Acromegaly is a rare disease and thus challenging to accurately quantify epidemiologically. In this comprehensive literature review, we compare different approaches to studying acromegaly from an... Show moreAcromegaly is a rare disease and thus challenging to accurately quantify epidemiologically. In this comprehensive literature review, we compare different approaches to studying acromegaly from an epidemiological perspective and describe the temporal evolution of the disease pertaining to epidemiological variables, clinical presentation and mortality. We present updated epidemiological data from the population-based Danish cohort of patients with acromegaly (AcroDEN), along with meta-analyses of existing estimates from around the world.Based on this, we conclude that the incidence, prevalence and age at acromegaly diagnosis are all steadily increasing, but with considerable variation between studies. An increased number of incidental cases may contribute to the increase in incidence and age at diagnosis, respectively. The clinical features at presentation are trending toward a milder disease phenotype at diagnosis, and advances in therapeutic options have reduced the mortality of patients with acromegaly to a level similar to that of the general population. Moreover, the underlying cause of death has shifted from cardiovascular to malignant neoplastic diseases. Show less
Purpose Recent data have shown a decreasing overall mortality in acromegaly over the last decades. However, cancer incidence and cancer-related mortality still appear to be increased. Our aim was... Show morePurpose Recent data have shown a decreasing overall mortality in acromegaly over the last decades. However, cancer incidence and cancer-related mortality still appear to be increased. Our aim was to obtain updated epidemiological data from Norway in a clinically well-defined cohort with complete register-based follow-up.Methods Patients diagnosed with acromegaly from South-Eastern Norway between 1999-2019 (n = 262) and age and sex matched population controls (1:100) were included (n = 26,200). Mortality and cancer data were obtained from the Norwegian Cause of Death and Cancer Registry. Mortality and cancer incidence were compared by Kaplan-Meier analyses and Cox regression; we report hazard ratios (HRs) with 95% confidence intervals (95% CI).Results Median age at diagnosis was 48.0 years (interquartile range (IQR): 37.6-58.0). Mean annual acromegaly incidence rate was 4.7 (95% CI 4.2-5.3) cases/10(6) person-years, and the point prevalence (2019) was 83 (95% CI 72.6-93.5) cases/10(6) persons. Overall mortality was not increased in acromegaly, HR 0.8 (95% CI 0.5-1.4), cancer-specific and cardiovascular-specific mortality was also not increased (HR: 0.7 (95% CI 0.3-1.8) and 0.8 (95% CI: 0.3-2.5) respectively). The HR for all cancers was 1.45 (1.0-2.1; p = 0.052).Conclusion In this large cohort study, covering the period 1999-2019, patients were treated with individualized multimodal management. Mortality was not increased compared to the general population and comparable with recent registry studies from the Nordic countries and Europe. Overall cancer risk was slightly, but not significantly increased in the patients. Show less
Lyko, C.; Blum, M.R.; Abolhassani, N.; Stuber, M.J.; Giovane, C. del; Feller, M.; ... ; Rodondi, N. 2022
Background Antithyroid antibodies increase the likelihood of developing overt hypothyroidism, but their clinical utility remains unclear. No large randomized controlled trial (RCT) has assessed... Show moreBackground Antithyroid antibodies increase the likelihood of developing overt hypothyroidism, but their clinical utility remains unclear. No large randomized controlled trial (RCT) has assessed whether older adults with subclinical hypothyroidism (SHypo) caused by autoimmune thyroid disease derive more benefits from levothyroxine treatment (LT4). Objective To determine whether older adults with SHypo and positive antibodies derive more clinical benefits from LT4 than those with negative antibodies. Methods We pooled individual participant data from two RCTs, Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism and IEMO 80+. Participants with persistent SHypo were randomly assigned to receive LT4 or placebo. We compared the effects