Pharmacovigilance in hospice/palliative care: Net effect of amitriptyline or nortriptyline on neuropathic pain: UTS/IMPACCT Rapid programme international consecutive cohort.

BACKGROUND: Real-world effectiveness of interventions in palliative care need to be systematically quantified to inform patient/clinical decisions. Neuropathic pain is prevalent and difficult to palliate. Tricyclic antidepressants have an established role for some neuropathic pain aetiologies, but this is less clear in palliative care. AIM: To describe the real-world use and outcomes from amitriptyline or nortriptyline for neuropathic pain in palliative care. DESIGN: An international, prospective, consecutive cohort post-marketing/phase IV/pharmacovigilance/quality improvement study of palliative care patients with neuropathic pain where the treating clinician had already made the decision to use a tricyclic antidepressant. Data were entered at set times: baseline, and days 7 and 14. Likert scales graded benefits and harms. SETTING/PARTICIPANTS: Twenty-one sites (inpatient, outpatient, community) participated in six countries between June 2016 and March 2019. Patients had clinician-diagnosed neuropathic pain. RESULTS: One hundred and fifty patients were prescribed amitriptyline (110) or nortriptyline (40) of whom: 85% had cancer; mean age 73.2 years (SD 12.3); mean 0-4 scores for neuropathic pain at baseline were 1.8 (SD 1.0). By day 14, doses of amitriptyline were 57 mg (SD 21) and nortriptyline (48 mg (SD 21). Fifty-two (34.7%) patients had pain improvement by day 14 (amitriptyline (45/110 (43.3%); nortriptyline (7/40 (18.9%)). Thirty-nine (27.7%) had new harms; (amitriptyline 29/104 (27.9%); nortriptyline 10/37 (27.0%); dizziness (n = 23), dry mouth (n = 20), constipation (n = 14), urinary retention (n = 10)). Benefits without harms occurred (amitriptyline (26/104 (25.0%); nortriptyline (4/37 (10.8%)). CONCLUSIONS: Benefits favoured amitriptyline while harms were similar for both medications.

Premature deaths due to head and neck cancers in canada: A nationwide analysis from 1980 to 2010.

OBJECTIVES/HYPOTHESIS: To examine if there has been a reduction in premature mortality due to head and neck cancers and their subtypes in the Canadian population between 1980 and 2010. STUDY DESIGN: Retrospective database review. METHODS: Mortality data for head and neck cancers were obtained from the World Health Organization's mortality database. Years of life lost (YLL) was calculated according to Canadian life tables. A new measure, average lifespan shortened (ALSS), was calculated as a ratio of YLL over the expected lifespan. RESULTS: During the period of interest, decreases in age standardized rates of death adjusted to the World Standard Population were observed mainly among men. The adjusted YLL rates remained unchanged with respect to oral cancers in women, but slightly decreased for oral cancers in men and for laryngeal cancers in both sexes. Our new measure of ALSS showed that in 1980, patients with oral cancers lost an average of 20% of their lifespan, whereas in 2010, men and women still lost approximately 20% and 18%, respectively. Patients with laryngeal cancers lost 18% of their lifespan in both sexes in 1980 and 17% in 2010. The ALSS subanalysis showed that the largest gain of lifespan was observed for cancers of the hypopharynx in men and for cancers of the floor of mouth and nasopharynx in women. CONCLUSIONS: There appears to be modest improvements in premature mortality due to head and neck cancers in Canada over a 30-year period, with the exception of oral cancers in men. Changes in premature mortality varied slightly by cancer subtypes. LEVEL OF EVIDENCE: NA Laryngoscope, 130:911-917, 2020.

Pharmacovigilance in Hospice/Palliative Care: Net Effect of Haloperidol for Nausea or Vomiting.

BACKGROUND: Haloperidol is widely prescribed as an antiemetic in patients receiving palliative care, but there is limited evidence to support and refine its use. OBJECTIVE: To explore the immediate and short-term net clinical effects of haloperidol when treating nausea and/or vomiting in palliative care patients. DESIGN: A prospective, multicenter, consecutive case series. SETTING/SUBJECTS: Twenty-two sites, five countries: consultative, ambulatory, and inpatient services. MEASUREMENTS: When haloperidol was started in routine care as an antiemetic, data were collected at three time points: baseline; 48 hours (benefits); day seven (harms). Clinical effects were assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE). RESULTS: Data were collected (May 2014-March 2016) from 150 patients: 61% male; 86% with cancer; mean age 72 (standard deviation 11) years and median Australian-modified Karnofsky Performance Scale 50 (range 10-90). At baseline, nausea was moderate (88; 62%) or severe (11; 8%); 145 patients reported vomiting, with a baseline NCI CTCAE vomiting score of 1.0. The median (range) dose of haloperidol was 1.5 mg/24 hours (0.5-5 mg/24 hours) given orally or parenterally. Five patients (3%) died before further data collection. At 48 hours, 114 patients (79%) had complete resolution of their nausea and vomiting, with greater benefit seen in the resolution of nausea than vomiting. At day seven, 37 (26%) patients had a total of 62 mild/moderate harms including constipation 25 (40%); dry mouth 13 (21%); and somnolence 12 (19%). CONCLUSIONS: Haloperidol as an antiemetic provided rapid net clinical benefit with low-grade, short-term harms.