Multi-state models for the analysis of time-to-treatment modification among HIV patients under highly active antiretroviral therapy in Southwest Ethiopia.

BACKGROUND: Highly active antiretroviral therapy (HAART) has shown a dramatic change in controlling the burden of HIV/AIDS. However, the new challenge of HAART is to allow long-term sustainability. Toxicities, comorbidity, pregnancy, and treatment failure, among others, would result in frequent initial HAART regimen change. The aim of this study was to evaluate the durability of first line antiretroviral therapy and to assess the causes of initial highly active antiretroviral therapeutic regimen changes among patients on HAART. METHODS: A Hospital based retrospective study was conducted from January 2007 to August 2013 at Jimma University Hospital, Southwest Ethiopia. Data on the prescribed ARV along with start date, switching date, and reason for change was collected. The primary outcome was defined as the time-to-treatment change. We adopted a multi-state survival modeling approach assuming each treatment regimen as state. We estimate the transition probability of patients to move from one regimen to another. RESULT: A total of 1284 ART naive patients were included in the study. Almost half of the patients (41.2%) changed their treatment during follow up for various reasons; 442 (34.4%) changed once and 86 (6.69%) changed more than once. Toxicity was the most common reason for treatment changes accounting for 48.94% of the changes, followed by comorbidity (New TB) 14.31%. The HAART combinations that were robust to treatment changes were tenofovir (TDF) + lamivudine (3TC)+ efavirenz (EFV), tenofovir + lamivudine (3TC) + nevirapine (NVP) and zidovudine (AZT) + lamivudine (3TC) + nevirapine (NVP) with 3.6%, 4.5% and 11% treatment changes, respectively. CONCLUSION: Moving away from drugs with poor safety profiles, such as stavudine(d4T), could reduce modification rates and this would improve regimen tolerability, while preserving future treatment options.

Malaria incidence and assessment of entomological indices among resettled communities in Ethiopia: a longitudinal study.

BACKGROUND: Population resettlement has been considered among factors that may increase risk of malaria transmission. This study reports, the impact of resettlement on malaria incidence and entomological indices among communities resettled in suburbs of Jimma town, southwestern Ethiopia. METHODS: A cohort of 604 study participants (302 resettlers and 302 non-resettlers) was monthly followed-up from September to November 2013 using active case detection. Moreover, longitudinal entomological study was conducted from June to November 2013. Anopheline mosquitoes were collected using CDC light traps and pyrethrum spray catches. Sporozoite ELISA was performed to determine Plasmodium infection rates. RESULTS: Overall, 112 malaria cases were recorded during the three-month follow-up, of which 74.1% of the cases were from resettlement villages. Plasmodium falciparum incidence from resettlement and non-resettlement villages was 52.5 and 14.5/1,000 person-months at risk, respectively. Resettlement villages were three times at higher risk of Plasmodium infection (OR = 2.8, 95% CI: 1.22-6.48). Anopheles gambiae s.l. was the predominant (86.6%) of all the collected anopheline mosquito species. Plasmodium sporozoite rate in the resettlement and non-resettlement villages was 2.1 and 0.72%, respectively. Plasmodium falciparum entomological inoculation rate (EIR) for An. gambiae s.l. in the resettlement and non-resettlement villages was 13.1 and 0 infective bites/person/night, respectively. Both sporozoite rate and EIR were significantly higher in the resettlement villages (p < 0.05). CONCLUSION: Resettled communities were at higher risk of malaria infection as compared to non-resettled communities. Special attention should be given to malaria control interventions during resettlement programmes.

Opioid use, postoperative complications, and implant survival after unicompartmental versus total knee replacement: a population-based network study.

