Jewish cultural and religious factors and uptake of population-based BRCA testing across denominations: a cohort study.

OBJECTIVE: To evaluate the association of Jewish cultural and religious identity and denominational affiliation with interest in, intention to undertake and uptake of population-based BRCA (Breast Cancer Gene)-testing. DESIGN: Cohort-study set within recruitment to GCaPPS-trial (ISRCTN73338115). SETTING: London Ashkenazi-Jewish (AJ) population. POPULATION OR SAMPLE: AJ men and women, >18 years. METHODS: Participants were self-referred, and attended recruitment clinics (clusters) for pre-test counselling. Subsequently consenting individuals underwent BRCA testing. Participants self-identified to one Jewish denomination: Conservative/Liberal/Reform/Traditional/Orthodox/Unaffiliated. Validated scales measured Jewish Cultural-Identity (JI) and Jewish Religious-identity (JR). Four-item Likert-scales analysed initial 'interest' and 'intention to test' pre-counselling. Item-Response-Theory and graded-response models, modelled responses to JI and JR scales. Ordered/multinomial logistic regression modelling evaluated association of JI-scale, JR-scale and Jewish Denominational affiliation on interest, intention and uptake of BRCA testing. MAIN OUTCOME MEASURES: Interest, intention, uptake of BRCA testing. RESULTS: In all, 935 AJ women/men of mean age = 53.8 (S.D = 15.02) years, received pre-test education and counselling through 256 recruitment clinic clusters (median cluster size = 3). Denominational affiliations included Conservative/Masorti = 91 (10.2%); Liberal = 82 (9.2%), Reform = 135 (15.1%), Traditional = 212 (23.7%), Orthodox = 239 (26.7%); and Unaffiliated/Non-practising = 135 (15.1%). Overall BRCA testing uptake was 88%. Pre-counselling, 96% expressed interest and 60% intention to test. JI and JR scores were highest for Orthodox, followed by Conservative/Masorti, Traditional, Reform, Liberal and Unaffiliated Jewish denominations. Regression modelling showed no significant association between overall Jewish Cultural or Religious Identity with either interest, intention or uptake of BRCA testing. Interest, intention and uptake of BRCA testing was not significantly associated with denominational affiliation. CONCLUSIONS: Jewish religious/cultural identity and denominational affiliation do not appear to influence interest, intention or uptake of population-based BRCA testing. BRCA testing was robust across all Jewish denominations. TWEETABLE ABSTRACT: Jewish cultural/religious factors do not affect BRCA testing, with robust uptake seen across all denominational affiliations.

Attitudes towards risk-reducing early salpingectomy with delayed oophorectomy for ovarian cancer prevention: a cohort study.

OBJECTIVE: To determine risk-reducing early salpingectomy and delayed oophorectomy (RRESDO) acceptability and effect of surgical prevention on menopausal sequelae/satisfaction/regret in women at increased ovarian cancer (OC) risk. DESIGN: Multicentre, cohort, questionnaire study (IRSCTN:12310993). SETTING: United Kingdom (UK). POPULATION: UK women without OC ≥18 years, at increased OC risk, with/without previous RRSO, ascertained through specialist familial cancer/genetic clinics and BRCA support groups. METHODS: Participants completed a 39-item questionnaire. Baseline characteristics were described using descriptive statistics. Logistic/linear regression models analysed the impact of variables on RRESDO acceptability and health outcomes. MAIN OUTCOMES: RRESDO acceptability, menopausal sequelae, satisfaction/regret. RESULTS: In all, 346 of 683 participants underwent risk-reducing salpingo-oophorectomy (RRSO). Of premenopausal women who had not undergone RRSO, 69.1% (181/262) found it acceptable to participate in a research study offering RRESDO. Premenopausal women concerned about sexual dysfunction were more likely to find RRESDO acceptable (odds ratio [OR] = 2.9, 95% CI 1.2-7.7, P = 0.025). Women experiencing sexual dysfunction after premenopausal RRSO were more likely to find RRESDO acceptable in retrospect (OR = 5.3, 95% CI 1.2-27.5, P < 0.031). In all, 88.8% (143/161) premenopausal and 95.2% (80/84) postmenopausal women who underwent RRSO, respectively, were satisfied with their decision, whereas 9.4% (15/160) premenopausal and 1.2% (1/81) postmenopausal women who underwent RRSO regretted their decision. HRT uptake in premenopausal individuals without breast cancer (BC) was 74.1% (80/108). HRT use did not significantly affect satisfaction/regret levels but did reduce symptoms of vaginal dryness (OR = 0.4, 95% CI 0.2-0.9, P = 0.025). CONCLUSION: Data show high RRESDO acceptability, particularly in women concerned about sexual dysfunction. Although RRSO satisfaction remains high, regret rates are much higher for premenopausal women than for postmenopausal women. HRT use following premenopausal RRSO does not increase satisfaction but does reduce vaginal dryness. TWEETABLE ABSTRACT: RRESDO has high acceptability among premenopausal women at increased ovarian cancer risk, particularly those concerned about sexual dysfunction.

