Opioid Access among Advanced Cancer Patients in Low- and Middle-Income Countries in Asia.

CONTEXT: Most cancer-associated pain is experienced in low- and middle-income countries (LMICs) due to inequitable access to opioids. OBJECTIVE: To determine opioid access as estimated by both patients and providers and to understand patient and facility-level factors influencing access among patients with advanced cancer in LMICs in Asia using the Behavioral Model of Health Services Use. METHODS: The APPROACH cross-sectional study was conducted in seven LMICs in Asia, involving in-depth surveys with providers and advanced cancer patients. A hierarchical logistic regression model was used to assess predisposing (i.e. individual factors), enabling (i.e. health care system and facility-level resources) and need (i.e. pain severity) factors predicting opioid access. RESULTS: Among patient participants (n=1,933), approximately 40% reported opioid use. Meanwhile 80% of facilities, as reported by providers, indicated at least half of their advanced cancer patients receive oral morphine prescriptions. Predisposing characteristics factored in the least in the model, with patient education positively associated with access (Odds ratio (OR): 1.01; 95% CI=1.00, 1.03). Facility-level enabling resources, factoring the most, included oral morphine prescription duration >14 days (OR: 1.27; 95% CI=1.05, 1.53) and the extent of physician palliative care training (extensive (>160 hours) OR: 3.95; CI=3.19, 4.88; basic (up to 40 hours) OR: 1.03; CI=1.03, 1.04). Patient need as indicated by greater pain severity predicted access (OR: 1.55; CI=1.47, 1.64). CONCLUSION: Study findings emphasize the importance of palliative care training-even a minimal amount-in supporting access to opioids for advanced cancer patients. This study also highlights pragmatic site-level policies, such as extended morphine prescription durations, enabling access.

hTERT antagonizes p53-induced apoptosis independently of telomerase activity.

The p53 tumor suppressor controls cell growth and survival through transcriptional regulation of gene expression. Previously, we found that the human telomerase reverse transcriptase (hTERT) gene is downregulated by p53. To investigate if hTERT downregulation has a role in p53-dependent apoptosis, we tested if constitutive expression of telomerase could inhibit p53-induced apoptosis. Here we show that constitutive hTERT expression results in increased survival following activation of exogenous temperature-sensitive p53 in BL41 Burkitt lymphoma cells. Similarly, constitutive hTERT expression inhibited wild-type p53-dependent apoptosis in response to mitomycin C or 5-fluorouracil in HCT116 colon carcinoma cells carrying endogenous p53. A telomerase-inactive hTERT mutant was equally efficient in antagonizing p53-induced apoptosis. These findings support the notion that hTERT has antiapoptotic activity and demonstrate that p53-mediated downregulation of hTERT is critical for efficient p53-dependent apoptosis.