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  < 0.001, n  = 40) and 59.5% in the SoC arm ( P  < 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.

Adjuvant VACcination against HPV in surgical treatment of Cervical Intra-epithelial Neoplasia (VACCIN study) a study protocol for a randomised controlled trial.

BACKGROUND: Cervical cancer is caused by Human Papilloma viruses (HPV) and is preceded by precursor stages: Cervical Intraepithelial Neoplasia (CIN). CIN is mostly found in women in their reproductive age and treated with a Loop Electrosurgical Excision Procedure (LEEP). The recurrence or residual disease rate after treatment is up to 17%. These women have a lifelong increased risk of recurrent CIN, cervical cancer and other HPV related malignancies. Furthermore, LEEP treatments are associated with complications such as premature birth. Limited data show that prophylactic HPV vaccination at the time of LEEP reduces recurrence rates, therefore leading to a reduction in repeated surgical interventions and side effect like preterm birth. The primary study objective is to evaluate the efficacy of the nonavalent HPV vaccination in women with a CIN II-III (high-grade squamous intraepithelial lesion (HSIL) lesion who will undergo a LEEP in preventing recurrent CIN II-III after 24 months. METHODS: This study is a randomised, double blinded, placebo controlled trial in 750 patients without prior HPV vaccination or prior treatment for CIN and with histologically proven CIN II-III (independent of their hrHPV status) for whom a LEEP is planned. Included patients will be randomised to receive either three injections with nonavalent (9 HPV types) HPV vaccine or placebo injections (NaCL 0.9%) as a comparator. Treatment and follow-up will be according the current Dutch guidelines. Primary outcome is recurrence of a CIN II or CIN III lesion at 24 months. A normal PAP smear with negative hrHPV test serves as surrogate for absence of CIN. At the start and throughout the study HPV typing, quality of life and cost effectiveness will be tested. DISCUSSION: Although prophylactic HPV vaccines are highly effective, little is known about the effectivity of HPV vaccines on women with CIN. Multiple LEEP treatments are associated with complications. We would like to evaluate the efficacy of HPV vaccination in addition to LEEP treatment to prevent residual or recurrent cervical dysplasia and decrease risks of repeated surgical treatment. TRIAL REGISTRATION: Medical Ethical Committee approval number: NL66775.078.18. Affiliation: Erasmus Medical Centre. Dutch trial register: NL 7938. Date of registration 2019-08-05.

External validation of three prognostic models for overall survival in patients with advanced-stage epithelial ovarian cancer.

BACKGROUND: For various malignancies, prognostic models have shown to be superior to traditional staging systems in predicting overall survival. The purpose of this study was to validate and compare the performance of three prognostic models for overall survival in patients with advanced-stage epithelial ovarian cancer. METHODS: A multi-institutional epithelial ovarian cancer database was used to identify patients and to evaluate the predictive performance of two nomograms, a prognostic index and FIGO (International Federation of Obstetrics and Gynecology) stage. All patients were treated for advanced-stage epithelial ovarian cancer between January 1996 and January 2009 in 11 hospitals in the eastern part of The Netherlands. RESULTS: In total, 542 patients were found to be eligible. Overall performance did not differ between the three prognostic models and FIGO stage. The discriminative performance for Chi's model was moderately good (c indices 0.65 and 0.68) and for the models of Gerestein and Teramukai reasonable (c indices between 0.60 and 0.62). The c indices of FIGO stage ranged between 0.54 and 0.62. After recalibration, the three models showed almost perfect calibration, whereas calibration of FIGO stage was reasonable. CONCLUSION: The three prediction models showed general applicability and a reasonably well-predictive performance, especially in comparison to FIGO stage. To date, there are no studies available that analyse the impact of these prognostic models on decision-making and patient outcome. Therefore, the usefulness of these models in daily clinical practice remains to be investigated.

Adherence to a Mediterranean dietary pattern in early life is associated with lower arterial stiffness in adulthood: the Amsterdam Growth and Health Longitudinal Study.

