Antihypertensive drug concentration measurement combined with personalized feedback in resistant hypertension:a randomized controlled trial

Background:Adherence to antihypertensive drugs (AHDs) is crucial for controlling blood pressure (BP). We aimed to determine the effectiveness of measuring AHD concentrations using a dried blood spot (DBS) sampling method to identify nonadherence, combined with personalized feedback, in reducing resistant hypertension.Methods:We conducted a multicenter, randomized, controlled trial (RHYME-RCT, ICTRP NTR6914) in patients with established resistant hypertension. Patients were randomized to receive either an intervention with standard of care (SoC) or SoC alone. SoC consisted of BP measurement and DBS sampling at baseline, 3 months (t3), 6 months (t6), and 12 months (t12); AHD concentrations were measured but not reported in this arm. In the intervention arm, results on AHD concentrations were discussed during a personalized feedback conversation at baseline and t3. Study endpoints included the proportion of patients with RH and AHD adherence at t12.Results:Forty-nine patients were randomized to receive the intervention+SoC, and 51 were randomized to receive SoC alone. The proportion of adherent patients improved from 70.0 to 92.5% in the intervention+SoC arm (P = 0.008, n = 40) and remained the same in the SoC arm (71.4%, n = 42). The difference in adherence between the arms was statistically significant (P = 0.014). The prevalence of resistant hypertension decreased to 75.0% in the intervention+SoC arm (P &lt; 0.001, n = 40) and 59.5% in the SoC arm (P &lt; 0.001, n = 42) at t12; the difference between the arms was statistically nonsignificant (P = 0.14).Conclusion:Personalized feedback conversations based on DBS-derived AHD concentrations improved AHD adherence but did not reduce the prevalence of RH.</p

Establishment of reference values for endocrine tests. Part VII: Growth hormone deficiency

Background: Plasma insulin-like growth factor (IGF-I) concentration can be used as a rough indicator of the growth-hormone status. However, for the diagnosis of growth hormone deficiency, dynamic tests are required. The growth hormone (GH) response in the insulin tolerance test (ITT) is considered to be the gold standard in this respect. An alternative for the ITT is the GHRH/ GHRP-6 test, which has fewer side effects. In this study we established reference values for IGF-I levels and for the GH response in both dynamic tests. Methods: We studied 296 subjects recruited from the general population, equally distributed according to sex and aged between 20 and 70 years. Serum IGF-I level was measured in all subjects and an insulin tolerance test (0.15 U/kg Actrapid iv) and GHRH/GHRP-6 test (1 mg GHRH/kg and 1 mg GHRP-6/kg) were performed in 49 subjects. Results: In multivariate analyses both IGF-I and the GH response in the ITT were significantly influenced by age, whereas the GH response in the GHRH/GHRP-6 test was significantly affected by BMI. There was no sex difference in IGF-I and in the GHRH/GHRP-6 test, but in the ITT males had a higher GH peak. There was a significant correlation between the GH responses in both tests, and the GH response was significantly higher in the GHRH/GHRP-6 test than in the ITT. Age-adjusted reference values were established for each test. Conclusion: We have established age-adjusted reference values for serum IGF-I and for the GH response in the ITT and GHRH/GHRP-6 tes

Chemoradiotherapy with capecitabine for locally advanced anal carcinoma : an alternative treatment option

BACKGROUND: Capecitabine is an established treatment alternative to intravenous 5-fluorouracil (5-FU) for patients with rectal cancer receiving chemoradiotherapy. Its place in the treatment of locally advanced anal carcinoma (AC), however, remains undetermined. We investigated whether capecitabine is as effective as 5-FU in the treatment of patients with locally advanced AC. METHODS: One hundred and five patients with squamous cell AC stage T2-4 (T2>4 cm), N0-1, M0 or T1-4, N2-3, M0, were included in this retrospective study. Forty-seven patients were treated with continuous 5-FU (750 mg m(-2)) on days 1-5 and 29-33, mitomycin C (MMC, 10 mg m(-2)) on day 1, and radiotherapy; 58 patients were treated with capecitabine (825 mg m(-2) b.i.d. on weekdays), MMC (10 mg m(-2)) on day 1, and radiotherapy. The primary end points of the study were: clinical complete response rate, locoregional control (LRC) and overall survival (OS). Secondary end points were: colostomy-free survival (CFS), toxicity and associations of genetic polymorphisms (GSTT1, GSTM1, GSTP1 and TYMS) with outcome and toxicity. RESULTS: Clinical complete response was achieved in 41/46 patients (89.1%) with 5-FU and in 52/58 patients (89.7%) with capecitabine. Three-year LRC was 76% and 79% (P=0.690, log-rank test), 3-year OS was 78% and 86% (P=0.364, log-rank test) and CFS was 65% and 79% (P=0.115, log-rank test) for 5-FU and capecitabine, respectively. GSTT1 and TYMS genotypes were associated with severe (grade 3-4) toxicity. CONCLUSIONS: Capecitabine combined with MMC and radiotherapy was equally effective as 5-FU-based chemoradiotherapy. This study shows that capecitabine can be used as an acceptable alternative to 5-FU for the treatment of AC

HPV-negative squamous cell carcinoma of the anal canal is unresponsive to standard treatment and frequently carries disruptive mutations in TP53

Background:Human papillomavirus (HPV), p16 expression, and TP53 mutations are known prognostic factors in head and neck squamous cell carcinoma, but their role in squamous cell carcinoma of the anal canal (SCCAC) is less well established. The objective of this study was to determine the prognostic significance of tumour HPV status, p16 and p53 expression, and mutations in TP53 in patients with SCCAC receiving (chemo)radiotherapy.Methods:Human papillomavirus DNA was determined using an INNO-LiPA-based assay in tumour tissue of 107 patients with locally advanced SCCAC. Patients were treated with radiotherapy, with or without concurrent chemotherapy consisting of a fluoropyrimidine and mitomycin C. Expression of p16 and p53 was determined using immunohistochemistry. Exons 2-11 of TP53 in tumour tissue were sequenced.Results:DNA of high-risk HPV types was detected in 93 out of 107 tumours (87%), all of which overexpressed p16 (HPV+/p16+). Of 14 HPV-negative (HPV-) tumours (13%), 10 (9%) were p16-negative (HPV-/p16-) and 4 (4%) overexpressed p16 (HPV-/p16+). Patients with HPV-/p16-disease had inferior 3-year locoregional control (LRC) (15%) compared with patients with HPV+/p16+ tumours (82%,