Exceptions to the rule of informed consent for research with an intervention

Background In specific situations it may be necessary to make an exception to the general rule of informed consent for scientific research with an intervention. Earlier reviews only described subsets of arguments for exceptions to waive consent. Methods Here, we provide a more extensive literature review of possible exceptions to the rule of informed consent and the accompanying arguments based on literature from 1997 onwards, using both Pubmed and PsycINFO in our search strategy. Results We identified three main categories of arguments for the acceptability of a consent waiver: data validity and quality, major practical problems, and distress or confusion of participants. Approval by a medical ethical review board always needs to be obtained. Further, we provide examples of specific conditions under which consent waiving might be allowed, such as additional privacy protection measures. Conclusions The reasons legitimized by the authors of the papers in this overview can be used by researchers to form their own opinion about requesting an exception to the rule of informed consent for their own study. Importantly, rules and guidelines applicable in their country, institute and research field should be followed. Moreover, researchers should also take the conditions under which they feel an exception is legitimized under consideration. After discussions with relevant stakeholders, a formal request should be sent to an IRB

The method of detection of ductal carcinoma in situ has no therapeutic implications: results of a population-based cohort study

Multivariable-adjusted Cox regression analysis of ipsilateral and contralateral invasive breast cancer in women aged 49–75 years at DCIS diagnosis (DCIS diagnostic period 1989–2004). Age was the primary time scale, time since DCIS diagnosis (0–5, 5–10, and ≥10 years) the secondary time scale, and DCIS treatment a time-varying covariable (DOCX 22 kb

Women's adjustment trajectories during IVF and impact on mental health 11–17 years later

STUDY QUESTION Do patients present different adjustment trajectories during and after IVF treatment? SUMMARY ANSWER Most women show resilient trajectories during and after IVF treatment but 37% show temporary or chronic maladjustment during IVF and 10% are maladjusted 11–17 years after treatment. WHAT IS KNOWN ALREADY Research on patient psychosocial adjustment during treatment has contributed to identifying the most distressful stages of IVF treatment and profiling patients at risk for emotional maladjustment at these specific stages. This knowledge is currently driving the deliverance of psychosocial care at fertility clinics by tailoring it to patients' risk profiles and specific treatment stages. However, current care does not take into consideration how individuals adjust across the entire treatment pathway. This can be assessed by profiling individual adjustment trajectories. STUDY DESIGN, SIZE, DURATION A longitudinal cohort study with five assessment moments that combines data from two different studies, the STRESSIVF and OMEGA projects. Participants enrolled in the STRESSIVF study (started IVF in 1998–2000) were assessed before and after the first IVF treatment cycle and 6 months and 2.5 years after the last IVF cycle. A subset participated in the OMEGA project (started IVF in 1995–2000) and reported on their mental health 11–17 years after treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS Three hundred and forty-eight women participated in the STRESSIVF project and 108 of these in the OMEGA. Anxiety was measured with the State and Trait Anxiety Inventory, depression with the Beck Depression Inventory and mental health with the Mental Health Inventory. Latent class growth mixed modelling was carried out to identify distinct anxiety and depression trajectories over the four STRESSIVF study assessment moments. Multinominal logistic regressions were conducted to investigate predictors of trajectory membership, and stepwise linear regressions were performed to investigate if adjustment trajectories predicted mental health 11–17 years after IVF treatment. MAIN RESULTS AND THE ROLE OF CHANCE A total of 67 and 86% of women showed normal levels of anxiety and depression, respectively, throughout treatment (resilient trajectories), 24 and 33% experienced anxiety and depression only during treatment (recovery trajectories), 4.6 and 4.9% experienced anxiety and depression only after treatment (delayed trajectories), and 4.3% showed chronic anxiety (chronic trajectory, not identified for depression). Non-resilient trajectories were associated with unsuccessful treatment, marital dissatisfaction, lack of social support and negative infertility cognitions. One in 10 women had a delayed or chronic trajectory and these trajectories predicted serious mental health impairment 11–17 years after treatment. LIMITATIONS, REASONS FOR CAUTION The study only focuses on women. In the OMEGA project adjustment was assessed using a mental health measure. Although we could investigate how trajectories predicted mental health, it would have been preferable to map anxiety and depression trajectories up to 11–17 years after treatment. Missing analysis showed selective dropout from the study but this was accounted for by using mixed models and imputation procedures. Finally, data on other life stressors were not collected; therefore any contribution from these events cannot be assessed. WIDER IMPLICATIONS OF THE FINDINGS Fertility health-care providers have been called upon considering their responsibility in supporting patients in the aftermath of treatment. Results show it is possible to profile different groups of at-risk women at the start of the treatment and tailor psychosocial support to risk profile to promote health adjustment during treatment and thereafter

