cardiovascular collapse rather than fluid overload appeared tocontribute most to excess deaths with rapid fluid resuscitation. These resultsshould prompt a re-evaluation of evidence on fluid resuscitation for shock and are-appraisal of the rate, composition and volume of resuscitation fluids. ISRCTN69856593

Elucidating Emergence and Transmission of Multidrug-Resistant Tuberculosis in Treatment Experienced Patients by Whole Genome Sequencing

Abstract: BACKGROUND Understanding the emergence and spread of multidrug-resistant tuberculosis (MDR-TB) is crucial for its control. MDR-TB in previously treated patients is generally attributed to the selection of drug resistant mutants during inadequate therapy rather than transmission of a resistant strain. Traditional genotyping methods are not sufficient to distinguish strains in populations with a high burden of tuberculosis and it has previously been difficult to assess the degree of transmission in these settings. We have used whole genome analysis to investigate M. tuberculosis strains isolated from treatment experienced patients with MDR-TB in Uganda over a period of four years. METHODS AND FINDINGS We used high throughput genome sequencing technology to investigate small polymorphisms and large deletions in 51 Mycobacterium tuberculosis samples from 41 treatment-experienced TB patients attending a TB referral and treatment clinic in Kampala. This was a convenience sample representing 69% of MDR-TB cases identified over the four year period. Low polymorphism was observed in longitudinal samples from individual patients (2-15 SNPs). Clusters of samples with less than 50 SNPs variation were examined. Three clusters comprising a total of 8 patients were found with almost identical genetic profiles, including mutations predictive for resistance to rifampicin and isoniazid, suggesting transmission of MDR-TB. Two patients with previous drug susceptible disease were found to have acquired MDR strains, one of which shared its genotype with an isolate from another patient in the cohort. CONCLUSIONS Whole genome sequence analysis identified MDR-TB strains that were shared by more than one patient. The transmission of multidrug-resistant disease in this cohort of retreatment patients emphasises the importance of early detection and need for infection control. Consideration should be given to rapid testing for drug resistance in patients undergoing treatment to monitor the emergence of resistance and permit early intervention to avoid onward transmission.

Relapse more common than reinfection in recurrent tuberculosis 1-2 years post treatment in urban Uganda.

Abstract: OBJECTIVE To determine the proportion of recurrent tuberculosis (TB) due to relapse with the patient's initial strain or reinfection with a new strain of Mycobacterium tuberculosis 1-2 years after anti-tuberculosis treatment in Uganda, a sub-Saharan TB-endemic country. DESIGN Records of patients with culture-confirmed TB who completed treatment at an urban Ugandan clinic were reviewed. Restriction fragment length polymorphism (RFLP) patterns were used to determine relapse or reinfection. Associations between human immunodeficiency virus (HIV) positivity and type of TB recurrence were determined. RESULTS Of 1701 patients cured of their initial TB episode with a median follow-up of 1.24 years, 171 (10%) had TB recurrence (8.4 per 100 person-years). Rate and risk factors for recurrence were similar to other studies from sub-Saharan Africa. Insertion sequence (IS) 6110-based RFLP of paired isolates from 98 recurrences identified 80 relapses and 18 reinfections. Relapses among HIV-positive and -negative patients were respectively 79% and 85% of recurrences. CONCLUSIONS Relapse was more common and presented earlier than reinfection in both HIV-positive and -negative TB patients 1-2 years after completing treatment. These findings impact both the choice of retreatment drug regimen, as relapsing patients are at higher risk for acquired drug resistance, and clinical trials of new TB regimens with relapse as clinical endpoint.

The acceptability and safety of the Shang Ring for adult male circumcision in Rakai, Uganda.