of LT4 versus placebo in participants with and without anti-thyroid peroxidase (TPO) at baseline. The two primary outcomes were 1-year change in Hypothyroid Symptoms and Tiredness scores on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire. Results Among 660 participants (54% women) >= 65 years, 188 (28.5%) had positive anti-TPO. LT4 versus placebo on Hypothyroid Symptoms lead to an adjusted between-group difference of -2.07 (95% confidence interval: -6.04 to 1.90) for positive antibodies versus 0.89 (-1.76 to 3.54) for negative antibodies (p for interaction = 0.31). Similarly, there was no treatment effect modification by baseline antibody status for Tiredness scores-adjusted between-group difference 1.75 (-3.60 to 7.09) for positive antibodies versus 1.14 (-1.90 to 4.19) for negative antibodies (p for interaction = 0.98). Positive anti-TPO were not associated with better quality of life, improvement in handgrip strength, or fewer cardiovascular outcomes with levothyroxine treatment. Conclusions Among older adults with SHypo, positive antithyroid antibodies are not associated with more benefits on clinical outcomes with LT4. Show less
Endt, V.H.W. van der; Milders, J.; Vries, B.B.L.P. de; Trines, S.A.; Groenwold, R.H.H.; Dekkers, O.M.; ... ; Jong, Y. de 2022
Aims Multiple risk scores to predict ischaemic stroke (IS) in patients with atrial fibrillation (AF) have been developed. This study aims to systematically review these scores, their validations... Show moreAims Multiple risk scores to predict ischaemic stroke (IS) in patients with atrial fibrillation (AF) have been developed. This study aims to systematically review these scores, their validations and updates, assess their methodological quality, and calculate pooled estimates of the predictive performance.Methods and results We searched PubMed and Web of Science for studies developing, validating, or updating risk scores for IS in AF patients. Methodological quality was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). To assess discrimination, pooled c-statistics were calculated using random-effects meta-analysis. We identified 19 scores, which were validated and updated once or more in 70 and 40 studies, respectively, including 329 validations and 76 updates-nearly all on the CHA(2)DS(2)-VASc and CHADS(2). Pooled c-statistics were calculated among 6 267 728 patients and 359 373 events of IS. For the CHA(2)DS(2)-VASc and CHADS(2), pooled c-statistics were 0.644 [95% confidence interval (CI) 0.635-0.653] and 0.658 (0.644-0.672), respectively. Better discriminatory abilities were found in the newer risk scores, with the modified-CHADS(2) demonstrating the best discrimination [c-statistic 0.715 (0.674-0.754)]. Updates were found for the CHA(2)DS(2)-VASc and CHADS(2) only, showing improved discrimination. Calibration was reasonable but available for only 17 studies. The PROBAST indicated a risk of methodological bias in all studies.Conclusion Nineteen risk scores and 76 updates are available to predict IS in patients with AF. The guideline-endorsed CHA(2)DS(2)-VASc shows inferior discriminative abilities compared with newer scores. Additional external validations and data on calibration are required before considering the newer scores in clinical practice. Show less
Electronic health record (EHR) data not only offer many exciting research opportunities but also come with their own inherent limitations. Researchers may not always realise the challenges... Show moreElectronic health record (EHR) data not only offer many exciting research opportunities but also come with their own inherent limitations. Researchers may not always realise the challenges associated with the use of EHR data for research, or the fact that using large datasets of 'real-world data' does not necessarily provide valuable real-world evidence. This article discusses some of the main differences between EHR data and data collected primarily for research purposes, and the challenges encountered when using EHR data for research. It also offers suggestions on how to deal with these challenges based on worked-out examples. It therefore serves as a quick guide for researchers interested in either reading or performing EHR-based research. Show less
