Background: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for ...patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Delta 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Delta 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Delta 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion: With 35 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDES and DDFS with no new safety signals.
Background
Neurological complications, including peripheral polyneuropathy, have been reported in β-thalassemia patients that negatively impact their quality of life. Chronic hypoxia, iron overload, ...average age, and iron chelators-induced neurotoxicity might contribute to the development of neuropathy. However, the leading offender of this complication remains not clear. We aimed to study the frequency and potential risk factors of polyneuropathy in β-thalassemia patients. We performed a cross-section study on 150 transfusion-dependent β-thalassemia major patients with a mean age of 16.44 ± 3.32 years. We performed electrophysiological studies for motor and sensory nerves.
Results
We found that 31.3% of cases had neurological manifestations with significant relation to age, duration of the disease, and frequent transfusion. Out of 47 patients with neurological manifestations, 12 (25.5%) had abnormal nerve conduction velocity (NCV). Abnormal median, peroneal, and tibial nerve motor amplitudes were detected in 10.6%, 10.6%, and 14.9% of patients respectively. Abnormal median, peroneal, and sural nerve sensory amplitudes were detected in 4.3%, 2.2%, and 10.6% of patients respectively. Apart from a significant relation between abnormal NCV and older ages, no significant relation was detected with other studied clinical and laboratory parameters.
Conclusion
We detected a high frequency of motor and sensory polyneuropathy in B-thalassemia patients. Polyneuropathy was predominately detected in older ages highlighting that neuropathy in thalassemia patients is probably age-dependent. Other factors including disease duration, transfusion frequency, and iron overload might have a contributing effect, however, that could not be confirmed in this study. Further studies are needed to verify the frequency and predictors of polyneuropathy in B-thalassemia patients.
The burden of chronic kidney disease and associated risk of kidney failure are increasing in Africa. The management of people with chronic kidney disease is fraught with numerous challenges because ...of limitations in health systems and infrastructures for care delivery. From the third iteration of the International Society of Nephrology Global Kidney Health Atlas, we describe the status of kidney care in the ISN Africa region using the World Health Organization building blocks for health systems. We identified limited government health spending, which in turn led to increased out-of-pocket costs for people with kidney disease at the point of service delivery. The health care workforce across Africa was suboptimal and further challenged by the exodus of trained health care workers out of the continent. Medical products, technologies, and services for the management of people with nondialysis chronic kidney disease and for kidney replacement therapy were scarce due to limitations in health infrastructure, which was inequitably distributed. There were few kidney registries and advocacy groups championing kidney disease management in Africa compared with the rest of the world. Strategies for ensuring improved kidney care in Africa include focusing on chronic kidney disease prevention and early detection, improving the effectiveness of the available health care workforce (e.g., multidisciplinary teams, task substitution, and telemedicine), augmenting kidney care financing, providing quality, up-to-date health information data, and improving the accessibility, affordability, and delivery of quality treatment (kidney replacement therapy or conservative kidney management) for all people living with kidney failure.
Background Neurological complications, including peripheral polyneuropathy, have been reported in -thalassemia patients that negatively impact their quality of life. Chronic hypoxia, iron overload, ...average age, and iron chelators-induced neurotoxicity might contribute to the development of neuropathy. However, the leading offender of this complication remains not clear. We aimed to study the frequency and potential risk factors of polyneuropathy in -thalassemia patients. We performed a cross-section study on 150 transfusion-dependent -thalassemia major patients with a mean age of 16.44 ± 3.32 years. We performed electrophysiological studies for motor and sensory nerves. Results We found that 31.3% of cases had neurological manifestations with significant relation to age, duration of the disease, and frequent transfusion. Out of 47 patients with neurological manifestations, 12 (25.5%) had abnormal nerve conduction velocity (NCV). Abnormal median, peroneal, and tibial nerve motor amplitudes were detected in 10.6%, 10.6%, and 14.9% of patients respectively. Abnormal median, peroneal, and sural nerve sensory amplitudes were detected in 4.3%, 2.2%, and 10.6% of patients respectively. Apart from a significant relation between abnormal NCV and older ages, no significant relation was detected with other studied clinical and laboratory parameters. Conclusion We detected a high frequency of motor and sensory polyneuropathy in B-thalassemia patients. Polyneuropathy was predominately detected in older ages highlighting that neuropathy in thalassemia patients is probably age-dependent. Other factors including disease duration, transfusion frequency, and iron overload might have a contributing effect, however, that could not be confirmed in this study. Further studies are needed to verify the frequency and predictors of polyneuropathy in B-thalassemia patients.
Recent studies have suggested that Epstein-Barr virus (EBV) may play a role in the aetiology of Hodgkin's disease. To determine the role of EBV in childhood Hodgkin's disease in different ...geographical areas, immunohistochemical staining and in situ hybridisation were used to analyse latent membrane protein 1 (LMP 1) and small nuclear non-transcribed RNAs (EBER-1) respectively. Testing for EBV within the Reed-Sternberg and Hodgkin's cells was carried out in childhood Hodgkin's disease from 10 different countries. The proportion of LMP 1 positive cases varied significantly, being 50% of cases from the United Kingdom (38/75), South Africa (9/18), Egypt (7/14), and Jordan (8/16), 60% from the United Arab Emirates (6/10), 70% from Australia (11/16), 81% from Costa Rica (34/42), 88% from Iran (7/8), 90% from Greece (20/22), and 100% of the 56 cases from Kenya. A sensitive polymerase chain reaction based EBV strain typing technique was established using archival tissues. EBV strain type 1 was shown to be predominant in childhood Hodgkin's disease from the United Kingdom, South Africa, Australia, and Greece. Type 2 was predominant in Egypt. EBV strain types 1 and 2 were both detected in some cases of childhood Hodgkin's disease in the United Kingdom, Costa Rica, and Kenya. The high incidence of EBV and the presence especially in developing countries of dual infection with both strain types 1 and 2 may reflect socioeconomic conditions leading to malnutrition induced immunological impairment. The possibility of HIV infection also needs to be explored.
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