Breast cancer, breast cancer-directed radiation therapy and risk of hypothyroidism: A systematic review and meta-analysis.

OBJECTIVE: Breast cancer and breast cancer-directed radiation therapy (RT) may increase the risk of late effects, such as hypothyroidism. We conducted a systematic review and meta-analysis to investigate the association between breast cancer, RT, and risk of hypothyroidism in breast cancer survivors. METHODS: Through February 2022, we searched PubMed, EMBASE, and references of relevant articles, to identify papers on breast cancer and breast cancer-directed RT and subsequent risk of hypothyroidism. Articles were screened by title and abstract and reviewed for eligibility. We used a pre-formed data extraction sheet and identified key design elements that could potentially introduce bias. The main outcome was the confounder-adjusted relative risk (RR) of hypothyroidism in breast cancer survivors versus women without breast cancer, and in breast cancer survivors according to the receipt of RT to the supraclavicular lymph nodes. We used a random-effects model to calculate pooled RRs and associated 95% confidence intervals (95% CI). RESULTS: From 951 papers screened by title and abstract, 34 full-text papers were reviewed for eligibility. We included 20 studies published between 1985 and 2021-19 were cohort studies. Compared with women without breast cancer, the pooled RR of hypothyroidism in breast cancer survivors was 1.48 (95% CI: 1.17, 1.87), with highest risk associated with RT to the supraclavicular region (RR = 1.69, 95% CI: 1.16, 2.46). The most important limitations of the studies were small sample size yielding estimates with low precision, and lack of data on potential confounders. CONCLUSION: Breast cancer and radiation therapy to the supraclavicular lymph nodes is associated with an increased risk of hypothyroidism.

Effectiveness and safety of oral anticoagulation treatment beyond 1 year after venous thromboembolism in patients at intermediate recurrence risk.

Effectiveness and safety of long-term anticoagulation treatment are uncertain in venous thromboembolism (VTE) patients at intermediate risk of recurrence. We examined the association between treatment beyond 1 year and outcomes in a Danish nationwide register-based study. VTE patients at intermediate risk of recurrence, that is, non-cancer patients with a first-time unprovoked VTE, who started oral anticoagulation treatment within 30 days and were alive 365 days after the index VTE were included and followed between 2007 and 2015. Exposure was extended (>365 days) or intermediate (91-365 days) treatment. Analyses were done using Cox regression on a propensity score weighted population. We included 18 609 patients with 7232 (38.9%) receiving extended treatment. Mean duration of follow-up was 2.6 years. Compared with intermediate treatment, treatment beyond 365 days was associated with a lower weighted risk of recurrent VTE (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.49-0.65) and all-cause mortality (HR 0.81, 95% CI 0.72-0.90) and an increased risk of major bleeding (HR 1.87, 95% CI 1.58-2.22). In conclusion, extended anticoagulation treatment (predominantly warfarin) beyond 1 year was in real-life settings associated with a lower risk of recurrent VTE and all-cause mortality among VTE patients with an intermediate risk of recurrence. However, an increased bleeding risk should be considered.

Patient-related healthcare disparities in the quality of acute hip fracture care: a 10-year nationwide population-based cohort study.

OBJECTIVES: To characterise and quantify possible patient-related disparities in hip fracture care including temporal changes. DESIGN: Population-based cohort study. SETTING: All Danish hospitals treating patients with hip fracture. PARTICIPANTS: 60 275 hip fracture patients from 2007 to 2016. INTERVENTIONS: Quality of care was defined as fulfilment of eligible care process measures for the individual patient recommended by an expert panel. Using yearly logistic regression models, we predicted the individual patient's probability for receiving high-quality care, resulting in a distribution of adjusted probabilities based on age, sex, comorbidity, fracture type, education, family mean income, migration status, cohabitation status, employment status, nursing home residence and type of municipality. Based on the distribution, we identified best-off patients (ie, the 10% of patients with the highest probability) and worst-off patients (ie, the 10% of patients with the lowest probability). We evaluated disparities in quality of care by measuring the distance in fulfilment of outcomes between the best-off and worst-off patients. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was fulfilment of all-or-none, defined as receiving all relevant process measures. Secondary outcomes were fulfilment of the individual process measures including preoperative optimisation, early surgery, early mobilisation, assessment of pain, basic mobility, nutritional risk and need for antiosteoporotic medication, fall prevention and a postdischarge rehabilitation programme. RESULTS: The proportion of patients receiving high-quality care varied over time for both best-off and worst-off patients. The absolute difference in percentage points between the best-off and worst-off patients for receiving all-or-none of the eligible process measures was 12 (95% CI 6 to 18) in 2007 and 23 (95% CI 19 to 28) in 2016. Disparities were consistent for a range of care processes, including assessment of pain, mobilisation within 24 hours, assessment of need for antiosteoporotic medication and nutritional risk assessment. CONCLUSIONS: Disparity of care between best-off and worst-off patients remained substantial over time.

