Prevalence, patterns, and factors associated with tobacco use among patients with priority tobacco related illnesses at four Kenyan national referral hospitals, 2022.

Tobacco use is a risk factor for many chronic health conditions. Quantifying burden of tobacco use among people with tobacco-related illnesses (TRI) can strengthen cessation programs. This study estimated prevalence, patterns and correlates of tobacco use among patients with TRI at four national referral hospitals in Kenya. We conducted a cross-sectional study among patients with five TRI (cancer, cardiovascular diseases, cerebrovascular disease, chronic obstructive pulmonary disease, and pulmonary tuberculosis) during January-July 2022. Cases identified from medical records were interviewed on socio-demographic, tobacco use and cessation information. Descriptive statistics were used to characterize patterns of tobacco use. Multiple logistic regression models were used to identify associations with tobacco use. We identified 2,032 individuals with TRI; 46% (939/2,032) had age ≥60 years, and 61% (1,241/2,032) were male. About 45% (923/2,032) were ever tobacco users (6% percent current and 39% former tobacco users). Approximately half of smokers and 58% of smokeless tobacco users had attempted quitting in the last month; 42% through cessation counselling. Comorbidities were present in 28% of the participants. Most (92%) of the patients had been diagnosed with TRI within the previous five years. The most frequent TRI were oral pharyngeal cancer (36% [725/2,032]), nasopharyngeal cancer (12% [246/2.032]) and lung cancer (10% [202/2,032]). Patients >60 years (aOR 2.24, 95% CI: 1.84, 2.73) and unmarried (aOR 1.21, 95% CI: 1.03, 1.42) had higher odds of tobacco use. Female patients (aOR 0.35, 95% CI: 0.30, 0.41) and those with no history of alcohol use (aOR 0.27, 95% CI: 0.23, 0.31), had less odds of tobacco use. Our study shows high prevalence of tobacco use among patients with TRI in Kenya, especially among older, male, less educated, unmarried, and alcohol users. We recommend tobacco use screening and cessation programs among patients with TRI as part of clinical care.

Rethinking the syndemic of tuberculosis and dysglycaemia: a Kenyan perspective on dysglycaemia as a neglected risk factor for tuberculosis.

Background: The END TB 2035 goal has a long way to go in low-income and low/middle-income countries (LICs and LMICs) from the perspective of a non-communicable disease (NCD) control interaction with tuberculosis (TB). The World Health Organization has identified diabetes as a determinant for, and an important yet neglected risk factor for tuberculosis. National guidelines have dictated testing time points, but these tend to be at an isolated time point rather than over a period of time. This article aims to give perspective on the syndemic interaction of tuberculosis and dysglycaemia and how the gaps in addressing the two may hamper progress towards END TB 2035. Main text: Glycated haemoglobin (HbA1C) has a strong predictive association with the progression to subsequent diabetes. Therefore, screening using this measure could be a good way to screen at TB initiation therapy, in lieu of using the random blood sugar or fasting plasma glucose only. HbA1C has an observed gradient with mortality risk making it an informative predictor of outcomes. Determining the progression of dysglycaemia from diagnosis to end of treatment and shortly after may offer information on the best time point to screen and follow-up. Despite TB and Human Immunodeficiency Virus (HIV) disease care being free, hidden costs remain. These costs are additive if there is accompanying dysglycaemia. Regardless of receiving TB treatment, it is estimated that almost half of persons affected by pulmonary TB develop post-TB lung disease (PTLD) as an outcome and the contribution of dysglycaemia is not well described. Conclusions: Establishing costs of treating TB with diabetes/prediabetes alone and in the additional context of HIV co-infection will inform policy makers on what it takes, financially, to treat these patients and subsidize dysglycaemia care. In Kenya, cardiovascular disease is only rivalled by infectious disease as a cause of mortality, and diabetes is a well-described risk factor for cardiac disease. In poor countries, communicable diseases are responsible for majority of the mortality burden, but societal shifts and rural-urban migration may have contributed to the observed increase of NCDs.

Quasi-experimental evaluation of Kenya's pictorial health warnings versus Zambia's single text-only warning: findings from the International Tobacco Control (ITC) Project.

