Investigating two mobile just-in-time adaptive interventions to foster psychological resilience: research protocol of the DynaM-INT study.

BACKGROUND: Stress-related disorders such as anxiety and depression are highly prevalent and cause a tremendous burden for affected individuals and society. In order to improve prevention strategies, knowledge regarding resilience mechanisms and ways to boost them is highly needed. In the Dynamic Modelling of Resilience - interventional multicenter study (DynaM-INT), we will conduct a large-scale feasibility and preliminary efficacy test for two mobile- and wearable-based just-in-time adaptive interventions (JITAIs), designed to target putative resilience mechanisms. Deep participant phenotyping at baseline serves to identify individual predictors for intervention success in terms of target engagement and stress resilience. METHODS: DynaM-INT aims to recruit N = 250 healthy but vulnerable young adults in the transition phase between adolescence and adulthood (18-27 years) across five research sites (Berlin, Mainz, Nijmegen, Tel Aviv, and Warsaw). Participants are included if they report at least three negative burdensome past life events and show increased levels of internalizing symptoms while not being affected by any major mental disorder. Participants are characterized in a multimodal baseline phase, which includes neuropsychological tests, neuroimaging, bio-samples, sociodemographic and psychological questionnaires, a video-recorded interview, as well as ecological momentary assessments (EMA) and ecological physiological assessments (EPA). Subsequently, participants are randomly assigned to one of two ecological momentary interventions (EMIs), targeting either positive cognitive reappraisal or reward sensitivity. During the following intervention phase, participants' stress responses are tracked using EMA and EPA, and JITAIs are triggered if an individually calibrated stress threshold is crossed. In a three-month-long follow-up phase, parts of the baseline characterization phase are repeated. Throughout the entire study, stressor exposure and mental health are regularly monitored to calculate stressor reactivity as a proxy for outcome resilience. The online monitoring questionnaires and the repetition of the baseline questionnaires also serve to assess target engagement. DISCUSSION: The DynaM-INT study intends to advance the field of resilience research by feasibility-testing two new mechanistically targeted JITAIs that aim at increasing individual stress resilience and identifying predictors for successful intervention response. Determining these predictors is an important step toward future randomized controlled trials to establish the efficacy of these interventions.

Comparison of negative inotropic and vasodilator effects of isradipine and nifedipine after complete autonomic blockade in ischemic heart disease.

The cardiodepressant and vasodilator effects of an intravenous (i.v.) infusion of 0.5 mg isradipine or 2 mg nifedipine were interindividually (10 vs. 10 patients) compared in a double-blind study in patients with stable coronary heart disease. To minimize vasodilation-induced autonomic reflex mechanisms, which may counterbalance negative inotropic effects after acute administration of calcium antagonists, i.v. autonomic blockade was produced by 0.2 mg/kg propranolol and 0.04 mg/kg atropine. Systemic hemodynamics were measured before and 15 min after the end of the 15-min calcium antagonist infusion. After administration of both drugs, heart rate (HR) decreased similarly during the observation period (isradipine from 93 +/- 10 to 88 +/- 9 beats/min and nifedipine from 84 +/- 9 to 79 +/- 6 beats/min, both p less than or equal to 0.01). The reduction in total peripheral resistance (TPR) was significantly (p less than or equal to 0.01) greater after isradipine (from 1,376 +/- 285 to 1,002 +/- 224 dynes s cm-5) than after nifedipine (1,258 +/- 262 to 1,112 +/- 225 dynes s cm-5). Between the two drugs, the difference in the reduction of afterload independent dP/dt40, determined by tip-manometry, reached borderline significance (p = 0.08) (isradipine from 1,197 +/- 258 to 1,157 +/- 225 mm Hg/s, NS and nifedipine 1,228 +/- 226 to 1,109 +/- 227 mm Hg/s, p less than or equal to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute and chronic effects of nitrendipine in patients with precapillary pulmonary hypertension due to pulmonary fibrosis.