Abstract: OBJECTIVES Medical male circumcision (MMC) is recommended for HIV prevention in men. We assessed the acceptability and safety of the Shang Ring device compared with those of the dorsal slit method. METHODS HIV-negative, uncircumcised men aged 18 years or older who requested free MMC services in rural Rakai, Uganda, were informed about the Shang Ring and dorsal slit procedures and offered a free choice of procedure. Men were followed at 7 days postoperatively to assess adverse events related to surgery and to remove the Shang Ring. Wound healing was assessed at 4 weeks postoperatively. RESULTS Six hundred twenty-one men were enrolled, of whom 508 (81.8%) chose the Shang Ring and 113 the dorsal slit. The Shang Ring was provided to 504 men, among whom there were 4 failures of Ring placement (0.8%) that required surgical hemostasis and wound closure. Five hundred men received the Shang Ring and postoperative surgery-related moderate adverse events were 1.0%, compared with 0.8% among dorsal slit recipients. Complete wound healing at 4 weeks was 84% with the Ring and 100% with the dorsal slit (P < 0001). Resumption of intercourse before 4 weeks was 7.0% with the Ring and 15.0% with the dorsal slit (P = 0.01.) The mean time for surgery was 6.1 minutes with the Ring and 17.7 minutes with the dorsal slit. The mean time for Ring removal was 2.2 minutes. CONCLUSIONS The Shang Ring is highly acceptable and safe in this setting, and could improve the efficiency of MMC services. However, back-up surgical services are needed in cases of Ring placement failures.

Presenting features of newly diagnosed rheumatic heart disease patients in Mulago Hospital: a pilot study.

Abstract: Introduction : Rheumatic heart disease (RHD) continues to cause gross distortions of the heart and the associated complications of heart failure and thromboembolic phenomena in this age of numerous high-efficacy drugs and therapeutic interventions. Due to the lack of contemporary local data, there is no national strategy for the control and eradication of the disease in Uganda. This study aimed to describe the presenting clinical features of newly diagnosed patients with RHD, with particular reference to the frequency of serious complications (atrial fibrillation, systemic embolism, heart failure and pulmonary hypertension) in the study group. Methods : One hundred and thirty consecutive patients who satisfied the inclusion criteria were recruited over a period of eight months from June 2011 to January 2012 at the Mulago Hospital, Uganda. Data on demographic characteristics, disease severity and presence of complications were collected by means of a standardised questionnaire. Results : Seventy-one per cent of the patients were female with a median age of 33 years. The peak age of the study group was 20 to 39 years, with the commonest presenting symptoms being palpitations, fatigue, chest pain and dyspnoea. The majority of the patients presented with moderate-to-severe valvular disease. Pure mitral regurgitation was the commonest valvular disease (40.2%), followed by mitral regurgitation plus aortic regurgitation (29%). Mitral regurgitation plus aortic regurgitation plus mitral stenosis was found in 11% of patients. There was only one case involving the tricuspid valve. The pulmonary valves were not affected in all patients; 45.9% of patients presented in severe heart failure in NYHA class III/IV, 53.3% had pulmonary hypertension, 13.9% had atrial fibrillation and 8.2% had infective endocarditis. All patients presented with dilated atria (g 49 mm). Conclusion : A significant proportion of RHD patients present to hospital with severe disease associated with severe complications of advanced heart failure, pulmonary hypertension, infective endocarditis and atrial fibrillation. There is a need to improve awareness of the disease among the population, and clinical suspicion in primary health workers, so that early referral to specialist management can be done before severe damage to the heart ensues.

LPS-Binding Protein and IL-6 Mark Paradoxical Tuberculosis Immune Reconstitution Inflammatory Syndrome in HIV Patients

Abstract: Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB co-infected patients initiating antiretroviral therapy (ART). The role of the innate immune system in TB-IRIS is becoming increasingly apparent, however the potential involvement in TB-IRIS of a leaky gut and proteins that interfere with TLR stimulation by binding PAMPs has not been investigated before. Here we aimed to investigate the innate nature of the cytokine response in TB-IRIS and to identify novel potential biomarkers. Methods: From a large prospective cohort of HIV-TB co-infected patients receiving TB treatment, we compared 40 patients who developed TB-IRIS during the first month of ART with 40 patients matched for age, sex and baseline CD4 count who did not. We analyzed plasma levels of lipopolysaccharide (LPS)-binding protein (LBP), LPS, sCD14, endotoxin-core antibody, intestinal fatty acid-binding protein (I-FABP) and 18 pro-and anti-inflammatory cytokines before and during ART. Results: We observed lower baseline levels of IL-6 (p = 0.041), GCSF (p = 0.036) and LBP (p = 0.016) in TB-IRIS patients. At IRIS event, we detected higher levels of LBP, IL-1RA, IL-4, IL-6, IL-7, IL-8, G-CSF (p ≤ 0.032) and lower I-FABP levels (p = 0.013) compared to HIV-TB co-infected controls. Only IL-6 showed an independent effect in multivariate models containing significant cytokines from pre-ART (p = 0.039) and during TB-IRIS (p = 0.034). Conclusion: We report pre-ART IL-6 and LBP levels as well as IL-6, LBP and I-FABP levels during IRIS-event as potential biomarkers in TB-IRIS. Our results show no evidence of the possible contribution of a leaky gut to TB-IRIS and indicate that IL-6 holds a distinct role in the disturbed innate cytokine profile before and during TB-IRIS. Future clinical studies should investigate the importance and clinical relevance of these markers for the diagnosis and treatment of TB-IRIS. Copyright: © 2013 Goovaerts et al.

