[Don't stop medication too abruptly: advice about the discontinuation of medication]. / Stop niet te snel, dan lukt het wél.

Polypharmacy may result in interactions and side effects that lead to morbidity and mortality. Therefore, it is important to evaluate on a regular basis the possibility to stop medication. Sometimes it is necessary to temporarily discontinue certain medication, for example when a patient is unable to swallow or suffers from a delirium. Not all drugs can be stopped abruptly, since this can result in a rebound-effect or withdrawal symptoms Especially drugs that act on the central nervous system (e.g. psychotropic drugs, dopaminergic drugs, opioids) are known to cause (severe) withdrawal symptoms when stopped abruptly In addition, beta-blockers, corticosteroids and proton-pump inhibitors cause symptoms when stopped without tapering. Gradually tapering off these medicines is needed, sometimes under guidance from a specialist. Moreover, it is important to realize that stopping medication can also introduce interactions.

[N-of-1 trials: the one and only]. / Zoals N = 1 is er geen één.

Personalized care is a topical issue: the demand for an optimal, individualized treatment instead of uniformity and strict guidelines in increasing. Implementing these ideals in clinical practice often appears to be challenging, as a result of heterogeneity in treatment effects and the influence of patient-specific factors. N-of-1 trials are double-blind, randomized, placebo-controlled trials in an individual patient and can be used to objectively examine the (side)effects of a specific drug, and to compare two or more drugs or variants of the same drug. The results can be used when aiming of deprescribing, but also for evaluating patient-reported intolerances or (in)effectiveness. This article discusses the use and advantages of N-of-1-trials in clinical practice, and addresses its specific concerns and possibilities. The N-of-1-trial is an effective, cost-reducing method to evaluate the effects of a certain drug, which is accessible to nearly every physician and can contribute to safe and effective personalized medicine.

Predictors for Remission after Transsphenoidal Surgery in Acromegaly: A Dutch Multicenter Study.

CONTEXT: Transsphenoidal surgery (TSS) is the primary treatment of choice in acromegaly. It is important to identify patients in whom surgical cure is not attainable at an early stage, both to inform patients on expected treatment outcome and to select those who are more likely to need additional therapy. OBJECTIVE: To identify predictors for remission after TSS in acromegaly. METHODS: Large multicenter study with retrospective data collection from 3 tertiary neurosurgical referral centers in The Netherlands. We analyzed clinical data since 2000 from 3 cohorts (Groningen, Nijmegen, and Rotterdam, total n = 282). Multivariate regression models were used to identify predictors of early biochemical remission (12 weeks to 1 year postoperatively) according to the 2010 consensus criteria, long-term remission (age- and sex-normalized insulin-like growth factor 1 [IGF-1] and the absence of postoperative treatment until last follow-up), and relative IGF-1 and growth hormone [GH] reduction. RESULTS: A larger maximum tumor diameter (odds ratio [OR] 0.91, 95% CI 0.87-0.96, P ≤ .0001) was associated with a lower chance of early biochemical remission. A larger maximum tumor diameter (OR 0.93, 95% CI 0.89-0.97, P = .0022) and a higher random GH concentration at diagnosis (OR 0.98, 95% CI 0.96-0.99, P = .0053) were associated with a lower chance of long-term remission. CONCLUSION: Maximum tumor diameter and random GH concentration at diagnosis are the best predictors for remission after TSS in acromegaly.

Voice Characteristics in Patients with Acromegaly during Treatment.

BACKGROUND: Active acromegaly is characterized by Growth Hormone and Insulin-like Growth Factor (IGF)-1 excess. Voice complaints are common in active acromegaly and are suggested to be caused by effects of Growth Hormone or IGF-1 on vocal folds and the surrounding soft tissues. Prospective studies on the course of voice characteristics in acromegaly patients are scarce and results are conflicting. This study investigates objective changes in voice parameters, self-reported perception of voice and laryngostroboscopic features during the first 2.5 years of acromegaly treatment. MATERIAL AND METHOD: In this prospective study, acoustic voice analysis (and videolaryngostroboscopic examination were performed in 27 consecutive treatment-naive acromegaly patients at diagnosis (T0), after 1 year (T1) and after 2.5 years (T2) of treatment. The voice handicap index (VHI-30) questionnaire was taken. RESULTS: During acromegaly treatment, VHI scores decreased, and mucosal edema & hypertrophy diminished. No significant changes in objective voice parameters were detected. The within-subject change in serum IGF-1 levels (97.3 (40.6-208) to 22.4 (10.2-34.1) nmol/L (P < 0.001)) during follow-up correlated positively with the changes in VHI questionnaire scores (R 0.32-0.45; P = 0.002-0.03). CONCLUSIONS: At diagnosis and during acromegaly treatment, mean VHI scores were in the normal range, although they decreased during follow-up. Mucosal edema and hypertrophy largely resolved during treatment. No significant changes in objective voice parameters were observed. Voice characteristics are in the normal range in patients with acromegaly, but may change during treatment. However, voice complaints are important to discuss, since they may influence quality of life.

Acromegaly, inflammation and cardiovascular disease: a review.

