The Cost-Effectiveness of an Internet Intervention to Facilitate Mental Health Help-Seeking by Young Adults: Randomized Controlled Trial.

BACKGROUND: Little empirical evidence is available to support the effectiveness and cost-effectiveness of internet interventions to increase help-seeking behavior for mental health in young adults. OBJECTIVE: The aim of this study was to evaluate the cost-effectiveness of a Web-based mental health help-seeking navigation tool (Link) in comparison with usual help-seeking strategies. METHODS: A cost-utility analysis alongside the main randomized trial of Link was conducted from the Australian health care sector perspective. Young adults aged 18 to 25 years were randomized to the Link intervention (n=205) or usual care (n=208) with 1- and 3-month follow-ups. The primary outcome of this study was quality-adjusted life years (QALYs) measured by the assessment of quality of life-4D. Costs were calculated based on the self-reported resource use questionnaire and were reported in 2015 Australian dollars. Primary analyses were conducted as intention-to-treat and reported as incremental cost-effectiveness ratios. Completer analyses were conducted in a sensitivity analysis. RESULTS: Significantly more QALYs were gained in the intervention group than the control group (0.15 vs 0.14; P<.001). The intervention was associated with significantly lower health professional consultation costs at 1-month follow-up (mean costs Aus $98 vs Aus $162; P<.05). Costs of hospital services were lower at 3 months in the intervention arm (mean costs Aus $47 vs Aus $101); however, there was insufficient sample size to detect a significant difference between the groups. There were no statistically significant differences in the total costs between the 2 arms. Relative to the control group, those who received the intervention experienced 0.01 more QALYs (0.00-0.02) and had lower total health sector costs of Aus -$81 (Aus -$348 to Aus $186) over 3 months. The intervention was found to be more effective and less costly compared with usual help-seeking strategies. The intervention was 100% likely to be cost-effective below a willingness-to-pay value-for-money threshold of Aus $28,033 per QALY. Results were robust in the sensitivity analysis. CONCLUSIONS: Our study found that the online youth mental health help-seeking Web service is a cost-effective intervention for young people aged 18 to 25 years compared with usual search strategies. Further research is required to confirm these results. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12614001223628; https://www.anzctr.org.au /Trial/Registration/TrialReview.aspx?id=366731.

Effectiveness of a Mental Health Service Navigation Website (Link) for Young Adults: Randomized Controlled Trial.

BACKGROUND: Mental health and substance use disorders are the main causes of disability among adolescents and young adults yet fewer than half experiencing these problems seek professional help. Young people frequently search the Web for health information and services, suggesting that Web-based modalities might promote help-seeking among young people who need it. To support young people in their help-seeking, we developed a Web-based mental health service navigation website called Link. Link is based on the Theory of Planned Behavior and connects young people with treatment based on the type and severity of mental health symptoms that they report. OBJECTIVE: The study aimed to investigate the effect of Link on young people's positive affect (PA) compared with usual help-seeking strategies immediately post intervention. Secondary objectives included testing the effect of Link on negative affect (NA), psychological distress, barriers to help-seeking, and help-seeking intentions. METHODS: Young people, aged between 18 and 25 years, were recruited on the Web from an open access website to participate in a randomized controlled trial. Participants were stratified by gender and psychological distress into either the intervention arm (Link) or the control arm (usual help-seeking strategies). Baseline, immediate postintervention, 1-month, and 3-month surveys were self-reported and administered on the Web. Measures included the PA and NA scales, Kessler psychological distress scale (K10), barriers to adolescent help-seeking scale (BASH), and the general help-seeking questionnaire (GHSQ). RESULTS: In total 413 young people were recruited to the trial (intervention, n=205; control, n=208) and 78% (160/205) of those randomized to the intervention arm visited the Link website. There was no evidence to support a difference between the intervention and control arms on the primary outcome, with PA increasing equally by approximately 30% between baseline and 3 months in both arms. NA decreased for the intervention arm compared with the control arm with a difference of 1.4 (95% CI 0.2-2.5) points immediately after the intervention and 2.6 (95% CI 1.1-4.1) at 1 month. K10 scores were unchanged and remained high in both arms. No changes were found on the BASH or GHSQ; however, participants in the intervention arm appeared more satisfied with their help-seeking process and outcomes at 1 and 3 months postintervention. CONCLUSIONS: The process of prompting young people to seek mental health information and services appears to improve their affective state and increase help-seeking intentions, regardless of whether they use a Web-based dedicated youth-focused tool, such as Link, or their usual search strategies. However, young people report greater satisfaction using tools designed specifically for them, which may encourage future help-seeking. The ability of Web-based tools to match mental health needs with appropriate care should be explored further. CLINICAL TRIAL: Australian New Zealand Clinical Trials Registry ACTRN12614001223628; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366731.