Incidence of hypothyroidism after treatment for breast cancer-a Danish matched cohort study.

BACKGROUND: Breast cancer survivors (BCS) may have increased risk of hypothyroidism, but risk according to treatment modality is unclear. We estimated the incidence of hypothyroidism in women with breast cancer, and according to cancer treatment. METHODS: Using nationwide registries, we identified all Danish women aged ≥ 35 years diagnosed with non-metastatic breast cancer (1996-2009). We matched up to five cancer-free women (controls) for each BCS. We excluded women with prevalent thyroid disease. Cancer treatment was chemotherapy with or without radiotherapy (RT) targeting the breast/chest wall only, or also the lymph nodes (RTn). We identified hypothyroidism using diagnostic codes, and/or levothyroxine prescriptions. We calculated the cumulative incidence, incidence rates (IR) per 1000 person-years, and used Cox regression to estimate hazard ratios (HR) and associated 95% confidence intervals (CIs) of hypothyroidism, adjusting for comorbidities. RESULTS: We included 44,574 BCS and 203,306 matched controls with 2,631,488 person-years of follow-up. BCS had a slightly higher incidence of hypothyroidism than controls [5-year cumulative incidence, 1.8% (95%CI = 1.7-1.9) and 1.6% (95%CI = 1.5-1.6), respectively]. The overall IR was 4.45 (95%CI = 4.25-4.67) and 3.81 (95%CI = 3.73-3.90), corresponding to an adjusted HR = 1.17 (95%CI = 1.11-1.24). BCS who received RTn with chemotherapy (HR = 1.74, 95%CI = 1.50-2.02) or without chemotherapy (HR = 1.31, 95%CI = 1.14-1.51) had an elevated risk of hypothyroidism compared with matched controls and compared with BCS who underwent surgery alone [HR = 1.71, 95%CI = 1.45-2.01 and HR = 1.36, 95%CI = 1.17-1.58, respectively]. CONCLUSIONS: BCS have an excess risk of hypothyroidism compared with age-matched controls. BCS and those working in cancer survivorship settings ought to be aware that this risk is highest in women treated with radiation therapy to the lymph nodes and chemotherapy.

Hypothyroidism and the risk of breast cancer recurrence and all-cause mortality - a Danish population-based study.

BACKGROUND: Hypothyroidism may occur as a late effect of breast cancer-directed treatment, particularly after radiotherapy, but little is known whether hypothyroidism affects the prognosis after breast cancer. We investigated the association between hypothyroidism and breast cancer recurrence, and all-cause mortality. METHODS: In this population-based cohort study, we used national medical registries to identify all Danish women 35 years or older diagnosed with stage I-III, operable breast cancer between 1996 and 2009. Hypothyroidism was defined as hospital diagnoses ascertained via diagnostic codes, or as prescriptions for levothyroxine. Two analytic models were used: (i) hypothyroidism present at the time of the breast cancer diagnosis (prevalent) and (ii) hypothyroidism diagnosed during follow-up as a time-varying exposure lagged by 1 year (incident). Breast cancer recurrence was defined as any local, regional, or distant recurrence or contralateral breast cancer. All-cause mortality included death from any cause in any setting. We used Cox regression models accounting for competing risks to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer recurrence and all-cause mortality. RESULTS: The study cohort included 35,463 women with breast cancer with 212,641 person-years of follow-up. At diagnosis, 1272 women had hypothyroidism and 859 women developed hypothyroidism during follow-up. In total, 5810 patients developed recurrent breast cancer. Neither prevalent nor incident hypothyroidism was associated with breast cancer recurrence (adjusted HRprevalent 1.01, 95% CI 0.87-1.19; adjusted HRincident 0.93, 95% CI 0.75-1.16, respectively). Furthermore, no differences were seen for all-cause mortality for prevalent or incident hypothyroidism (adjusted HRprevalent 1.02, 95% CI 0.92-1.14, and HRincident 1.08, 95% CI 0.95-1.23, respectively). Stratification by menopausal status, oestrogen receptor status, chemotherapy, or radiotherapy did not alter the estimates. CONCLUSIONS: Hypothyroidism present at diagnosis or during follow-up was not associated with breast cancer recurrence or all-cause mortality in women with breast cancer. Our findings provide reassurance to patients and their physicians that hypothyroidism is unlikely to impact on the clinical course of breast cancer or survival.

