2 Minute Medicine Rewind April 27 – May 3, 2015

In this section, we highlight the key high-impact studies, updates, and analyses published in medicine during the past week.

Effect of a Retrievable Inferior Vena Cava Filter Plus Anticoagulation vs Anticoagulation Alone on Risk of Recurrent Pulmonary Embolism

The placement of inferior vena cava (IVC) filters as an adjunct to anticoagulation therapy in patients with acute venous thromboembolism has been increasing over the past 3 decades. One previous randomized study demonstrated that among patients with proximal deep vein thrombosis, the placement of a permanent IVC filter in combination with anticoagulation significantly reduced the risk of recurrent pulmonary embolism (PE) compared with anticoagulation alone. However, this was not associated with a significant decrease in all-cause mortality since benefits were balanced by an increased risk of recurrent deep vein thrombosis from filter thrombosis. In this study, investigators sought to assess whether placing a temporary IVC filter in combination with anticoagulation was more effective than anticoagulation alone for preventing pulmonary embolism recurrence in patients with acute, symptomatic pulmonary embolism associated with lower-limb vein thrombosis. 200 patients were randomized to receive IVC filters plus anticoagulation and 199 patients received anticoagulation alone. 193 of the intervention group patients had successful IVC filter placement with 153 of them having the IVC filter retrieved by 3 months. Investigators found that at 3 months, 3% of the filter group had had recurrent PE compared with 1.5% of patients in the control group. However this difference was not significant (RR 2.00, 95% CI 0.51-7.89, p = 0.50). Results were similar at 6 months. This study therefore found no clear evidence for benefit in using IVC filters as an adjunct to anticoagulation in preventing recurrent PE during the first 3 months after the initial incident.

Emergency Department–Initiated Buprenorphine/Naloxone Treatment for Opioid Dependence

Opioid dependence remains a major public health problem and is often seen in patients who utilize the emergency department (ED) as their primary source of medical care. Although currently most ED physicians are limited to referring these patients to addiction treatment services, there exists opportunities for ED physicians to take on more active roles in beginning interventions for longer-term opioid dependence treatment. In this randomized control trial, 329 opioid-dependent patients were randomized to one of three groups: (1) screening and referral to treatment (referral group), (2) screening, brief intervention, and facilitated referral to community-based treatment services (brief intervention group), or (3) screening, brief intervention, ED-initiated treatment with buprenorphine/naloxone and referral to primary care for 10-week follow-up (buprenorphine group). Investigators found that 78% (95% CI 70-85%) of patients in the buprenorphine group were engaged in addiction treatment after 30 days compared with 45% in the brief intervention group (36-54%) and 37% (28-47%) in the referral group (p < 0.001). Additionally, those in the buprenorphine group had a significant reduction in the number of days of self-reported illicit opioid use per week from 5.4 days (95% CI 5.1-5.7) to 0.9 days (0.5-1.3) compared with reductions from 5.6 days (5.3-5.9) to 2.4 days (1.8-3.0) in the brief intervention group and from 5.4 days (5.1-5.7) to 2.3 days (1.7-3.0) in the referral group (p < 0.001 for both time and intervention effects, p = 0.02 for interaction effect). However, when patients were tested with urine samples, there was no statistically significant difference in the proportion of patients testing negative for opioids across the groups: 57.6% (95% CI 47-68%) in the buprenorphine group, 42.9% (31-55%) in the brief intervention group, 53.8% (42-65%) in the referral group. There was similarly no difference in HIV risk across the groups. Nevertheless, there was a significant decrease in the use of inpatient addiction treatment services in the buprenorphine group compared with the other two groups (11% of patients vs. 35% in the brief intervention group and 37% in the referral group, p < 0.001). This study therefore shows that ED-initiated buprenorphine treatment significantly increased the rate of engagement in outpatient addiction treatment and decreased the rate of inpatient addiction treatment usage when compared to brief intervention or referral only strategies. While patients also self-reported lower rates of opioid usage in this group, there was no difference in the rate of positive urine opioids tests between the buprenorphine group and the other groups.