Rossen, T.M. van; Ooijevaar, R.E.; Vandenbroucke-Grauls, C.M.J.E.; Dekkers, O.M.; Kuijper, E.J.; Keller, J.J.; Prehn, J. van 2022
Objectives: Clostridioides difficile infection (CDI), its subsequent recurrences (rCDIs), and severe CDI (sCDI) provide a significant burden for both patients and the healthcare system. Identifying... Show moreObjectives: Clostridioides difficile infection (CDI), its subsequent recurrences (rCDIs), and severe CDI (sCDI) provide a significant burden for both patients and the healthcare system. Identifying patients diagnosed with initial CDI who are at increased risk of developing sCDI/rCDI could lead to more cost-effective therapeutic choices. In this systematic review we aimed to identify clinical prognostic factors associated with an increased risk of developing sCDI or rCDI.Methods: PubMed, Embase, Emcare, Web of Science and COCHRANE Library databases were searched from database inception through March, 2021. The study eligibility criteria were cohort and caseecontrol studies. Participants were patients >= 18 years old diagnosed with CDI, in which clinical or laboratory factors were analysed to predict sCDI/rCDI. Risk of bias was assessed by using the Quality in Prognostic Research (QUIPS) tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool modified for prognostic studies. Study selection was performed by two independent reviewers. Overview tables of prognostic factors were constructed to assess the number of studies and the respective effect direction and statistical significance of an association.Results: 136 studies were included for final analysis. Greater age and the presence of multiple comorbidities were prognostic factors for sCDI. Identified risk factors for rCDI were greater age, healthcareassociated CDI, prior hospitalization, proton pump inhibitors (PPIs) started during or after CDI diagnosis, and previous rCDI.Conclusions: Prognostic factors for sCDI and rCDI could aid clinicians to make treatment decisions based on risk stratification. We suggest that future studies use standardized definitions for sCDI/rCDI and systematically collect and report the risk factors assessed in this review, to allow for meaningful metaanalysis of risk factors using data of high-quality trials. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. Show less
Voorend, C.G.N.; Oevelen, M. van; Verberne, W.R.; Wittenboer, I.D. van den; Dekkers, O.M.; Dekker, F.; ... ; Bos, W.J.W. 2022
Background Non-dialytic conservative care (CC) has been proposed as a treatment option for patients with kidney failure. This systematic review and meta-analysis aims at comparing survival outcomes... Show moreBackground Non-dialytic conservative care (CC) has been proposed as a treatment option for patients with kidney failure. This systematic review and meta-analysis aims at comparing survival outcomes between dialysis and CC in studies where patients made an explicit treatment choice. Methods Five databases were systematically searched from origin through 25 February 2021 for studies comparing survival outcomes among patients choosing dialysis versus CC. Adjusted and unadjusted survival rates were extracted and meta-analysis performed where applicable. Risk of bias analysis was performed according to the Cochrane Risk Of Bias In Non-randomized Studies of Interventions. Results A total of 22 cohort studies were included covering 21 344 patients. Most studies were prone to selection bias and confounding. Patients opting for dialysis were generally younger and had fewer comorbid conditions, fewer functional impairments and less frailty than patients who chose CC. The unadjusted median survival from treatment decision or an estimated glomerular filtration rate <15 mL/min/1.73 m(2) ranged from 20 and 67 months for dialysis and 6 and 31 months for CC. Meta-analysis of 12 studies that provided adjusted hazard ratios (HRs) for mortality showed a pooled adjusted HR of 0.47 (95% confidence interval 0.39-0.57) for patients choosing dialysis compared with CC. In subgroups of patients with older age or severe comorbidities, the reduction of mortality risk remained statistically significant, although analyses were unadjusted. Conclusions Patients opting for dialysis have an overall lower mortality risk compared with patients opting for CC. However, a high risk of bias and heterogeneous reporting preclude definitive conclusions and results cannot be translated to an individual level. Show less
