Poor continuity of care for TB diagnosis and treatment in Zambian Prisons: a situation analysis.

OBJECTIVES: Prisons act as infectious disease reservoirs. We aimed to explore the challenges of TB control and continuity of care in prisons in Zambia. METHODS: We evaluated treatment outcomes for a cohort of inmates diagnosed with TB during a TB REACH funded screening programme initiated by the Zambia Prisons Service and the Centre for Infectious Disease Research in Zambia. RESULTS: Between October 2010 and September 2011, 6282 inmates from six prisons were screened for TB, of whom 374 (6.0%) were diagnosed. TB treatment was initiated in 345 of 374 (92%) inmates. Of those, 66% were cured or completed treatment, 5% died and 29% were lost to follow-up. Among those lost to follow-up, 11% were released into the community and 13% were transferred to other prisons. CONCLUSIONS: Weak health systems within the Zambian prison service currently undermines continuity of care, despite intensive TB screening and case-finding interventions. To prevent TB transmission and the development of drug resistance, we need sufficient numbers of competent staff for health care, reliable health information systems including electronic record keeping for prison facilities, and standard operating procedures to guide surveillance, case-finding and timely treatment initiation and completion.

Accuracy of giant African pouched rats for diagnosing tuberculosis: comparison with culture and Xpert® MTB/RIF.

SETTING: Enhanced tuberculosis (TB) case finding using detection rats in Tanzania. OBJECTIVES: To assess the diagnostic accuracy of detection rats compared with culture and Xpert® MTB/RIF, and to compare enhanced case-finding algorithms using rats in smear-negative presumptive TB patients. DESIGN: A fully paired diagnostic accuracy study in which sputum of new adult presumptive TB patients in Tanzania was tested using smear microscopy, 11 detection rats, culture and Xpert. RESULTS: Of 771 eligible participants, 345 (45%) were culture-positive for Mycobacterium tuberculosis, and 264 (34%) were human immunodeficiency virus (HIV) positive. The sensitivity of the detection rats was up to 75.1% (95%CI 70.1-79.5) when compared with culture, and up to 81.8% (95%CI 76.0-86.5) when compared with Xpert, which was statistically significantly higher than the sensitivity of smear microscopy. Corresponding specificity was 40.6% (95%CI 35.9-45.5) compared with culture. The accuracy of rat detection was independent of HIV status. Using rats for triage, followed by Xpert, would result in a statistically higher yield than rats followed by light-emitting diode fluorescence microscopy, whereas the number of false-positives would be significantly lower than when using Xpert alone. CONCLUSION: Although detection rats did not meet the accuracy criteria as standalone diagnostic or triage testing for presumptive TB, they have additive value as a triage test for enhanced case finding among smear-negative TB patients if more advanced diagnostics are not available.

High prevalence of tuberculosis in newly enrolled HIV patients in Zambia: need for enhanced screening approach.

SETTING: Tuberculosis (TB) remains a leading cause of morbidity and mortality in sub-Saharan Africa. In Zambia, smear microscopy and chest radiography (CXR) are the primary TB diagnostic tools, and most cases are not bacteriologically confirmed. OBJECTIVE: We implemented enhanced screening to determine the TB burden among new human immunodeficiency virus (HIV) clinic enrollees. DESIGN: Consecutive adult HIV clinic enrollees were screened, regardless of symptoms. All underwent microscopy (Ziehl-Neelsen/fluorescence microscopy) on three sputum specimens, physical examination, and digital CXR. Sputum, blood and urine specimens were cultured. Xpert(®) MTB/RIF testing was performed retrospectively. RESULTS: From July 2011 to April 2012, 399 patients were enrolled. The median age was 34.4 years; body mass index was 20.8 kg/m(2), CD4 count was 202 cells/µl and 86% were symptomatic. Culture-confirmed TB was diagnosed in 72/399 (18%) patients; an additional 31/399 (8%) were culture-negative but diagnosed clinically. Symptom screening for any cough, fever, weight loss or night sweats had high sensitivity (95%) but low specificity (14%) for detecting culture-confirmed cases. Among culture-confirmed cases, 35/72 (49%) were missed clinically and detected only by culture. Xpert was 64% sensitive and 98% specific. CONCLUSIONS: High TB prevalence was found in Zambians newly enrolled into HIV care. Screening with sensitive diagnostics should be considered with culture when feasible in this population.

Integrating active tuberculosis case finding in antenatal services in Zambia.