Predictors of the effectiveness of accreditation on hospital performance: A nationwide stepped-wedge study.

OBJECTIVE: To identify predictors of the effectiveness of hospital accreditation on process performance measures. DESIGN: A multi-level, longitudinal, stepped-wedge, nationwide study. PARTICIPANTS: All patients admitted for acute stroke, heart failure, ulcers, diabetes, breast cancer and lung cancer at Danish hospitals. INTERVENTION: The Danish Healthcare Quality Programme that was designed to create a framework for continuous quality improvement. MAIN OUTCOME MEASURE(S): Changes in week-by-week trends of hospitals' process performance measures during the study period of 269 weeks prior to, during and post-accreditations. Process performance measures were based on 43 different processes of care obtained from national clinical quality registries. Analyses were stratified according to condition, type of care (i.e. treatment, diagnostics, secondary prevention and patient monitoring) and hospital characteristics (i.e. university affiliation, location, size, experience with accreditation and accreditation compliance). RESULTS: A total of 1 624 518 processes of care were included. The impact of accreditation differed across the conditions. During accreditation, heart failure and breast cancer showed less improvement than other disease areas. Across all conditions, diagnostic processes improved less rapidly than other types of processes. However, after stratifying the data by hospital characteristics, process performance measures improved more uniformly. In respect of the measures that had an unsatisfactory level of quality, the processes related to diabetes, diagnostics and patient monitoring all responded to accreditation and showed an increased improvement during the preparatory work. CONCLUSION: Hospital characteristics were not found to be predictors for the effects of accreditation, whereas conditions and types of care to some extent predicted the effectiveness.

Improvement in quality of hospital care during accreditation: A nationwide stepped-wedge study.

OBJECTIVE: To assess changes over time in quality of hospital care in relation to the first accreditation cycle in Denmark. DESIGN, SETTING AND PARTICIPANTS: We performed a multi-level, longitudinal, stepped-wedge, nationwide study of process performance measures to evaluate the impact of a mandatory accreditation programme in all Danish public hospitals. Patient-level data (n = 1 624 518 processes of care) on stroke, heart failure, ulcer, diabetes, breast cancer and lung cancer care were obtained from national clinical quality registries. INTERVENTION: The Danish Healthcare Quality Programme was introduced in 2009, aiming to create a framework for continuous quality improvement. MAIN OUTCOME: Changes in week-by-week trends of hospital care during the study period of 269 weeks prior to, during and post-accreditation. RESULTS: The quality of hospital care improved over time throughout the study period. The overall positive change in trend odds ratio (OR) = 1.002 per week; 95% confidence interval (CI: 0.997-1.006) observed when comparing the period during accreditation with the period prior to accreditation was not significant. However, when restricting the analyses to processes of care where the performance did not meet target values for satisfactory quality prior to accreditation, we found a significant positive change in trend (OR = 1.006 per week; 95% CI: 1.001-1.011). When comparing the post-accreditation period with the period during accreditation, we found a significantly reduced trend (OR = 0.994 per week; 95% CI: 0.988-0.999), indicating the improvement in quality of care continued but at a lower rate than during accreditation. CONCLUSION: These findings support the hypothesis that hospital accreditation leads to improvements in patient care.