BACKGROUND: Population studies in mostly high-income countries have shown that pictorial health warnings (PHWs) are much more effective than text-only warnings. This is the first quasi-experimental evaluation of the introduction of PHWs in Africa, comparing the change from text-only to PHWs in Kenya to the unchanged text-only health warning in Zambia. METHODS: Data were from International Tobacco Control (ITC) Surveys in Kenya (n=1495), and Zambia (n=1628), cohort surveys of nationally representative samples of adult smokers in each country. The ITC Kenya Survey was conducted in 2012 and 2018 (2 years after the 2016 introduction of three PHWs). The ITC Zambia Survey was conducted in 2012 and 2014 with no change to the single text-only warning. Validated indicators of health warning effectiveness (HWIs) (salience: noticing, reading; cognitive reactions: thinking about health risks, thinking about quitting; and behavioural reactions: avoiding warnings; forgoing a cigarette because of the warnings), and a summary measure-the Labels Impact Index (LII)-measured changes in warning impact between the two countries. RESULTS: PHWs implemented in Kenya led to a significant increase in all HWIs and the LII, compared with the text-only warning in Zambia. The failure to implement PHWs in Zambia led to a substantial missed opportunity to increase warning effectiveness (eg, an estimated additional 168 392 smokers in Zambia would have noticed the warnings). CONCLUSIONS: The introduction of PHWs in Kenya substantially increased the effectiveness of warnings. These results provide strong empirical support for 34 African countries that still have text-only warnings, of which 31 are Parties of the Framework Convention on Tobacco Control and are thus obligated to implement PHWs.

Prevalence, perceptions and factors associated with menthol cigarette smoking: findings from the ITC Kenya and Zambia Surveys.

BACKGROUND: Menthol masks the harshness of cigarette smoke, promotes youth smoking and encourages health-concerned smokers who incorrectly believe that menthols are less harmful to smoke menthols. This study of smokers in Kenya and Zambia is the first study in Africa to examine menthol use, smokers' beliefs about its harmfulness and the factors associated with menthols. METHODS: Data were from the International Tobacco Control (ITC) Kenya Wave 2 (2018) and Zambia Wave 2 Survey (2014), involving nationally representative samples of smokers. This study focuses on 1246 adult smokers (644 in Kenya, 602 in Zambia) who reported smoking a usual brand of cigarettes (menthol or non-menthol). RESULTS: Overall, menthol use was significantly higher among smokers in Zambia than in Kenya (48.0% vs 19.0%), females (45.6% vs 31.2% males), non-daily smokers (43.8% vs 30.0% daily) and those who exclusively smoked factory-made (FM) cigarettes (43.0% vs 15.2%). The erroneous belief that menthols are less harmful was more likely among smokers in Zambia than in Kenya (53.4% vs 29.3%) and among female smokers (38.5% vs 28.2%). In Kenya, menthol smoking was associated with being female (adjusted odds ratios (AOR)=3.07; p=0.03), worrying about future health (AOR=2.28; p=0.02) and disagreeing with the statement that smoking was calming (AOR=2.05; p=0.04). In Zambia, menthol use was associated with being female (AOR=3.91; p=0.002), completing primary school (AOR=2.14; p=0.03), being a non-daily smoker (AOR=2.29; p=0.03), exclusively using FM cigarettes (AOR=14.7; p<0.001), having a past quit attempt (AOR=1.54; p=0.02), believing that menthols are less harmful (AOR=3.80; p<0.001) and choosing menthols because they believed it was less harmful (AOR=3.52; p<0.001). CONCLUSIONS: Menthols are highly prevalent among females in both countries. There is a need in African countries to combat the myth that menthols are less harmful and to ban menthol and other flavourings.

Novel approaches for long-term lung transplant survival.

Allograft failure remains a major barrier in the field of lung transplantation and results primarily from acute and chronic rejection. To date, standard-of-care immunosuppressive regimens have proven unsuccessful in achieving acceptable long-term graft and patient survival. Recent insights into the unique immunologic properties of lung allografts provide an opportunity to develop more effective immunosuppressive strategies. Here we describe advances in our understanding of the mechanisms driving lung allograft rejection and highlight recent progress in the development of novel, lung-specific strategies aimed at promoting long-term allograft survival, including tolerance.

