Unusual presentation of Gilbert disease with high levels of unconjugated bilirubin. Report of two cases.

Gilbert's syndrome is a benign condition characterized by asymptomatic sporadic episodes of jaundice, due to a mild unconjugated hyperbilirubinemia caused by a deficiency in bilirubin glucoronidation. Under certain physiologic or pathologic events bilirubin level rises but according to literature it does not reach out more than 3 mg/dl. We report 2 cases of Gilbert's syndrome, genetically tested, which presented with bilirubin levels above 6 mg/dl without any trigger or coexisting condition. In conclusion, bilirubin levels higher than 6 mg/dL in Gilbert syndrome are rare, hemolytic and other metabolism diseases must be ruled out, and genetic testing may be necessary in some cases.

IMPORTANCE trial: a provisional study-design of a single-center, phase II, double-blinded, placebo-controlled, randomized, 4-week study to compare the efficacy and safety of intranasal esketamine in chronic opioid refractory pain.

Background:  Cancer is the second leading cause of death globally. Up to 86% of advanced cancer patients experience significant pain, while 10-20% live in chronic pain. Besides, increasing prescription of opioids resulted in 33,000 deaths in the US in 2015. Both reduce patients' functional status and quality of life. While cancer survival rates are increasing, therapeutic options for chronic opioid refractory pain are still limited. Esketamine is the s-enantiomer of ketamine, with superior analgesic effect and less psychotomimetic side effects. Intranasal esketamine was approved by the FDA for treatment-resistant depression. However, its use in chronic cancer pain has never been tested. Therefore, we propose a phase II, randomized, placebo-controlled trial to evaluate the efficacy and safety of intranasal esketamine in chronic opioid refractory cancer pain. Methods and analysis: We will recruit 120 subjects with chronic opioid refractory pain, defined as pain lasting more than 3 months despite optimal therapy with high dose opioids (>60 mg morphine equivalent dose/day) and optimal adjuvant therapy. Subjects will be randomized into two groups: intranasal esketamine (56mg) and placebo. Treatment will be administered twice a week for four consecutive weeks. The primary outcome is defined as reduction in the Numeric Pain Rating Scale (NPRS) after first application. Secondary outcomes include NPRS reduction after four weeks, the number of daily morphine rescue doses, functional status and satisfaction, and depression. Conclusion: This study may extend therapeutic options in patients with chronic pain, thus improving their quality of life and reducing opioid use. Trial registration: Clinical Trials.gov, NCT04666623. Registered on 14 December 2020.

Comparison of characteristics in Mexican women with breast cancer according to healthcare coverage.

OBJECTIVE: To compare the sociodemographic, diagnostic, clinical, and treatment-related characteristics and outcomes of patients with breast cancer in two hospitals in Mexico according to type of healthcare coverage. METHODS: A retrospective cohort study of women with breast cancer according to public or private healthcare coverage in two hospitals was done. Patients were treated by the same group of physicians and healthcare infrastructure. Groups were compared using the chi-square test for categorical variables, Mann-Whitney U-test and Student's t-test for quantitative variables, and Kaplan-Meier estimator and log-rank test for time dependent outcomes (including recurrence-free and overall survival). A value of p < 0.05 was considered statistically significant. RESULTS: A total of 282 women were included. Mean age at diagnosis was 52 years. Women with public healthcare coverage were diagnosed more frequently with self-detected tumors (82.8% vs 47.9%, p < 0.001) and advanced clinical stage (III and IV) (31.1% vs 17.8%, p = 0.014). More women with public healthcare insurance underwent initial systemic treatment (41.1% vs 17.8%, p < 0.001) and mastectomy (70.1% vs 54.9%, p = 0.020), and received more chemotherapy (79.4% vs 43.8%, p < 0.001) and adjuvant radiotherapy (68.9% vs 53.4%, p = 0.017). Overall, no differences were found in survival outcomes according to healthcare coverage. Trends suggesting worse recurrence-free and overall survival were observed in patients with public coverage at 3 years follow-up in stage III (85.7% vs 67.3% and 100% vs 84.6%, respectively) and triple negative disease (83.3% vs 74.5% and 100% vs 74.1%, respectively). CONCLUSION: Strategies to promote preventive medicine, diagnostic mammograms, and prompt diagnosis of breast cancer in Mexican women with public health coverage are needed. Access to the main treatment modalities by Seguro Popular and good quality care by an experienced group of physicians likely explains the similar outcomes between patients with private and public healthcare coverage. However, trends suggesting worse survival for patients with public medical coverage with stage III and triple-negative disease should encourage close follow-up.

Palliative Care Needs in an Acute Internal Medicine Ward in Mexico.

BACKGROUND: Palliative care is an evolving but underdeveloped practice in Mexico. OBJECTIVE: The primary end point of this prospective observational study was to identify internal medicine inpatients fulfilling advanced criteria within a second-level hospital. Secondary end points were symptom burden, treatment, resource utilization, and one-year survival. DESIGN AND MEASUREMENTS: The 390-sample size calculation was based on previous studies where 15% of inpatients fulfilled palliative care needs. Consecutive admissions were assessed to identify patients with any of the following: cancer, cardiac, renal, hepatic insufficiency, COPD, AIDS, stroke, or fragility until sample size was completed. After obtaining informed consent, interview to patient, attending physician, and chart review was completed to identify any of the following advanced disease criteria in each patient: (1) Surprise question to attending physician of the possibility of the patient dying in the following year, (2) Palliative Performance Scale (PPS) <50, and (3) Advanced disease specific criteria. Interview also included presence of symptoms, functional capacity, and previous resource utilization. Treatment offered was analyzed only on day of admission. One-year follow-up to assess survival was done through the state death certificates. RESULTS: Out of 390 patients, 131 (34%) had any of the diseases studied. Out of 131 patients, 86 (66%) had at least one of the three inclusion criteria for advanced disease. Out of 86 patients, 70 (81%) advanced disease patients died after one-year follow-up. Comparison between patients with no advanced disease (no criteria) versus advanced disease (at least one criteria) showed a significant difference in mean PPS, nutrition status, survival days, inhospital death, weight loss, dependency on activities of daily living, and previous multiple emergency room visits. Advanced disease patients with no death at one year follow-up had significantly more new admissions to that hospital. CONCLUSIONS: The number of patients requiring palliative care in internal medicine wards may be excessive to the current palliative care structures available.