Haneveld, M.J.K.; Treijen, M.J.C. van; Pieterman, C.R.C.; Dekkers, O.M.; Ven, A. van de; Herder, W.W. de; ... ; Leeuwaarde, R.S. van 2021
Context Nonfunctioning pancreatic neuroendocrine tumors (NF-pNETs) are highly prevalent and constitute an important cause of mortality in patients with multiple endocrine neoplasia type 1 (MEN1).... Show moreContext Nonfunctioning pancreatic neuroendocrine tumors (NF-pNETs) are highly prevalent and constitute an important cause of mortality in patients with multiple endocrine neoplasia type 1 (MEN1). Still, the optimal age to initiate screening for pNETs is under debate. Objective The aim of this work is to assess the age of occurrence of clinically relevant NF-pNETs in young MEN1 patients. Methods Pancreatic imaging data of MEN1 patients were retrieved from the DutchMEN Study Group database. Interval-censored survival methods were used to describe age-related penetrance, compare survival curves, and develop a parametric model for estimating the risk of having clinically relevant NF-pNET at various ages. The primary objective was to assess age at occurrence of clinically relevant NF-pNET (size >= 20 mm or rapid growth); secondary objectives were the age at occurrence of NF-pNET of any size and pNET-associated metastasized disease. Results Five of 350 patients developed clinically relevant NF-pNETs before age 18 years, 2 of whom subsequently developed lymph node metastases. No differences in clinically relevant NF-pNET-free survival were found for sex, time frame, and type of MEN1 diagnosis or genotype. The estimated ages (median, 95% CI) at a 1%, 2.5%, and 5% risk of having developed a clinically relevant tumor are 9.5 (6.5-12.7), 13.5 (10.2-16.9), and 17.8 years (14.3-21.4), respectively. Conclusion Analyses from this population-based cohort indicate that start of surveillance for NF-pNETs with pancreatic imaging at age 13 to 14 years is justified. The psychological and medical burden of screening at a young age should be considered. Show less
Background: First-line treatment for prolactinomas is a medical treatment with dopamine agonists (DAs), which effectively control hyperprolactinaemia in most patients, although post-withdrawal... Show moreBackground: First-line treatment for prolactinomas is a medical treatment with dopamine agonists (DAs), which effectively control hyperprolactinaemia in most patients, although post-withdrawal remission rates are approximately 34%. Therefore, many patients require prolonged DA treatment, while side effects negatively impact health-related quality of life (HRQoL). Endoscopic transsphenoidal resection is reserved for patients with severe side effects, or with DA-resistant prolactinoma. Surgery has a good safety profile and high probability of remission and may thus deserve a more prominent place in prolactinoma treatment. The hypothesis for this study is that early or upfront surgical resection is superior to DA treatment both in terms of HRQoL and remission rate in patients with a non-invasive prolactinoma of limited size.Methods: We present a combined randomised clinical trial and observational cohort study design, which comprises three unblinded randomised controlled trials (RCTs; PRolaCT-1, PRolaCT-2, PRolaCT-3), and an observational study arm (PRolaCT-O) that compare neurosurgical counselling, and potential subsequent endoscopic transsphenoidal adenoma resection, with current standard care. Patients with a non-invasive prolactinoma (< 25 mm) will be eligible for one of three RCTs based on the duration of pre-treatment with DAs: PRolaCT-1: newly diagnosed, treatment-naive patients; PRolaCT-2: patients with limited duration of DA treatment (4-6 months); and PRolaCT-3: patients with persisting prolactinoma after DA treatment for > 2 years. PRolaCT-O will include patients who decline randomisation, due to e.g. a clear treatment preference. Primary outcomes are disease remission after 36 months and HRQoL after 12 months.Discussion: Early or upfront surgical resection for patients with a limited-sized prolactinoma may be a reasonable alternative to the current standard practice of DA treatment, which we will investigate in three RCTs and an observational cohort study. Within the three RCTs, patients will be randomised between neurosurgical counselling and standard care. The observational study arm will recruit patients who refuse randomisation and have a pronounced treatment preference. PRolaCT will collect randomised and observational data, which may facilitate a more individually tailored practice of evidence-based medicine. Show less