SETTING: Three out-patient antenatal care (ANC) clinics in Lusaka, Zambia. OBJECTIVE: To estimate tuberculosis (TB) prevalence in human immunodeficiency virus (HIV) infected and symptomatic, non-HIV-infected pregnant women and explore the feasibility of routine TB screening in ANC settings. DESIGN: Peer educators administered TB symptom questionnaires to pregnant women attending their first ANC clinic visit. Presumptive TB patients were defined as all HIV-infected women and symptomatic non-HIV-infected women. Sputum samples were tested using smear microscopy and culture to estimate TB prevalence. RESULTS: All 5033 (100%) women invited to participate in the study agreed, and 17% reported one or more TB symptoms. Among 1152 presumed TB patients, 17 (1.5%) had previously undiagnosed culture-confirmed TB; 2 (12%) were smear-positive. Stratified by HIV status, TB prevalence was 10/664 (1.5%, 95%CI 0. 7-2.8) among HIV-infected women and 7/488 (1.4%, 95%CI 0.6-2.9) among symptomatic non-HIV-infected women. In HIV-infected women, the only symptom significantly associated with TB was productive cough; symptom screening was only 50% sensitive. CONCLUSION: There is a sizable burden of TB in pregnant women in Zambia, which may lead to adverse maternal and infant outcomes. TB screening in ANC settings in Zambia is acceptable and feasible. More sensitive diagnostics are needed.

Derivation of a tuberculosis screening rule for sub-Saharan African prisons.

SETTING: Lusaka Central Prison, Zambia. OBJECTIVE: To derive screening rules for tuberculosis (TB) using data collected during a prison-wide TB and human immunodeficiency virus (HIV) screening program. DESIGN: We derived rules with two methodologies: logistic regression and classification and regression trees (C&RT). We evaluated the performance of the derived rules as well as existing World Health Organization (WHO) screening recommendations in our cohort of inmates, as measured by sensitivity, specificity, and positive and negative predictive values. RESULTS: The C&RT-derived rule recommended diagnostic testing of all inmates who were underweight (defined as body mass index [BMI] < 18.5 kg/m(2)] or HIV-infected; the C&RT-derived rule had 60% sensitivity and 71% specificity. The logistic regression-derived rule recommended diagnostic testing of inmates who were underweight, HIV-infected or had chest pain; the logistic regression-derived rule had 74% sensitivity and 57% specificity. Two of the WHO recommendations had sensitivities that were similar to our logistic regression rule but had poorer specificities, resulting in a greater testing burden. CONCLUSION: Low BMI and HIV infection were the most robust predictors of TB in our inmates; chest pain was additionally retained in one model. BMI and HIV should be further evaluated as the basis for TB screening rules for inmates, with modification as needed to improve the performance of the rules.

Early lessons from the integration of tuberculosis and HIV services in primary care centers in Lusaka, Zambia.

BACKGROUND: Zambia faces overlapping tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics; however, care for co-infected patients often occurs through separate, vertical programs. OBJECTIVE: To establish a program to integrate TB and HIV services in Lusaka primary care centers. METHODS: In collaboration with the Zambian Ministry of Health, TB-HIV integration activities began in December 2005 and were expanded to seven health centers by March 2007. Principal activities included developing staff capacity to manage co-infected patients, implementing HIV testing within TB departments and establishing referral systems between departments. RESULTS: Using a provider-initiated approach, 2053 TB patients were offered HIV testing. Seventy-seven per cent agreed to be tested; 69% of those tested were HIV-infected. Of these, 59% were enrolled in HIV care. The proportion of antiretroviral treatment (ART) program enrollees who were TB-HIV co-infected increased by 38% after program implementation. The median CD4 count among co-infected patients was 161 cells/microl, with 88% eligible for ART. CONCLUSION: Integration of HIV testing and referral services into urban primary care centers identified many co-infected patients and significantly increased the proportion of TB patients among people accessing HIV care. Ongoing challenges include maximizing the number of patients accepting HIV testing and overcoming barriers to enrollment into HIV care.

Meta-analysis of randomised controlled trials comparing latanoprost with brimonidine in the treatment of open-angle glaucoma, ocular hypertension or normal-tension glaucoma.

