2 Minute Medicine Rewind June 25, 2018

Association of Stress-Related Disorders with Subsequent Autoimmune Disease

Previous studies have shown that trauma and stressful life events may contribute to the development of psychiatric disorders in some individuals. In addition, these events have also been shown to be associated with significant physiologic alterations in the hypothalamic-pituitary-adrenal axis and the autonomic nervous system. There is, however, limited data surrounding the relationship between stress-related disorders and autoimmune disease. In this retrospective cohort study, 106,464 patients with stress-related disorders were matched by birth year and sex with 1,064,640 individuals without stress-related disorders to assess the association between stress-related disorders and subsequent risk of autoimmune disease. A sibling comparison study was also conducted to control for familial factors, and comprised 78,635 exposed individuals and 126,652 unexposed siblings. Stress-related disorder diagnoses included post-traumatic stress disorder, acute stress reaction, adjustment disorder and other stress reactions. Patients were followed up from 1981 through 2013, during which a total of 41 distinct autoimmune diseases were diagnosed. Researchers found that the incidence of autoimmune disease during the follow-up period was higher in the exposed cohort group (incidence rate 9.1, 95% CI 8.9 to 9.3) than in the unexposed (incidence rate 6.0, 95% CI 5.9 to 6.0) and sibling cohort groups (incidence rate, 6.5, 95% CI 6.4 to 6.7). After controlling for confounders, patients in the exposed cohort were at an increased risk of developing autoimmune disease as compared to the matched unexposed group (HR 1.36, 95%CI 1.33 to 1.40) and the sibling cohort group (HR 1.27, 95% CI 1.20 to 1.34).  Notably, the observed excess risk decreased following persistent use of selective serotonin reuptake inhibitors (SSRIs) during the first year after PTSD diagnosis (HR 3.64, 95% CI 2.00 to 6.62 for ≤ 179 days of SSRI use; HR 1.82, 95% CI 1.09 to 3.02 for ≥ 320 days). The study was limited by surveillance bias, the exclusion of diagnoses made in primary care settings, and the lack of corroboration for diagnoses of stress-related disorders. Overall, this study underlines an association between stress-related disorders and an increased risk of autoimmune disease. These findings align with previous studies linking psychological stress to immune system impairment, although future studies are warranted in delineating underlying mechanisms.

A Randomized Trial of a Family-Support Intervention in Intensive Care Units

In intensive care settings, discussions regarding end-of-life decisions frequently involve patients’ surrogate decision-makers. Miscommunication during these discussions can lead to short and long-term emotional distress in surrogates. Therefore, validated interventions to address the affective and cognitive challenges facing surrogate decision-makers are warranted. In this cluster-randomized controlled trial, five intensive care units (ICUs) provided usual care (control phase) then transitioned to a multicomponent family-support intervention at a randomly assigned time to study the impact on surrogate symptoms of anxiety and depression 6 months after hospital discharge, as assessed using the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes included surrogates’ rating of the quality of clinician-family communication on the Quality of Communication scale (QOC) and of patient- and family-centeredness of care on the Patient Perception of Patient Centeredness scale (PPPC), and the mean length of stay in the ICU after trial entry. A total of 1,420 patients were included in the trial, and surrogates for 809 of those patients completed long-term follow-up. At baseline, there was an older mean age of patients and higher scores for severity of acute illness and number of chronic illnesses in the intervention group than in the control group. Researchers found that there was no significant difference in the mean HADS score at 6 months between the intervention and control groups (11.7 and 12.0 respectively; beta coefficient for estimated effect of intervention -0.34, 95% CI -1.67 to 0.99, p=0.61). However, the quality of clinician-family communication during hospitalization was significantly better in the intervention group than in the control group (mean QOC score 69.1 vs. 62.7, beta coefficient 6.39, 95% CI 2.57 to 10.20, p=0.001), as was the perceived patient- and family-centeredness of care (mean modified PPPC score 1.7 vs. 1.8, beta coefficient -0.15, 95% CI-0.26 to -0.04, p=0.006). Additionally, the mean length of stay in the ICU among patients who died was significantly shorter in the intervention group than in the control group (4.4 vs. 6.8 days, incidence rate ratio 0.64, 95% CI 0.52 to 0.78, p<0.001). The study was limited by differences in baseline characteristics of the treatment groups and possible subsequent confounding. Overall, this study suggests that, while family-support interventions may not impact surrogates’ depression and anxiety symptoms following ICU stays, such interventions have the capacity to improve perception of clinician-family communication and patient-centeredness of care and decrease length of ICU stay.