Randomised trial of population-based BRCA testing in Ashkenazi Jews: long-term outcomes.

OBJECTIVE: Unselected population-based BRCA testing provides the opportunity to apply genomics on a population-scale to maximise primary prevention for breast-and-ovarian cancer. We compare long-term outcomes of population-based and family-history (FH)/clinical-criteria-based BRCA testing on psychological health and quality of life. DESIGN: Randomised controlled trial (RCT) (ISRCTN73338115) GCaPPS, with two-arms: (i) population-screening (PS); (ii) FH/clinical-criteria-based testing. SETTING: North London Ashkenazi-Jewish (AJ) population. POPULATION/SAMPLE: AJ women/men. METHODS: Population-based RCT (1:1). Participants were recruited through self-referral, following pre-test genetic counselling from the North London AJ population. INCLUSION CRITERIA: AJ women/men >18 years old; exclusion-criteria: prior BRCA testing or first-degree relatives of BRCA-carriers. INTERVENTIONS: Genetic testing for three Jewish BRCA founder-mutations: 185delAG (c.68_69delAG), 5382insC (c.5266dupC) and 6174delT (c.5946delT), for (i) all participants in PS arm; (ii) those fulfilling FH/clinical criteria in FH arm. Linear mixed models and appropriate contrast tests were used to analyse the impact of BRCA testing on psychological and quality-of-life outcomes over 3 years. MAIN OUTCOME MEASURES: Validated questionnaires (HADS/MICRA/HAI/SF12) used to analyse psychological wellbeing/quality-of-life outcomes at baseline/1-year/2-year/3-year follow up. RESULTS: In all, 1034 individuals (691 women, 343 men) were randomised to PS (n = 530) or FH (n = 504) arms. There was a statistically significant decrease in anxiety (P = 0.046) and total anxiety-&-depression scores (P = 0.0.012) in the PS arm compared with the FH arm over 3 years. No significant difference was observed between the FH and PS arms for depression, health-anxiety, distress, uncertainty, quality-of-life or experience scores associated with BRCA testing. Contrast tests showed a decrease in anxiety (P = 0.018), health-anxiety (P < 0.0005) and quality-of-life (P = 0.004) scores in both PS and FH groups over time. Eighteen of 30 (60%) BRCA carriers identified did not fulfil clinical criteria for BRCA testing. Total BRCA prevalence was 2.9% (95% CI 1.97-4.12%), BRCA1 prevalence was 1.55% (95% CI 0.89-2.5%) and BRCA2 prevalence was 1.35% (95% CI 0.74-2.26%). CONCLUSION: Population-based AJ BRCA testing does not adversely affect long-term psychological wellbeing or quality-of-life, decreases anxiety and could identify up to 150% additional BRCA carriers. TWEETABLE ABSTRACT: Population BRCA testing in Ashkenazi Jews reduces anxiety and does not adversely affect psychological health or quality of life.

The economic burden of tuberculosis and latent tuberculosis in people living with HIV in Brazil: a cost study from the patient perspective.