The proportion of postmenopausal breast cancer cases in the Netherlands attributable to lifestyle-related risk factors

We aimed to estimate the proportion of Dutch postmenopausal breast cancer cases in 2010 that is attributable to lifestyle-related risk factors. We calculated population attributable fractions (PAFs) of potentially modifiable risk factors for postmenopausal breast cancer in Dutch women aged >50 in 2010. First, age-specific PAFs were calculated for each risk factor, based on their relative risks for postmenopausal breast cancer (from meta-analyses) and age-specific prevalence in the population (from national surveys) around the year 2000, assuming a latency period of 10 years. To obtain the overall PAF, age-specific PAFs were summed in a weighted manner, using the age-specific breast cancer incidence rates (2010) as weights. 95 % confidence intervals for PAF estimates were derived by Monte Carlo simulations. Of Dutch women >40 years, in 2000, 51 % were overweight/obese, 55 % physically inactive (<5 days/week 30 min activity), 75 % regularly consumed alcohol, 42 % ever smoked cigarettes and 79 % had a low-fibre intake (<3.4 g/1000 kJ/day). These factors combined had a PAF of 25.7 % (95 % CI 24.2–27.2), corresponding to 2,665 Dutch postmenopausal breast cancer cases in 2010. PAFs were 8.8 % (95 % CI 6.3–11.3) for overweight/obesity, 6.6 % (95 % CI 5.2–8.0) for alcohol consumption, 5.5 % (95 % CI 4.0–7.0) for physical inactivity, 4.6 % (95 % CI 3.3–6.0) for smoking and 3.2 % (95 % CI 1.6–4.8) for low-fibre intake. Our findings imply that modifiable risk factors are jointly responsible for approximately one out of four Dutch postmenopausal breast cancer cases. This suggests that incidence rates can be lowered substantially by living a more healthy lifestyle

Cancer risk in children, adolescents, and young adults conceived by ART in 1983-2011

STUDY QUESTION: Do children, adolescents, and young adults born after ART, including IVF, ICSI and frozen-thawed embryo transfer (FET), have an increased risk of cancer compared with children born to subfertile couples not conceived by ART and children from the general population? SUMMARY ANSWER: After a median follow-up of 18 years, the overall cancer risk was not increased in children conceived by ART, but a slight risk increase was observed in children conceived after ICSI. WHAT IS KNOWN ALREADY: There is growing evidence that ART procedures could perturb epigenetic processes during the pre-implantation period and influence long-term health. Recent studies showed (non-)significantly increased cancer risks after ICSI and FET, but not after IVF. STUDY DESIGN, SIZE, DURATION: A nationwide historical cohort study with prospective follow-up was carried out, including all live-born offspring from women treated with ART between 1983 and 2011 and subfertile women not treated with ART in one of the 13 Dutch IVF clinics and two fertility centers. PARTICIPANTS/MATERIALS, SETTING, METHODS: Children were identified through the mothers' records in the Personal Records Database. Information on the conception method of each child was collected through the mother's medical record. In total, the cohort comprises 89 249 live-born children of subfertile couples, of whom 51 417 were conceived using ART and 37 832 were not (i.e. conceived naturally, through ovulation induction, or after IUI). Cancer incidence was ascertained through linkage with the Netherlands Cancer Registry for the period 1989-2019. Cancer risk in children conceived using ART was compared with risk in children born to subfertile couples but not conceived by ART (hazard ratio (HR)) and children from the general population (standardized incidence ratios (SIRs)). MAIN RESULTS AND THE ROLE OF CHANCE: In total, 358 cancers were observed after a median follow-up of 18 years. Overall cancer risk was not increased in children conceived using ART, when compared with the general population (SIR = 0.96, 95% CI = 0.81-1.12) or with children from subfertile couples not conceived by ART (HR = 1.06, 95% CI = 0.84-1.33). Compared with children from subfertile couples not conceived by ART, the use of IVF or FET was not associated with increased cancer risk, but ICSI was associated with a slight risk increase (HR = 1.58, 95% CI = 1.08-2.31). Risk of cancer after ART did not increase at older ages (≥18 years, HR = 1.26, 95% CI = 0.88-1.81) compared to cancer risk in children not conceived by ART. LIMITATIONS, REASONS FOR CAUTION: The observed increased risk among children conceived using ICSI must be interpreted with caution owing to the small number of cases. WIDER IMPLICATIONS OF THE FINDINGS: After a median follow-up of 18 years, children conceived using ART do not have an increased overall cancer risk. Many large studies with prolonged follow-up are needed to investigate cancer risk in (young) adults conceived by different types of ART. In addition, international pooling of studies is recommended to provide sufficient power to study risk of specific cancer sites after ART. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by The Dutch Cancer Society (NKI 2006-3631) that funded the OMEGA-women's cohort, Children Cancer Free (KIKA; 147) that funded the OMEGA-I-II offspring cohort. The OMEGA-III offspring cohort was supported by a Postdoc Stipend of Amsterdam Reproduction &amp; Development, and the Eunice Kennedy Shriver National Institute of Child Health &amp; Human Development of the National Institutes of Health under Award Number R01HD088393. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no competing interests. TRIAL REGISTRATION NUMBER:N/A.</p