AZD9291 in EGFR Inhibitor–Resistant Non–Small-Cell Lung Cancer

Epidermal growth factor receptor (EGFR) mutations are detected in a significant portion of non-small-cell lung cancers (NSCLCs), and EGFR tyrosine kinase inhibitors such as gefitinib, erlotinib, and afatinib have had dramatic effects in helping prolong progression-free survival in these patients by a median of 10-14 months. Nevertheless, EGFR resistance eventually develops to these medications and second-line treatments are poor. In this investigation, scientists studied a new potential drug called AZD9291 which has been shown in vitro to be a potent inhibitor of resistant EGFR with the mutation T790M. In this phase 1 trial, investigators treated a total of 253 patients with advanced lung cancer who had previous treatment with EGFR tyrosine kinase inhibitors and now demonstrated disease progression. 31 patients were enrolled in dose-escalation cohorts and 222 patients were treated in expansion cohorts. Scientists fond that there were no dose-limiting toxic effects at the various doses tested in the dose-escalation cohorts.The most common adverse events were diarrhea, rash, nausea, and depressed appetite. The overall tumor response rate was 51% (95% CI 45-58%). Among those with biopsy confirmed EGFR T790M mutations, the response rate was 61% (95% CI 52-70%). The median progression-free survival in these patients was 9.6 months (95% CI 8.3 months to not reached). In contrast only 21% (95% CI 12-34) of patients with wild type EGFR showed a response and had a median progression-free survival time of 2.8 months (95% CI 2.1-4.3 months). This study therefore shows that AZD9291 is a promising drug candidate for treating EGFR T790M mutant NSCLCs with few serious adverse effects.

Adult mental health consequences of peer bullying and maltreatment in childhood: two cohorts in two countries

A combination of childhood maltreatment by adults and bullying by peers is known to have long-term adverse mental effects in children including increased rates of anxiety, depression, substance abuse, among other problems. However, given that maltreatment and bullying likely have similarly deleterious effects, the unique contribution of peer bullying alone in producing the observed mental health consequences are not clearly understood. In this cohort study, investigators used data from two longitudinal studies: the Avon Longitudinal Study of Parents and Children in the UK (ALSPAC) and the Great Smoky Mountains Study in the US (GSMS) to study the effects of maltreatment and bullying in combination and in isolation on overall mental health problems defined as any anxiety, depression, or self-harm. Researchers found that in comparison to children who were neither maltreated nor bullied, children who were only maltreated had an increased risk of depression in young adulthood among the GSMS cohort (OR 4.1 95% CI 1.5-11.7) and no increase in any mental health problems in the ALSPAC cohort. In contrast, among children who were only bullied, there was a significant increase in mental health problems seen in both cohorts (ALSPAC OR 1.6, 95% CI 1.1-2.2, p = 0.005; GSMS 3.8, 1.8-7.9, p < 0.001) with specific differences in anxiety, depression and self-harm. When in combination, children who had experienced both maltreatment and bullying similarly also were at an increased risk for overall mental health problems, anxiety, and depression. This study therefore shows that being bullied by peers in childhood had significantly adverse effects on mental health. These effects lasted into adulthood and were independent and potentially worse than those resulting from adult maltreatment.

The association between smoking cessation and glycaemic control in patients with type 2 diabetes: a THIN database cohort study

While smoking is well known to increase the risk of developing type 2 diabetes, several studies indicate that stopping smoking may also increase the risk of type 2 diabetes in the short term. The clear effects of this relationship, however, remain unknown. In this retrospective cohort study, investigators studied 10,692 adult smokers with type 2 diabetes and examined whether smoking cessation could be associated with altered diabetes control, the duration of such an effect, and whether or not the effect was mediated through weight change. Researchers found that of the 3131 smokers who had quit and remained abstinent for 1 year, the HbA1c increased by 0.21% (95% CI 0.17-0.25, p < 0.001) within the first year after quitting. However, HbA1c levels then decreased as smoking abstinence continued and became comparable to those found in continual smokers after 3 years. The initial increase in HbA1c was not found to be mediated by weight change. This study confirms that smoking cessation does appear to result in deterioration in glycemic control during the first 3 years of abstinence. This effect, though, is temporary and does not appear to be related to weight gain.

Image: PD

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