Cancer mortality and morbidity among patients with schizophrenia: A hospital-based cohort study, 1992-2020.

OBJECTIVE: Due to the inconsistency of the evidence about the cancer risk among patients with schizophrenia, the aim of this study was to analyse cancer mortality and morbidity in patients with schizophrenia treated in a single centre in Lithuania during the study period of 1992-2020. MATERIALS AND METHODS: A retrospective cohort study was conducted in Vilnius Republican Psychiatric Hospital, the biggest specialised psychiatric hospital in Lithuania, with approximately 5000 hospital admissions annually. The patients' cohort was established by identifying all patients with the diagnosis of schizophrenia (ICD-10 code F20) in the hospital database from 1 January 1992 until 31 December 2017. The cancer cases and cancer deaths in the cohort were identified in the Lithuanian Cancer Register through linkage procedures. The analysis of risk was based on a comparison of observed and expected numbers of cancers and deaths. Expected number of cancer cases were calculated by multiplication of the exact person-years under observation in the cohort by sex, calendar year and a 5-year age-group-specific national incidence and mortality rate. All statistical analyses were carried out using STATA 15 statistical software. RESULTS: During the follow-up, out of 8553 patients, 673 cases of cancer were diagnosed in both sexes. Statistically significantly lower risk for overall cancer incidence was observed in men (SIR 0.74, 95% CI 0.66-0.83), but not in women (SIR 1.07, 95% CI 0.97-1.18). Statistically significant lower overall cancer mortality risk was observed in men (SMR 0.82, 95% CI 0.70-0.96), while in the women's group, risk of cancer deaths was significantly higher compared to the general population (SMR 1.28, 95% CI 1.11-1.48). We observed lower risk for pancreatic cancer (SIR 0.36, 95% CI 0.14-0.96), non-melanoma skin cancer (SIR 0.54, 95% CI 0.33-0.88) and prostate cancer (SIR 0.69, 95% CI 0.55-0.87) in men and higher risk for malignant neoplasm of liver (SIR 2.58, 95% CI 1.53-4.36) and skin melanoma (SIR 2.03, 95% CI 1.12-3.66) in men and for breast cancer (SIR 1.38, 95% CI 1.14-1.66) and corpus uteri cancer (SIR 1.56, 95% CI 1.18-2.07) in women. CONCLUSIONS: The current results of our study indicate lower risk of overall cancer incidence and mortality in male patients with schizophrenia, while female patients had a higher mortality risk, alongside variations in the risk of different cancer types. This information is important not only for patients, but for healthcare specialists to develop effective disease-specific preventive interventions and programmes.

Paclitaxel with or without trametinib or pazopanib in advanced wild-type BRAF melanoma (PACMEL): a multicentre, open-label, randomised, controlled phase II trial.

BACKGROUND: Advanced melanoma treatments often rely on immunotherapy or targeting mutations, with few treatment options for wild-type BRAF (BRAF-wt) melanoma. However, the mitogen-activated protein kinase pathway is activated in most melanoma, including BRAF-wt. We assessed whether inhibiting this pathway by adding kinase inhibitors trametinib or pazopanib to paclitaxel chemotherapy improved outcomes in patients with advanced BRAF-wt melanoma in a phase II, randomised and open-label trial. PATIENTS AND METHODS: Patients were randomised (1 : 1 : 1) to paclitaxel alone or with trametinib or pazopanib. Paclitaxel was given for a maximum of six cycles, while 2 mg trametinib and 800 mg pazopanib were administered orally once daily until disease progression or unacceptable toxicity. Participants and investigators were unblinded. The primary end point was progression-free survival (PFS). Key secondary end points included overall survival (OS) and objective response rate (ORR). RESULTS: Participants were randomised to paclitaxel alone (n = 38), paclitaxel and trametinib (n = 36), or paclitaxel and pazopanib (n = 37). Adding trametinib significantly improved 6-month PFS [time ratio (TR), 1.47; 90% confidence interval (CI) 1.08-2.01, P = 0.04] and ORR (42% versus 13%; P = 0.01) but had no effect on OS (P = 0.25). Adding pazopanib did not benefit 6-month PFS; (TR 1.36; 90% CI 0.96-1.93; P = 0.14), ORR, or OS. Toxicity increased in both combination arms. CONCLUSION: In this phase II trial, adding trametinib to paclitaxel chemotherapy for BRAF-wt melanoma improved PFS and substantially increased ORR but did not impact OS.This study was registered with the EU Clinical Trials Register, EudraCT number 2011-002545-35, and with the ISRCTN registry, number 43327231.

Genotypes of Helicobacter pylori in Lithuanian families.

BACKGROUND: Infection by Helicobacter pylori is very common in Eastern Europe, but the genotypes of predominant strains and prevalence of single vs. multiple infection in this geographic region have not been much studied. MATERIALS AND METHODS: H. pylori was cultured from 13 Lithuanians belonging to six families, and characterized by arbitrarily primed PCR (RAPD) DNA fingerprinting, and by hybridization and PCR tests for polymorphic virulence-associated and neutral genetic markers. RESULTS: Eleven distinct strains were identified: seven carried the cag pathogenicity island (PAI) and the s1 (generally toxigenic) allele of the vacuolating cytotoxin gene (vacA); the other four were cag- and carried the vacA s2 (nontoxigenic) allele; five of the seven vacA s1 strains carried an m1 middle region allele of vacA, whereas all other strains carried m2 alleles, which are generally less toxigenic; four strains carried the virulence-associated iceA1 gene, and the other seven carried the completely unrelated iceA2 gene at the same locus. Insertion sequences IS605 and IS606 and a plasmid replication gene (repA) were also found in some strains. RAPD fingerprinting identified a mixed infection in just one of the 13 persons. In two families, two of the members harbored the same strain, whereas in the other four families each member tested carried a different strain. Resistance to metronidazole (Mtz) was found in two persons; each of them also carried MtzS strains that were indistinguishable from the coresident MtzR strain by RAPD fingerprinting, and that were thus closely related in overall genotype. CONCLUSION: The distribution of genotypes of Lithuanian H. pylori strains resembles that seen in Western Europe. This finding has important implications for understanding modes of H. pylori transmission and evolution.