Factors that influence outcomes in cochlear implantation in adults, based on patient-related characteristics - a retrospective study.

OBJECTIVE: Outcomes in speech perception following cochlear implantation in adults vary widely. Many studies have been carried out to identify and quantify factors that influence outcomes. This study adds a new dimension to pre-existing literature. DESIGN: Single-centre retrospective cohort study. SETTING: University Medical Center Utrecht, the Netherlands. PARTICIPANTS: A total of 428 adults with bilateral severe-to-profound sensorineural hearing loss, unilaterally implanted between February 1988 and March 2014. MAIN OUTCOME MEASURES: Univariable and multivariable linear regression analyses were carried out to identify factors that may influence outcome after cochlear implantation. Consonant-vowel-consonant word scores were recorded pre- and post-implant and were used as outcome measure in two groups of patients (prelingually and postlingually deafened adults). As an added dimension, multiple imputation was implemented and evaluated to tackle 4% (17/407) missing data. RESULTS: For postlinguals, pre-implant speech perception score and age at onset of deafness are positive predictors and meningitis and otosclerosis as cause of deafness are negative predictors of post-implant speech perception. This model accounted for 26% of variance. For prelinguals, pre-implant speech perception score is the only strong positive predictor (ß 0.524; P < 0.001). This model accounted for 31% of variance. Age at implantation was not a significant predictor in either group. CONCLUSIONS: Speech perception is predicted by pre-implant speech perception, age at onset of deafness and aetiology (meningitis and otosclerosis) for postlinguals and solely pre-implant speech perception for prelinguals. Age at implantation is of lesser importance in predicting speech perception outcome post-implant. Multiple imputation is a useful statistical technique when analysing incomplete data sets.

Association studies suggest a key role for endothelin-1 in the pathogenesis of preeclampsia and the accompanying renin-angiotensin-aldosterone system suppression.

Women with preeclampsia display low renin-angiotensin-aldosterone system activity and a high antiangiogenic state, the latter characterized by high levels of soluble Fms-like tyrosine kinase (sFlt)-1 and reduced placental growth factor levels. To investigate whether renin-angiotensin-aldosterone system suppression in preeclampsia is because of this disturbed angiogenic balance, we measured mean arterial pressure, creatinine, endothelin-1 (ET-1), and renin-angiotensin-aldosterone system components in pregnant women with a high (≥85; n=38) or low (<85; n=65) soluble Fms-like tyrosine kinase-1/placental growth factor ratio. Plasma ET-1 levels were increased in women with a high ratio, whereas their plasma renin activity and plasma concentrations of renin, angiotensinogen, and aldosterone were decreased. Plasma renin activity-aldosterone relationships were identical in both the groups. Multiple regression analysis revealed that plasma renin concentration correlated independently with mean arterial pressure and plasma ET-1. Plasma ET-1 correlated positively with soluble Fms-like tyrosine kinase-1 and negatively with plasma renin concentration, and urinary protein correlated with plasma ET-1 and mean arterial pressure. Despite the lower plasma levels of renin and angiotensinogen in the high-ratio group, their urinary levels of these components were elevated. Correction for albumin revealed that this was because of increased glomerular filtration. Subcutaneous arteries obtained from patients with preeclampsia displayed an enhanced, AT2 receptor-mediated response to angiotensin II. In conclusion, a high antiangiogenic state associates with ET-1 activation, which together with the increased mean arterial pressure may underlie the parallel reductions in renin and aldosterone in preeclampsia. Because ET-1 also was a major determinant of urinary protein, our data reveal a key role for ET-1 in the pathogenesis of preeclampsia. Finally, the enhanced angiotensin responsiveness in preeclampsia involves constrictor AT2 receptors.

The long-term efficacy and safety profile of barnidipine.

Two multicentre trials have investigated the efficacy and tolerability of treatment with once-daily barnidipine, in patients with mild to moderate essential hypertension. The long-term efficacy and safety of barnidipine were demonstrated in a long-term, multicentre, open-label study. In total, 106, 79 and 32 patients were followed for the first, second and third year, respectively. Patients received barnidipine at a dose titrated to achieve a sitting DBP > or = 90 mmHg or a decrease in sitting BDP > or = 10 mmHg. If necessary, another antihypertensive agent was added to achieve normalisation of blood pressure. In the first year, normalisation of blood pressure was achieved in 91% of patients. This was maintained in 91% and 81% of patients in the second and third years, respectively. At the end of treatment in both years, over 60% of patients remained on barnidipine monotherapy (10 or 20 mg/day). A low incidence of adverse events possibly or probably related to barnidipine (10 or 20 mg/day) monotherapy was reported in the first and second years with headache, peripheral oedema and palpitations the most commonly reported. In the third year of follow-up, only one adverse event, an ECG abnormality, was considered to be possibly related to the study medication. The effective 24 hour control of blood pressure with barnidipine monotherapy was confirmed in a randomised, double-blind, placebo-controlled, cross-over study of 20 patients. These patients were given 6 week regimens of both barnidipine (20 mg/day) and placebo. Office and 24 hour ambulatory blood pressures were recorded at the end of each treatment phase. Barnidipine lowered blood pressure to a significantly greater extent than placebo both at night and during the day. Adverse events were classified as mild or moderate and fewer adverse events were reported with barnidipine treatment compared with placebo. Barnidipine monotherapy (20 mg/day) is safe and effective in providing 24 hour control of blood pressure. Furthermore, the efficacy and tolerability of barnidipine monotherapy (10 or 20 mg/day) are maintained for at least 2 years.