Aspirations for quality health care in Uganda: How do we get there?

Abstract: Despite significant investments and reforms, health care remains poor for many in Africa. To design an intervention to improve access and quality of health care at health facilities in eastern Uganda, we aimed to understand local priorities for qualities in health care, and factors that enable or prevent these qualities from being enacted. In 2009 to 2010, we carried out 69 in-depth interviews and 6 focus group discussions with 65 health workers at 17 health facilities, and 10 focus group discussions with 113 community members in Tororo District, Uganda. Health-care workers and seekers valued technical, interpersonal and resource qualities in their aspirations for health care. However, such qualities were frequently not enacted, and our analysis suggests that meeting aspirations required social and financial resources to negotiate various power structures. We argue that achieving aspirations for qualities valued in health care will require a genuine reorientation of focus by health workers and their managers toward patients, through renewed respect and support for these providers as professionals.

Reach and cost-effectiveness of the PrePex device for safe male circumcision in Uganda.

Abstract: Introduction Modelling, supported by the USAID Health Policy Initiative and UNAIDS, performed in 2011, indicated that Uganda would need to perform 4.2 million medical male circumcisions (MMCs) to reach 80% prevalence. Since 2010 Uganda has completed 380,000 circumcisions, and has set a national target of 1 million for 2013. Objective To evaluate the relative reach and cost-effectiveness of PrePex compared to the current surgical SMC method and to determine the effect that this might have in helping to achieve the Uganda national SMC targets. Methods A cross-sectional descriptive cost-analysis study conducted at International Hospital Kampala over ten weeks from August to October 2012. Data collected during the performance of 625 circumcisions using PrePex was compared to data previously collected from 10,000 circumcisions using a surgical circumcision method at the same site. Ethical approval was obtained. Results The moderate adverse events (AE) ratio when using the PrePex device was 2% and no severe adverse events were encountered, which is comparable to the surgical method, thus the AE rate has no effect on the reach or cost-effectiveness of PrePex. The unit cost to perform one circumcision using PrePex is $30.55, 35% ($7.90) higher than the current surgical method, but the PrePex method improves operator efficiency by 60%, meaning that a team can perform 24 completed circumcisions compared to 15 by the surgical method. The cost-effectiveness of PrePex, comparing the cost of performing circumcisions to the future cost savings of potentially averted HIV infections, is just 2% less than the current surgical method, at a device cost price of $20. Conclusion PrePex is a viable SMC tool for scale-up with unrivalled potential for superior reach, however national targets can only be met with effective demand creation and availability of trained human resource.

Research site monitoring for compliance with ethics regulatory standards: review of experience from Uganda

Abstract: On site monitoring of research is one of the most effective ways to ensure compliance during research conduct. However, it is least carried out primarily for two reasons: presumed high costs both in terms of human resources and finances; and the lack of a clear framework for undertaking site monitoring. In this paper we discuss a model for research site monitoring that may be cost effective and feasible in low resource settings. This was a retrospective review of research site monitoring reports covering a period of four years. The monitoring was conducted by the Uganda National Council for Science and Technology, the National Drug Authority and the National HIV/AIDS Research and Ethics Committee over the period 2007 to 2010. The monitoring team was usually three members comprising of two experts in research ethics and an assistant. A total of 28 site monitoring visits covering 40 research projects were reviewed. 25% of the site monitoring reports revealed violation of the regulatory requirement for valid ethical approval. 36% of the site reports showed some instances of informed consent violation, 28% showed violation of the rights and welfare of research participants, 38% revealed that sites did not report SAEs to regulatory authorities and many sites lacked adequate GCP and GCLP. However, most of the sites monitored had adequate facilities to conduct the respective studies and good working practices. This model employed by the monitoring teams to evaluate research compliance is effective in auditing ethical practice. Compliance monitoring is feasible and affordable in a resource limited setting. Research protocol non compliance is still a major problem in Uganda, and there is need for a pro-active approach to this vice by all stake holders if ethical conduct of research is to be achieved.