OBJECTIVE: The objective of this study was to evaluate the direct and indirect costs of tuberculosis (TB) (active and latent TB [LTB]) and HIV co-infection from the patient perspective. STUDY DESIGN: Costing study conducted alongside a pragmatic clinical trial. METHODS: The study was conducted in Brazil in a referral service for HIV/AIDS. We applied a standardised questionnaire to collect data about out-of-pocket expenses and indirect cost. The questionnaire was applied at every patient's appointment in the referral service after TB or LTB diagnosis. We followed all patients' pathways during the prediagnosis period and treatment period. For patients on sickness benefit due to TB/HIV, income loss was calculated as the difference between an employee's wages forgone and the sickness benefit received. The monetary value of the time loss was calculated based on the Brazilian minimum wage/2015. RESULTS: Among 239 people living with HIV recruited in the first year of the trial, 31 patients were included into the costing study, 26 patients who were diagnosed and treated for TB/HIV and five patients who were diagnosed and treated for LTB/HIV. TB/HIV patients incurred higher total costs than LTB/HIV (US$ 1,429 vs US$ 166). The main cost component for TB/HIV was indirect costs, especially income loss (US$ 749). CONCLUSIONS: Public health policies may address ways to prevent high patients' costs through the introduction of more accurate algorithms for TB diagnosis to prevent delays in the diagnosis and treatment.

Cost and logistics of alternative roll-out options for implementing human papillomavirus testing as a triage in cervical screening: results of the sentinel sites study.

BACKGROUND: Previous studies have indicated that human papillomavirus (HPV) testing as a triage for managing equivocal cytology is cost-effective. The aim of this study was to assess the costs of alternative roll-out options. METHODS: Detailed cost estimates were collected from six laboratories where HPV triage had been implemented. Costs were assessed for the two different service delivery models that were implemented; a 'hub and spoke model' of central HPV testing in a microbiology laboratory with separate cytology laboratories, and an 'integrated model' where HPV testing was conducted within the cytology laboratory. RESULTS: Comparison of alternative delivery models indicated that setting up HPV processing within existing cytology laboratory, i.e., an 'integrated cytology/HPV laboratory' generated savings in staff time amounting to between £2.54 and 4.86 per sample processed. Running full HPV testing batches was also an important consideration. For full batches to be run on a twice weekly basis requires having no more than two laboratories per Strategic Health Authority. CONCLUSIONS: To be cost-efficient, and to meet turn-around times, HPV testing needs to be conducted at integrated cytology/HPV testing centres with sufficient throughput to run full batches of HPV tests.

Women's preferences regarding options for management of atypical, borderline or low-grade cervical cytological abnormalities: a review of the evidence.

OBJECTIVES: To review the evidence on women's preferences for and valuation of alternative management pathways following identification of low-grade cytological abnormalities as part of routine cervical cancer screening. The aim was to identify empirical studies evaluating women's preferences regarding alternative management pathways and to compare the impact of alternative elicitation methods on results. METHODS: A systematic review of the literature was conducted using the online bibliographic information service PubMed database. Empirical studies were identified that elicited general preferences, utilities or valuations based on willingness to pay (WTP) with respect to management of low-grade cytology results. Data were extracted on the methodology used and the empirical results. RESULTS: Where quality of life data were elicited directly from patients that were undergoing management of low-grade abnormalities utilizing direct elicitation techniques such as WTP, general preference questionnaires and the Euroqol, the studies tended towards a preference in favour of HPV testing (and colposcopy referral if HPV positive) rather than repeat cytology. In contrast, where studies included the general population and presented hypothetical scenarios of treatment pathways, and explicitly tried to incorporate assessment of process utility, the evidence indicated a slight tendency to favour repeat cytology. CONCLUSION: Consideration of patient preferences in the management of low-grade cytology is important for designing screening protocols. The reviewed studies indicate that potentially different conclusions may be drawn depending on the elicitation methodology and selection of participants in the research.

MAVARIC - a comparison of automation-assisted and manual cervical screening: a randomised controlled trial.