Liquid Ventilation Reconditions Isolated Rat Lungs Following Ischemia-Reperfusion Injury.

Lung transplantation remains the only curative treatment for end-stage pulmonary disease. Lung ischemia-reperfusion injury (IRI) is a major contributor to primary allograft dysfunction and donor organ nonutilization. The alveolar macrophage is a key inflammatory mediator in IRI. Ex vivo lung perfusion (EVLP) has been investigated to rehabilitate lungs before transplant but has failed to provide significant improvements after IRI. We hypothesized that liquid ventilation (LV) could be utilized for ex vivo lung reconditioning in a rat IRI model. We compared EVLP with LV in an isolated ex vivo rat lung with an aqueous ventilant using quantitative physiological and immunological parameters. We observed improved physiological parameters and mechanical clearance of alveolar macrophages and cytokines halting the propagation of the inflammatory response in IRI. While the wide applicability to large animal or human transplantation have yet to be explored, these findings represent a method for lung reconditioning in the setting of significant IRI that could widen the lung organ donation pool and limit morbidity and mortality associated with ischemia-induced primary graft dysfunction.

Determinants of household catastrophic costs for drug sensitive tuberculosis patients in Kenya.

BACKGROUND: Despite free diagnosis and treatment for tuberculosis (TB), the costs during treatment impose a significant financial burden on patients and their households. The study sought to identify the determinants for catastrophic costs among patients with drug-sensitive TB (DSTB) and their households in Kenya. METHODS: The data was collected during the 2017 Kenya national patient cost survey from a nationally representative sample (n = 1071). Treatment related costs and productivity losses were estimated. Total costs exceeding 20% of household income were defined as catastrophic and used as the outcome. Multivariable Poisson regression analysis was performed to measure the association between selected individual, household and disease characteristics and occurrence of catastrophic costs. A deterministic sensitivity analysis was carried using different thresholds and the significant predictors were explored. RESULTS: The proportion of catastrophic costs among DSTB patients was 27% (n = 294). Patients with catastrophic costs had higher median productivity losses, 39 h [interquartile range (IQR): 20-104], and total median costs of USD 567 (IQR: 299-1144). The incidence of catastrophic costs had a dose response with household expenditure. The poorest quintile was 6.2 times [95% confidence intervals (CI): 4.0-9.7] more likely to incur catastrophic costs compared to the richest. The prevalence of catastrophic costs decreased with increasing household expenditure quintiles (proportion of catastrophic costs: 59.7%, 32.9%, 23.6%, 15.9%, and 9.5%) from the lowest quintile (Q1) to the highest quintile (Q5). Other determinants included hospitalization: prevalence ratio (PR) = 2.8 (95% CI: 1.8-4.5) and delayed treatment: PR = 1.5 (95% CI: 1.3-1.7). Protective factors included receiving care at a public health facility: PR = 0.8 (95% CI: 0.6-1.0), and a higher body mass index (BMI): PR = 0.97 (95% CI: 0.96-0.98). Pre TB expenditure, hospitalization and BMI were significant predictors in all sensitivity analysis scenarios. CONCLUSIONS: There are significant inequities in the occurrence of catastrophic costs. Social protection interventions in addition to existing medical and public health interventions are important to implement for patients most at risk of incurring catastrophic costs.

A Mixed-chimerism Protocol Utilizing Thymoglobulin and Belatacept Did Not Induce Lung Allograft Tolerance, Despite Previous Success in Renal Allotransplantation.

BACKGROUND: In kidney transplantation, long-term allograft acceptance in cynomolgus macaques was achieved using a mixed-chimerism protocol based on the clinically available reagents, rabbit anti-thymocyte globulin (ATG), and belatacept. Here, we have tested the same protocol in cynomolgus macaques transplanted with fully allogeneic lung grafts. METHODS: Five cynomolgus macaques underwent left orthotopic lung transplantation. Initial immunosuppression included equine ATG and anti-IL6RmAb induction, followed by triple-drug immunosuppression for 4 mo. Post-transplant, a nonmyeloablative conditioning regimen was applied, including total body and thymic irradiation. Rabbit ATG, belatacept, anti-IL6RmAb, and donor bone marrow transplantation (DBMT) were given, in addition to a 28-d course of cyclosporine. All immunosuppressant drugs were stopped on day 29 after DBMT. RESULTS: One monkey rejected its lung before DBMT due to AMR, after developing donor-specific antibodies. Two monkeys developed fatal post-transplant lymphoproliferative disorder, and both monkeys had signs of cellular rejection in their allografts upon autopsy. The remaining 2 monkeys showed severe cellular rejection on days 42 and 70 post-DBMT. Cytokine analysis suggested higher levels of pro-inflammatory markers in the lung transplant cohort, as compared to kidney recipients. CONCLUSION: Although the clinically applicable protocol showed success in kidney transplantation, the study did not show long-term survival in a lung transplant model, highlighting the organ-specific differences in tolerance induction.