Personalised perioperative care by e-health after intermediate-grade abdominal surgery: a multicentre, single-blind, randomised, placebo-controlled trial

Despite recent advances in minimally invasive surgical techniques, recovery times remain longer than expected. This may be, in part, due to the paucity of resources available in providing patients with thorough postoperative care instructions. Thus, there may be a role for an interactive, personalized electronic program to help patients achieve postoperative recovery more rapidly. In this randomized controlled trial, 344 patients scheduled for laparoscopic cholecystectomy, inguinal hernia surgery, or laparoscopic adnexal surgery for a benign indication were randomized to participate in an e-health-care program or receive usual care to examine the impact of such an intervention on time from surgery to the patient’s return to normal activities. The intervention was designed to manage recovery expectations and provide postoperative guidance. Patients in the control group were able to access a website containing standard non-personalized recovery advice. At baseline, patients in the control group expected to return to work earlier than those in the intervention group. Researchers found that the time until return to normal activities was significantly shorter in the intervention group than in the control group (21 days vs. 26 days, adjusted HR 1.38, 95% CI 1.09 to 1.73, p=0.007). In addition, time until full resumption of work was significantly shorter in the intervention group than in the control group (median 18 days vs. 19 days, adjusted HR 1.31, 95% CI 1.01 to 1.70, p=0.045). There was no significant difference in total health care costs between the two groups, and no negative effects of the e-health intervention were noted. The study was limited by low eligibility (38%), mostly due to refusal to participate, and the inability to mask healthcare providers to random allocation. In summary, this study suggests that a personalized perioperative e-health program may significantly shorten hospital stays and recovery times after surgery, and thus should be considered for widespread implementation.

Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts

The Mediterranean diet centers on the consumption of olive oil, fruit, nuts, vegetables, and wine, and minimizes the intake of dairy products, red meat, and sweets. It has been associated with lower cardiovascular risk in observational cohort studies. In this randomized controlled trial, 7,447 patients at a high risk for cardiovascular events were randomized to either a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with nuts, or a control diet to study the impact on a composite of myocardial infraction, stroke, and death from cardiovascular causes. Participants were followed up for a median of 4.8 years. Adherence was assessed based on a 14-item questionnaire distributed at baseline, and biomarker measurements in random subsamples of participants were collected at 1, 3, and 5 years. Overall, questionnaire responses and biomarkers indicated good adherence to dietary assignments. Researchers found that the incidence of cardiovascular events was reduced in the Mediterranean diet with extra-virgin olive oil group (3.8%) and the Mediterranean diet with nuts group (3.4%) as compared with the control group (4.4%). After adjustment for baseline participant characteristics, the risk of cardiovascular events was reduced in both the diet with extra-virgin olive oil group (HR 0.69, 95% CI 0.53 to 0.91) and the diet with nuts group (HR 0.72, 95% CI 0.54 to 0.95). After adjusting for adherence, the risk of cardiovascular events was still reduced in the Mediterranean-diet group as compared with the control group (HR 0.42, 95% CI 0.24 to 0.63). Interestingly, the retention rate was higher in the Mediterranean diet with extra-virgin olive oil group than in the other two groups. Most study participants had already been consuming a baseline diet similar to the Mediterranean diet prior to study enrollment. Therefore, this study may be limited in its applicability to high-risk individuals in other countries, but overall suggests that a Mediterranean diet may aid in the prevention of cardiovascular disease.

Phase 3 Trial of Ibrutinib plus Rituximab in Waldenstrom’s Macroglobulinemia

Waldenstrom’s macroglobulinemia is a rare form of B-cell lymphoma, characterized by elevated serum IgM levels and widespread organ infiltration by clonal lymphoplasmacytic cells. Rituximab has shown substantial activity in patients with Waldenstrom’s macroglobulinemia, and more recently, ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has also gained acceptance as a treatment option in affected individuals. In this randomized controlled trial, 150 symptomatic patients with Waldenstrom’s macroglobulinemia were randomized to receive either once daily oral ibrutinib or placebo until disease progression or unacceptable toxic effects to assess impact on progression-free survival. All participants also received extended intravenous rituximab infusions at weeks 1 to 4 and 17 to 20. Researchers found that the 30-month progression-free survival rate was significantly higher in the ibrutinib-rituximab group than in the placebo-rituximab group (82% vs. 28% respectively, HR for progression or death 0.20, 95% CI 0.11 to 0.38, p<0.001), independent of genotype. In addition, ibrutinib-rituximab was associated with significantly higher response rates than placebo-rituximab with respect to overall response (92% vs. 47%, p<0.001). The 30-month overall survival rate was not significantly different between the two groups (94% with ibrutinib-rituximab vs. 92% with placebo-rituximab). Serious adverse events were more common in the ibrutinib-rituximab group than in the placebo-rituximab group (43% vs. 33%), and included pneumonia (8%) and atrial fibrillation (7%). Overall, this study suggests that ibrutinib-rituximab may be a highly efficacious treatment option for Waldenstrom’s macroglobulinemia. The risk of treatment-related adverse events, however, must be taken into consideration when employing this pharmacotherapy.

Image: PD

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