OBJECTIVES: To investigate whether adherence to a Mediterranean dietary pattern during adolescence and early adulthood affects arterial stiffness in adulthood, and the extent to which any such association may be attributed to a beneficial impact of this diet on cardiovascular disease risk factors such as blood pressure, central fatness and dyslipidaemia. SETTING: The Amsterdam Growth and Health Longitudinal Study. DESIGN AND SUBJECTS: We compared longitudinal levels of adherence to a Mediterranean dietary pattern (aMED score with range 0-9) during adolescence and adulthood (two to eight repeated measures obtained between the ages of 13 and 36) between individuals with different levels of arterial stiffness in adulthood. The study population included 373 (196 women) apparently healthy adults in whom properties of the carotid, brachial and femoral arteries were assessed using ultrasonography at 36 years of age. RESULTS: After adjustments for potential confounders, individuals with stiffer carotid arteries (defined on the basis of the most adverse tertile of, for instance, the distensibility coefficient) had lower aMED scores (-0.32, 95% CI -0.60; -0.06) and were less likely to have adhered to this dietary pattern (aMED score ≥5, odds ratio 0.69, 95% CI 0.50; -0.94) during the preceding 24 years compared with those with less stiff arteries. Differences in aMED scores were already present in adolescence and were only in part explained by the favourable associations between the Mediterranean dietary pattern and other cardiovascular disease risk factors (up to 26%), particularly mean blood pressure (up to 19%). CONCLUSIONS: Promoting the Mediterranean diet in adolescence and early adulthood may constitute an important means of preventing arterial stiffness in adulthood.

Predicting mortality of psychogeriatric patients: a simple prognostic frailty risk score.

BACKGROUND AND AIMS: Frailty and mortality in psychogeriatric patients are hard to predict but important in counselling and therapeutic decision making. We have therefore developed a simple frailty risk score to predict mortality this population. STUDY DESIGN: Prospective observational study including 401 community dwelling psychogeriatric patients (249 women; mean (SD) age 78.0 (6.5) years), who had been referred to a multidisciplinary diagnostic observation centre. We used Cox proportional hazards regression models to identify and select baseline characteristics for the development and validation of a risk score for the prediction of 3 year mortality. RESULTS: A total of 116 subjects died during follow-up (median follow-up duration of 26 months). Baseline characteristics associated with mortality were: age (hazard ratio (HR) 1.44, 95% confidence interval (CI)1.02 to 2.04), male sex (HR 2.93, 95% CI 1.89 to 4.59), living alone (HR 1.53, 95% CI 0.99 to 2.38), body mass index (BMI) <18.5 kg/m(2) (HR 4.09, 95% CI 2.06 to 8.14), cardiovascular disease (HR 1.42, 95% CI 0.94 to 2.15), elderly mobility score <20 (HR 1.92, 95% CI 1.24 to 2.98), number of medicines > or =2 (HR 2.28, 95% CI 1.21 to 4.31), and impaired motor (HR 1.47, 95% CI 0.93 to 2.32) and process skills (HR 1.92, 95% CI 1.12 to 2.98) in activities of daily living. These predictors were translated into an easy-to-use frailty risk score and patients were stratified into very good (<45 points), good (45-50) moderate (51-55), poor (56-61) and very poor (>61) prognosis groups. Three year mortality rates across these groups were 8.0%, 15.9%, 25.9%, 41.5%, and 68.8%, respectively (p<0.001). The area under the receiver operating characteristic curve (AUC) of the risk score was 0.78 (95% CI 0.73 to 0.82), indicating good discriminative performance. CONCLUSIONS: We developed and validated a risk score for the prediction of 3 year mortality. This risk score can be used to stratify patients into different risk categories, thereby informing patient counselling and tailored diagnostic and therapeutic decisions in clinical practice.

Plasma pipecolic acid is frequently elevated in non-peroxisomal disease.

We reviewed our data on patients in whom plasma pipecolic acid was analysed. Mild to moderate elevations of pipecolic acid were frequently found in non-peroxisomal disorders and this should be taken into account when interpreting the laboratory data.

Systemic effects of inhalational methyl bromide poisoning: a study of nine cases occupationally exposed due to inadvertent spread during fumigation.

Systemic methyl bromide (CH3Br) poisoning with signs and symptoms of varying severity developed in nine greenhouse workers after acute inhalational exposure on two consecutive days. Measurements of CH3Br, carried out at the site within hours after the accident, suggest that exposure on the second day may have been in excess of 200 ppm (800 mg/m3) CH3Br. All workers were admitted for observation. Seven of them were discharged after an uneventful overnight observation and residual symptoms, if any, subsided within three weeks of the accident. Two patients needed intensive care for several weeks because of severe reactive myoclonus and tonic-clonic generalised convulsions. These conditions were unresponsive to repeated doses of diazepam, clonazepam, and diphenylhydantoin but could be suppressed effectively by induction of a thiopental coma that had to be continued for three weeks. In some of the patients prior subchronic exposure to CH3Br, as shown by their occupational histories and high serum bromide (Br-) concentrations, is likely to have been a factor contributing to the severity of their symptoms. A direct association between serum Br- concentrations and the severity of neurological symptoms, however, seemed to be absent. An on site investigation into the circumstances leading to the accident showed the presence of an empty and out of use drainage system that covered both sections of the greenhouse. This was probably the most important factor contributing to the rapid and inadvertent spread of CH3Br.