Ugandan medical and health sciences interns' infection control knowledge and practices.

Abstract: Background: We assessed the level of knowledge, attitudes, and practices of recent graduates of clinical health sciences who started their one-year internship in Uganda. Methodology: This was a cross-sectional survey responded to by 209 (response rate of 70%) new interns who started their internships in August 2011 in different Ugandan hospitals. Validated self-administered questionnaires with knowledge, attitude, and practices questions were distributed to the participants during a two-day internship orientation organized by the national internship committee. Results: Out of 299 subjects approached, the survey was completed and returned by 209 (70%). More nurses (51.4%) failed the questions on odds of HIV transmission after a needle stick injury compared to 23.0% and 36.4% of medical and dental graduates, respectively(χ 2 = 24.06 p = 0.001). There was no difference in proportions of those who re-sheath needles. Respondents who had an encounter with positive tuberculosis history when taking clinical notes while unprotected were not more motivated to use masks (χ 2 = 7.06; p = 0.07). Nurses and dentists reported more regular hand washing before and after patient contact compared to medical doctors. Conclusion: Overall, the knowledge of infection control was not impressive and the attitudes and practices appeared to be heavily influenced by the lack of an enabling environment in training hospitals and internship hospitals. There is little likelihood of change due to internship experience except for those who go to missionary hospitals that have stricter infection control protocols. More effort must be made in teaching hospitals to encourage better infection control.

The effect of blood storage age on treatment of lactic acidosis by transfusion in children with severe malarial anaemia: a pilot, randomized, controlled trial

Abstract: Severe malarial anaemia requiring blood transfusion is a life-threatening condition affecting millions of children in sub-Saharan Africa. Up to 40% of children with severe malarial anaemia have associated lactic acidosis. Lactic acidosis in these children is strongly associated with fatal outcomes and is corrected by blood transfusion. However, it is not known whether the storage age of blood for transfusion affects resolution of lactic acidosis. The objective of this pilot study was to evaluate the effect of blood storage age on resolution of lactic acidosis in children with severe malarial anaemia and demonstrate feasibility of conducting a large trial. Children aged six to 59 months admitted to Acute Care Unit of Mulago Hospital (Kampala, Uganda) with severe malarial anaemia (haemoglobin ≤ 5 g/dL) and lactic acidosis (blood lactate ≥5 mmol/L), were randomly assigned to receive either blood of short storage age (one to 10 days) or long storage age (21–35 days) by gravity infusion. Seventy-four patients were enrolled and randomized to two equal-sized study arms. Physiological measurements, including blood lactate, oxygen saturation, haemoglobin, and vital signs, were taken at baseline, during and after transfusion. The primary outcome variable was the proportion of children whose lactic acidosis resolved by four hours after transfusion. Thirty-four of 37 (92%) of the children in the short storage treatment arm compared to 30/37 (81%) in the long storage arm achieved a blood lactate <5 mmol/L by four hours post transfusion (p value = 0.308). The mean time to lactic acidosis resolution was 2.65 hours (95% CI; 2.25–3.05) in the short storage arm, compared to 3.35 hours (95% CI; 2.60–4.10) in the long storage arm (p value = 0.264). Pilot data suggest that among children with severe malarial anaemia and lactic acidosis transfused with packed red blood cells, the storage age of blood does not affect resolution of lactic acidosis. The results support a larger and well-powered study which is under way. clinicaltrials.gov NCT01580111

Anal protrusion of an ileo-colic intussusception in an adult with persistent ascending and descending mesocolons: a case report.

