Joint modeling of two longitudinal outcomes and competing risk data

Aortic gradient and aortic regurgitation are echocardiographic markers of aortic valve function. Both are biomarkers repeatedly measured in patients with valve abnormalities, and thus, it is expected that they are biologically interrelated. Loss of follow‐up could be caused by multiple reasons, including valve progression related, such as an intervention or even the death of the patient. In that case, it would be of interest and appropriate to analyze these outcomes jointly. Joint models have recently received much attention because they cover a wide range of clinical applications and have promising results. We propose a joint model consisting of two longitudinal outcomes, one continuous (aortic gradient) and one ordinal (aortic regurgitation), and two time‐to‐events (death and reoperation). Moreover, we allow for more flexibility for the average evolution and the subject‐specific profiles of the continuous repeated outcome by using B‐splines. A disadvantage, however, is that when adopting a non‐linear structure for the model, we may have difficulties when interpreting the results. To overcome this problem, we propose a graphical approach. In this paper, we apply the proposed joint models under the Bayesian framework, using a data set including serial echocardiographic measurements of aortic gradient and aortic regurgitation and measurements of the occurrence of death and reoperation in patients who received a human tissue valve in the aortic position. The interpretation of the results will be discussed. Copyright © 2014 John Wiley & Sons, Ltd.     

Incidence and predictors of relapse during continuation treatment of major depression with SSRI, interpersonal psychotherapy, or their combination

Background: Despite the availability of many effective treatments, patients with major depression remain at risk for relapse following remission of a depressive episode. The aims of this report are to estimate the relapse rates associated with the acute treatment strategies employed in this study and to investigate demographic and clinical predictors of relapse. Methods: The study sample includes 225 patients who entered the 6‐month continuation treatment phase after remitting from an acute depressive episode. Treatment during the acute phase was interpersonal psychotherapy, SSRI (escitalopram), or the combination of the two when monotherapy did not lead to response. Relapse was defined by a Hamilton Depression Rating Scale score ≥15, confirmed by the diagnosis of major depression. The probability of relapsing was modeled using logistic regression. Three separate models were fit with subgroups of covariates. Results: Of the 225 patients, 29 (12.9%) relapsed and 28 (12.4%) discontinued the protocol prematurely. The proportion of patients who relapsed among the group requiring combination treatment to achieve remission was three times as high as among patients who had remitted with monotherapy. In the final logistic regression model, older age, higher baseline HDRS scores, last month (residual) depressive mood spectrum factor score, and requiring combination treatment to achieve remission were each associated with an increased likelihood of relapse. Conclusions: Our results suggest that greater initial depression severity, greater difficulty in stabilizing symptoms, and presence of residual mood spectrum symptoms once remission is achieved are predictive of relapse. Risk of relapse is more likely as age increases, partly because aging confers lower resilience. Depression and Anxiety, 2011. © 2011 Wiley Periodicals, Inc.     

Health behaviors and mental health of students attending alternative high schools: a review of the research literature

Purpose. The purpose of this review is to describe current knowledge about health‐risk behaviors and mental health among alternative high school students. Conclusions. Substance use, diet and/or physical activity, sexual‐risk behaviors, mental health, and violence were reviewed. Students were described as marginalized youth facing significant social environmental challenges. Findings from 43 studies published from 1997–2010 suggested a high prevalence of health‐risk behaviors among alternative high school students. Very few studies were conducted by nurse researchers. Suggestions for future research include addressing social environmental factors, resiliency, and emotional/mental health outcomes. Practice Implications. Alternative high schools offer a venue to conduct research and implement nursing interventions with high‐risk, yet resilient, youth.     

Sorafenib Continuation after First Disease Progression Could Reduce Disease Flares and Provide Survival Benefits in Patients with Hepatocellular Carcinoma: a Pilot Retrospective Study

Background: Sorafenib is a promising drug for advanced hepatocellular carcinoma (HCC); however,treatment may be discontinued for multiple reasons, such as progressive disease, adverse events, or the costof treatment. The consequences of sorafenib discontinuation and continuation are uncertain. Materials andMethods: We retrospectively analyzed 88 HCC patients treated with sorafenib from July 2007 to January 2013.Overall survival (OS), post-disease progression overall survival (pOS), and time to disease progression (TTP)were compared for survival analysis. Cox proportional hazard regression was performed to assess the effectof important factors on OS in the overall patient population and on pOS in patients who continued sorafenibtreatment. Results: Sorafenib was discontinued and continued in 24 and 64 patients, respectively. The medianOS (355 vs 517 days respectively; p=0.015) and median post-PD OS (260 vs 317 days, respectively; p=0.020) werestatistically different between the discontinuation and continuation groups. Neither the median time to first PDnor the time to second PD were significantly different between the 2 groups. In the discontinuation group, 3 of the24 patients (12.5%) suffered disease outbreaks. In Cox proportional hazard regression analysis after correctionfor confounding factors, BCLC stage (p=0.002) and PD site (p=0.024) were significantly correlated with pOS inpatients who continued sorafenib treatment. Conclusions: Sorafenib discontinuation may cause HCC flares oroutbreaks. It is advisable to continue sorafenib treatment after first PD, particularly in patients with BarcelonaClinic Liver Cancer stage B disease or only intrahepatic PD.     