Medication Errors and Blood Pressure Control Among Patients Managed for Hypertension in Public Ambulatory Care Clinics in Botswana.

Background The prevalence of hypertension in low- and middle-income countries is rapidly increasing, with most cases undiagnosed and many poorly controlled among those diagnosed. Medication reconciliation studies from high-income countries have demonstrated a high occurrence of antihypertensive medication errors and a strong association between medication errors and inadequate blood pressure control, but data from low- and middle-income countries are lacking. Methods and Results We conducted a cross-sectional study from April to October 2018 of adult patients on pharmacologic management for known hypertension at 7 public health facilities in Kweneng East District, Botswana. Our aims included to evaluate the frequency of uncontrolled hypertension, the frequency and type of medication errors causing discrepancies between patient-reported and prescribed antihypertensive medications, and the association between medication errors and uncontrolled hypertension. Descriptive analyses and multivariable logistic regression were used. The prevalence of uncontrolled hypertension was 55% among 280 enrolled adult patients, and 95 (34%) had ≥1 medication error. The most common errors included patients taking medications incorrectly (11.1%; 31/280), patients omitting medications (7.9%; 22/280), and unfilled prescriptions caused by pharmacy stock outs (7.5%%; 21/280). Uncontrolled hypertension was significantly associated with having ≥1 medication error compared with no errors (adjusted odds ratio, 3.26; 95% CI, 1.75-6.06; P<0.001). Conclusions Medication errors are strongly associated with poor blood pressure control in this setting. Further research is warranted to assess whether medication reconciliation and other low-cost interventions addressing root causes of medication errors can improve the control of hypertension and other chronic conditions in low- and middle-income countries.

Identifying factors associated with quit intentions among smokers from two nationally representative samples in Africa: Findings from the ITC Kenya and Zambia Surveys.

It is well established that intentions to quit smoking is the strongest predictor of future quit attempts. However, most studies on quit intentions have been conducted in high-income countries with very few in low- and middle-income countries particularly in Africa. This is the first population-based study to compare factors associated with quit intentions among smokers in two African countries. Data were from the International Tobacco Control (ITC) Kenya and Zambia Surveys (2012), face-to-face surveys of nationally representative samples of 2291 adult smokers (Kenya = 1103; Zambia = 1188). Multivariate logistic regression analyses were conducted to identify predictors of quit intentions. Most Kenyan (65.1%) and Zambian (69.1%) smokers had quit intentions of which 54.8% planned to quit within the next 6 months. Five factors were significantly associated with quit intentions in both countries: being younger, having tried to quit previously, perceiving that quitting is beneficial to health, worrying about future health consequences of smoking, and being low in nicotine dependence. The predictive strength of these factors did not differ in the two countries. Four additional factors were significant predictors in Zambia only: having a quit attempt lasting six months or more, lower smoking enjoyment, having a negative opinion about smoking, and concern about cigarette expenses. The factors predicting quit intentions were similar to those in other ITC countries including Canada, US, UK, China and Mauritius. These findings highlight the need for stronger tobacco control policies in Kenya and Zambia including increased taxation, greater access to cessation services, and anti-smoking campaigns denormalizing tobacco use.

Extended criteria donor lungs do not impact recipient outcomes in pediatric transplantation.

