Novel mutations in the BRCA1 and BRCA2 genes in Iranian women with early-onset breast cancer

BACKGROUND: Breast cancer is the most common female malignancy and a major cause of death in middle-aged women. So far, germline mutations in the BRCA1 and BRCA2 genes in patients with early-onset breast and/or ovarian cancer have not been identified within the Iranian population. METHODS: With the collaboration of two main centres for cancer in Iran, we obtained clinical information, family history and peripheral blood from 83 women under the age of 45 with early-onset breast cancer for scanning of germline mutations in the BRCA1 and BRCA2 genes. We analysed BRCA1 exons 11 and BRCA2 exons 10 and 11 by the protein truncation test, and BRCA1 exons 2, 3, 5, 13 and 20 and BRCA2 exons 9, 17, 18 and 23 with the single-strand conformation polymorphism assay on genomic DNA amplified by polymerase chain reaction. RESULTS: Ten sequence variants were identified: five frameshifts (putative mutations – four novel); three missense changes of unknown significance and two polymorphisms, one seen commonly in both Iranian and British populations. CONCLUSIONS Identification of these novel mutations suggests that any given population should develop a mutation database for its programme of breast cancer screening. The pattern of mutations seen in the BRCA genes seems not to differ from other populations studied. Early-onset breast cancer (less than 45 years) and a limited family history is sufficient to justify mutation screening with a detection rate of over 25% in this group, whereas sporadic early-onset breast cancer (detection rate less than 5%) is unlikely to be cost-effective

Fifteen-minute consultation: public health for paediatricians-adolescent public health

Paediatricians have a key role to play in ensuring a holistic, integrated approach is taken to meeting adolescent health needs. There is increasing evidence that failure to do so can lead to poor healthcare experience, avoidable ill health and increased need for healthcare services, both in the short term and in adult life. This article aims to guide paediatricians in answering the questions 'How well are the public health and clinical needs of the adolescent population in my area being met? And how can we improve?

Mutation analysis of BRCA1 and BRCA2 genes in Iranian high risk breast cancer families

Background: Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal stability leading to cellular immortalization. Telomerase has been associated with negative prognostic indicators in some studies. The present study aims to detect any association between telomerase sub-units: hTERT and hTR and the prognostic indicators including tumour's size and grade, nodal status and patient's age. Methods: Tumour samples from 46 patients with primary invasive breast cancer and 3 patients with benign tumours were collected. RT-PCR analysis was used for the detection of hTR, hTERT, and PGM1 (as a housekeeping) genes expression. Results: The expression of hTR and hTERT was found in 31(67.4%) and 38 (82.6%) samples respectively. We observed a significant association between hTR gene expression and younger age at diagnosis (p = 0.019) when comparing patients ≤ 40 years with those who are older than 40 years. None of the benign tumours expressed hTR gene. However, the expression of hTERT gene was revealed in 2 samples. No significant association between hTR and hTERT expression and tumour's grade, stage and nodal status was seen. Conclusion: The expression of hTR and hTERT seems to be independent of tumour's stage. hTR expression probably plays a greater role in mammary tumourogenesis in younger women (≤ 40 years) and this may have therapeutic implications in the context of hTR targeting strategies

Experience of primary care services among early adolescents in England and association with health outcomes

This document is the Accepted Manuscript version of the following article: Arrash A. Yassaee, Dougal S. Hargreaves, Kayleigh Chester, Stephanie Lamb, Ann Hagell, and Fiona Brooks, Experience of Primary Care Services Among Early Adolescents in England and Associated with Health Outcomes, Journal of Adolescent Health, Vol. 60 (4): 388-394, first published 1 December 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ The version of record is available online at doi: http://dx.doi.org/10.1016/j.jadohealth.2016.09.22 © 2016 Society for Adolescent Health and Medicine. All rights reserved.Purpose The aim of this study was to investigate adolescents' (11–15 years) experience of their general practitioner (GP), whether poor reported GP experience was associated with worse physical and mental health measures and whether poor previous GP experience was linked to lower utilization of these services. Methods We used logistic regression to analyze data from the 2014 Health Behaviour in School-aged Children study. Four aspects of recent care experience were studied: feeling at ease, feeling treated with respect, satisfaction with doctor's explanation, and feeling able to discuss personal matters. Five dichotomized measures of health status were used: ever self-harmed; fair or poor self-reported health; frequent (at least weekly) low mood; sleeping problems; or headaches. Results Of 5,335 students, 4,149 reported having visiting their GP within the past year. Of these, 91.8% felt treated with respect, 78.7% felt at ease, 85.7% were satisfied with explanation, and 53.9% felt able to discuss personal matters. After adjusting for ethnicity, age, gender, and family affluence score, poor experience on any indicator was strongly associated with increased risk of self-harm (adjusted odds ratio range, 2.01–2.70; all p < .001); feeling low (AOR range, 1.53–2.11; all p < .001); and sleeping problems (AOR range, 1.49–1.91; all p ≤ .001). Poor experience on all indicators, except discussing personal matters, was associated with worse self-reported health. Conclusions Nearly half of this large, national study of adolescents did not feel able to discuss personal matters with their doctor. There was a consistent, strong association between reported lack of good GP experience and poor health measures.Peer reviewedFinal Accepted Versio

