Physician reported treatment patterns and outcomes in metastatic bladder cancer in the USA: the CancerMPact® Survey 2020.

Aim: This study assessed physician-reported treatment patterns for metastatic bladder cancer. Materials & methods: A total of 106 USA-based physicians were surveyed in 2020 using the CancerMPact® online survey. Results: Among cisplatin-eligible patients, 86.1% received first-line (1L) platinum-containing chemotherapy, most commonly cisplatin plus gemcitabine, and 9.8% received immune checkpoint inhibitor monotherapy. Among cisplatin-ineligible patients, 46.5% received 1L platinum-containing chemotherapy, most commonly carboplatin plus gemcitabine and 46.2% received 1L immune checkpoint inhibitor therapy. Approximately 44% of patients who received 1L treatment received second-line (2L) therapy after progression. Conclusion: Platinum-containing chemotherapy was the most widely reported 1L treatment approach. A high proportion of patients received no 2L therapy. Validation in an updated dataset is warranted following the practice-changing approvals of avelumab 1L maintenance and additional 2L options.

In 2020, researchers surveyed 106 US doctors about how they treated people with advanced bladder cancer. Cisplatin, a chemotherapy drug, was the most common first treatment that was given to patients with advanced bladder cancer. For people who were unable to receive cisplatin, doctors preferred to prescribe a similar chemotherapy drug called carboplatin or an immunotherapy drug. Immunotherapies help the body's immune system to fight cancer cells. Most people treated by the surveyed doctors did not receive a second treatment if their cancer got worse. New treatments are now available for bladder cancer, such as the immunotherapy, avelumab. Avelumab is given after chemotherapy to try and stop the cancer from getting worse or coming back. More research is needed to further understand how bladder cancer is treated.

Treatment patterns in metastatic bladder cancer in Japan: results of the CancerMPact® survey 2020.

Aim: To assess physician-reported treatment of metastatic bladder cancer in Japan. Methods: 76 physicians completed the CancerMPact® survey in July 2020, considering patients treated within 6 months. Results: Physicians treated a mean of 38.1 patients per month. Of cisplatin-eligible and -ineligible patients, 97.6 and 89.3%, respectively, received first-line platinum-based therapy, most commonly cisplatin plus gemcitabine (72.9%) and carboplatin plus gemcitabine (59.7%). 1.6 and 5.6% received first-line immune checkpoint inhibitors, respectively. 48.4 and 45.0%, respectively, progressed and received second-line therapy, most commonly with pembrolizumab (61.7%). Conclusion: In 2020, most patients with metastatic bladder cancer in Japan received first-line platinum-based chemotherapy; however, >50% received no subsequent treatment, highlighting the need for new treatment regimens to improve outcomes and maximize first-line treatment benefits.

In 2020, researchers surveyed 76 Japanese doctors who specialized in bladder and urinary system disorders about how they treated people with bladder cancer. Cisplatin, a type of chemotherapy drug, was the most common first treatment. For people who were unable to receive cisplatin, doctors often prescribed a similar chemotherapy drug called carboplatin. Just under half of the people received a second treatment for their cancer. New treatments are now available for bladder cancer, including the immunotherapy drug avelumab, which is given to people whose cancer stops growing or shrinks with their first chemotherapy treatment. More research is needed to better understand how bladder cancer is treated in Japan, including how new treatments are used.

Factors associated with the intensity of liver fibrosis in renal transplant patients with hepatitis B virus infection.