AIM: To compare the efficacy and tolerability of latanoprost versus brimonidine in the treatment of open-angle glaucoma, ocular hypertension or normal-tension glaucoma. METHOD: Systematic review of randomised controlled trials comparing latanoprost and brimondine, identified by searches including Medline, Embase and Cochrane Controlled Trials Register. Two reviewers independently assessed trials for eligibility and quality and extracted data. Data were synthesised (random effects model) and expressed as the absolute mean intraocular pressure (IOP) reduction difference from baseline to end point for efficacy and relative risk for adverse events. Subgroup analysis and regression were used to explore heterogeneity according to patient characteristics, trial design and quality. RESULTS: 15 publications reporting on 14 trials (1784 participants) were included for meta-analysis. IOP reduction favoured latanoprost (weighted mean difference (WMD) = 1.10 mm Hg (95% confidence interval (CI) 0.57 to 1.63)). Significant heterogeneity was present (chi(2)(13) = 38.29, p = 0.001, I(2) = 66.0%). Subgroup analysis showed greater WMD for studies where data were analysed from end points >6 months duration, cross-over design, open-angle glaucoma or ocular hypertension and monotherapy. Multiple regression showed no significant association of WMD with trial duration (t(9) = 1.92, p = 0.09), trial design (t(9) = 1.79, p = 0.11), trial quality (t(9) = -0.46, p = 0.66), or monotherapy or adjunctive therapy (t(9) = -2.14, p = 0.06). Fatigue was less commonly associated with latanoprost (RR = 0.27, 95% CI 0.08 to 0.88). Publication bias was not evident on visual inspection of a funnel plot. CONCLUSION: Latanoprost is more effective than brimonidine as monotherapy in lowering IOP. Brimonidine is associated with a higher rate of fatigue.

Antiretroviral therapy in sub-Saharan Africa: adherence lessons from tuberculosis and leprosy.

Declining drug costs and increases in international donor interest are leading to greater availability of antiretroviral treatment programmes for persons living with the human immunodeficiency virus in parts of sub-Saharan Africa. Ensuring adequate adherence to antiretroviral drug therapy is one of the principal challenges facing successful implementation in Africa, where 70% of the world's infected persons live. Tuberculosis and leprosy are two diseases of global importance whose control programmes can provide important lessons for developing antiretroviral drug adherence strategies. This paper examines various approaches used in tuberculosis and leprosy control which could help enhance adherence to antiretroviral therapy in resource-limited settings.

Influence of load orientation on the posteroanterior stiffness of the lumbar spine.

OBJECTIVE: To compare the posteroanterior (PA) stiffness of the lumbar spine when the load is applied in a vertical direction with the stiffness when the load is applied perpendicular to the spinal curve. DESIGN: The PA stiffness of the lumbar spine was assessed at L1, L3 and L5 on 24 normal subjects using a mechanical spinal mobilization apparatus. The PA stiffness was measured when the load was applied in a vertical direction and when the load was applied perpendicular to the spinal curve at the level being tested. SETTING: A university biomechanics laboratory. DESIGN: A repeated-measures design with pseudorandomization of the order of testing. MAIN OUTCOME MEASURES: Stiffness variable derived from force-displacement curve. RESULTS: The difference in PA stiffness between the two loading conditions was small at all three levels tested. The stiffness of L5 was significantly lower when the load was applied in the vertical direction compared with the application of the load in the perpendicular direction (p = .0001). Altering the angle of inclination of PA load had no statistically significant effect on PA stiffness at L1 and L3. The mean PA stiffness of the lumbar spine increased in a caudal direction (L1 = 10.4 N/mm, L3 = 11.4 N/mm, L5 = 11.6 N/mm). CONCLUSION: The orientation of the PA load had only a small effect on the measured PA stiffness and would be unlikely to be detected during manual examination of the spine. However, changes in the orientation of the PA load may be important when considered in relation to the symptom response.

Analysing potential harm in Australian general practice: an incident-monitoring study.

OBJECTIVE: To collect data on incidents of potential or actual harm to general practice patients and to evaluate the possible causes of these incidents. DESIGN: An observational study of incidents of potential harm based on a modified critical incidents technique. A non-random sample of general practitioners (GPs) anonymously submitted incident reports contemporaneously. SETTING AND PARTICIPANTS: Australian general practices between October 1993 and June 1995. During the study period, 324 GPs participated at some time. MAIN OUTCOME MEASURES: GP-reported free-text descriptions of incidents and structured responses for preventability, potential for harm, immediate consequences, predicted long-term outcomes, type of incident, contributing factors, mitigating factors, and additional resource use. RESULTS: 805 incidents were reported--76% were preventable; 27% had potential for severe harm. No long term harm was predicted for 66% of incidents. Incidents could relate to pharmacological management (51 per 100 incidents), nonpharmacological management (42 per 100 incidents), diagnosis (34 per 100 incidents) or equipment (5 per 100 incidents). The most common contributory factors were poor communication between patients and healthcare professionals and actions of others (23 per 100 incidents each) and errors in judgement (22 per 100 incidents). CONCLUSION: Human error and preventable system problems were identified. The incident monitoring technique provided useful data which could be applied to incident prevention strategies.