Состояние сексуального здоровья супругов после хирургического вмешательства на внутренних гениталиях женщин

Установлены влияние разных видов операции на сексуальную функцию женщин, причины развития и клинические формы дезадаптации супружеской пары. Сделано заключение о необходимости учитывать при психотерапевтической коррекции дезадаптации помимо объема операции психологические и социально-психологические факторы, способствующие формированию дезадаптации супругов, а в ряде случаев являющиеся ее причиной.The influence of various types of surgery on sexual function of women as well as the causes of development and clinical forms of spouse deadaptation were established. The author concludes about the necessity to consider mental and social-psychological factors contributing formation of spouse deadaptation and its cause in a number of cases in addition to the volume of the surgery at psychotherapeutic correction of deadaptation

Endometrial cancer survival after breast cancer in relation to tamoxifen treatment:Pooled results from three countries

Introduction: Tamoxifen is an effective treatment for breast cancer but an undesirable side-effect is an increased risk of endometrial cancer, particularly rare tumor types associated with poor prognosis. We investigated whether tamoxifen therapy increases mortality among breast cancer patients subsequently diagnosed with endometrial cancer. Methods: We pooled case-patient data from the three largest case-control studies of tamoxifen in relation to endometrial cancer after breast cancer (1,875 patients: Netherlands, 765; United Kingdom, 786; United States, 324) and collected follow-up information on vital status. Breast cancers were diagnosed in 1972 to 2005 with endometrial cancers diagnosed in 1978 to 2006. We used Cox proportional hazards survival analysis to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Results: A total of 1,104 deaths occurred during, on average, 5.8 years following endometrial cancer (32% attributed to breast cancer, 25% to endometrial cancer). Mortality from endometrial cancer increased significantly with unfavorable non-endometrioid morphologies (P <0.0001), International Federation of Gynaecology and Obstetrics staging system for gynecological malignancy (FIGO) stage (P <0.0001) and age (P <0.0001). No overall association was observed between tamoxifen treatment and endometrial cancer mortality (HR = 1.17 (95% CI: (0.89 to 1.55)). Tamoxifen use for at least five years was associated with increased endometrial cancer mortality (HR = 1.59 (1.13 to 2.25)). This association appeared to be due primarily to the excess of unfavorable histologies and advanced stage in women using tamoxifen for five or more years since the association with mortality was no longer significant after adjustment for morphological type and FIGO stage (HR = 1.37 (0.97 to 1.93)). Those patients with endometrioid tumors, who stopped tamoxifen use at least five years before their endometrial cancer diagnosis, had a greater mortality risk from endometrial cancer than endometrioid patients with no tamoxifen exposure (HR = 2.11 (1.13 to 3.94)). The explanation for this latter observation is not apparent. Conclusions: Patients with endometrial cancer after breast cancer who received tamoxifen treatment for five years for breast cancer have greater endometrial cancer mortality risk than those who did not receive tamoxifen. This can be attributed to non-endometrioid histological subtypes with poorer prognosis among long term tamoxifen users

The influence of adjuvant systemic regimens on contralateral breast cancer risk and receptor subtype