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Gene Assembling: a New Approach in Molecular Diagnosis of Hereditary Breast Cancer

Background:Many disease susceptibility genes are large and consist of many exons in which point mutations are scattered throughout. Scanning each exon individually represents a tedious task which can be time consuming and expensive. There has been increasing demand for rapid and accurate methods for full scanning of unknown point mutations in large multi-exon genes.Gene Assembling is a new method for creating chimeric DNA molecules using a modified PCR reaction that allows maximizing the length of sequence that can be scanned by sensitive downstream technique.Methods:In the present study assembling of exons 2,20,23 and 24 of the BRCA1 gene and their subsequent analysis by direct sequencing is demonstrated. The BRCA1 exons 2 and 20 are hot spot regions that are known to harbor particularly deleterious mutations. In order to avoid missing any mutation in these two exons, the four exons previously mentioned were assembled in the following order of preferences: 23, 20, 2 and 24. However, the order of fragments can be predetermined by primer design. Results: The order and sequence of the component exons in the gene-assembled products were characterized by direct sequencing as predicted. Gene-assembled products from three previously ascertained heterozygotes for BRCA1 mutations were directly sequenced and gave the same sequence patterns.Conclusion:This experience suggests that Gene Assembling technique could be applied as a highly sensitive and cost-effective method in identifying mutation in complex genes such as BRCA and ColA1/2 helping clinical molecular diagnostic laboratories,to fulfill the demand for scanning complex genetic diseases at a lower cost

Use of Telemedicine in Pediatric Services for 4 Representative Clinical Conditions: Scoping Review

BackgroundTelemedicine is becoming routine in health care. Postpandemic, a universal return to face-to-face consultations may risk a loss of some of the advantages of telemedicine. However, rapid implementation and adoption without robust evaluation of usability, efficacy, and effectiveness could potentially lead to suboptimal health outcomes and downstream challenges to providers. ObjectiveThis review assesses telemedicine interventions against international guidance and sufficiency of evidence to support postpandemic utilization in pediatric settings. MethodsThis scoping review was performed following searches on PubMed, Embase, and CINAHL databases on April 15, 2021, and May 31, 2022, and examined studies focused on telemedicine, remote consultation, video call, or remote patient monitoring in children (0-18 years) receiving outpatient care for diabetes, asthma, epilepsy, or renal disease. Exclusion criteria included studies published before 2011 as the technologies used have likely been improved or replaced, studies in adult populations or where it was not possible to disaggregate data for participants younger than 18 years as the focus of the review was on pediatric care, and studies not published in English. Data were extracted by 4 authors, and the data were corroborated by a second reviewer. Studies were examined for feasibility and usability, clinical and process outcomes, and cost-effectiveness. ResultsOf the 3158 studies identified, 56 were suitable for final inclusion and analysis. Data on feasibility or usability of interventions (48 studies) were overwhelmingly positive in support of telemedicine interventions, with common themes including convenience, perceived cost savings, and ease of use. However, use in preference to usual care was rarely explored. Clinical and process outcome data (31 studies) were mostly positive. Across all studies, there was limited measurement of standardized clinical outcomes, although these were more commonly reported in asthma (peak flow) and diabetes (glycated hemoglobin [HbA1c]). Implementation science data generally supported cost-effectiveness of telemedicine with a reduction of health care costs. ConclusionsThere is promising evidence supporting telemedicine in pediatric settings. However, there is a lack of evaluation of telemedicine in comparison with usual outpatient care for noninferiority of clinical outcomes, and this review highlights the need for a more standardized approach to evaluation of digital interventions