Pap smears in general practice: a secondary analysis of the Australian Morbidity and Treatment Survey 1990 to 1991.

We investigated the characteristics of Australian general practice that predict performance of Pap smears by secondary analysis of the Australian Morbidity and Treatment Survey 1990 to 1991. Chi-squared analysis identified potential associations between Pap smear rate and patient, doctor and practice variables. Significant associations were examined using logistic regression and generalised estimating equations. Participants were 495 general practitioners who collected information on 113,468 doctor-patient encounters, of which 43,211 encounters involved females aged 18 to 70 years. Pap smear encounter (2449) were identified and classified as patient-requested (62 per cent), diagnostic (5 per cent) or opportunistic (33 per cent). The large difference in the unadjusted Pap smear rates per 100 female encounters for female general practitioners (11.7) and male general practitioners (4.2) required separate analysis by sex of the general practitioner. For male general practitioners, a Pap smear was less likely: as patient age increased; for new patients; for general practitioners with less general practice experience; for general practitioners with no postgraduate qualifications; with metropolitan practice location; and if the practice had more than 25 per cent of patients with English as a second language. For female general practitioners, a Pap smear was less likely: for older known patients; as the age of the general practitioners increased; and for management of fewer problems per 100 encounters. A Pap smear was less likely to be opportunistic: as patient age increased; for general practitioners who were Australian graduates; and for general practitioners with no postgraduate qualifications. Consideration of patient, doctor, and general practice characteristics may facilitate the design of interventions to improve cervical cancer screening.

The potential role of integrin receptor subunits in the formation of local recurrence and distant metastasis by mouse breast cancer cells.

BACKGROUND: The mechanisms by which surgical injury fosters tumor growth are examined. METHODS: TA3Ha mouse breast tumor line and its subline (TA3AD) differing in their metastatic abilities as tested by two models were used. In model a, TA3Ha/TA3AD tumors were grown in the mammary fat pads of mice and then surgically removed with a curative intent. In model b, TA3Ha/TA3AD cells were injected intravenously into mice subjected to liver or spleen wedge resection. Frequency of tumor formation at various sites was assessed. Expression of integrin, immunoglobulin, and proteoglycan cell adhesion receptors on TA3Ha and TA3AD cells was examined by flow cytometry. The roles of these receptors in metastasis were examined by blocking them by selected ligands and/or antibodies. RESULTS: Frequencies of local recurrence and axillary metastasis after surgical resection, were 43% (32/74), and 37% (27/74) with TA3Ha tumors and 4% (1/29) at both sites with TA3AD tumors. Tumors at surgically injured spleen and the liver were seen in 75% (141/189) and 45% (107/240) of the mice with TA3Ha cells and in 8% (3/38) and 10% (4/42) of the mice with TA3AD cells. alpha 5 and CD44 receptors were expressed by TA3Ha cells but not by TA3AD cells. Other receptors examined were similarly expressed by both cell lines. Blocking of alpha 5 receptor by fibronectin reduced tumor implantation in a dose-dependent manner. CONCLUSIONS: The data suggest a correlation among the ability to implant at surgically injured sites, to form local recurrence, and to express the fibronectin receptor subunit.

Endocrine and paracrine hormones in the promotion, progression and recurrence of breast cancer.

Both normal and neoplastic breast tissues are stimulated by endocrine and paracrine hormones. Epidemiological studies have demonstrated the significant role that hormones, growth factors and cytokines have in the promotion, progression and recurrence of breast cancer. Significant variations in the hormonal environment occur based on age, the cyclical changes occurring during the menstrual cycle and (mammographically determined) variations in breast composition. These variations have a significant influence on rates of local recurrence of breast cancer and survival. This review analyses data relevant to these issues and suggests means by which operative results may be improved.

Pre-, peri-, and postoperative chemotherapy for breast cancer: is one better than the other?