[Conversion from oral ACE inhibitor to intravenous quinaprilat administration in mild to moderate essential hypertension]. / Umstellung oraler ACE-Hemmer auf intravenös verabreichtes Quinaprilat bei leichter bis mittelschwerer essentieller Hypertonie.

AIM: This study was designed to evaluate the efficacy of intravenous quinaprilat in maintaining blood pressure control and to assess the safety of directly switching from oral angiotensin-converting enzyme (ACE) inhibitors to intravenous quinaprilate. PATIENTS AND METHOD: Following an initial 1-day open-label phase, patients with essential mild to moderate hypertension controlled by ACE inhibitor monotherapy were randomly assigned to treatment with intravenous quinaprilate (n = 36) or oral quinapril (n = 19) for a 3-day double-blind period. Quinaprilate (2.5, 5, or 10 mg BID) and quinapril (10, 20, or 40 mg OD) dosages were based on the patient's previous ACE inhibitor doses. The intravenously used dosages were half the dosages of orally administered enalapril, lisinopril and quinapril. Patients returned to their previous ACE inhibitor therapy during a second 1-day open-label phase. RESULTS: Quinaprilate and quinapril maintained diastolic blood pressure control at levels comparable to those during the initial open-label ACE inhibitor treatment. The mean difference between quinaprilate and quinapril treatment groups in diastolic blood pressure showed no clinically relevant differences between treatment groups with regard to mean changes from baseline. Mean reductions in systolic blood pressure were similar to those of diastolic blood pressure. CONCLUSION: Quinaprilate, at half the dose of quinapril, administered BID maintains blood pressure control, is well tolerated, and allows for safe conversion from previously applied oral ACE inhibitors. This finding is important for the antihypertensive treatment of patients in intensive care units or peri/post-operatively who cannot swallow orally administered drugs.

Efficacy and tolerability of a new controlled-release formulation of metoprolol: a comparison with conventional metoprolol tablets in mild to moderate hypertension.

In a double-blind study with parallel groups 195 hypertensive patients were randomly allocated to treatment with either conventional tablets of metoprolol, 100 mg once daily, or a new controlled-release (CR) formulation of metoprolol, 100 mg once daily. The dose was doubled if the patient's diastolic blood pressure remained greater than or equal to 95 mmHg after six weeks on 100 mg, whereas well-controlled patients continued on 100 mg once daily for a further six-week period. In the metoprolol tablet group the 200 mg dose was administered in the form of Durules. There was a significant reduction from the placebo baseline in systolic and diastolic blood pressure and heart rate at 24 h after both six weeks and 12 weeks of active treatment; no significant difference in the mean reduction from baseline between the two groups was demonstrated. However, significantly more patients responded to treatment with metoprolol CR when compared with those patients taking metoprolol tablets. After six weeks of active treatment 61% of the metoprolol CR group and 56% of the conventional metoprolol tablet group had a diastolic blood pressure less than 95 mmHg. After another six weeks the corresponding figures were 83% and 69% respectively. Between week 6 and 12, 36% of patients in the metoprolol CR group and 42% of patients in the conventional metoprolol tablet group were receiving a 200 mg dose. All formulations of metoprolol were well-tolerated. Fewer subjective symptoms were reported during active treatment than during the placebo phase. There were no differences between the groups with regard to changes in laboratory variables from baseline, changes in all combined symptoms, or changes in any one symptom.

Comparison of the antihypertensive effect of a double dose of metoprolol versus the addition of hydrochlorothiazide to metoprolol.

In 27 hypertensive patients whose blood pressure could not be adequately controlled with 200 mg metoprolol Durules alone, the effect of a double dose of metoprolol Durules (400 mg once daily) was compared with a fixed combination of 200 mg metoprolol and 25 mg hydrochlorothiazide (Selokomb). The study followed a double-blind cross-over schedule in 2 parallel groups. The reduction in diastolic blood pressure (p less than 0.01) was comparable in the two groups. A significant fall (p less than 0.01) in systolic blood pressure occurred with the metoprolol/hydrochlorothiazide combination. The subsequent change from the double dose of metoprolol Durules to the combination therapy also resulted in a fall in systolic blood pressure (p less than 0.05). Mean serum potassium and blood glucose levels did not change after each alteration in therapy. Most of the side-effects mentioned were mild and transient in character.