How to assess the external validity of therapeutic trials: a conceptual approach

Background External validity of study results is an important issue from a clinical point of view. From a methodological point of view, however, the concept of external validity is more complex than it seems to be at first glance. Methods Methodological review to address the concept of external validity. Results External validity refers to the question whether results are generalizable to persons other than the population in the original study. The only formal way to establish the external validity would be to repeat the study for that specific target population. We propose a three-way approach for assessing the external validity for specified target populations. (i) The study population might not be representative for the eligibility criteria that were intended. It should be addressed whether the study population differs from the intended source population with respect to characteristics that influence outcome. (ii) The target population will, by definition, differ from the study population with respect to geographical, temporal and ethnical conditions. Pondering external validity means asking the question whether these differences may influence study results. (iii) It should be assessed whether the study's conclusions can be generalized to target populations that do not meet all the eligibility criteria. Conclusion Judging the external validity of study results cannot be done by applying given eligibility criteria to a single target population. Rather, it is a complex reflection in which prior knowledge, statistical considerations, biological plausibility and eligibility criteria all have plac

Post-contrast acute kidney injury. Part 2: risk stratification, role of hydration and other prophylactic measures, patients taking metformin and chronic dialysis patients: Recommendations for updated ESUR Contrast Medium Safety Committee guidelines

Objectives: The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 2011 guidelines on the prevention of post-contrast acute kidney injury (PC-AKI). The results of the literature review and the recommendations based on it, which were used to prepare the new guidelines, are presented in two papers. Areas covered in part 2: Topics reviewed include stratification of PC-AKI risk, the need to withdraw nephrotoxic medication, PC-AKI prophylaxis with hydration or drugs, the use of metformin in diabetic patients receiving contrast medium and the need to alter dialysis schedules in patients receiving contrast medium. Key points: \u2022 In CKD, hydration reduces the PC-AKI risk \u2022 Intravenous normal saline and intravenous sodium bicarbonate provide equally effective prophylaxis \u2022 No drugs have been consistently shown to reduce the risk of PC-AKI \u2022 Stop metformin from the time of contrast medium administration if eGFR < 30 ml/min/1.73 m2 \u2022 Dialysis schedules need not change when intravascular contrast medium is given

Post-contrast acute kidney injury \u2013 Part 1: Definition, clinical features, incidence, role of contrast medium and risk factors: Recommendations for updated ESUR Contrast Medium Safety Committee guidelines

Purpose: The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 2011 guidelines on the prevention of post-contrast acute kidney injury (PC-AKI). The results of the literature review and the recommendations based on it, which were used to prepare the new guidelines, are presented in two papers. Areas covered in part 1: Topics reviewed include the terminology used, the best way to measure eGFR, the definition of PC-AKI, and the risk factors for PC-AKI, including whether the risk with intravenous and intra-arterial contrast medium differs. Key Points: \u2022 PC-AKI is the preferred term for renal function deterioration after contrast medium. \u2022 PC-AKI has many possible causes. \u2022 The risk of AKI caused by intravascular contrast medium has been overstated. \u2022 Important patient risk factors for PC-AKI are CKD and dehydration

Dwelling, house and home: towards a home-led perspective on dementia care

“Home” is well known from everyday experience, plays a crucial role in all kinds of narratives about human life, but is hardly ever systematically dealt with in the philosophy of medicine and health care. The notion of home is ambiguous, is often used in a metaphorical way, and is closely related to concepts such as house and dwelling. In this paper the phenomenon of home is explored by means of some phenomenological writings of Heidegger, Bollnow, Bachelard and Levinas. Common in their views is that being at home and dwelling mean something more fundamental than an activity we do along with other activities, such as working and travelling. Dwelling, building a house and being at home are fundamental aspects of human existence. Being human is dwelling. While exploring the relevance of this phenomenological perspective for medical theory and practice, the focus is on the care of people suffering from dementia

Adjuvant platinum-based chemotherapy in radically resected adrenocortical carcinoma: a cohort study

Background After radical resection, patients with adrenocortical carcinoma (ACC) frequently experience recurrence and, therefore, effective adjuvant treatment is urgently needed. The aim of the study was to investigate the role of adjuvant platinum-based therapy. Methods In this retrospective multicentre cohort study, we identified patients treated with adjuvant platinum-based chemotherapy after radical resection and compared them with patients without adjuvant chemotherapy. Recurrence-free and overall survival (RFS/OS) were investigated in a matched group analysis and by applying a propensity score matching using the full control cohort (n = 268). For both approaches, we accounted for immortal time bias. Results Of the 31 patients in the platinum cohort (R0 n = 25, RX n = 4, R1 n = 2; ENSAT Stage II n = 11, III n = 16, IV n = 4, median Ki67 30%, mitotane n = 28), 14 experienced recurrence compared to 29 of 31 matched controls (median RFS after the landmark at 3 months 17.3 vs. 7.3 months; adjusted HR 0.19 (95% CI 0.09-0.42; P < 0.001). Using propensity score matching, the HR for RFS was 0.45 (0.29-0.89, P = 0.021) and for OS 0.25 (0.09-0.69; P = 0.007). Conclusions Our study provides the first evidence that adjuvant platinum-based chemotherapy may be associated with prolonged recurrence-free and overall survival in patients with ACC and a very high risk for recurrence.Clinical epidemiolog