The purpose of the present study was to determine the relative efficacy of pre-, peri-, and postoperative chemotherapy in the prevention of breast cancer relapse and prolongation of host survival. The studies were performed using an experimental mouse breast cancer model. TA3Ha mouse mammary adenocarcinoma was transplanted into the mammary fat pad of syngeneic mice to obtain tumors in their natural organ. The tumors were surgically excised with a "curative" intent. A single treatment with 10 mg/kg doxorubicin was given intravenously pre-, peri-, or postoperatively. Among 74 mice whose tumors were resected but no doxorubicin was given, local recurrence, axillary metastasis, and lung metastasis were seen in 43%, 37%, and 16% of the mice, respectively. Seventeen (23%) mice had no evidence of disease. Doxorubicin given 4 days preoperatively reduced the rate of growth of primary tumor. Local recurrence was reduced in these mice by 30% and metastasis to the axillary lymph nodes and lung was completely prevented. Disease-free survival was increased to 70% (P < 0.01). Similar beneficial effects were obtained when chemotherapy was administered 2 days prior to surgery. The peri-operative chemotherapy group showed 8% (2/26) local recurrence, 4% axillary metastasis, and 0% lung metastasis. Proportion of mice without any evidence of disease increased to 92% (P < 0.00001). Chemotherapy given 4 days postoperatively resulted in 63% (10/16) local recurrence, 38% axillary metastasis, and 6.3% lung metastasis. Only 38% of the mice were disease-free. Thus in the model studied, perioperative chemotherapy offers the best chance for reduced recurrence and for improved disease-free survival.

Role of cytokines and growth factors in promoting the local recurrence of breast cancer.

The pathogenesis of local recurrence in breast cancer is not well understood. Breast-conserving surgery is particularly prone to local recurrence as it leaves behind breast tissue that may harbour occult cancer, and lends itself to enhanced intraoperative shedding of cancer cells due to narrower resection margins and transection of lymphatic channels. A review of clinical breast cancer studies as well as experimental research strongly suggests that these persisting cancerous cells are unlikely to develop into clinically evident disease if their environment remains unstimulated. However, an inordinately high local recurrence rate occurs at the surgical scar, and such recurrence must be triggered by the release of growth factors and cytokines into the healing wound. These factors can stimulate any available cancer cells which express the proper growth factor receptors. Perioperative strategies to neutralize this tumour cell-growth factor interaction should maximize local control.

Influence of smoking on the development of lung metastases from breast cancer.

BACKGROUND: This study examined the association between cigarette smoking status and the development of lung metastases in a group of 835 women diagnosed with primary malignant unilateral breast cancer. METHOD: Female patients with breast cancer diagnosed between 1982 and 1991 at Roswell Park Cancer Institute (RPCI) in Buffalo, New York, who provided information on their cigarette smoking history at the time of their diagnosis were included. The subsequent disease status of patients was monitored by the RPCI Tumor Registry. The Cox regression model was used to estimate the relationship between smoking status and the development of lung metastases, adjusting for the patient's age, stage of disease at diagnosis, and body weight. RESULTS: Of those patients who developed lung metastases, 8.7% were nonsmokers, 14.1% were former smokers, and 14.3% were current smokers. Tests showed that nonsmokers had significantly fewer lung metastases than either of the two smoking groups (P < 0.01). The estimated relative rates of lung metastases developing adjusting for age, stage, and body weight in women who smoked less than 10,000, between 10,001 and 20,000, and more than 20,000 packs over their lifetimes compared with nonsmokers were 1.06 (95% CI, 0.51-2.20), 3.10 (95% CI, 1.5-6.3), and 3.73 (95% CI, 1.6-8.9) respectively. The Cox regression model showed that every 1000 packs of cigarettes consumed over a lifetime increased a woman's risk of developing lung metastases by about 3% to 7% (P < 0.001). CONCLUSION: This study found a significant association between cigarette smoking history and risk of lung metastases developing in women diagnosed with primary invasive unilateral breast cancer. The risk of lung metastases developing increased as the number of cigarettes smoked in a lifetime increased.

Health status, life satisfaction and health practices: a study of Pacific Asian and Native Hawaiian elderly cohorts.

This article describes the sociodemographic characteristics, self-ratings of health status, life satisfaction and health practices of Pacific Asian and Native Hawaiian elderly groups. The data were gathered from two separate, non-equivalent elderly cohorts enrolled in an elderly self-care education program in Hawaii during the period 1989-1992. The findings generally reflected favorable self-ratings of health status, high life satisfaction levels, and positive health practices for both of these minority elderly groups. The exceptions regarding several health practices relate to snacking between meals, overweight problems and insufficient sleep for a sizable proportion of both groups. Slight to moderate differences between the two groups were also evident in 1) eating habits; 2) snacking; 3) types of physical activities; 4) weight control; 5) sleep patterns; 6) alcohol use; and 7) smoking. Despite the article's exploratory nature and limitation in the generalizability of its findings, the data offer a beginning database for Asian and Pacific Island elderly which is sorely lacking.