BACKGROUND: Hepatitis B may show a more aggressive course after kidney transplantation, but the factors associated with the progression of fibrosis in this group have not been identified. OBJECTIVES: To determine the influence of hepatitis B virus (HBV) viral load and host-related factors on the progression of hepatic fibrosis in hepatitis B virus-infected renal transplant recipients. PATIENTS AND METHODS: Renal transplant patients positive for HBV surface antigen (HBsAg) and submitted to a liver biopsy because of evidence of viral replication were included. Patients with advanced fibrosis (METAVIR F3-F4) were compared with patients with mild fibrosis (F0-F2) regarding sex, age, estimated time since infection, post-transplant time, donor type, history of renal transplantation, alanine aminotransferase, anti-hepatitis C virus, HBeAg and quantitative hepatitis B virus-DNA. Logistic regression analysis was applied to identify variables independently associated with more advanced fibrosis. RESULTS: Fifty-five patients (75% men, 41+/-11 years) with a mean post-transplant time of 5+/-4 years were included. HBeAg was detected in 67% of the patients and anti-hepatitis C virus in 35%. The median hepatitis B virus-DNA level was 2.8 x 10(8) copies/ml. Seventeen (31%) patients had advanced fibrosis. Using logistic regression analysis, the only variable that showed an independent association with more advanced stages of fibrosis was post-transplant time (P=0.03, odds ratio: 1.2, 95% confidence interval: 1.02-1.45). CONCLUSION: Hepatitis B virus viral load, although very high, and hepatitis B virus/hepatitis C virus coinfection are not related to the intensity of liver fibrosis in renal transplant patients infected with hepatitis B virus. Post-transplant time was the only factor independently associated with more advanced liver fibrosis, suggesting the influence of immunosuppression on the progression of liver disease in these patients.

Telethonin protein expression in neuromuscular disorders.

Telethonin is a 19-kDa sarcomeric protein, localized to the Z-disc of skeletal and cardiac muscles. Mutations in the telethonin gene cause limb-girdle muscular dystrophy type 2G (LGMD2G). We investigated the sarcomeric integrity of muscle fibers in LGMD2G patients, through double immunofluorescence analysis for telethonin with three sarcomeric proteins: titin, alpha-actinin-2, and myotilin and observed the typical cross striation pattern, suggesting that the Z-line of the sarcomere is apparently preserved, despite the absence of telethonin. Ultrastructural analysis confirmed the integrity of the sarcomeric architecture. The possible interaction of telethonin with other proteins responsible for several forms of neuromuscular disorders was also analyzed. Telethonin was clearly present in the rods in nemaline myopathy (NM) muscle fibers, confirming its localization to the Z-line of the sarcomere. Muscle from patients with absent telethonin showed normal expression for the proteins dystrophin, sarcoglycans, dysferlin, and calpain-3. Additionally, telethonin showed normal localization in muscle biopsies from patients with LGMD2A, LGMD2B, sarcoglycanopathies, and Duchenne muscular dystrophy (DMD). Therefore, the primary deficiency of calpain-3, dysferlin, sarcoglycans, and dystrophin do not seem to alter telethonin expression.

Investigation of 15q11-q13, 16p11.2 and 22q13 CNVs in autism spectrum disorder Brazilian individuals with and without epilepsy.

Copy number variations (CNVs) are an important cause of ASD and those located at 15q11-q13, 16p11.2 and 22q13 have been reported as the most frequent. These CNVs exhibit variable clinical expressivity and those at 15q11-q13 and 16p11.2 also show incomplete penetrance. In the present work, through multiplex ligation-dependent probe amplification (MLPA) analysis of 531 ethnically admixed ASD-affected Brazilian individuals, we found that the combined prevalence of the 15q11-q13, 16p11.2 and 22q13 CNVs is 2.1% (11/531). Parental origin could be determined in 8 of the affected individuals, and revealed that 4 of the CNVs represent de novo events. Based on CNV prediction analysis from genome-wide SNP arrays, the size of those CNVs ranged from 206 kb to 2.27 Mb and those at 15q11-q13 were limited to the 15q13.3 region. In addition, this analysis also revealed 6 additional CNVs in 5 out of 11 affected individuals. Finally, we observed that the combined prevalence of CNVs at 15q13.3 and 22q13 in ASD-affected individuals with epilepsy (6.4%) was higher than that in ASD-affected individuals without epilepsy (1.3%; p<0.014). Therefore, our data show that the prevalence of CNVs at 15q13.3, 16p11.2 and 22q13 in Brazilian ASD-affected individuals is comparable to that estimated for ASD-affected individuals of pure or predominant European ancestry. Also, it suggests that the likelihood of a greater number of positive MLPA results might be found for the 15q13.3 and 22q13 regions by prioritizing ASD-affected individuals with epilepsy.