Kooij, M.K. van der; Suijkerbuijk, K.P.M.; Dekkers, O.M.; Kapiteijn, E. 2021
Risk prediction is one of the central goals of medicine. However, ultimate prediction-perfectly predicting whether individuals will actually get a disease-is still out of reach for virtually all... Show moreRisk prediction is one of the central goals of medicine. However, ultimate prediction-perfectly predicting whether individuals will actually get a disease-is still out of reach for virtually all conditions. One crucial assumption of ultimate personalized prediction is that individual risks in the relevant sense exist. In the present paper we argue that perfect prediction at the individual level will fail-and we will do so by providing pragmatic, epistemic, conceptual, and ontological arguments. Show less
Marques, P.; Vries, F. de; Dekkers, O.M.; Furth, W.R. van; Korbonits, M.; Biermasz, N.R.; Pereira, A.M. 2020
Objective Full blood count (FBC) and serum inflammation-based scores reflect systemic inflammation and predict outcomes in cancer, but little is known in pituitary adenomas (PAs). We aimed to... Show moreObjective Full blood count (FBC) and serum inflammation-based scores reflect systemic inflammation and predict outcomes in cancer, but little is known in pituitary adenomas (PAs). We aimed to characterise FBC and inflammation-based scores in PA patients and investigate their usefulness in predicting challenging disease course. Methods We studied 424 PA patients first operated at our centre with available pre-operative biochemical data. Patients with infection, malignancies, autoimmune or haematological conditions were excluded. Inflammation-based scores studied: Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Lymphocyte-to-Monocyte Ratio (LMR), Systemic Immune-Inflammation Index (SII), Neutrophil-Platelet Score (NPS), Prognostic Nutrition Index (PNI), and Glasgow Prognostic Score (GPS). Results Cushing's disease patients had more platelets, leucocytes, neutrophils and monocytes, and higher NLR, NPS and SII. Serum inflammation-based scores didn't differ among non-Cushing PA subtypes. The glucocorticoid excess severity influenced leucocyte, eosinophil, basophil and platelet counts, and GPS in Cushing's disease. Patients with functioning non-Cushing PAs with suprasellar extension, cavernous sinus invasion and hypopituitarism had GPS >= 1, while NPS >= 1 was associated with suprasellar extension. More invasive and difficult to treat corticotrophinomas were associated with fewer platelets pre-operatively (< 299.5 x 10(9)/L predicting multimodal treatment). Non-functioning PA patients who suffered apoplexy had more leucocytes, neutrophils and monocytes, higher GPS >= 1 and fewer platelets; re-operated cases had fewer lymphocytes, higher NLR and PLR. Conclusions Serum inflammation-based scores may predict invasive/refractory PAs: GPS and PNI in non-functioning and functioning non-Cushing PAs; NPS in functioning non-Cushing PAs; NLR and PLR in non-functioning PAs. Platelets < 299.5 x 10(9)/L predict multimodal treatment in Cushing's disease. Further studies are needed to confirm these observations. Show less
Malignant transformation of fibrous dysplasia lesions has been reported in patients with fibrous dysplasia/McCune-Albright syndrome (FD/MAS). Recently, we have observed an increased risk for breast... Show moreMalignant transformation of fibrous dysplasia lesions has been reported in patients with fibrous dysplasia/McCune-Albright syndrome (FD/MAS). Recently, we have observed an increased risk for breast cancer. In this study, the prevalence of skeletal and extraskeletal malignancies in patients with FD/MAS in the Netherlands was assessed by analyzing data from our cohort of FD/MAS patients, the Dutch Pathology Registry (PALGA), and the Netherlands Cancer Registry (NCR). We extracted data on sex, age at diagnosis of FD/MAS, type of FD/MAS, type of malignancy, and age at diagnosis