Abstract: Background: Intussusception is one of the less common causes of intestinal obstruction among adults. It is usually covert (concealed) in its clinical presentation. The ileo-colic type with accompanying anal protrusion is extremely rare. The case at hand is that of both an ileo-colic intussusception with anal protrusion, in the presence of a persistence of both the ascending and descending mesocolons; a case possibly yet to be documented in literature. Case presentation: A 32 year-old African-Ugandan woman presented with complaints of a mass protruding per anus for 2 weeks. It was reducible and associated with colicky abdominal pain, loose stools, and bloody-mucoid discharge per anus. She had previously had a one and a half month’s history of abdominal pain; periodically continuous, while other times colicky in character. Examination and investigations revealed an intussusception with a partial intestinal obstruction. At laparotomy she was found to have an ileo-colic intussusception with a freely mobile colon throughout its length. There were persistent ascending and descending mesocolons, and absent hepatocolic and splenocolic ligaments. The intussusceptum was ‘milked’ but not completely reducible. A right hemicolectomy was done, with ileo-transverse colonic anastomosis. Histopathological examination revealed no preexisting pathologic lesion as a lead point. Conclusion: The persistence of the ascending and descending mesocolons (azygosis) best explains the anal protrusion of an ileo-colic intussusception with partial obstruction. In this case zygosis (normal retroperitoneal ascending and descending colonic positioning) failed embryologically. This experience is particularly beneficial to general surgeons, radiologists, gastroenterologists, colorectal surgeons and pathologists.

Tuberculin skin test conversion among HIV patients on antiretroviral therapy in Uganda.

Abstract: SETTING A human immunodeficiency virus (HIV) clinic in a setting of high tuberculosis (TB) and HIV prevalence. OBJECTIVE To study the incidence of and factors associated with tuberculin skin test (TST) conversion in HIV patients on antiretroviral therapy (ART). DESIGN Prospective cohort study of TST-negative, ART-naive HIV patients (CD4 cell count < 250 cells/l) without active TB. TST was repeated at 2 months and, if negative, at 6 months. TST positivity was defined as an induration of ≥5 mm. Clinical examination, chest X-ray and CD4 cell counts were performed at baseline and follow-up. Proportions and incidence of TST conversion were calculated, and logistic regression analyses were performed. RESULTS Of the 142 patients, 105 (75.5%) were females. The mean age was 35.9 years (standard deviation 8.1) and the median CD4 cell count was 119 cells/l (interquartile range 42168). The incidence of TST conversion was 30.2/100 person years (95%CI 19.546.8). Conversion was not associated with clinical, CD4 cell count or chest radiography findings. CONCLUSIONS A high incidence of TST conversion was observed, supporting the World Health Organization recommendation to provide isoniazid preventive therapy (IPT) to all HIV patients in high TB prevalence settings. If case-control programmes choose to provide IPT only to TST-positive patients, repeat TST should be considered following initiation of ART.

Metastatic colorectal carcinoma mimicking primary ovarian carcinoma presenting as 'giant' ovarian tumors in an individual with probable Lynch syndrome: a case report.

Abstract: Ovarian metastases occur in 3 to 8% of women with primary colon cancer. In the setting of a pre-existing colorectal carcinoma this would constitute a hereditary non-polyposis colorectal cancer, Lynch 2 syndrome, accounting for 5 to 10% of colon cancer cases. We unveil a case of ‘giant’ ovarian tumors mimicking primary ovarian cancer; ostensibly the first reported in East Africa. A 58-year-old African woman was diagnosed with colorectal adenocarcinoma in June 2009. She had a right hemicolectomy with the tumor staged as regional cancer, following histopathological examination. Chemotherapy was administered both adjuvantly and 1 year later for what was thought to be a recurrence of tumor. Despite this, her general condition deteriorated. Following re-evaluation and an exploratory laparotomy she was found to have bilateral ‘giant’ ovarian tumors, with peritoneal seedlings and subcutaneous metastases (colonic in origin). A bilateral salpingo-oophorectomy was done, accompanied by histopathological analysis with institution of chemotherapy for ovarian cancer. Following immunohistochemistry tests and microsatellite instability analysis it was found that the ovarian tumors were secondaries from the colon. She was also identified as a Lynch syndrome case or a case of sporadic microsatellite instability, although with no suggestive family cancer history. The treatment regimen was changed to suit metastatic disease. The case presents a diagnostic and thus treatment conundrum. Two primary tumors (suspected Lynch syndrome) had been perceived yet there is actually only metastatic colorectal cancer. We also have a rare and unusual metastatic presentation: ‘giant’ bilateral ovarian tumors and subcutaneous nodules, concurrently. Further still, she is a case of probable Lynch syndrome, requiring genetic analysis for definitive classification and surveillance for hereditary non-polyposis colorectal cancer-associated cancers. Important inferences are drawn. Firstly, ‘giant’ ovarian tumors diagnosed as primary ovarian cancer may actually be colonic secondaries. Secondly, immunohistochemistry and microsatellite instability analysis tests ought to be part of the diagnostic package in colon cancer management, particularly for identifying tumor origin and the Lynch syndrome (a condition which has had little attention in resource-limited countries). Thirdly, multidisciplinary team collaboration is emphasized in colorectal cancer management.

