Assessment of health system challenges and opportunities for possible integration of diabetes mellitus and tuberculosis services in South-Eastern Amhara Region, Ethiopia: a qualitative study.

BACKGROUND: The double burden of tuberculosis (TB) and diabetes mellitus (DM) is a significant public health problem in low and middle income countries. However, despite the known synergy between the two disease conditions, services for TB and DM have separately been provided. The objective of this study was to explore health system challenges and opportunities for possible integration of DM and TB services. METHODS: This was a descriptive qualitative study which was conducted in South-Eastern Amhara Region, Ethiopia. Study participants included health workers (HWs), program managers and other stakeholders involved in TB and DM prevention and control activities. Purposive sampling was applied to select respondents. In order to capture diversity of opinions among participants, maximum variation sampling strategy was applied in the recruitment of study subjects. Data were collected by conducting four focus group discussions and 12 in-depth interviews. Collected data were transcribed verbatim and were thematically analyzed using NVivo 10 software program. RESULT: A total of 44 (12 in-depth interviews and 32 focus group discussion) participants were included in the study. The study participants identified a number of health system challenges and opportunities affecting the integration of TB-DM services. The main themes identified were: 1. Unavailability of system for continuity of DM care. 2. Inadequate knowledge and skills of health workers. 3. Frequent stockouts of DM supplies. 4. Patient's inability to pay for DM services. 5. Poor DM data management. 6. Less attention given to DM care. 7. Presence of a well-established TB control program up to the community level. 8. High level of interest and readiness among HWs, program managers and leaders at different levels of the health care delivery system. CONCLUSION: The study provided insights into potential health systems challenges and opportunities that need to be considered in the integration of TB-DM services. Piloting TB and DM integrated services in selected HFs of the study area is needed to assess feasibility for possible full scale integration of services for the two comorbid conditions.

Costs and clinical outcome of neoadjuvant systemic chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from gastric cancer.

BACKGROUND: The costs for loco-regional treatment of peritoneal carcinomatosis from gastric cancer are not well investigated. The aims of this study were to evaluate the costs and clinical outcome of systemic chemotherapy followed by cytoreductive surgery and intraperitoneal chemotherapy compared to systemic chemotherapy only in patients with peritoneal carcinomatosis from gastric cancer. MATERIAL AND METHODS: Ten patients were scheduled for systemic chemotherapy followed by loco-regional treatment. A reference group of 10 matched control patients treated with systemic chemotherapy only were used and both groups were evaluated with respect to clinical outcome and cost. RESULTS: The mean overall cost in the loco-regional group was $145,700 (range $49,900-$487,800) and $59,300 (range $23,000-$94,800) for the control group. The mean overall survival for the loco-regional group was 17.4 months (range 6.0-34.3), and 11.1 months (range 0.1-24.2) for the systemic chemotherapy only group. The gain in life-years was 0.52 and in quality-adjusted life-years 0.49, leading to incremental cost per life-year and quality-adjusted life-years gained of $166,716 and $175,164, for loco-regional group compared to systemic chemotherapy. DISCUSSION: Treatment of peritoneal carcinomatosis from gastric cancer is costly irrespective of treatment modality. If the survival benefit from adding loco-regional treatment to systemic chemotherapy indicated from this comparison is true, the incremental cost is considered high.

Assessment of normal and tumor tissue uptake of MAG-CPT, a polymer-bound prodrug of camptothecin, in patients undergoing elective surgery for colorectal carcinoma.

PURPOSE: MAG-camptothecin (MAG-CPT) is the lead compound of a novel drug delivery system in which an active cytotoxic moiety, camptothecin (CPT), is covalently linked to a soluble polymeric carrier (MAG) to form an inactive prodrug. The mechanism of action of CPT remains unaltered, but the delivery system is thought to allow the carrier-bound drug to accumulate in tumor tissues and release the active CPT locally. This proof-of-concept clinical study was designed to determine whether MAG-CPT was preferentially delivered to or retained in tumor tissue compared to adjacent normal tissue or plasma, and to estimate the degree of intratissue release of CPT. METHODS: This was an open, non-randomized study in ten adult patients scheduled for elective surgery for colorectal cancer. Patients received a single dose of 60 mg/m2 (CPT equivalent) of MAG-CPT 24 h, 3 days or 7 days prior to surgery. Plasma, tumor, and adjacent normal tissue samples were collected simultaneously at the time of surgery and analyzed for MAG-bound and released CPT concentrations. RESULTS: MAG-bound and free CPT concentrations in plasma, tumor, and normal tissue achieved equilibrium by 24 h after dosing, declining in parallel up to 7 days after dosing. MAG-bound CPT was delivered to similar levels to tumor and normal tissue. At 24 h after dosing, the mean+/-SD MAG-bound CPT concentrations were 861+/-216 ng/g in tumor and 751+/-215 ng/g in adjacent normal tissue, and free CPT concentrations were lower in tumor than in normal tissue (12.2+/-4.7 ng/g and 21.9+/-6.7 ng/g, respectively). At 24 h after dosing, mean+/-SD ratios of MAG-bound and free CPT in tumor and plasma were 0.13+/-0.03 and 0.22+/-0.09, respectively, and the ratios did not change for up to 7 days after dosing, indicating a lack of preferential retention of MAG-bound CPT or release of free CPT in tumor. These results are in marked contrast to previous data from animal tumor xenograft studies, where MAG-CPT levels were higher in tissue than in plasma at 3 and 7 days after a single i.v. dose. CONCLUSIONS: Delivery of CPT to the target tumor tissue is achievable by means of the MAG-CPT polymer-bound delivery system, with the equilibrium between plasma and tumor tissue concentrations of released CPT being established within 24 h after dosing. However, preferential retention of MAG-bound or released CPT in the tumor relative to normal tissue or plasma was not detected during the 7 days after dosing. The methods employed in our study could be of use in making "go/no-go" decisions on further development of anticancer drugs.