of malignancy and histology of bone and malignant tissue when available, including GNAS-mutation analysis from patients' medical records. Standardized Morbidity Ratios (SMRs) with 95% confidence intervals were calculated. Twelve malignancies were identified in the LUMC FD/MAS cohort and 100 in the PALGA cohort. In this cohort, SMR was increased for osteosarcoma (19.7, 95% CI 3.5-48.9), cervical cancer (4.93, 95%CI 1.7-8.2), thyroid cancer (3.71, 95% CI 1.1-7.8), prostate cancer (3.08, 95% CI 1.8-4.6), and melanoma (2.01, 95%CI 1.2-3.1). SMRs for pancreatic cancer or hepatocellular carcinoma could not be calculated due to low numbers. The small number of malignancies identified in our FD/MAS cohort precluded the calculation of SMRs for our cohort specifically. Our findings show that patients with FD/MAS appear to have an increased risk for osteosarcoma, cervical, thyroid, and prostate cancer and melanoma. However, these data should be interpreted with caution, as true incidence rates of the identified malignancies may be influenced by the inclusion of only patients with histologically confirmed FD/MAS. The etiology of this increased risk for malignancies still needs to be elucidated. Show less
Controlled human infection trials, whereby a small group of healthy participants is deliberately exposed to a pathogen under controlled circumstances, can provide preliminary data for vaccine... Show moreControlled human infection trials, whereby a small group of healthy participants is deliberately exposed to a pathogen under controlled circumstances, can provide preliminary data for vaccine efficacy and for the selection of the most promising candidate vaccines for field trials. Because of the potential harm to participants through the deliberate exposure to a pathogen, the use of smaller groups minimises the cumulative risk. As such, a control group that receives a placebo vaccine followed by controlled exposure to a pathogen should be scientifically well justified. As these types of trials are designed to generate consistent infection rates and thus comparable outcomes across populations and trial sites, data from past studies (historical data) could be used as a valid alternative to placebo groups. In this Personal View, we review this option and highlight the considerations for choosing historical data as a suitable control. For the widespread application of this method, responsibility for the centralisation and sharing of data from controlled human infection trials lies with the scientific community. Show less
OBJECTIVE In patients with type 1 diabetes and end-stage renal disease, it is controversial whether a simultaneous pancreas-kidney (SPK) transplantation improves survival compared with kidney... Show moreOBJECTIVE In patients with type 1 diabetes and end-stage renal disease, it is controversial whether a simultaneous pancreas-kidney (SPK) transplantation improves survival compared with kidney transplantation alone. We compared long-term survival in SPK and living- or deceased-donor kidney transplant recipients. RESEARCH DESIGN AND METHODS We included all 2,796 patients with type 1 diabetes in the Netherlands who started renal replacement therapy between 1986 and 2016. We used multivariable Cox regression analyses adjusted for recipient age and sex, dialysis modality and vintage, transplantation era, and donor age to compare all-cause mortality between deceased- or living-donor kidney and SPK transplant recipients. Separately, we analyzed mortality between regions where SPK transplant was the preferred intervention (80% SPK) versus regions where a kidney transplant alone was favored (30% SPK). RESULTS Of 996 transplanted patients, 42%, 16%, and 42% received a deceased- or living-donor kidney or SPK transplant, respectively. Mean (SD) age at transplantation was 50 (11), 48 (11), and 42 (8) years, respectively. Median (95% CI) survival time was 7.3 (6.2; 8.3), 10.5 (7.2; 13.7), and 16.5 (15.1; 17.9) years, respectively. SPK recipients with a functioning pancreas graft at 1 year (91%) had the highest survival (median 17.4 years). Compared with deceased-donor kidney transplant recipients, adjusted hazard ratios (95% CI) for 10- and 20-year all-cause mortality were 0.79 (0.49; 1.29) and 0.98 (0.69; 1.39) for living-donor kidney and 0.67 (0.46; 0.98) and 0.79 (0.60; 1.05) for SPK recipients, respectively. A treatment strategy favoring SPK over kidney transplantation alone showed 10- and 20-year mortality hazard ratios of 0.56 (0.40; 0.78) and 0.69 (0.52; 0.90), respectively. CONCLUSIONS Compared with living- or deceased-donor kidney transplantation, SPK transplant was associated with improved patient survival, especially in recipients with a long-term functioning pancreatic graft, and resulted in an almost twofold lower 10-year mortality rate. Show less