OBJECTIVES: The principal objective was to compare automation-assisted reading of cervical cytology with manual reading using the histological end point of cervical intraepithelial neoplasia grade II (CIN2) or worse (CIN2+). Secondary objectives included (i) an assessment of the slide ranking facility of the Becton Dickinson (BD) FocalPoint™ Slide Profiler (Becton Dickinson, Franklin Lakes, NJ, USA), especially 'No Further Review', (ii) a comparison of the two approved automated systems, the ThinPrep® Imaging System (Hologic, Bedford, MA, USA) and the BD FocalPoint Guided Screener Imaging System, and (iii) automated versus manual in terms of productivity and cost-effectiveness. DESIGN: A 1 : 2 randomised allocation of slides to either manual reading or automation-assisted paired with manual reading. Cytoscreeners were blinded to whether samples would be read only manually or manually paired with automated. Slide reading procedures followed real-life laboratory protocol to produce a final result and, for paired readings, the worse result determined the management. Costs per event were estimated and combined with productivity to produce a cost per slide, per woman and per CIN2+ and cervical intraepithelial neoplasia grade III (CIN3) or worse (CIN3+) lesion detected. Cost-effectiveness was estimated using cost per CIN2+ detected. Lifetime cost-effectiveness in terms of life-years and quality-adjusted life-years was estimated using a mathematical model. SETTING: Liquid-based cytology samples were obtained in primary care, and a small number of abnormal samples were obtained from local colposcopy clinics, from different women, in order to enrich the proportion of abnormals. All of the samples were read in a single large service laboratory. Liquid residues used for human papillomavirus (HPV) triage were tested (with Hybrid Capture 2, Qiagen, Crawley, UK) in a specialist virology laboratory in Edinburgh, UK. Histopathology was read by a specialist gynaecological pathology team blinded to HPV results and type of reading. PARTICIPANTS: Samples were obtained from women aged 25-64 years undergoing primary cervical screening in Greater Manchester, UK, with small proportions from women outside this age range and from women undergoing colposcopy. INTERVENTIONS: The principal intervention was automation-assisted reading of cervical cytology slides which was paired with a manual reading of the same slide. Low-grade cytological abnormalities (borderline and mild dyskaryosis) were triaged with HPV testing to direct colposcopy referral. Women with high-grade cytology were referred for colposcopy and those with negative cytology were returned to recall. MAIN OUTCOME MEASURES: The principal outcome measure was the sensitivity of automation-assisted reading relative to manual for the detection of CIN2+. A secondary outcome measure was cost-effectiveness of each type of reading to detect CIN2+. The study was powered to detect a relative sensitivity difference equivalent to an absolute difference of 5%. RESULTS: The principal finding was that automated reading was 8% less sensitive relative to manual, 6.3% in absolute terms. 'No further review' was very reliable and, if restricted to routine screening samples, < 1% of CIN2+ would have been missed. Automated and manual were very similar in terms of cost-effectiveness despite a 60%-80% increase in productivity for automation-assisted reading. CONCLUSIONS: The significantly reduced sensitivity of automated reading, combined with uncertainty over cost-effectiveness, suggests no justification at present to recommend its introduction. The reliability of 'no further review' warrants further consideration as a means of saving staff time. TRIAL REGISTRATION: Current Controlled Trials ISRCTN66377374. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 15, No. 3. See the HTA programme website for further project information.

The psychological impact of human papillomavirus testing in women with borderline or mildly dyskaryotic cervical smear test results: 6-month follow-up.

State anxiety (S-STAI-6), distress (GHQ-12), concern and quality of life (EuroQoL-EQ-5D) 6 months after human papillomavirus (HPV) testing in women with borderline or mildly dyskaryotic smear test results were assessed based on a prospective questionnaire study, with 6-month follow-up after the smear test result. Two centres participated in an English pilot study of HPV testing. Participants included two groups of women receiving abnormal smear test results: (tested for HPV and found to be (a) HPV positive (n=369) or (b) HPV negative (n=252)) and two groups not tested for HPV (those receiving (c) abnormal smear test results (n=102) or (d) normal smear test results (n=288)). There were no differences in anxiety, distress or health-related quality of life between the four study groups at 6 months. Levels of concern about the smear test result remained elevated in all groups receiving an abnormal smear test result, and were highest in the group untested for HPV. Predictors of concern across all groups receiving an abnormal smear test were perceived risk of developing cancer, being HPV positive or untested for HPV, sexual health worries and the smear being a woman's first smear test. The raised anxiety and distress observed in women immediately after being informed of an abnormal smear test result and that they are HPV positive was no longer evident at 6 months. Concern about the smear test result was however still raised in these women and those who tested negative for HPV, and particularly among those who did not undergo HPV testing.