Forward-planned intensity modulated radiation therapy using a cobalt source: A dosimetric study in breast cancer.

Abstract: This analysis evaluates the feasibility and dosimetric results of a simplified intensity-modulated radiotherapy (IMRT) treatment using a cobalt-therapy unit for post-operative breast cancer. Fourteen patients were included. Three plans per patient were produced by a cobalt-60 source: A standard plan with two wedged tangential beams, a standard tangential plan optimized without the use of wedges and a plan based on the forward-planned "field-in-field" IMRT technique (Co-FinF) where the dose on each of the two tangential beams was split into two different segments and the two segments weight was determined with an iterative process. For comparison purposes, a 6-MV photon standard wedged tangential treatment plan was generated. Dmean, D98%, D2%, V95%, V107%, homogeneity, and conformity indices were chosen as parameters for comparison. Co-FinF technique improved the planning target volume dose homogeneity compared to other cobalt-based techniques and reduced maximum doses (D2%) and high-dose volume (V110%). Moreover, it showed a better lung and heart dose sparing with respect to the standard approach. The higher dose homogeneity may encourage the adoption of accelerated-hypofractionated treatments also with the cobalt sources. This approach can promote the spread of breast conservative treatment in developing countries.

Effect of chronic alcohol consumption on the red blood cell count and RBC indices in the HIV infected patients on d4T/3TC/NVP drug regimen in Uganda

Abstract: Alcohol consumption is common problem in Uganda. Among the types of alcohols consumed include beers, spirits, liqueurs, wines and traditional brew. These alcohols are easily accessible and consumed by many people including the HIV infected patients who are on the d4T/3TC/NVP regimen. The aim of this study was to determine the effect of chronic alcohol intake on the red blood cell count (RBC) and the RBC indices in the HIV-infected patients on d4T/3TC/NVP regimen. It was a case control study that used a repeated measures design model where serial measurements of the red blood cell count (RBC) and RBC indices were determined at 3 month interval for 9 months. A total of 41 HIV infected patients were recruited and grouped into two arms; the control group had 21 patients and the chronic alcohol group had 20 patients. The RBC and RBC indices of the whole blood were determined using automated hematological Coulter CBC-5 Hematology Analyzer system using standard procedures. The data was sorted into alcohol-use self reporting by WHO AUDIT tool and alcohol-use biomarkers groups. It was analysed using the SAS 2003 version 9.1 statistical package with the repeated measures fixed model. The means were compared using the student t-test. The mean MCV and MCH values in the chronic alcohol use group were higher than in the control group and there was a significant difference between the 2 groups (p<0.05) for both the WHO AUDIT tool group and chronic alcohol use biomarkers group. The mean RBC count, Hct, HGB and MCHC values in both the control and chronic alcohol use groups were within the normal reference ranges for both groups though the trend was lower in alcohol group. Chronic alcohol use affects the RBC and RBC indices in the HIV infected patients on d4T/3TC/NVP treatment regimen.

Cutaneous T-cell lymphoma in sub-Saharan Africa.

Abstract: The incidence and economic burden of cancer in sub-Saharan Africa is increasing, and innovative strategies are needed to improve prevention and care in this population. This article uses a case of cutaneous T-cell lymphoma in Uganda to propose guidelines for the diagnosis and treatment of this disease in resource-limited settings. These guidelines were developed from the consensus opinion of specialists at the Uganda Cancer Institute and Fred Hutchinson Cancer Research Center as part of an established collaboration. Areas for future investigation that can improve the care of patients in this region are identified.