Eleven patients with histologically confirmed fibrosis of the lung were investigated for the effects of the dihydropyridine calcium antagonist nitrendipine on pulmonary hemodynamics. After 5 mg of acute sublingual nitrendipine, mean pulmonary artery pressure was significantly lowered (p less than or equal to 0.05) from 32 +/- 3 to 29 +/- 3 mmHg at rest, and significantly lowered (p less than or equal to 0.05) during exercise from 55 +/- 4 to 49 +/- 4 mmHg. Short-term oxygen application at rest significantly reduced this parameter to 28 +/- 3 mmHg (p less than or equal to 0.001). Nitrendipine lowered total pulmonary vascular resistance during both rest (from 412 +/- 50 to 351 +/- 49 dyn.s.cm-5; p less than or equal to 0.05), although it did not affect pulmonary arteriolar resistance. Also, oxygen treatment at rest influenced only total pulmonary vascular resistance (reduction from 412 +/- 50 to 373 +/- 48 dyn.s.cm-5; p less than or equal to 0.01), but not pulmonary arteriolar resistance. Pressure-flow curves, which were derived from cardiac output at rest and during exercise and from the corresponding gradient between mean pulmonary artery pressure and pulmonary capillary wedge pressure, remained unchanged by acute medication. Since a change in arterial oxygen partial pressure was not noticed after nitrendipine, arteriovenous shunting or a worsening of ventilation perfusion relationships can be excluded. Long-term (3 weeks) treatment (double-blind parallel design) with 10 mg of nitrendipine (4 patients) once daily showed no advantage in comparison to placebo (6 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of 5 mg sublingual nitrendipine in patients with precapillary pulmonary hypertension due to pulmonary fibrosis.

In 10 patients with precapillary pulmonary hypertension due to pulmonary fibrosis, the arterial blood pressure, right heart hemodynamics, cardiac output, and arterial oxygen partial pressure were measured to evaluate the benefits of acute sublingual (5 mg) nitrendipine. Additionally, the effect of oxygen enriched air was compared to control. At rest, nitrendipine significantly diminished arterial blood pressure [102 +/- 3 to 93 +/- 3 mm Hg (mean +/- SEM)], right atrial pressure (5.7 +/- 0.9 to 3.4 +/- 0.8 mm Hg), mean pulmonary artery pressure (33.4 +/- 3.5 to 29.8 +/- 3.3 mm Hg), and pulmonary artery wedge pressure (13.0 +/- 2.0 to 6.8 +/- 0.8 mm Hg). During exercise, nitrendipine reduced mean pulmonary artery pressure (54.5 +/- 4.8 to 49.3 +/- 4.7 mm Hg) and right atrial pressure (9.3 +/- 1.3 to 6.8 +/- 1.4 mm Hg). A diminuation of arterial partial oxygen pressure did not occur at rest (63.2 +/- 3.8 mm Hg) or during exercise (50.9 +/- 5.1 mm Hg). Thus, nitrendipine causes a slight but significant improvement of right heart hemodynamics. The occurrence of arteriovenous intrapulmonary shunting due to vasodilatating effects of nitrendipine can be excluded. Also, nitrendipine can safely be used in combined arterial hypertension and pulmonary fibrosis.

The Frankfurt experience in restenosis after coronary angioplasty.

