H. Groenewoud

Study Heterogeneity and Estimation of Prevalence of Primary Aldosteronism: A Systematic Review and Meta-Regression Analysis.

CONTEXT For health care planning and allocation of resources, realistic estimation of the prevalence of primary aldosteronism is necessary. Reported prevalences of primary aldosteronism are highly variable, possibly due to study heterogeneity. OBJECTIVE Our objective was to identify and explain heterogeneity in studies that aimed to establish the prevalence of primary aldosteronism in hypertensive patients. DATA SOURCES PubMed, EMBASE, Web of Science, Cochrane Library, and reference lists from January 1, 1990, to January 31, 2015, were used as data sources. STUDY SELECTION Description of an adult hypertensive patient population with confirmed diagnosis of primary aldosteronism was included in this study. DATA EXTRACTION Dual extraction and quality assessment were the forms of data extraction. DATA SYNTHESIS Thirty-nine studies provided data on 42 510 patients (nine studies, 5896 patients from primary care). Prevalence estimates varied from 3.2% to 12.7% in primary care and from 1% to 29.8% in referral centers. Heterogeneity was too high to establish point estimates (I(2) = 57.6% in primary care; 97.1% in referral centers). Meta-regression analysis showed higher prevalences in studies 1) published after 2000, 2) from Australia, 3) aimed at assessing prevalence of secondary hypertension, 4) that were retrospective, 5) that selected consecutive patients, and 6) not using a screening test. All studies had minor or major flaws. CONCLUSIONS This study demonstrates that it is pointless to claim low or high prevalence of primary aldosteronism based on published reports. Because of the significant impact of a diagnosis of primary aldosteronism on health care resources and the necessary facilities, our findings urge for a prevalence study whose design takes into account the factors identified in the meta-regression analysis.

Timing of Surgery for Primary Exotropia in Children

Objective To compare the postoperative alignment and sensory functions in patients with primary exotropia who had been operated at an early age (< 7 years) with those in patients who had been operated at an older age (> 7 years). Methods In a consecutive retrospective cohort study, 112 patients who had had a surgical intervention for primary exotropia between 1997 and 2003 were evaluated for postoperative results. After applying criteria for eligibility, the group of patients was divided into two groups: those who had had surgery before the age of seven years (n = 24) and those who had had surgery after the age of seven years (n = 36). Age at surgery, preoperative alignment and sensory functions were correlated with the postoperative status. The follow-up was at least one year (1.0 year to 7 years; median: 2.3 and 3.5 years, respectively). Results Patients who had had surgery before the age of seven had significantly better alignment and sensory functions. The univariate logistic regression model confirmed a statistically significant association between motor outcome (exodeviation less than 10 diopters) and age at the time of surgery (before or after the age of seven; p = 0.002). In the multivariate model, the association between age at time of surgery and motor outcome was even stronger. The number of re-operations in the group operated before the age of 7 years was significantly less than in the group operated after the age of seven (2 versus 12, p = 0.023). Conclusion The postoperative alignment and sensory functions for patients with primary exotropia who had had a surgical intervention before the age of seven years were, in this study, better than those in patients who had had surgery after the age of seven years.

Quality of Life in Primary Aldosteronism: a Comparative Effectiveness Study of Adrenalectomy and Medical Treatment.