BACKGROUND: Pediatric lung transplantation remains the only curative treatment option for some end-stage lung diseases in childhood. Recipient numbers outnumber potential donor organs, and therefore a broader group of donor organs must be considered for pediatric lung transplantation. Herein we describe the outcome of utilizing extended criteria donor organs in pediatric lung transplantation. METHODS: A retrospective analysis was performed on all pediatric lung transplantations performed at the Hannover Medical School between April 2010 and December 2016. Donors were assigned to a group fulfilling standard donor criteria (International Society for Heart and Lung Transplantation [ISHLT] 2003) or not. Recipients' early- and mid-term morbidity and mortality were recorded. RESULTS: A total of 57 pediatric lung transplantations were performed: 27 donors fulfilled standard donor criteria (standard criteria donor [SCD] group) and 30 donors were extended criteria donors not fulfilling standard donor criteria (extended criteria donor [ECD] group). Pre-operative recipient characteristics, including age (median [IQR]: 14 [10‒15] vs 13 [10.8‒15] years, p = 0.71), underlying disease, admission to intensive care unit (37.0% vs 50%, p = 0.42), mechanical ventilation (14.8% vs 10.0%, p = 0.70), and extracorporeal membrane oxygenation (ECMO) support (11.1% vs 23.3%, p = 0.30) of both groups were similar. In the ECD group, more atypical volume reductions of the allograft were performed (0% vs 16.7%, p = 0.05), yet incidence of post-operative ECMO support was similar for the 2 groups. ECD recipients spent significantly less time on mechanical ventilation (median [IQR]: 2 [1‒2] vs 1 [1‒2] days, p = 0.04)] after surgery, but total intensive care unit stay and total hospital stay were similar between groups. Pulmonaryfunction testing results at discharge from initial hospital stay, after 1 year, and at last assessment were also similar. Freedom from chronic lung allograft dysfunction at 1 and 5years after transplantation showed no significant differences between groups. Survival rates up to 5years (67.9% vs 90.5%, p = 0.35) after transplantation were comparable between groups, yet, counterintuitively, long-term survival in the ECD group showed superior trends compared with the SCD group. CONCLUSIONS: ECD lungs can be used safely for pediatric lung transplantation without compromising short- and mid-term results.

Kenya tuberculosis prevalence survey 2016: Challenges and opportunities of ending TB in Kenya.

BACKGROUND: We aimed to determine the prevalence of pulmonary TB amongst the adult population (≥15 years) in 2016 in Kenya. METHOD: A nationwide cross-sectional survey where participants first underwent TB symptom screening and chest x-ray. Subsequently, participants who reported cough >2weeks and/or had a chest x-ray suggestive of TB, submitted sputum specimen for laboratory examination by smear microscopy, culture and Xpert MTB/RIF. RESULT: The survey identified 305 prevalent TB cases translating to a prevalence of 558 [95%CI 455-662] per 100,000 adult population. The highest disease burden was reported among people aged 25-34 years (716 [95% CI 526-906]), males (809 [(95% CI 656-962]) and those who live in urban areas (760 [95% CI 539-981]). Compared to the reported TB notification rate for Kenya in 2016, the prevalence to notification ratio was 2.5:1. The gap between the survey prevalence and notification rates was highest among males, age groups 25-34, and the older age group of 65 years and above. Only 48% of the of the survey prevalent cases reported cough >2weeks. In addition, only 59% of the identified cases had the four cardinal symptoms for TB (cough ≥2 weeks, fever, night sweat and weight loss. However, 88.2% had an abnormal chest x-ray suggestive of TB. The use of Xpert MTB/RIF identified 77.7% of the cases compared to smear microscopy's 46%. Twenty-one percent of the survey participants with respiratory symptoms reported to have sought prior health care at private clinics and chemists. Among the survey prevalent cases who reported TB related symptoms, 64.9% had not sought any health care prior to the survey. CONCLUSION: This survey established that TB prevalence in Kenya is higher than had been estimated, and about half of the those who fall ill with the disease each year are missed.