Facilitating mental health help-seeking by young adults with a dedicated online program: a feasibility study of Link.

OBJECTIVE: To explore the feasibility of a dedicated online youth mental health help-seeking intervention and to evaluate using a randomised controlled trial (RCT) study design in order to identify any modifications needed before commencement of the full-scale RCT. DESIGN: A pilot RCT with 1:1 randomisation to either the intervention or comparison arm. SETTING: An online study conducted Australia-wide. PARTICIPANTS: 18-25 year olds living in Australia were recruited via social media. INTERVENTION: Link is a dedicated online mental health help-seeking navigation tool that matches user's mental health issues, severity and service-type preferences (online, phone and face-to-face) with appropriate youth-friendly services. The comparison arm was usual help-seeking strategies with a link to Google.com. MAIN OUTCOME MEASURES: The primary outcome was the number of acceptability and feasibility criteria successfully met. Intervention and study design acceptability and feasibility were assessed by nine criteria. Secondary outcomes, via online surveys (at baseline, 1 week and 1 month) measured service use, help-seeking intentions, psychological distress, barriers to help-seeking, attitudes towards mental health help-seeking, mental health literacy, satisfaction and trust. RESULTS: Fifty-one participants were randomised (intervention: n=24; comparison: n=27). Three out of four of the intervention and two out of five of the study design criteria were met. Unmet criteria could be addressed by modifications to the study design. Qualitative analysis demonstrated that Link was useful to participants and may have increased their positive experiences towards help-seeking. There were no observable differences between arms in any outcome measures and no harms were detected. CONCLUSION: Generally, the Link intervention and study design were acceptable and feasible with modifications suggested for the four out of nine unmet criteria. The main trial will hence have shorter surveys and a simpler recruitment process, use positive affect as the primary outcome and will not link to Google.com for the comparison arm. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry, ACTRN12614000386639.

Chronic amiodarone-induced inhibition of the Na+-K+ pump in rabbit cardiac myocytes is thyroid-dependent: comparison with dronedarone.

OBJECTIVE: To examine the thyroid-dependence of the effect of amiodarone on the sarcolemmal Na(+)-K(+) pump, and the effect on the pump of dronedarone, a deiodinated amiodarone congener without influence on thyroid status. METHODS: New Zealand white rabbits underwent total thyroidectomy, sham thyroidectomy or thyroidectomy and concomitant oral amiodarone therapy. After 5 weeks, Na(+)-K(+) pump current was measured using the whole-cell patch-clamp technique in isolated ventricular myocytes. Pump current was also measured in myocytes isolated from a separate group of rabbits not subjected to thyroidectomy but treated with dronedarone, or placebo for 3 weeks. RESULTS: Treatment of thyroidectomised rabbits with amiodarone caused a significant prolongation of the corrected QT interval (QT(c)) and sinus cycle length. Na(+)-K(+) pump current measured in myocytes isolated from thyroidectomised rabbits was significantly lower than pump current in myocytes from sham-operated controls. However, treatment of thyroidectomised rabbits with amiodarone did not cause any additional decrease in pump current. Treatment with dronedarone caused prolongation of QT(c). However, it had no effect on Na(+)-K(+) pump current. CONCLUSIONS: The inhibitory effect of amiodarone on Na(+)-K(+) pump current is thyroid-dependent, whereas the effects on heart rate and QT(c) are at least partially mediated by thyroid-independent mechanisms. In contrast to its parent compound, dronedarone has no significant effects on the activity of the Na(+)-K(+) pump.

Alloxan-induced diabetes reduces sarcolemmal Na+-K+ pump function in rabbit ventricular myocytes.