Support surfaces for pressure ulcer prevention.

BACKGROUND: Pressure ulcers (also known as bedsores, pressure sores, decubitus ulcers) are areas of localised damage to the skin and underlying tissue due to pressure, shear or friction. They are common in the elderly and immobile and costly in financial and human terms. Pressure-relieving beds, mattresses and seat cushions are widely used as aids to prevention in both institutional and non-institutional settings. OBJECTIVES: This systematic review seeks to answer the following questions: to what extent do pressure-relieving cushions, beds, mattress overlays and mattress replacements reduce the incidence of pressure ulcers compared with standard support surfaces? how effective are different pressure-relieving surfaces in preventing pressure ulcers, compared to one another? SEARCH STRATEGY: The Specialised Trials Register of the Cochrane Wounds Group (compiled from regular searches of many electronic databases including MEDLINE, CINAHL and EMBASE plus handsearching of specialist journals and conference proceedings) was searched up to January 2004, Issue 3, 2004 of the Cochrane Central Register of Controlled Trials was also searched. The reference sections of included studies were searched for further trials. SELECTION CRITERIA: Randomised controlled trials (RCTs), published or unpublished, which assessed the effectiveness of beds, mattresses, mattress overlays, and seating cushions for the prevention of pressure ulcers, in any patient group, in any setting. RCTs were eligible for inclusion if they reported an objective, clinical outcome measure such as incidence and severity of new of pressure ulcers developed. Studies which only reported proxy outcome measures such as interface pressure were excluded. DATA COLLECTION AND ANALYSIS: Trial data were extracted by one researcher and checked by a second. The results from each study are presented as relative risk for dichotomous variables. Where deemed appropriate, similar studies were pooled in a meta analysis. MAIN RESULTS: 41 RCTs were included in the review. Foam alternatives to the standard hospital foam mattress can reduce the incidence of pressure ulcers in people at risk. The relative merits of alternating and constant low pressure devices, and of the different alternating pressure devices for pressure ulcer prevention are unclear.Pressure-relieving overlays on the operating table have been shown to reduce postoperative pressure ulcer incidence, although one study indicated that an overlay resulted in adverse skin changes. One trial indicated that Australian standard medical sheepskins prevented pressure ulcers. There is insufficient evidence to draw conclusions on the value of seat cushions, limb protectors and various constant low pressure devices as pressure ulcer prevention strategies.A study of Accident & Emergency trolley overlays did not identify a reduction in pressure ulcer incidence. There are tentative indications that foot waffle heel elevators, a particular low air loss hydrotherapy mattress and an operating theatre overlay are harmful. REVIEWERS' CONCLUSIONS: In people at high risk of pressure ulcer development, consideration should be given to the use of higher specification foam mattresses rather than standard hospital foam mattresses. The relative merits of higher-tech constant low pressure and alternating pressure for prevention are unclear. Organisations might consider the use of pressure relief for high risk patients in the operating theatre, as this is associated with a reduction in post-operative incidence of pressure ulcers. Seat cushions and overlays designed for use in Accident & Emergency settings have not been adequately evaluated.

Incidence and costs of unintentional falls in older people in the United Kingdom.