Effects of some common additives on the antimicrobial activities of alcohol-based hand sanitizers

Objective:To study the effects of some common additives on the antimicrobial activities of alcohol-based hand sanitizers.Methods:The antibacterial activities of varying aqueous concentrations of ethanol and isopropyl alcohol were tested by the agar well diffusion method. The influences of different concentrations of glycerin was similarly tested. Finally, isopropyl alcohol and benzalkonium chloride were combined in different ratios within the safe use concentrations of each, and the effects of these combinations were compared with values obtained for the two agents used alone. Statistical methods, such as student t test and one-way ANOVA were used when appropriate to evaluate the differences in activity.Results:The activities of the alcohols showed marked concentration dependence, and both showed peak activity at 85%–95% concentration range. Over the concentration range of 60%–100%, isopropyl alcohol inhibited more bacterial and fungal organisms than ethanol, though the inhibition zone diameters it produced were not statistically different from those of ethanol for organisms which were sensitive to both of them. Addition of glycerin reduced the antimicrobial activities of the isopropyl alcohol, as shown by reduction in the inhibition zone diameters produced in vitro, which may be due to reduced drug diffusion with increase in viscosity. Addition of benzalkonium to isopropyl alcohol systems improved the activity of the alcohol, but the overall activity of the combination was not superior to that seen in the use of benzalkonium alone.Conclusion:Alcohol-based hand sanitizers should not be used outside the concentration range of 85%–95% and isopropyl alcohol inhibits more bacterial and fungal organisms than ethanol for most concentrations. Inclusion of benzalkonium improves the antimicrobial spectrum and activity of isopropyl alcohol, and the combination may justifiably be used to achieve both immediate and long lasting effect. Glycerin may adversely affect the antimicrobial activities of isopropyl alcohol-based hand sanitizers and should be used with caution.

Erratum: The Management of Kienböck Disease: A Survey of the ASSH Membership.

[This corrects the article DOI: 10.1055/s-0035-1544225.].

The Management of Kienböck Disease: A Survey of the ASSH Membership.

Background The purpose of this study was to determine the current trends and common practices for the treatment of Kienböck disease at different stages. Question/Purpose To determine the current trends and common practices by hand surgeons for the treatment of Kienböck disease. Methods A survey with hypothetical Kienböck disease cases stratified by the Lichtman staging system was distributed to the American Society for Surgery of the Hand (ASSH) members. Questions and responses reflected common treatment strategies. Results Of a total of 375 worldwide respondents, preferred treatments of Kienböck disease were as follows: for Stage I disease, an initial trial of splinting was favored (74%), followed by radial shortening osteotomy for continued symptoms. For Stage II disease, 63% of surgeons preferred surgical intervention, particularly radial shortening osteotomy. For Stage IIIa with negative ulnar variance, 69% chose radial shortening osteotomy. Responses were heterogeneous for Stage IIIa Kienböck with positive variance, and capitate shortening osteotomy and vascularized bone grafting were preferred. Salvage procedures predominated for Stage IIIb disease, including proximal row carpectomy (PRC; 42%), intracarpal arthrodesis (21%), and total wrist fusion (10.7%). Similarly, Stage IV disease was treated by 87% of respondents by either PRC or wrist fusion. Without regard to stage of disease, 90% of participants reported using the same Lichtman staging to guide treatment and would also alter treatment strategy based upon ulnar variance. Conclusions Most respondents used Lichtman staging and ulnar variance to guide treatment decisions. Results indicate that the most common surgical treatments were radial shortening osteotomy for early disease and PRC in later stages. Level of Evidence Level IV, Economic/Decision Analysis.

Convection-enhanced delivery of etoposide is effective against murine proneural glioblastoma.

BACKGROUND: Glioblastoma subtypes have been defined based on transcriptional profiling, yet personalized care based on molecular classification remains unexploited. Topoisomerase II (TOP2) contributes to the transcriptional signature of the proneural glioma subtype. Thus, we targeted TOP2 pharmacologically with etoposide in proneural glioma models. METHODS: TOP2 gene expression was evaluated in mouse platelet derived growth factor (PDGF)(+)phosphatase and tensin homolog (PTEN)(-/-)p53(-/-) and PDGF(+)PTEN(-/-) proneural gliomas and cell lines, as well as human glioblastoma from The Cancer Genome Atlas. Correlation between TOP2 transcript levels and etoposide susceptibility was investigated in 139 human cancer cell lines from the Cancer Cell Line Encyclopedia public dataset and in mouse proneural glioma cell lines. Convection-enhanced delivery (CED) of etoposide was tested on cell-based PDGF(+)PTEN(-/-)p53(-/-) and retroviral-based PDGF(+)PTEN(-/-) mouse proneural glioma models. RESULTS: TOP2 expression was significantly higher in human proneural glioblastoma and in mouse proneural tumors at early as well as late stages of development compared with normal brain. TOP2B transcript correlated with susceptibility to etoposide in mouse proneural cell lines and in 139 human cancer cell lines from the Cancer Cell Line Encyclopedia. Intracranial etoposide CED treatment (680 µM) was well tolerated by mice and led to a significant survival benefit in the PDGF(+)PTEN(-/-)p53(-/-) glioma model. Moreover, etoposide CED treatment at 80 µM but not 4 µM led to a significant survival advantage in the PDGF(+)PTEN(-/-) glioma model. CONCLUSIONS: TOP2 is highly expressed in proneural gliomas, rendering its pharmacological targeting by intratumoral administration of etoposide by CED effective on murine proneural gliomas. We provide evidence supporting clinical testing of CED of etoposide with a molecular-based patient selection approach.