Context In primary aldosteronism (PA), two subtypes are distinguished: aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH). In general, these are treated by adrenalectomy (ADX) and mineralocorticoid receptor antagonists (MRA), respectively. Objective To compare the effects of surgical treatment and medical treatment on quality of life (QoL). Design Post hoc comparative effectiveness study within the Subtyping Primary Aldosteronism: A Randomized Trial Comparing Adrenal Vein Sampling and Computed Tomography Scan (SPARTACUS) trial. Setting Twelve Dutch hospitals and one Polish hospital. Participants Patients with PA (n = 184). Interventions ADX or MRAs. Main Outcome Measures At baseline and 6-month and 1-year follow-up, we assessed QoL by two validated questionnaires: RAND 36-Item Health Survey 1.0 (RAND SF-36) and European Quality of Life-5 Dimensions (EQ-5D). Results At baseline, seven of eight RAND SF-36 subscales and both summary scores, as well as three of five EQ-5D dimensions and the visual analog scale, were lower in patients with PA compared with the general population, especially in women. The beneficial effects of ADX were larger than for MRAs for seven RAND SF-36 subscales, both summary scores, and health change. For the EQ-5D, we detected a difference in favor of ADX in two dimensions and the visual analog scale. Most differences in QoL between both treatments exceeded the minimally clinically important difference. After 1 year, almost all QoL measures had normalized for adrenalectomized patients. For patients on medical treatment, most QoL measures had improved but not all to the level of the general population. Conclusion Both treatments improve QoL in PA, underscoring the importance of identifying these patients. QoL improved more after ADX for suspected APA than after initiation of medical treatment for suspected BAH.

The yield of diagnostic work-up of patients presenting with myalgia, exercise intolerance, or fatigue: A prospective observational study

Myalgia, fatigue, and exercise intolerance are cause for referral to a neurologist. However, the diagnostic value of history, neurological examination, and ancillary investigations in patients with these symptoms is unknown. This study provides a sound footing for deciding which ancillary investigations should be conducted. A prospective observational study of the diagnostic approach in 187 patients with myalgia, exercise intolerance, or fatigue as their predominant symptom was performed. The primary outcomes were independent contribution of referral letter, history, examination, and ancillary investigations to a myopathy diagnosis. The secondary outcome was diagnostic value of combined ancillary investigations. 27% of patients had a myopathy. Positive family history (OR 3.2), progressive symptoms (OR 2.2), atrophy (OR 9.7), weakness (OR 10.9), and hyporeflexia (OR 4.4) were associated with a myopathy. Positive predictive values for myopathy were calculated for CK (0.32), EMG (0.66), ultrasound (0.47), and muscle biopsy (0.78). All contributed significantly in predicting myopathy. Multivariate analysis yielded a diagnostic algorithm facilitating a more efficient work-up in future patients. CK levels, EMG, ultrasound, and muscle biopsy independently contribute to predicting a myopathy. The diagnostic algorithm shows which combination of ancillary investigations should be employed in different subgroups and when to omit invasive techniques. This algorithm may drastically improve diagnostic efficiency.

Real-life Data on Patient Characteristics, Cost and Effectiveness of Field-directed Treatment for Actinic Keratoses: An Observational Study

Actinic keratoses (AK) occur frequently; however, real-life clinical data on personalized treatment choice and costs are scarce. This multicentre one-year observational study investigated patient-characteristics, cost and effectiveness of methylaminolaevulinate photodynamic therapy (MAL-PDT), imiquimod (IMI) and 5-fluorour-acil (5-FU) in patients with AKs on the face/scalp. A total of 104 patients preferred MAL-PDT, 106 preferred IMI and 110 preferred 5-FU. At baseline, significant differences between treatment groups were found; most patients were severely affected (mean 32.5 AK in PDT-group, 20.2 in IMI-group, 22.8 in 5-FU-group). A mean reduction in lesions of 81% after MAL-PDT, 82% after IMI and 88% after 5-FU was found after one year. Annual costs were €1,950 for MAL-PDT, €877 for IMI and €738 for 5-FU. These results show that, compared with clinical trials, in the real-life clinical setting AK patients are usually more severely affected and treatment costs are much higher. Furthermore, patient characteristics are important factors in treatment choice.