Padrões de tratamento, uso de recursos e custo do câncer de pulmão de não pequenas células avançado em instituições brasileiras privadas / Treatment patterns, resource use and cost-of-illness of advanced non-small lung cancer in Brazilian private institutions

Objetivo: No Brasil, dados clínicos e custos econômicos do câncer de pulmão de não pequenas células (CPNPC) são escassos. Portanto, conduzimos este estudo para coletar dados de mundo real sobre padrões de tratamento e uso de recursos para CPNPC avançado (CPNPCa) em pacientes em instituições privadas brasileiras. Métodos: Coletamos dados de prontuários de seis instituições privadas no Brasil. Os pacientes elegíveis tinham diagnóstico de CPNPC avançado ou recorrente (estágios IIIB e IV) entre janeiro de 2011 e julho de 2014, e haviam recebido pelo menos duas linhas de quimioterapia. Dados foram resumidos usando estatísticas descritivas e os custos foram estimados pela abordagem bottom-up. Resultados: Dos 430 pacientes selecionados, 152 foram elegíveis para coleta de dados. A idade mediana dos pacientes foi de 62 anos e 55,9% eram do sexo masculino. Entre os pacientes, 57,2% e 31,6% receberam três e quatro linhas de tratamento, respectivamente. Dezesseis e vinte regimes foram utilizados como tratamentos de primeira e segunda linha. Bevacizumabe carboplatina + paclitaxel (n = 32; 21,1%) foi o mais frequente na primeira linha, enquanto docetaxel isolado (n = 36; 23,7%) foi o regime mais comum de segunda linha. Hospitalizações e visitas ao pronto-socorro foram registradas em 52% e 25% dos pacientes, respectivamente. O custo total da coorte foi de R$ 47.692.195,1 (US$ 14.803.425,4). Conclusões: Os padrões de tratamento para pacientes com CPNPCa em instituições privadas brasileiras são heterogêneos. O alto uso e custos de recursos observados entre os pacientes da CPNPCa têm um impacto econômico significativo para o sistema de saúde privado brasileiro.

Objective: In Brazil, data on clinical and economic burden of non-small cell lung cancer (NSCLC) are scarce. Therefore, we conducted this study to gather real-world data on treatment patterns and resource use for advanced NSCLC (aNSCLC) patients in Brazilian private institutions. Methods: We collected data from medical charts from six private institutions in Brazil. Eligible patients were diagnosed with advanced or recurrent NSCLC (stages IIIB and IV) between January 2011 and July 2014, and had received at least two lines of chemotherapy. Data were summarized using descriptive statistics and costs estimated by bottom-up approach. Results: Out of 430 charts screened, 152 were eligible for data collection. Patients' median age was 62 years, 55.9% were male. Among patients, 57.2% and 31.6% had received three and four treatment lines, respectively. Sixteen and twenty regimens were used as first and second-line treatments, respectively. Bevacizumab + carboplatin + paclitaxel (n = 32; 21.1%) was the most frequent first-line regimens, while docetaxel (n = 36; 23.7%) the most common second-line regimen. Hospitalizations and ER visits were recorded from 52% and 25% of the patients, respectively. Total cohort costs were R$ 47,692,195.1 (US$ 14,803,425.4). Conclusions: Treatment patterns for patients with aNSCLC in Brazilian private institutions are heterogeneous. The observed high resource use and costs among aNSCLC patients have a significant economic impact to the Brazilian private healthcare system.