The effects on tuberculosis treatment adherence from utilising community health workers: a comparison of selected rural and urban settings in Kenya.

INTRODUCTION: Community Health Workers (CHWs) have been utilised for various primary health care activities in different settings especially in developing countries. Usually when utilised in well defined terms, they have a positive impact. To support Kenya's policy on engagement of CHWs for tuberculosis (TB) control, there is need to demonstrate effects of utilising them. OBJECTIVES: This study assessed TB treatment adherence among patients who utilised CHWs in management of their illness in comparison to those who did not in urban and rural settings. METHODS: A retrospective cohort study was conducted in selected health facilities using standard clinical records for each TB patient registered for treatment between 2005 to 2011. Qualitative data was collected from CHWs and health care providers. RESULTS: The study assessed 2778 tuberculosis patients and among them 1499 (54%) utilized CHWs for their TB treatment. The urban setting in comparison with the rural setting contributed 70% of patients utilising the CHWs (p<0.001). Overall treatment adherence of the cohort was 79%. Categorizing by use of CHWs, adherence among patients who had utilized CHWs was 83% versus 68% among those that had not (p<0.001). In comparison between the rural and urban settings adherence was 76% and 81.5% (p<0.001) respectively and when categorized by use of CHWs it was 73% and 90% (p<0.001) for the rural and urban set ups respectively. Utilisation of CHWs remained significant in enhancing treatment adherence in the cohort with unadjusted and adjusted ORs; OR 2.25, (95% 1.86-2.73) p<0.001 and OR 1.98 (95% 1.51-2.5) p<0.001 respectively. It was most effective in the urban set-up, OR 2.65 (95% 2.02-3.48, p<0.001) in comparison to the rural set up, OR 0.74 (95% 0.56-0.97) p = 0.032. CONCLUSION: Utilisation of CHWs enhanced TB treatment adherence and the best effects were in the urban set-up.

A rat model of chondrocyte death after closed intra-articular fracture.

OBJECTIVE: The development of osteoarthritis after intra-articular fractures has been described for decades, although the exact mechanical and cellular changes that occur remain poorly understood. There are several animal models to study this phenomenon, but they are mechanistically different from physiologic fractures in several important ways. This article describes a novel model that recreates the kinematics present in high-energy trauma and intra-articular fractures. METHODS: We designed a "drop tower" for the creation of intercondylar femoral fractures in rats and tested it on cadaveric rats to determine the optimal kinetic parameters. Intra-articular fractures were then created in live rats and the animals were killed at 0, 24, and 72 hours after the fracture. Cartilage samples were obtained for live/dead staining, and the relationships among fracture time, cartilage depth, and cell viability were evaluated. RESULTS: The model reproduced intra-articular fractures very similar to those seen in high-energy trauma, although we required significantly higher energies (3600 mJ) than those reported in other fracture models (40-200 mJ). Cartilage viability decreased with time (68% immediately after the fracture and 46% at 72 hours, P = 0.02) and increased with depth from the articular surface (47% at the surface vs. 66% in the deepest layer, P = 0.001). CONCLUSIONS: This model is a physiologically relevant reliable method for creating intra-articular fractures in rats and can produce meaningful data about the biologic changes occurring in cartilage after injury. Cell viability decreases with time postfracture and with proximity to the articular surface.