The effect of diabetes on sarcolemmal Na(+)-K(+) pump function is important for our understanding of heart disease associated with diabetes and design of its treatment. We induced diabetes characterized by hyperglycemia but no other major metabolic disturbances in rabbits. Ventricular myocytes isolated from diabetic rabbits and controls were voltage clamped and internally perfused with the whole cell patch-clamp technique. Electrogenic Na(+)-K(+) pump current (I(p), arising from the 3:2 Na(+)-to-K(+) exchange ratio) was identified as the shift in holding current induced by Na(+)-K(+) pump blockade with 100 micromol/l ouabain in most experiments. There was no effect of diabetes on I(p) recorded when myocytes were perfused with pipette solutions containing 80 mmol/l Na(+) to nearly saturate intracellular Na(+)-K(+) pump sites. However, diabetes was associated with a significant decrease in I(p) measured when pipette solutions contained 10 mmol/l Na(+). The decrease was independent of membrane voltage but dependent on the intracellular concentration of K(+). There was no effect of diabetes on the sensitivity of I(p) to extracellular K(+). Pump inhibition was abolished by restoration of euglycemia or by in vivo angiotensin II receptor blockade with losartan. We conclude that diabetes induces sarcolemmal Na(+)-K(+) pump inhibition that can be reversed with pharmacological intervention.

Dependence of Na+-K+ pump current-voltage relationship on intracellular Na+, K+, and Cs+ in rabbit cardiac myocytes.

To examine effects of cytosolic Na+, K+, and Cs+ on the voltage dependence of the Na+-K+ pump, we measured Na+-K+ pump current (Ip) of ventricular myocytes voltage-clamped at potentials (Vm) from 100 to +60 mV. Superfusates were designed to eliminate voltage dependence at extracellular pump sites. The cytosolic compartment of myocytes was perfused with patch pipette solutions with a Na+ concentration ([Na]pip) of 80 mM and a K+ concentration from 0 to 80 mM or with solutions containing Na+ in concentrations from 0.1 to 100 mM and K+ in a concentration of either 0 or 80 mM. When [Na]pip was 80 mM, K+ in pipette solutions had a voltage-dependent inhibitory effect on Ip and induced a negative slope of the Ip-Vm relationship. Cs+ in pipette solutions had an effect on Ip qualitatively similar to that of K+. Increases in Ip with increases in [Na]pip were voltage dependent. The dielectric coefficient derived from [Na]pip-Ip relationships at the different test potentials was 0.15 when pipette solutions included 80 mM K+ and 0.06 when pipette solutions were K+ free.

Dietary cholesterol alters Na+/K+ selectivity at intracellular Na+/K+ pump sites in cardiac myocytes.

A modest diet-induced increase in serum cholesterol in rabbits increases the sensitivity of the sarcolemmal Na+/K+ pump to intracellular Na+, whereas a large increase in cholesterol levels decreases the sensitivity to Na+. To examine the mechanisms, we isolated cardiac myocytes from controls and from rabbits with diet-induced increases in serum cholesterol. The myocytes were voltage clamped with the use of patch pipettes that contained osmotically balanced solutions with Na+ in a concentration of 10 mM and K+ in concentrations ([K+]pip) ranging from 0 to 140 mM. There was no effect of dietary cholesterol on electrogenic Na+/K+ current (Ip) when pipette solutions were K+ free. A modest increase in serum cholesterol caused a [K+]pip-dependent increase in Ip, whereas a large increase caused a [K+]pip-dependent decrease in Ip. Modeling suggested that pump stimulation with a modest increase in serum cholesterol can be explained by a decrease in the microscopic association constant KK describing the backward reaction E1 + 2K+ --> E2(K+)2, whereas pump inhibition with a large increase in serum cholesterol can be explained by an increase in KK. Because hypercholesterolemia upregulates angiotensin II receptors and because angiotensin II regulates the Na+/K+ pump in cardiac myocytes in a [K+]pip-dependent manner, we blocked angiotensin synthesis or angiotensin II receptors in vivo in cholesterol-fed rabbits. This abolished cholesterol-induced pump inhibition. Because the epsilon-isoform of protein kinase C (epsilonPKC) mediates effects of angiotensin II on the pump, we included specific epsilonPKC-blocking peptide in patch pipette filling solutions. The peptide reversed cholesterol-induced pump inhibition.