Three hundred and thirty-three of 356 patients underwent angiographic follow-up from 1 to 18 months (mean 5.6 months) after percutaneous transluminal coronary angioplasty (PTCA). This is a reangiography rate of 94%. Recurrence rate after the first PTCA was 15% (n = 289). Restenosis rate was defined as an increase from immediate post-PTCA stenosis of more than 30%, or the loss of at least half of the initial gain in luminal diameter. Patients who needed a second angioplasty due to restenosis (n = 30) had a restenosis rate of 33%. Patients with angioplasty in the aortocoronary bypass (n = 14) had a restenosis rate of 45%. All patients were treated before, during and at least 4 to 6 months after the procedure with 60 to 100 mg of isosorbide dinitrate daily plus 160 to 360 mg of verapamil or 100 to 150 mg of gallopamil and 1.5 g of acetylsalicylic acid. In a second retrospective study 111 of 399 patients had the acetylsalicylic acid therapy discontinued or decreased. Forty-two of them developed restenosis (38%), whereas only 49 of 288 patients who continued to receive 1.5 g aspirin developed restenosis (17%). The restenosis rate was 32% in those who received the reduced dose of aspirin. Thus, a large dose of acetylsalicylic acid given before, during and 4 to 6 months after the procedure seems to be necessary to achieve a low rate of restenosis after PTCA.

Relation of antianginal efficacy of nifedipine to degree of coronary arterial narrowing and to presence of coronary collateral vessels.

Thirty-six patients with chronic stable angina pectoris or with stable and vasospastic components of angina pectoris were classified by coronary arteriographic findings into 4 groups. Patients in group A had a single stenotic coronary artery; patients in groups B, C and D had occluded arteries, but these arteries had been collateralized to varying degrees, and an epicardial coronary steal phenomenon was possible. All patients underwent multiple exercise tests before and after randomized, double-blind, crossover treatment with 20 mg of nifedipine, 20 mg of isosorbide dinitrate, a combination of both, and placebo. Maximal and mean ST-segment depression, occurrence of angina pectoris and heart rate were evaluated. After nifedipine treatment, mean ischemic ST-segment depression was reduced 21% in group A (p less than 0.05), but was not significantly altered in the other groups (group B, 2% decrease; group C, 10% increase; group D, 3% decrease). However, isosorbide dinitrate reduced ST-segment depression significantly in all groups (group A, 29%, p less than 0.001; group B, 18%, p less than 0.01; group C, 19%, p less than 0.05; group D, 33%, p less than 0.05). The combination with nifedipine did not further improve the effect of isosorbide dinitrate. Maximal ST-segment depression and angina pectoris paralleled the changes in mean ST depression during the different medications. Heart rate at rest was not significantly changed after nifedipine treatment in any group, but increased significantly after isosorbide dinitrate treatment in groups B and C (group B, 12%, p less than 0.01; group C, 9%, p less than 0.05); heart rate during exercise did not differ significantly in any group or after any form of medication from placebo.

[Anti-angina effectiveness of the calcium antagonist nifedipine in relation to coronary involvement]. / Antianginöse Wirksamkeit des Kalziumantagonisten Nifedipin in Abhängigkeit vom Koronarbefall.

36 patients with chronic stable or the variant form of angina pectoris were subdivided according to their coronary angiogram into 4 groups: Group A with a single highgrade stenosis in one coronary artery, Groups B, C and D with different patterns of occluded, but collateralized coronary arteries supplying noninfarcted myocardium. All patients underwent multiple exercise step tests before (K) and after randomly assigned crossover treatment with 20 mg nifedipine (N), 20 mg isosorbiddinitrate (I), the combination of both (I + N) and Placebo (P). Peak and mean ischemic ST-segment depression, the occurrence of angina pectoris and heart rate were evaluated. The mean ischemic ST-segment depression decreased significantly after N in group A by -28% (p less than 0.01), but was not significantly altered in the groups B, C and D (B: -12%, C: +7%, D: +2%). After I, mean ST-segment depression decreased significantly in all groups (A: -36%, p less than 0.001; B: -27%, p less than 0.001; C: -22%, p less than 0.01; D: -29%, p less than 0.05). The combination of I + N was not better than I alone. Peak ST-depression and angina pectoris paralleled the results of mean ST-depression. The resting heart rate increased significantly after N only in group A (+9%, p less than 0.01) and increased after I in the groups A, B and C (A: +11%, p less than 0.05; B: +12%, p less than 0.05; C: +12%, p less than 0.01). During exercise, heart rate was not significantly different in any group or after any type of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)