Palliative two-dimensional radiotherapy of pancreatic carcinoma: a feasibility study.

Abstract: AIMS AND BACKGROUND The aim of the study was to analyze the dose to be administered with two-dimensional involved-field palliative radiotherapy in advanced pancreatic carcinoma with respect to current dose-volume constraints (QUANTEC). METHODS AND STUDY DESIGN The following standard regimens were evaluated: 30 Gy at 3 Gy/fraction (regimen A), 36 Gy at 2.4 Gy/fraction (regimen B), 45 Gy at 1.8 Gy/fraction (regimen C), and 50 Gy at 2 Gy /fraction (regimen D). The following constraints were considered: spinal cord Dmax 10/15 patients of constraints for kidneys and liver. Therefore, minor violations (<10%) of the constraints for these organs were accepted (in less than 5/15 patients), in consideration of the palliative aim of treatment. RESULTS In regimen A (30 Gy, 3 Gy/fraction), evaluated constraints were respected in all patients, regardless of the type of energy. In regimen B (36 Gy, 2.4 Gy/fraction), constraints were met in all patients undergoing irradiation with 6 and 15 MV photons. However, using the cobalt unit, kidney constraint was respected only in 5 of 15 patients. In regimens C and D (45 Gy, 1.8 Gy/fraction and 50 Gy, 2 Gy/fraction, respectively), the constraint for the kidney was respected only in 2-5 patients, depending on the energy used. Furthermore, using 50 Gy, the spinal cord constraint was not respected in 2-3 patients, depending on the beam used. Therefore, only the following treatments were considered acceptable: 1) 30 Gy, 3 Gy/fraction, regardless of the energy used; 2) 36 Gy, 2.4 Gy/fraction, only for treatments performed with linear accelerator (6-15 MV). CONCLUSIONS The clinical benefits of radiotherapy in pancreatic tumors should not be withheld from patients treated in centers only with two-dimensional technology. Prospective trials, particularly in developing countries, would be useful to evaluate the efficacy in this setting of involved-field two-dimensional treatments using the dose and fractionation defined in this analysis.

Does chronic alcohol use by HIV-infected patients on d4T/3TC/NVP drug regimen effect the HIV viral load and what is the therapeutic window of the drugs, CD4+ count and WBC count in patients with high viral load during the 9 months period of follow up?

Abstract: The study investigated the effects of chronic alcohol use on HIV viral load in HIV-infected patients on d4T/3TC/ NVP drug regimen during 9 months follow up period. It also determined plasma drug concentrations of d4T, 3TC and NVP; CD4 + and WBC counts for patients with high HIV viral load. A case-control study using repeated measures with serial measurements was used. A total of 41 patients (20 alcohol group and 21 control group) were screened for alcohol use using WHO AUDIT tool and chronic alcohol use biomarkers. Blood sampling was done at 3 month intervals for a period of 9 months. HIV viral load was determined using Roche Amplicor HIV-1 monitor test, version 1.5 (Amplicor). The d4T, 3TC and NVP concentrations were determined by Shimadzu Class-VPTM HPLC Chromatography data system version 6.1. The CD4 + cell count was determined using FACSCalibur flow cytometer. T he WBC was determined using automated hematological Coulter CBC-5 Hematology Analyzer system. Results show that % patients with HIV viral load ≥400 copies/ml in control group was highest (23.8%, n=5) at 3 month while in chronic alcohol use group, it was at 0 month (35%, n=7) for both WHO AUDIT tool and chronic alcohol-use biomarkers groups. Generally patients with high viral load ≥400 copies/ml was observed in chronic alcohol use as compared to control group in both WHO AUDIT tool and biomarkers group despite of patients having high steady state d4T, 3TC and NVP plasma drug concentrations in circulation that is available to suppress HIV virus. The high viral load could be associated with the emergence of resistance of the HIV virus and these patients generally had a low CD4 + cell count. Some of these patients had no detectable d4T plasma drug concentrations in circulation and most of them with high viral load had sub-therapeutic NVP plasma drug concentrations in their blood circulation. Chronic ethanol use by HIV-infected patients on d4T/3TC/NVP drug regimen increased HIV viral load and the patients with high viral load had sub-therapeutic NVP plasma drug concentrations and some with undetectable d4T drug concentrations in their blood circulation.