BACKGROUND: There is uncertainty around whether to use unicompartmental knee replacement (UKR) or total knee replacement (TKR) for individuals with osteoarthritis confined to a single compartment of the knee. We aimed to emulate the design of the Total or Partial Knee Arthroplasty Trial (TOPKAT) using routinely collected data to assess whether the efficacy results reported in the trial translate into effectiveness in routine practice, and to assess comparative safety. METHODS: We did a population-based network study using data from four US and one UK health-care database, part of the Observational Health Data Sciences and Informatics network. The inclusion criteria were the same as those for TOPKAT; briefly, we identified patients aged at least 40 years with osteoarthritis who had undergone UKR or TKR and who had available data for at least one year prior to surgery. Patients were excluded if they had evidence of previous knee arthroplasty, knee fracture, knee surgery (except diagnostic), rheumatoid arthritis, infammatory arthropathies, or septic arthritis. Opioid use from 91-365 days after surgery, as a proxy for persistent pain, was assessed for all participants in all databases. Postoperative complications (ie, venous thromboembolism, infection, readmission, and mortality) were assessed over the 60 days after surgery and implant survival (as measured by revision procedures) was assessed over the 5 years after surgery. Outcomes were assessed in all databases, except for readmission, which was assessed in three of the databases, and mortality, which was assessed in two of the databases. Propensity score matched Cox proportional hazards models were fitted for each outcome. Calibrated hazard ratios (cHRs) were generated for each database to account for observed differences in control outcomes, and cHRs were then combined using meta-analysis. FINDINGS: 33 867 individuals who received UKR and 557 831 individuals who received TKR between Jan 1, 2005, and April 30, 2018, were eligible for matching. 32 379 with UKR and 250 377 with TKR were propensity score matched and informed the analyses. UKR was associated with a reduced risk of postoperative opioid use (cHR from meta-analysis 0·81, 95% CI 0·73-0·90) and a reduced risk of venous thromboembolism (0·62, 0·36-0·95), whereas no difference was seen for infection (0·85, 0·51-1·37) and readmission (0·79, 0·47-1·25). Evidence was insufficient to conclude whether there was a reduction in risk of mortality. UKR was also associated with an increased risk of revision (1·64, 1·40-1·94). INTERPRETATION: UKR was associated with a reduced risk of postoperative opioid use compared with TKR, which might indicate a reduced risk of persistent pain after surgery. UKR was associated with a lower risk of venous thromboembolism but an increased risk of revision compared with TKR. These findings can help to inform shared decision making for individuals eligible for knee replacement surgery. FUNDING: EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative (2) Joint Undertaking (EHDEN).

Risk Factors for Mortality among Adult HIV/AIDS Patients Following Antiretroviral Therapy in Southwestern Ethiopia: An Assessment through Survival Models.

Introduction: Efforts have been made to reduce HIV/AIDS-related mortality by delivering antiretroviral therapy (ART) treatment. However, HIV patients in resource-poor settings are still dying, even if they are on ART treatment. This study aimed to explore the factors associated with HIV/AIDS-related mortality in Southwestern Ethiopia. Method: A non-concurrent retrospective cohort study which collected data from the clinical records of adult HIV/AIDS patients, who initiated ART treatment and were followed between January 2006 and December 2010, was conducted, to explore the factors associated with HIV/AIDS-related mortality at Jimma University Specialized Hospital (JUSH). Survival times (i.e., the time from the onset of ART treatment to the death or censoring) and different characteristics of patients were retrospectively examined. A best-fit model was chosen for the survival data, after the comparison between native semi-parametric Cox regression and parametric survival models (i.e., exponential, Weibull, and log-logistic). Result: A total of 456 HIV patients were included in the study, mostly females (312, 68.4%), with a median age of 30 years (inter-quartile range (IQR): 23-37 years). Estimated follow-up until December 2010 accounted for 1245 person-years at risk (PYAR) and resulted in 66 (14.5%) deaths and 390 censored individuals, representing a median survival time of 34.0 months ( IQR: 22.8-42.0 months). The overall mortality rate was 5.3/100 PYAR: 6.5/100 PYAR for males and 4.8/100 PYAR for females. The Weibull survival model was the best model for fitting the data (lowest AIC). The main factors associated with mortality were: baseline age (>35 years old, AHR = 3.8, 95% CI: 1.6-9.1), baseline weight (AHR = 0.93, 95% CI: 0.90-0.97), baseline WHO stage IV (AHR = 6.2, 95% CI: 2.2-14.2), and low adherence to ART treatment (AHR = 4.2, 95% CI: 2.5-7.1). Conclusion: An effective reduction in HIV/AIDS mortality could be achieved through timely ART treatment onset and maintaining high levels of treatment adherence.

Modeling Outcomes of First-Line Antiretroviral Therapy and Rate of CD4 Counts Change among a Cohort of HIV/AIDS Patients in Ethiopia: A Retrospective Cohort Study.