STUDY OBJECTIVE: To estimate the number of accident and emergency (A&E) attendances, admissions to hospital, and the associated costs as a result of unintentional falls in older people. DESIGN: Analysis of national databases for cost of illness. SETTING: United Kingdom, 1999, cost to the National Health Service (NHS) and Personal Social Services (PSS). PARTICIPANTS: Four age groups of people 60 years and over (60-64, 65-69, 70-74, and >/=75) attending an A&E department or admitted to hospital after an unintentional fall. Databases analysed were the Home Accident Surveillance System (HASS) and Leisure Accident Surveillance System (LASS), and Hospital Episode Statistics (HES). MAIN RESULTS: There were 647,721 A&E attendances and 204,424 admissions to hospital for fall related injuries in people aged 60 years and over. For the four age groups A&E attendance rates per 10,000 population were 273.5, 287.3, 367.9, and 945.3, and hospital admission rates per 10,000 population were 34.5, 52.0, 91.9, and 368.6. The cost per 10,000 population was pound 300,000 in the 60-64 age group, increasing to pound 1,500,000 in the >/=75 age group. These falls cost the UK government pound 981 million, of which the NHS incurred 59.2%. Most of the costs (66%) were attributable to falls in those aged >/=75 years. The major cost driver was inpatient admissions, accounting for 49.4% of total cost of falls. Long term care costs were the second highest, accounting for 41%, primarily in those aged >/=75 years. CONCLUSIONS: Unintentional falls impose a substantial burden on health and social services.

The impact of diabetes-related complications on healthcare costs: results from the United Kingdom Prospective Diabetes Study (UKPDS Study No. 65).

AIMS: To develop a model for estimating the immediate and long-term healthcare costs associated with seven diabetes-related complications in patients with Type 2 diabetes participating in the UK Prospective Diabetes Study (UKPDS). METHODS: The costs associated with some major complications were estimated using data on 5102 UKPDS patients (mean age 52.4 years at diagnosis). In-patient and out-patient costs were estimated using multiple regression analysis based on costs calculated from the length of admission multiplied by the average specialty cost and a survey of 3488 UKPDS patients' healthcare usage conducted in 1996-1997. RESULTS: Using the model, the estimate of the cost of first complications were as follows: amputation pound 8459 (95% confidence interval pound 5295, pound 13 200); non-fatal myocardial infarction pound 4070 ( pound 3580, pound 4722); fatal myocardial infarction pound 1152 ( pound 941, pound 1396); fatal stroke pound 3383 ( pound 1935, pound 5431); non-fatal stroke pound 2367 ( pound 1599, pound 3274); ischaemic heart disease pound 1959 ( pound 1467, pound 2541); heart failure pound 2221 ( pound 1690, pound 2896); cataract extraction pound 1553 ( pound 1320, pound 1855); and blindness in one eye pound 872 ( pound 526, pound 1299). The annual average in-patient cost of events in subsequent years ranged from pound 631 ( pound 403, pound 896) for heart failure to pound 105 ( pound 80, pound 142) for cataract extraction. Non-in-patient costs for macrovascular complications were pound 315 ( pound 247, pound 394) and for microvascular complications were pound 273 ( pound 215, pound 343) in the year of the event. In each subsequent year the costs were, respectively, pound 258 ( pound 228, pound 297) and pound 204 ( pound 181, pound 255). CONCLUSIONS: These results provide estimates of the immediate and long-term healthcare costs associated with seven diabetes-related complications.

Are we blind to injuries in the visually impaired? A review of the literature.

OBJECTIVES: To review the literature on the risks and types of injuries associated with visual impairment, and to identify pertinent areas for future research. METHODS: A search of bibliographic databases was conducted in April 2000 for studies published since 1980 and selected studies that met two or more of the following criteria: formal ophthalmic assessment was used; adjustment for confounding variables; large sample size including numbers of visually impaired; and clear definitions and outcomes. RESULTS: Thirty one studies were selected. The majority of these studies (20) assessed falls (including eight on hip fracture and four on multiple falls), eight studies reported traffic related injuries, and three studies assessed occupational injury. The evidence on falls, which relate predominantly to older people, suggests that those with reduced visual acuity are 1.7 times more likely to have a fall and 1.9 times more likely to have multiple falls compared with fully sighted populations. The odds of a hip fracture are between 1.3 and 1.9 times greater for those with reduced visual acuity. Studies of less severe injuries and other causes of injury were either poorly designed, underpowered, or did not exist. CONCLUSIONS: There are substantial gaps in research on both injuries to which people with visual impairment are especially susceptible and in evaluating interventions to reduce these injuries. It is recommended that in future studies the minimum data captured includes: formal ophthalmic assessment of visual fields and visual acuity, outcome measurement, control for confounders, and the costs of health care resource use and any interventions.