| 1. |
|
|
| 2. |
- Ercan, Ayse Bahar, et al.
(författare)
-
Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.
- 2024
-
Ingår i: The Lancet. Oncology. - 1474-5488. ; 25:5, s. 668-682
-
Tidskriftsartikel (refereegranskat)abstract
- Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD.In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries. Clinical data were extracted from the IRRDC database, medical records, and physician-completed case record forms. The primary objective was to describe the clinical features, cancer spectrum, and biology of the condition. Secondary objectives included estimations of cancer incidence and of the impact of the specific mismatch-repair gene and genotype on cancer onset and survival, including after cancer surveillance and immunotherapy interventions.We analysed data from 201 patients (103 males, 98 females) enrolled between June 5, 2007 and Sept 9, 2022. Median age at diagnosis of CMMRD or a related cancer was 8·9 years (IQR 5·9-12·6), and median follow-up from diagnosis was 7·2 years (3·6-14·8). Endogamy among minorities and closed communities contributed to high homozygosity within countries with low consanguinity. Frequent dermatological manifestations (117 [93%] of 126 patients with complete data) led to a clinical overlap with neurofibromatosis type 1 (35 [28%] of 126). 339 cancers were reported in 194 (97%) of 201 patients. The cumulative cancer incidence by age 18 years was 90% (95% CI 80-99). Median time between cancer diagnoses for patients with more than one cancer was 1·9 years (IQR 0·8-3·9). Neoplasms developed in 15 organs and included early-onset adult cancers. CNS tumours were the most frequent (173 [51%] cancers), followed by gastrointestinal (75 [22%]), haematological (61 [18%]), and other cancer types (30 [9%]). Patients with CNS tumours had the poorest overall survival rates (39% [95% CI 30-52] at 10 years from diagnosis; log-rank p<0·0001 across four cancer types), followed by those with haematological cancers (67% [55-82]), gastrointestinal cancers (89% [81-97]), and other solid tumours (96% [88-100]). All cancers showed high mutation and microsatellite indel burdens, and pathognomonic mutational signatures. MLH1 or MSH2 variants caused earlier cancer onset than PMS2 or MSH6 variants, and inferior survival (overall survival at age 15 years 63% [95% CI 55-73] for PMS2, 49% [35-68] for MSH6, 19% [6-66] for MLH1, and 0% for MSH2; p<0·0001). Frameshift or truncating variants within the same gene caused earlier cancers and inferior outcomes compared with missense variants (p<0·0001). The greater deleterious effects of MLH1 and MSH2 variants as compared with PMS2 and MSH6 variants persisted despite overall improvements in survival after surveillance or immune checkpoint inhibitor interventions.The very high cancer burden and unique genomic landscape of CMMRD highlight the benefit of comprehensive assays in timely diagnosis and precision approaches toward surveillance and immunotherapy. These data will guide the clinical management of children and patients who survive into adulthood with CMMRD.The Canadian Institutes for Health Research, Stand Up to Cancer, Children's Oncology Group National Cancer Institute Community Oncology Research Program, Canadian Cancer Society, Brain Canada, The V Foundation for Cancer Research, BioCanRx, Harry and Agnieszka Hall, Meagan's Walk, BRAINchild Canada, The LivWise Foundation, St Baldrick Foundation, Hold'em for Life, and Garron Family Cancer Center.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Ahmad, Alia
(författare)
-
Community Management of inland Fisheries in India and Bangladesh
- 2009
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- Inland fisheries have the characteractics of common-pool resources such as joint consumption and subtractability of resource flows. This creates problems of management either by state authorities or private owners. In recent years, community-based fisheries management projects have become widespread in developing countries and shown considerable success. This book deals with community-based fisheries management (CBFM) in Bangladesh and a fisher cooperative (TMS) in Madhya Pradesh, India. It focuses on the impact of community management on efficiency in resource use, well-being of the poor and sustainability of the resource base.It further investiges the role of external agents in promoting sustainable community institutions.
|
|
| 9. |
|
|
| 10. |
- Ahmad, Alia
(författare)
-
Decentralized Provision of Primary Healthcare in Rural Bangladesh: a study of government facilities
- 2007
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Bangladesh has made significant progress in health indicators in recent years in spite of her low level of income. This is mainly due to the commitment of the state supported by donors in providing preventive care with respect to child health and family planning. However, there are serious problems related to both access and quality of curative care that hurt the poor most. Infrastructures for service delivery exist at local level in rural areas but they function inefficiently. This paper deals with the systemic weaknesses of decentralized service provision of primary healthcare in Bangladesh and focuses on accountability links between different actors and functions of delegation, finance, performance, information and enforcement. The study is based on facility- and household-based data collected during 2005 in Khulna Division. The main findings of the study are: the health system in rural areas represents deconcentration rather than decentralization of central government functions where inter-sectoral discipline works poorly; local health providers are not accountable to local government, and poor citizens/clients are neither aware of their rights nor are capable of expressing their needs as effective channels do not exist.
|
|
