Does prophylactic antidepressant treatment boost interferon-alpha treatment completion in HCV?

Depression is often a side effect of interferon-alpha treatment for hepatitis C, and is recognized as a cause for treatment discontinuation. When detected, antidepressant treatment begins promptly. In contrast to this rescue approach, prophylactic antidepressant treatment has been considered as a superior approach. While studies indicate that depression is lower with prophylaxis, no study has prospectively evaluated the degree that treatment completion might be boosted by the prophylactic strategy. A structured literature search was conducted to discover all trials of antidepressant prophylaxis for patients undergoing antiviral treatment for chronic hepatitis C. Selection criteria included: antidepressant prophylaxis study; report of depression treatment outcome; report of numbers discontinuing and reason for discontinuation (including any of the following: discontinuation data for medical side effects (i.e., thrombocytopenia); discontinuation due to lack of antiviral response; discontinuation due to lack of antidepressant effect; discontinuation due to antidepressant side effects; discontinuation due to patient preference; discontinuation due to loss to follow-up; or unspecified discontinuation). Across the studies, total enrollees were determined for the prophylaxis arms and the rescue arms, and then, again across studies, those discontinuing for reasons other than lack of antiviral response or medical side effect were summed for each of these two arms. Twelve studies were discovered. One was a retrospective chart review, one was an uncontrolled trial, and ten were controlled trials. Discontinuation of antiviral therapy was not less common in the prophylaxis arms: of the 396 patients treated by the prophylaxis strategy, 47 (11.9%) discontinued; of the 380 patients in the rescue strategy, 45 (11.8%) discontinued. While the prophylaxis strategy seems to manage depression symptoms, it does not seem to boost treatment completion. Rescue was a very successful strategy when indicated. While antidepressant prophylaxis has benefit in antiviral treatment, it should not generally be valued for boosting the likelihood of treatment completion.     

High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy

Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens.     

The Role of One-Stage Exchange for Prosthetic Joint Infection

Purpose of Review

In an era of increasing numbers of hip and knee replacements, strategies to manage prosthetic joint infection (PJI) that are effective at infection control with good patient-reported outcomes and cost containment for health systems are needed. Interest in single-stage exchange for PJI is rising and we assess evidence from the last 5 years related to this treatment strategy.

Recent Findings

Only five series for total knee replacement and ten series for total hip replacement have been reported in the last five years. More review articles and opinion pieces have been written. Reinfection rates in these recent studies range from 0 to 65%, but a meta-analysis and systematic review of all studies showed a reinfection rate of 7.6% (95% CI 3.4–13.1) and 8.8% (95% CI 7.2–10.6) for single-stage and two-stage revisions respectively. There is emerging evidence to support single-stage revision in the setting of significant bony deficiency and atypical PJIs such as fungal infections.

Summary

Prospective randomised studies are recruiting and are necessary to guide the direction of single-stage revision selection criteria. The onus of surgical excellence in mechanical removal of implants, necrotic tissue, and biofilms lies with the arthroplasty surgeon and must remain the cornerstone of treatment. Single-stage revision may be considered the first-line treatment for all PJIs unless the organism is unknown, the patient is systemically septic, or there is a poor tissue envelope.

     

Alcohol policy impact on young risky drinkers and their support for proposed measures

Objective: To explore the impacts of existing policies on young Australian risky drinkers' access to alcohol and to gauge their support for proposed alcohol measures. Methods: The 16–19 year old participants were recruited from three Australian states using non‐random convenience sampling, for either a face‐to‐face or online quantitative survey (N=958). The sample was deliberately selected to represent drinkers whose consumption placed them in the riskiest drinking 20–25% of their age bracket. Results: Half (49%) the sample who were younger than the Australian legal purchase age reported it was ‘easy’ to buy alcohol from bottle stores, and 75% of those who had tried to purchase alcohol, said it was ‘easy’ the last time they tried. Half of those under 18, who had attempted to enter a licensed venue, reported they did not have their identification checked last time they gained access. Ninety per cent of all respondents drank within a private location at their last risky drinking session. Sixty‐five per cent supported ‘increasing the price of [alcohol by 20¢] a standard drink if the extra 20¢ was used to support prevention and treatment of alcohol problems'. Conclusions: Age‐ or intoxication‐based restrictions to alcohol were commonly bypassed. Implications: Point‐of‐sale alcohol controls require improvement to prevent under age access. Given that a significant proportion of drinking occasions for those under 18 were in private premises, prevention strategies need to target these locations. There were diverse levels of support for strategies to reduce harm, including potential community backing for an evidence‐based proposed price policy.     

An association between the CTLA4 exon 1 polymorphism and early rheumatoid arthritis with autoimmune endocrinopathies

OBJECTIVE: To examine the allelic association of the single nucleotide polymorphism (CTLA4A/G) in exon 1 of the cytotoxic T lymphocyte antigen-4 (CTLA4) gene with early rheumatoid arthritis (RA). METHODS: One hundred and twenty-three unrelated white probands with early RA from the north-east of England and 349 local ethnically matched controls were studied. The CTLA4A/G polymorphism was genotyped with a polymerase chain reaction (PCR) method and digestion with the restriction enzyme Bst71I. Probands were also screened by allele-specific PCR for alleles HLA DRB1*01 and DRB1*04. RESULTS: The frequency of the G allele at CTLA4A/G was significantly increased in probands with early RA compared with controls [43 vs 36%; P=0.028, odds ratio (OR) 1.35, 95% confidence interval (CI) 1.01-1.82]. Most of this increased frequency was attributable to RA individuals with coexisting autoimmune thyroid disease or type 1 diabetes (58 vs 36% in controls; P=0.005, OR 2.50, CI 1.29-4.84). The frequency of the G allele in RA patients without autoimmune endocrinopathy was 40%, which was not significantly different from that in controls (P=0.140). CONCLUSION: The association between the CTLA4 G allele and early RA is largely explained by individuals with RA who have coexisting autoimmune endocrinopathies.