The current landscape of European registries for rare endocrine conditions

Objective To identify cross-border international registries for rare endocrine conditions that are led from Europe and to understand the extent of engagement with these registries within a network of reference centres (RCs) for rare endocrine conditions. Methods Database search of international registries and a survey of RCs in the European Reference Network for rare endocrine conditions (Endo-ERN) with an overall response rate of 82%. Results Of the 42 conditions with orphacodes currently covered within Endo-ERN, international registries exist for 32 (76%). Of 27 registries identified in the Orphanet and RD-Connect databases, Endo-ERN RCs were aware of 11 (41%). Of 21 registries identified by the RC, RD-Connect and Orphanet did not have a record of 10 (48%). Of the 29 glucose RCs, the awareness and participation rate in an international registry was highest for rare diabetes at 75 and 56% respectively. Of the 37 sex development RCs, the corresponding rates were highest for disorders of sex development at 70 and 52%. Of the 33 adrenal RCs, the rates were highest for adrenocortical tumours at 68 and 43%. Of the 43 pituitary RCs, the rates were highest for pituitary adenomas at 43 and 29%. Of the 31 genetic tumour RCs, the rates were highest for MEN1 at 26 and 9%. For the remaining conditions, awareness and participation in registries was less than 25%. Conclusion Although there is a need to develop new registries for rare endocrine conditions, there is a more immediate need to improve the awareness and participation in existing registries.This publication is part of the project ‘777215/EuRRECa’ which has received funding from the European Union’s Health Programme (2014–2020)

The risk for breast cancer is not evidently increased in women with hyperprolactinemia

The question has been raised whether hyperprolactinemia in humans is associated with an excess risk for breast cancer. We aimed to assess the risk of breast cancer in a previously defined large cohort of patients treated for idiopathic hyperprolactinemia or prolactinomas. Based on the pattern of drug prescriptions we identified 11,314 subjects in the PHARMO network with at least one dispensing of dopamine agonists between 1996 and 2006. Of these, 1,607 subjects were considered to have dopamine agonist—treated hyperprolactinemia based on the prescribing pattern. For the present analysis, we included only women (n = 1,342). Patients with breast cancer were identified by hospital discharge codes. Data on breast cancer incidence in the Netherlands were derived from the Dutch cancer registry. Standardized mortality ratio (SMR) was the measure of outcome to assess the association between hyperprolactinemia and breast cancer. The 1,342 patients accounted for a total of 6,576 person years. Eight patients with breast cancer during follow-up were identified. Indirect standardization with incidence proportions from the general Dutch population revealed a 7.47 expected cases. The calculated SMR for breast cancer risk in patients treated hyperprolactinemia was 1.07 (95% confidence interval 0.50–2.03). In conclusion, there is no clear evidence for increased breast cancer risk in female patients treated for either idiopathic hyperprolactinemia or prolactinomas. The uncertainty about the exact risk that is due to the relatively low number of breast cancer cases, should be overcome by pooling results in a future meta-analysis

Progressive improvement of impaired visual acuity during the first year after transsphenoidal surgery for non-functioning pituitary macroadenoma

Improvement of visual field defects continues even years after the initial surgical treatment. Because this process of continuing improvement has not been documented for visual acuity, we audited our data to explore the pattern of recovery of visual acuity until 1 year after transsphenoidal surgery for non-functioning pituitary macroadenoma. Retrospective follow-up study. Forty-three patients (mean age 56 +/- 14 years), treated by transsphenoidal surgery for non-functioning pituitary macroadenoma, were included in this analysis. Visual acuity improved significantly within 3 months after transsphenoidal surgery. The mean visual acuity increased from 0.65 +/- 0.37 to 0.75 +/- 0.36 (P <0.01) (right eye), and from 0.60 +/- 0.32 to 0.82 +/- 0.30 (P <0.01) (left eye). Visual acuity was improved 1 year after transsphenoidal surgery compared to the 3 months postoperative values. The mean visual acuity increased from 0.75 +/- 0.36 to 0.82 +/- 0.34 (P <0.05) (right eye), and from 0.82 +/- 0.30 to 0.88 +/- 0.27 (P <0.05) (left eye). Visual acuity improves progressively after surgical treatment for non-functioning pituitary macroadenomas, at least within the first year after transsphenoidal surger