BACKGROUND: Antiretroviral therapy has shown to be effective in reducing morbidity and mortality in patients infected with HIV for the past couples of decades. However, there remains a need to better understand the characteristics of long-term treatment outcomes in resource poor settings. The main aim of this study was to determine and compare the long-term response of patients on nevirapine and efavirenz based first line antiretroviral therapy regimen in Ethiopia. METHODS: Hospital based retrospective cohort study was conducted from January 2009 to December 2013 at University hospital located in Northwest Ethiopia. Human subject research approval for this study was received from University of Gondar Research Ethics Committee and the medical director of the hospital. Cox-proportional hazards model was used to assess the effect of baseline covariates on composite outcome and a semi-parametric mixed effect model was used to investigate CD4 counts response to treatments. RESULTS: A total of 2386 HIV/AIDS naive patients were included in this study. Nearly one-in-four patients experienced the events, of which death, lost to follow up, treatment substitution and discontinuation of Non-Nucleoside Reverse Transcriptase Inhibitors(NNRTI) accounted: 99 (26.8%), 122 (33.0%), 137 (37.0%) and 12 (3.2%), respectively. The hazard of composite outcome on nevirapine compared with efavirenz was 1.02(95%CI: 0.52-1.99) with p-value = 0.96. Similarly, the hazard of composite outcome on tenofovir and stavudine compared with zidovudine were 1.87 (95%CI: 1.52-2.32), p-value < 0.0001 and 1.72(95% CI: 1.22-2.32), p-value = 0.002, respectively. The rate of CD4 increase in response to treatment was high during the first 10 months and stabilized later. CONCLUSIONS: This study revealed that treatment responses were comparable whether nevirapine or efavirenz was chosen to initiate antiretroviral therapy for HIV/AIDS patients in Ethiopia. There was significant difference on risk of composite outcome between patients who were initiated with Tenofovir containing ART regimen compared with zidovudine after controlling for NNRTI drug combinations.

Modeling time-to-cure from severe acute malnutrition: application of various parametric frailty models.

BACKGROUND: In developing countries about 3.5% of children aged 0-5 years are victims of severe acute malnutrition (SAM). Once the morbidity has developed the cure process takes variable period depending on various factors. Knowledge of time-to-cure from SAM will enable health care providers to plan resources and monitor the progress of cases with SAM. The current analysis presents modeling time-to-cure from SAM starting from the day of diagnosis in Wolisso St. Luke Catholic hospital, southwest Ethiopia. METHODS: With the aim of coming up with appropriate survival (time-to-event) model that describes the SAM dataset, various parametric clustered time-to-event (frailty) models were compared. Frailty model, which is an extension of the proportional hazards Cox survival model, was used to analyze time-to-cure from SAM. Kebeles (villages) of the children were considered as the clustering variable in all the models. We used exponential, weibull and log-logistic as baseline hazard functions and the gamma as well as inverse Gaussian for the frailty distributions and then based on AIC criteria, all models were compared for their performance. RESULTS: The median time-to-cure from SAM cases was 14 days with the maximum of 63 days of which about 83% were cured. The log-logistic model with inverse Gaussian frailty has the minimum AIC value among the models compared. The clustering effect was significant in modeling time-to-cure from SAM. The results showed that age of a child and co-infection were the determinant prognostic factors for SAM, but sex of the child and the type of malnutrition were not significant. CONCLUSIONS: The log-logistic with inverse Gaussian frailty model described the SAM dataset better than other distributions used in this study. There is heterogeneity between the kebeles in the time-to-cure from SAM, indicating that one needs to account for this clustering variable using appropriate clustered time-to-event frailty models.

Isolation of Intestinal Parasites of Public Health Importance from Cockroaches (Blattella germanica) in Jimma Town, Southwestern Ethiopia.

Cockroaches are claimed to be mechanical transmitters of disease causing microorganisms such as intestinal parasites, bacteria, fungi, and viruses. This study assessed the potential of the German cockroach Blattella germanica in the mechanical transmission of intestinal parasites of public health importance. A total of 2010 cockroaches were collected from 404 households in Jimma Town, southwestern Ethiopia. All the collected cockroaches were identified to species as B. germanica. The contents of their gut and external body parts were examined for the presence of intestinal parasites. Overall, 152 (75.6%) of the 210 batches were found to harbor at least one species of human intestinal parasite. Ascaris lumbricoides, Trichuris trichiura, Taenia spp, Strongyloides-like parasite, Entamoeba histolytica/dispar/moshkovski, Giardia duodenalis and Balantidium coli were detected from gut contents. Moreover, parasites were also isolated from the external surface in 22 (10.95%) of the batches. There was significant difference in parasite carriage rate of the cockroaches among the study sites (P = 0.013). In conclusion, B. germanica was found to harbor intestinal parasites of public health importance. Hence, awareness on the potential role of cockroaches in the mechanical transmission of human intestinal parasites needs to be created. Moreover, further identification of the Strongyloides-like worm is required using molecular diagnostics.