Nail Involvement as a Predictor of Disease Severity in Paediatric Psoriasis: Follow-up Data from the Dutch ChildCAPTURE Registry

Little is known about the relationship between nail psoriasis and psoriasis severity in children, and there has been no longitudinal assessment of psoriasis severity related to nail psoriasis. The aim of this study was to assess whether nail psoriasis could serve as a predictor for a more severe disease course. De-identified data were obtained from the ChildCAPTURE registry, a daily clinical practice cohort of children with psoriasis, from September 2008 to November 2015. Cross-sectional analyses were performed at baseline. Longitudinal data until 2-year follow-up were analysed by linear mixed models. Nail psoriasis was present in 19.0% of all 343 patients at baseline and cross-sectionally associated with higher Psoriasis Area and Severity Index (PASI) (p = 0.033). Longitudinal analysis demonstrated higher PASI (p <0.001) during 2-year follow-up in patients with nail involvement at baseline. These findings suggest that nail psoriasis is a potential clinical predictor for more severe disease course over time in paediatric psoriasis.

[OP.6B.04] DEVELOPMENT OF A PREDICTION MODEL FOR PATIENTS WITH SUSPECTED PRIMARY ALDOSTERONISM AND AN INCONCLUSIVE SALT LOADING TEST

Objective: To develop a prediction model to confirm or exclude primary aldosteronism (PA) in patients with an inconclusive salt loading test (SLT). Design and method: Our retrospective cohort comprised patients who underwent an SLT between 2005 and 2016 in our university medical center. We included 290 patients. The SLT was inconclusive (post-infusion aldosterone levels 140–280 pmol/L) in 115 patients. In 45/115 PA was present according to an expert meeting. Together with 101 patients with a positive SLT result this resulted in a total of 146/276 (missing data in n = 14) patients with PA. We used binary logistic regression analysis to identify variables independently associated with PA. Results: The decision model contained the following continuous variables increasing the likelihood of PA: low plasma renin concentration (PRC) before SLT, high plasma aldosterone concentration (PAC) after SLT, high potassium supplementation, and low plasma potassium concentration.1 In patients with an inconclusive SLT the model had a sensitivity of 84.4% and a specificity of 94.3%. The positive and negative predictive value were 90.5% and 90.4% respectively. 1Prediction score (p)† = ebx / (1+ebx) Where bx = 0.55– 0.290*PRC before saline infusion (mU/l) + 0.05*PAC after saline infusion (pmol/l) + 0.07*potassium supplementation prior to SLT (mmol/day) −2.75*plasma potassium concentration prior to SLT (mmol/l) †p > 0.59 indicates PA Conclusions: Our model may be helpful in deciding how to manage PA patients with an inconclusive SLT. External validation and prospective studies are necessary before implementing this model in clinical practice.

[PP.27.07] QUALITY OF LIFE IN PRIMARY ALDOSTERONISM IMPROVES MORE AFTER ADRENALECTOMY THAN AFTER MEDICAL THERAPY

Objective: To compare the effects of surgical and medical treatment on health-related quality of life (QoL) in primary aldosteronism Design and method: We did a post-hoc comparative effectiveness study within the SPARTACUS trial (n = 184) in thirteen hospitals. In case of aldosterone-producing adenoma we performed an adrenalectomy and for bilateral adrenal hyperplasia we treated patients with mineralocorticoid receptor antagonists. At baseline, six months and one year follow-up we assessed QoL by two validated questionnaires. Results: At baseline, seven out of eight RAND SF-36 subscales and both summary scores and three out of five EQ-5D dimensions and the visual analogue scale were lower in PA patients compared to the general population. The beneficial effects of adrenalectomy were larger than for mineralocorticoid receptor antagonists for seven RAND SF-36 subscales, both summary scores, and health change. For the EQ-5D, we detected a difference in favour of adrenalectomy in two of the five dimensions and the visual analogue scale. Most differences in QoL between both treatments exceeded the minimally clinically important difference. After one year we observed improvement of most QoL measures for both treatments, but only for adrenalectomy all returned to the level of the general population. Conclusions: Both treatments clearly improve QoL of patients with PA, underscoring the importance of identifying these patients. Improvement in QoL in patients with PA one year after surgical treatment for suspected aldosterone-producing adenoma is superior to that of medically treated patients with suspected bilateral adrenal hyperplasia.