Vaginal estrogen supplementation during Depo-Provera initiation: a randomized controlled trial

Background

Irregular bleeding is often cited as the reason for discontinuation of depot-medroxyprogesterone acetate (DMPA) after the first injection. Estrogen supplementation during DMPA initiation may decrease bleeding and improve continuation.

Study Design

This prospective, randomized, controlled trial evaluated estrogen supplementation during DMPA initiation. Women initiating DMPA were randomized to receive an estradiol vaginal ring for 3 months versus DMPA alone. Bleeding diaries and questionnaires at three and 6 months assessed bleeding, continuation and ring acceptability.

Results

Seventy-one participants enrolled; 49 completed the first follow-up period. The median number of bleeding or spotting days was 16 in the estrogen ring group (n=26) versus 28 in the DMPA alone group (n=23) (p=.19). Seventy-seven percent of the intervention group received a second injection compared with 70% in the DMPA alone group (p=.56). For each additional day of bleeding and/or spotting reported, women were 3% less likely to receive a second injection (OR 0.97, 95% CI 0.94-0.99). Acceptability of the vaginal ring was high among those in the intervention group.

Conclusions

Vaginal estrogen supplementation during DMPA initiation is acceptable to women and may decrease total bleeding.     

Adjusting the frequency of continuation and maintenance electroconvulsive therapy to prevent relapse of catatonic schizophrenia in middle-aged and elderly patients who are relapse-prone

The purpose of the present paper was to study the effect of continuation electroconvulsive therapy (ECT) on the prevention of relapse in middle-aged and elderly patients with intractable catatonic schizophrenia. It was found that continuation ECT is efficacious to sustain remission for patients who suffer relapse after response to acute ECT despite continuation neuroleptics. However, three patients suffered relapse during continuation ECT, therefore the effect of adjusting the frequency of continuation ECT and maintenance ECT was investigated in these patients with catatonic schizophrenia who relapsed during continuation ECT. These patients with DSM-IV catatonic schizophrenia who relapsed during continuation ECT were treated with more frequent continuation ECT and subsequent maintenance ECT after response to acute ECT. The patients' Brief Psychiatric Rating Scale (BPRS) scores were prospectively evaluated until relapse. Patients were considered to be relapsers if they had a BPRS score >or=37 for 3 consecutive days. The three patients with catatonic schizophrenia who relapsed during continuation ECT were treated successfully with more frequent continuation ECT and subsequent maintenance ECT. No patient experienced a severe adverse effect from continuation or maintenance ECT. More frequent continuation ECT and maintenance ECT deserves consideration in middle-aged and elderly patients with intractable catatonic schizophrenia who suffer relapse during continuation ECT. Large-scale systematic studies are warranted to investigate the optimum use of continuation and maintenance ECT in patients with catatonic schizophrenia.     

A Double-Blind Comparison of Sertraline and Imipramine in Outpatients with Major Depression: Acute (8 Weeks) and Continuation (16 Weeks) Treatment

In a double-blind multicentre trial in patients with major depression, the efficacy and the tolerability of sertraline were compared to those of imipramine, during an 8-week acute treatment phase followed by a 16-week continuation treatment phase in treatment responders. A total of 104 patients who met DSM-III-R criteria for major depression, HAM-D 17-item≥18 and Raskin Depression score>Covi Anxiety score, were randomized to receive either sertraline or imipramine. The initial daily dosage of 50 mg of sertraline or imipramine was rapidly titrated upwards in increments of 50 mg/day at weekly intervals, tolerability permitting, to a maximum of 200 mg/day by the fourth week. Eighty-eight patients completed at least 3 weeks of treatment and were included in the efficacy evaluable population. Both treatment groups demonstrated similar improvements on depression and anxiety rating scales during acute treatment, however, sertraline demonstrated significantly more improvement relative to imipramine on the HAM-D and Covi Anxiety scales after 1 week of treatment. Sertraline was more effective (HAM-D 17-item, CGI-S, SCL-56 Total score, SCL-56 Depression score, Covi Anxiety score) than imipramine in reducing depressive symptoms at the end of 24 weeks of treatment. There were significant improvements in all rating scales at week 24 relative to week 8 in the sertraline group but not in the imipramine group. The SCL-56 Total score, SCL-56 Depression score, Raskin Depression score and Covi Anxiety score at week 24 relative to week 8 showed significantly greater improvement in the sertraline group compared to the imipramine group. Imipramine was associated with a significantly higher incidence of dry mouth, sweating, constipation, palpitations, and a significantly higher heart rate and blood pressure. Sertraline was associated with a significantly higher incidence of diarrhoea/loose stools and insomnia. This study demonstrated a faster onset of therapeutic effect for sertraline relative to imipramine, reflecting the initiation of sertraline in a therapeutic dose of 50 mg/day and the need for gradual titration of imipramine to a therapeutic dose, at the beginning of treatment. Although efficacy was similar in both treatment groups at the end of the 8 weeks of acute therapy, sertraline-treated patients continued to manifest gradual improvements in depressive and anxiety symptoms during the 16 weeks of continuation therapy such that sertraline-treated patients were significantly more improved at the end of 24 weeks of therapy. © 1997 John Wiley & Sons, Ltd.