Purpose In the Netherlands, radiotherapy after breast-conserving surgery (BCS) is omitted in up to 30% of patients aged >= 75 years. Although omission of radiotherapy is considered an option for... Show morePurpose In the Netherlands, radiotherapy after breast-conserving surgery (BCS) is omitted in up to 30% of patients aged >= 75 years. Although omission of radiotherapy is considered an option for older women treated with endocrine treatment, the majority of these patients do not receive systemic treatment following Dutch treatment guidelines. Therefore, the aim of this study was to evaluate the effect of omission of radiotherapy on locoregional recurrence risk in this patient population.Methods Patients aged >= 75 years undergone BCS for T1-2N0 breast cancer diagnosed between 2003 and 2009 were selected from the Netherlands Cancer Registry. To minimize confounding by indication, hospital variation was used to assess the impact of radiotherapy-use on locoregional recurrence risk using cox proportional hazards regression. Hazards ratios with 95% confidence interval (CI) were estimated.Results Overall, 2390 patients were included. Of the patients with hormone receptor-positive breast cancer, 39.3% received endocrine treatment. Five-year incidences of locoregional recurrence were 1.9%, 2.8%, and 3.0% in patients treated at hospitals with higher (average radiotherapy-use 96.0%), moderate (88.0%), and lower radiotherapy-use (72.2%) respectively, and nine-year incidences were 2.2%, 3.1%, and 3.2% respectively. Adjusted hazard ratios were 1.46 (95% CI 0.77-2.78) and 1.50 (95% CI 0.79-2.85) for patients treated at hospitals with moderate and lower radiotherapy-use, compared to patient treated at hospitals with higher radiotherapy-use.Conclusions Despite endocrine treatment in only 39.3%, locoregional recurrence risk was low, even in patients treated at hospitals with lower radiotherapy-use. This provides reasonable grounds to consider omission of radiotherapy in patients aged >= 75 years with T1-2N0 breast cancer. Show less
Smit, R.A.J.; Trompet, S.; Dekkers, O.M.; Jukema, J.W.; Cessie, S. le 2019
Previous studies showed that statins reduce the progression of kidney function decline and proteinuria, but whether specific types of statins are more beneficial than others remains unclear. We... Show morePrevious studies showed that statins reduce the progression of kidney function decline and proteinuria, but whether specific types of statins are more beneficial than others remains unclear. We performed a network meta-analysis of randomized controlled trials (RCT) to investigate which statin most effectively reduces kidney function decline and proteinuria. We searched MEDLINE, Embase, Web of Science, and the Cochrane database until July 13, 2018, and included 43 RCTs (>110,000 patients). We performed a pairwise random-effects meta-analysis and a network meta-analysis according to a frequentist approach. We assessed network inconsistency, publication bias, and estimated for each statin the probability of being the best treatment. Considerable heterogeneity was present among the included studies. In pairwise meta-analyses, 1-year use of statins versus control reduced kidney function decline by 0.61(95%-CI: 0.27; 0.95) mL/min/1.73 m(2) and proteinuria with a standardized mean difference of -0.58 (95%-CI:-0.88; -0.29). The network meta-analysis for the separate endpoints showed broad confidence intervals due to the small number available RCTs for each individual comparison. In conclusion, 1-year statin use versus control attenuated the progression of kidney function decline and proteinuria. Due to the imprecision of individual comparisons, results were inconclusive as to which statin performs best with regard to renal outcome. Show less