Background: An increasing number of breast cancer (BC) survivors are at risk of developing contralateral breast cancer (CBC). We aimed to investigate the influence of various adjuvant systemic regimens on, subtype-specific, risk of CBC. Methods: This population-based cohort study included female patients diagnosed with first invasive BC between 2003 and 2010; follow-up was complete until 2016. Clinico-pathological data were obtained from the Netherlands Cancer Registry and additional data on receptor status through linkage with PALGA: the Dutch Pathology Registry. Cumulative incidences (death and distant metastases as competing risk) and hazard ratios (HRs) were estimated for all invasive metachronous CBC and CBC subtypes. Results: Of 83 144 BC patients, 2816 developed a CBC; the 10-year cumulative incidence was 3.8% (95% confidence interval [CI]=3.7% to 4.0%). Overall, adjuvant chemotherapy (HR=0.70, 95% CI=0.62 to 0.80), endocrine therapy (HR=0.46, 95% CI=0.41 to 0.52), and trastuzumab with chemotherapy (HR=0.57, 95% CI=0.45 to 0.73) were strongly associated with a reduced CBC risk. Specifically, taxane-containing chemotherapy (HR=0.48, 95% CI=0.36 to 0.62) and aromatase inhibitors (HR=0.32, 95% CI=0.23 to 0.44) were associated with a large CBC risk reduction. More detailed analyses showed that endocrine therapy statistically significantly decreased the risk of estrogen receptor (ER)-positive CBC (HR=0.41, 95% CI=0.36 to 0.47) but not ER-negative CBC (HR=1.32, 95% CI=0.90 to 1.93) compared with no endocrine therapy. Patients receiving chemotherapy for ER-negative first BC had a higher risk of ER-negative CBC from 5years of follow-up (HR=2.84, 95% CI=1.62 to 4.99) compared with patients not receiving chemotherapy for ER-negative first BC. Conclusion: Endocrine therapy, chemotherapy, as well as trastuzumab with chemotherapy reduce CBC risk. However, each adjuvant therapy regimen had a different impact on the CBC subtype distribution. Taxane-containing chemotherapy and aromatase inhibitors were associated with the largest CBC risk reduction

Cardiovascular Disease in Testicular Cancer Survivors:Identification of Risk Factors and Impact on Quality of Life

PURPOSE: Testicular cancer (TC) treatment is clearly associated with cardiovascular morbidity and mortality. To enable development of preventive strategies for cardiovascular disease (CVD), we assessed cardiometabolic risk factors and quality of life (QoL) in TC survivors.METHODS: Incidence of coronary artery disease, myocardial infarction, and heart failure after TC treatment was assessed in a multicenter cohort comprising 4,748 patients treated at the age of 12-50 years between 1976 and 2007. Patients who had developed CVD and a random sample from the cohort (subcohort) received a questionnaire on cardiometabolic risk factors and QoL. A subgroup of responders in the subcohort additionally underwent clinical evaluation of cardiovascular risk factors.RESULTS: After a median follow-up of 16 years, 272 patients had developed CVD. Compared with orchidectomy only, cisplatin combination chemotherapy was associated with an increased CVD risk (hazard ratio [HR], 1.9; 95% CI, 1.1 to 3.1). Patients who were obese or a smoker at diagnosis (HR, 4.6; 95% CI, 2.0 to 10.0 and HR, 1.7; 95% CI, 1.1 to 2.4, respectively), developed Raynaud's phenomenon (HR, 1.9; 95% CI, 1.1 to 3.6) or dyslipidemia (HR, 2.8; 95% CI, 1.6 to 4.7) or had a positive family history for CVD (HR, 2.9; 95% CI, 1.7 to 4.9) had higher CVD risk. More TC survivors with CVD reported inferior QoL on physical domains than survivors who did not develop CVD. Of 304 TC survivors who underwent clinical evaluation for cardiovascular risk factors (median age at assessment: 51 years), 86% had dyslipidemia, 50% had hypertension, and 35% had metabolic syndrome, irrespective of treatment.CONCLUSION: Cardiovascular events in TC survivors impair QoL. Many TC survivors have undetected cardiovascular risk factors. We advocate early lifestyle adjustments and lifelong follow-up with low-threshold treatment of cardiovascular risk factors, especially in obese and smoking patients treated with platinum-based chemotherapy.</p