2 Minute Medicine Rewind November 9 – November 16, 2014
In this section, we highlight the key high-impact studies, updates, and analyses published in medicine during the past week.
An Interferon-free Antiviral Regimen for HCV after Liver Transplantation
More than 40% of patients on the liver transplant waiting list are infected with the Hepatitis C Virus (HCV) and as many as 20-30% of successfully transplanted patients will experience graft cirrhosis secondary to recurrent HCV infection 5 years after transplant even with latest HCV treatment. Post-transplantation immunosuppression combined with toxic interferon-containing HCV treatments jeopardize the graft and make HCV especially difficult to treat in these patients. In this phase 2, open-label trial (CORAL-I), researchers tested an interferon-free antiviral regimen containing the NS5A inhibitor ombitasvir, the ritonavir-boosted protease inhibitor ABT-450 (ABT-450/r), the nonnucleoside NS5B polymerase inhibitor dasabuvir, and ribavirin. This intervention was prescribed to 34 liver-transplant recipients with recurrent HCV infection. Investigators found that 33 out of 34 patients (Response Rate: 97%, 95% CI: 85-100%) had a sustained virologic response at weeks 12 and 24 with minimal adverse effects of fatigue, headache, cough, and anemia responsive to erythropoietin. There were no episodes of graft rejection. This study therefore indicates promise for the efficacy of this multitargeted interferon-free HCV treatment regimen in liver transplant patients with recurrent HCV infection.
The most recent Institute of Medicine report Dying in America highlighted some of the difficulties in promoting palliative care and hospice services. While more patients are now receiving hospice care, the length of enrollment has decreased and the intensity of end-of-life care has increased. The effect of hospice on decreasing healthcare utilization and ultimately costs remains an area that is not well understood and is a barrier for better payor support for hospice programs. This matched cohort study looked at a sample of Medicare fee-for-service beneficiaries with poor-prognosis cancers who died in 2011, comparing 18,165 patients who enrolled in hospice before death with 18,165 matched patients who did not have hospice services at the end of life. Researchers found that compared to patients enrolled in hospice, those without hospice were significantly more likely to be hospitalized (RR: 1.5 (95% CI: 1.5-1.6)), receive intensive care (RR: 2.4 (2.3-2.5)), undergo invasive procedures (RR: 1.9 (1.9-2.0)), and die in the hospital or a nursing facility (74% of non-hospice patients vs. 14% of non-hospice patients). The total cost of care during the last year of life was $71,517 (95% CI: $70,543-$72,490) for non-hospice patients versus $62,819 ($62,082-$63,557) for hospice patients. This study therefore shows significant differences in the type of end of life care between these two patient groups and shows that hospice enrollment does decrease both hospital service utilization and ultimately, costs.
Male circumcision is known to prevent HIV-1 transmission. However, its effects on the transmission of other sexually transmitted diseases such as syphilis is less well understood. In this prospective cohort study conducted in Kenya and Uganda, 4716 HIV-1 serodiscordant heterosexual couples from the Partners PreEP Study were studied as to the rates of incident syphilis infection. Researchers found that the incidence of new syphilis infections was 21% in men with HIV, 34% in men without HIV, 24% in women with HIV, and 24% in women without HIV. Men who were circumcised had a 42% reduction in incident syphilis (Adjusted Hazard Ratio: 0.58, 95% CI: 0.37-0.91) with an especially large reduction of 62% among men with HIV (0.38, 0.18-0.81). Women with a circumcised male partner had a 59% reduction in incident syphilis (0.41, 0.25-0.69) with a 75% reduction among women without HIV (0.25, 0.08-0.86) and a 48% reduction among women with HIV (0.52, 0.27-0.97). This study demonstrates that male circumcision appears to reduce the transmission of syphilis with perhaps an even more significant effect among couples where the male partner is HIV positive.
Molecular Findings Among Patients Referred for Clinical Whole-Exome Sequencing
Whole-exome sequencing is being increasingly used to detect genetic disorders in patients with suspicious clinical findings. An initial pilot study with 250 patients reported that whole-exome sequencing was able to detect a new genetic disease in 25% of patients. This observational study sought to confirm the robustness of this rate of detection on a larger patient sample with additional refinements to the automated algorithms used in the process. Researchers studied 2000 consecutive patients between 2012 to 2014 who were referred to one genetics center in Texas. Patients were primarily pediatric and had a diversity of different clinical symptoms. Whole-exome sequencing successfully yielded a molecular diagnosis in 25.2% of patients. This rate of diagnosis was similar across different phenotypical groups (the neurological group, neurological plus other organ systems group, specific neurological group, and non-neurological group). Of the patients with a molecular diagnosis, 4.6% of patients had a blended phenotype from 2 single gene defects, 30% had a gene mutation first characterized after 2011, 4.6% received a diagnosis that had immediate implications for management, and 3% of patients had gene mutations that were recommended for reporting by the American College of Medical Genetics and Genomics. This study therefore shows that whole-exome sequencing can be effective in helping obtain a genetic diagnosis in a large proportion of patients and that a small but significant subset of these patients may have gene mutations that are clinically significant in terms of affecting medical management and genetic reporting.
Axillary lymph node dissection is the standard of therapy for women with breast cancer who have a positive sentinel node but is associated with adverse effects including axillary paresthesias, decreased upper extremity range of motion, and lymphedema. In this randomized control trial, investigators sought to assess whether less invasive axillary radiotherapy could provide equivalent outcomes. Investigators studied patients with T1-2 primary breast cancer and no palpable lymphadenopathy. Of the 1425 patients who were found to have a positive sentinel node, they randomized 744 patients to axillary lymph node dissection and 681 patients to axillary radiotherapy. After 5 years, the axillary recurrence rate was 0.43% (95% CI: 0.00-0.92) in the lymph node dissection group compared to 1.19% (0.31-2.08) in the radiotherapy group. Although the planned non-inferiority test was underpowered, the one-sided 95% CI for the underpowered non-inferiority test on the hazard ratio was 0.00-5.27. Lymphedema was significantly less frequent in the radiotherapy group compared to the dissection group at 1, 3, and 5 years. This study therefore suggests that axillary radiotherapy after a positive sentinel node may be similarly effective as lymph node dissection in preventing axillary recurrence of breast cancer and causes less procedure-related morbidity.
Image: PD
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