Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Clustering schizophrenia genes by their temporal expression patterns aids functional interpretation

Background Schizophrenia is a highly heritable brain disorder with a typical symptom onset in early adulthood. The 2-hit hypothesis posits that schizophrenia results from differential early neurodevelopment, predisposing an individual, followed by a disruption of later brain maturational processes that trigger the onset of symptoms. Study design We applied hierarchical clustering to transcription levels of 345 genes previously linked to schizophrenia, derived from cortical tissue samples from 56 donors across the lifespan. We subsequently calculated clustered-specific polygenic risk scores for 743 individuals with schizophrenia and 743 sex- and age-matched healthy controls. Study results Clustering revealed a set of 183 genes that was significantly upregulated prenatally and downregulated postnatally and 162 genes that showed the opposite pattern. The prenatally upregulated set of genes was functionally annotated to fundamental cell cycle processes, while the postnatally upregulated set was associated with the immune system and neuronal communication. We found an interaction between the 2 scores; higher prenatal polygenic risk showed a stronger association with schizophrenia diagnosis at higher levels of postnatal polygenic risk. Importantly, this finding was replicated in an independent clinical cohort of 3233 individuals. Conclusions We provide genetics-based evidence that schizophrenia is shaped by disruptions of separable biological processes acting at distinct phases of neurodevelopment. The modeling of genetic risk factors that moderate each other’s effect, informed by the timing of their expression, will aid in a better understanding of the development of schizophrenia

Eficiency and tolerance of olanzapina vs risperidona and tipical antipsicotics study of 3 years

Objetivo: evaluar los resultados de salud y los costos relacionados con los antipsicóticos disponibles, con énfasis en la olanzapina, en entornos ambulatorios naturalistas. Métodos: 572 pacientes con esquizofrenia (CIE-10 o DSM-IV) que iniciaron o cambiaron a un antipsicótico oral se inscribieron en bloques de diez: 5 pacientes para olanzapina y 5 para otro antipsicótico, según prescripción en ese momento. La eficacia se midió mediante el cambio medio en la puntuación en la Escala de Impresión Clínica Global de Severidad de la Enfermedad (GCI-S). La "respuesta clínica" se definió como la disminución ≥ "2 puntos en el GCI-S si la puntuación inicial era ≥" 4 y la disminución ≥ "1 si la línea base era ≤" 3. "Mínimamente sintomático" se definió como alcanzar una puntuación de 1 o 2 en el GCI-S después de la línea de base. Se registraron los eventos adversos resultantes del tratamiento, junto con el uso de cualquier medicación concomitante y las causas de interrupción de la medicación. Resultados: La Región Andina del SOHO inscribió a 272, 97 y 65 pacientes en monoterapia con olanzapina, antipsicóticos típicos (TA) y risperidona respectivamente. Tanto la olanzapina como la risperidona fueron más eficaces que la AT para mejorar los síntomas generales, positivos y negativos a los 12, 24 y 36 meses, pero solo la olanzapina mostró una diferencia estadísticamente significativa frente a la AT en los síntomas depresivos y cognitivos. Menos pacientes que recibieron olanzapina desarrollaron síntomas extrapiramidales (SEP) y eventos sexuales adversos. Los pacientes tratados con olanzapina demostraron la tasa más baja de discinesia tardía a los 3 años. Más pacientes que recibieron olanzapina aumentaron de peso con una diferencia estadísticamente significativa frente a risperidona y TA. El aumento de peso medio con olanzapina fue de 5 kg y el mayor aumento se registró en los primeros 12 meses de tratamiento. Conclusiones: la olanzapina, pero no la risperidona, fue más efectiva que los típicos mejorando los síntomas depresivos y cognitivos con diferencia estadística. La olanzapina se toleró mejor en términos de EPS, discinesia tardía y deterioro de la función sexual. Se registró una mayor ganancia de peso con olanzapina; sin embargo, la tasa de interrupción debido a la intolerancia fue la más baja. Estos resultados apoyan los mayores beneficios de Atypicals en términos de efectividad y tolerabilidad. © INNN, 2007. Conclusiones: la olanzapina, pero no la risperidona, fue más efectiva que los típicos mejorando los síntomas depresivos y cognitivos con diferencia estadística. La olanzapina se toleró mejor en términos de EPS, discinesia tardía y deterioro de la función sexual. Se registró una mayor ganancia de peso con olanzapina; sin embargo, la tasa de interrupción debido a la intolerancia fue la más baja. Estos resultados apoyan los mayores beneficios de Atypicals en términos de efectividad y tolerabilidad. © INNN, 2007. Conclusiones: la olanzapina, pero no la risperidona, fue más efectiva que los típicos mejorando los síntomas depresivos y cognitivos con diferencia estadística. La olanzapina se toleró mejor en términos de EPS, discinesia tardía y deterioro de la función sexual. Se registró una mayor ganancia de peso con olanzapina; sin embargo, la tasa de interrupción debido a la intolerancia fue la más baja. Estos resultados apoyan los mayores beneficios de Atypicals en términos de efectividad y tolerabilidad.Objective: to evaluate the health results and the costs related to the available antipsychotics, with emphasis on olanzapine, in naturalistic outpatient settings. Methods: 572 patients with schizophrenia (ICD-10 or DSM-IV) who began or changed to an oral, antipsychotic were enrolled in blocks of ten: 5 patients for olanzapine and 5 for another antipsychotic, according to the prescription at that time. The effectiveness was measured by the mean change in score on the Global Clinical Impression of Severity of illness Scale (GCI-S). "Clinical response" was defined as the decrease ≥" 2 points on the GCI-S if the baseline score was ≥" 4 and the decrease ≥" 1 if the baseline was ≤" 3. "Minimally symptomatic" was defined as reaching a score of 1 or 2 on the GCI-S after the baseline. Adverse events resulting from the treatment were recorded, along with the use of any concomitant medication and the causes of discontinuation of the medication. Results: The SOHO Andean Region enrolled 272, 97 and 65 patients in monotherapy with olanzapine, typical antipsychotics (TA) and risperidone respectively. Both olanzapine and risperidone were more effective than the TA in improving the general, positive and negative symptoms at 12, 24, and 36 months, but only olanzapine showed a statistically significant difference vs TA in depressive and cognitive symptoms. Less patients on olanzapine developed extrapyramidal symptoms (EPS) and adverse sexual events. The patients on olanzapine demonstrated the lowest rate of tardive dyskinesia at 3 years. More patients on olanzapine gained weight with a statistically significant difference vs risperidone and TA. The mean weight gain with olanzapine was 5 kg and the greatest increase was recorded in the first 12 months of treatment. Conclusions: olanzapine, but not risperidone, was more effective than typicals improving depressive and cognitive symptoms with statistical difference. Olanzapine was better tolerated in terms of EPS, tardive dyskinesia and sexual function impairment. A greater weight gain was recorded with olanzapine; however, the discontinuation rate due to intolerability was the lowest. These results support the greater benefits of Atypicals in terms of effectiveness and tolerability

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

Background: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial

Membro del gruppo collaborativo della ricerca pubblicata su "Lancet" 374(9692):796-80