Acromegaly is characterized by Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF-1) excess. Uncontrolled acromegaly is associated with a strongly increased risk of cardiovascular disease (CVD), and numerous cardiovascular risk factors remain present after remission. GH and IGF-1 have numerous effects on the immune and cardiovascular system. Since endothelial damage and systemic inflammation are strongly linked to the development of CVD, and have been suggested to be present in both controlled as uncontrolled acromegaly, they may explain the presence of both micro- and macrovascular dysfunction in these patients. In addition, these changes seem to be only partially reversible after remission, as illustrated by the often reported presence of endothelial dysfunction and microvascular damage in controlled acromegaly. Previous studies suggest that insulin resistance, oxidative stress, and endothelial dysfunction are involved in the development of CVD in acromegaly. Not surprisingly, these processes are associated with systemic inflammation and respond to GH/IGF-1 normalizing treatment.

The Course of Obstructive Sleep Apnea Syndrome in Patients With Acromegaly During Treatment.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is common in active acromegaly and negatively influences quality of life, morbidity, and mortality. This prospective study with 3 predetermined timepoints and a standardized treatment protocol investigates changes in sleep parameters during the first 2.5 years of acromegaly treatment. METHODS: Before initiation of acromegaly treatment (medical pretreatment followed by surgery), polysomnography (PSG) was performed in 27 consecutive patients with treatment-naive acromegaly. PSG was repeated after 1 year (N = 24) and 2.5 years (N = 23), and anthropometric and biochemical parameters were obtained. RESULTS: At baseline, 74.1% of the patients was diagnosed with OSAS. The respiratory disturbance index (RDI; P = 0.001), oxygen desaturation index (ODI; P = 0.001), lowest oxygen saturation (LSaO2; P = 0.007) and the Epworth Sleepiness Scale (ESS; P < 0.001) improved significantly during treatment, with the greatest improvement in the first year. After 2.5 years of treatment, all patients had controlled acromegaly. Of the 16 patients with repeated PSG and OSAS at baseline, 11 (68.8%) were cured of OSAS. Changes in RDI, ODI, LSaO2, and ESS correlated with insulin-like growth factor 1 levels. CONCLUSION: OSAS has a high prevalence in active acromegaly. There is a substantial decrease in prevalence and severity of OSAS following acromegaly treatment, with the largest improvement during the first year. Most patients recover from OSAS following surgical or biochemical control of the acromegaly. Therefore, a PSG is advised after diagnosis of acromegaly. When OSAS is present, it should be treated and PSG should be repeated during acromegaly treatment.

Postoperative use of somatostatin analogs and mortality in patients with acromegaly.

Objective To assess the effect of somatostatin analogs (SSAs) on mortality in relation to disease control of acromegaly after pituitary surgery. Design A retrospective study in two large tertiary referral centers in The Netherlands. Methods Overall, 319 patients with acromegaly in whom pituitary surgery was performed as primary therapy between January 1980 and July 2017 were included. Postoperative treatment with SSA was prescribed to 174 (55%) patients because of persistent or recurrent disease. Disease control at last visit was assessed by IGF1 standard deviation score (SDS). Adequate disease control was defined as IGF1 SDS ≤2. Univariate determinants of mortality and standardized mortality ratios (SMRs) were calculated for groups with and without SSA at any moment postoperatively and at last visit. Results In total, 27 deaths were observed. In univariate analysis, determinants of mortality were inadequate disease control (relative risk (RR): 3.41, P = 0.005), surgery by craniotomy (RR: 3.53, P = 0.013) and glucocorticoid substitution (RR: 2.11, P = 0.047). There was a strong trend toward increased mortality for patients who used SSA (RR: 2.01, P = 0.067) and/or dopamine agonists (RR: 2.54, P = 0.052) at last visit. The SMR of patients with adequate disease control who used SSA at any moment postoperatively (1.07, P = 0.785) and at last visit (1.19; P = 0.600) was not increased. Insufficiently controlled patients had a significantly raised SMR (3.92, P = 0.006). Conclusions Postoperative use of SSA is not associated with increased mortality in patients with acromegaly who attain adequate disease control. In contrast, inadequate disease control, primary surgery by craniotomy and glucocorticoid substitution are associated with increased mortality.

The acute effect of black tea consumption on resistance artery endothelial function in healthy subjects. A randomized controlled trial.

BACKGROUND & AIMS: Black tea is a main source of flavonoids in the Western diet and has been associated with reduced risk for cardiovascular disease, possibly through lowering blood pressure. These effects may be mediated through improving endothelial function of resistance arteries. The aim of this study was therefore to examine the acute impact of black tea on forearm resistance artery endothelial function in healthy, normotensive middle-aged subjects. METHODS: Twenty middle-aged men and women (age-range 45-75 years) were recruited into a double-blind, randomized, placebo-controlled crossover intervention study. Forearm resistance artery blood flow (FBF, measured using venous occlusion plethysmography) in response to incremental doses of acetylcholine, sodium nitroprusside and L-NG-monomethyl arginine were determined 2 h after consumption of either black tea containing ∼400 mg flavonoids (equivalent to 2-3 cups of tea) or a taste- and color-matched placebo. RESULTS: The mean FBF-response to acetylcholine after tea consumption was 23% higher compared to the response after placebo (95% CI: -20%, +88%), but this difference did not reach statistical significance (P = 0.32). No significant differences in the FBF-responses to sodium nitroprusside and L-NG-monomethyl arginine were found between the tea and placebo interventions (P = 0.96 and 0.74, respectively). Correcting FBF for changes in blood pressure did not alter the outcomes. CONCLUSIONS: We found no evidence that acute intake of black tea significantly altered endothelium-dependent vasodilation of forearm resistance arteries in healthy middle-aged subjects. Interventions with a longer duration of tea ingestion are required to further explore the (long-term) impact of tea flavonoids on blood pressure regulatory mechanisms. This trial was registered at clinicaltrials.gov as NCT02328339.