To the best of our knowledge, our study represents the largest trial-level meta-analysis to date of clinical trials in which ABC use was randomized. Our analysis found no association between ABC use and MI risk.
Strongyloides hyperinfection syndrome may be complicated by paralytic ileus that interferes with the absorption of oral anti-helminthics. We report on the administration of ivermectin as a rectal enema preparation to a renal transplant recipient with Strongyloides hyperinfection syndrome and progressive ileus. Attempts at treatment using nasogastric albendazole and ivermectin were unsuccessful despite clamping the nasogastric tube after drug administration. Ivermectin tablets were ground to a powder, resuspended in a commercially available suspending agent, and administered per rectum. The suspending agent was chosen for its near-physiologic osmolality to allow longer retention, in contrast to many enema preparations that have a laxative effect. The patient improved markedly within 72 hours of initiation of the therapy per rectum and recovered fully. Ivermectin administered as an enema may be beneficial in patients with severe strongyloidiasis who are unable to absorb or tolerate oral therapy.
Cutaneous fungal infections in solid-organ transplant patients present in a variety of nonspecific ways, requiring a high index of suspicion to diagnose correctly. In the present series of four transplant recipients, subsequent primary cutaneous fungal infections presented as papules, plaques, ulcers and subcutaneous nodules. Transplantations included one cardiac, two renal and one renal-pancreatic transplant. Fungal infections were limited to the skin; there was no evidence of disseminated disease in any case. The pathogens isolated were Scedosporium apiospermum (Pseudallescheria boydii), Alternaria species, Aspergillus fumigatus, and a coelomycete in the Coniothyrium-Microsphaeropsis complex of dark molds. Individuals were successfully treated with surgical debridement, antifungal agents, and reduction of immunosuppressive therapy. All patients and allografts survived. Accurate diagnosis, aggressive surgery and appropriate antifungal therapy, combined with close outpatient follow-up, optimize the likelihood of a cure in a transplant population.
Pneumocystis carinii pneumonia (PCP) can be diagnosed by direct microscopic examination of induced sputum or by bronchoalveolar lavage (BAL). However, many institutions have little diagnostic success with induced sputum, and BAL is invasive and expensive. This prospective, blinded study assessed oral washes as a more convenient specimen than either sputum or BAL fluid and used a dissociation-enhanced lanthanide fluoroimmunoassay time-resolved fluorescent hybridization polymerase chain reaction (PCR) detection system that is feasible for clinical laboratories. The study assessed 175 oral washes, each paired with either an induced sputum that was positive for Pneumocystis or a BAL sample. The PCR test based on the Pneumocystis major surface glycoprotein primers had a sensitivity of 91% and a specificity of 94%, compared with a test based on mitochondrial large subunit rRNA primers, which had a sensitivity of 75% and a specificity of 96%. These results suggest that oral washes can provide a useful sample for diagnosis of PCP when a sensitive PCR detection system is used.
The resounding success of combination antiretroviral efficacy for both treatment-naïve and -experienced patients – with 70% – 90% viral suppression rates in recent studies–has made registration trials for new agents challenging. With the inevitable specter of drug resistance, new agents must have a pathway to approval. The Forum for Collaborative HIV Research obtained input from concerned stakeholders including industry, clinical sciences, community advocacy and regulatory sciences (Food and Drug Administration and European Medicines Agency) to discuss how safety and efficacy of new agents could be demonstrated. Recognizing the shortfalls of superiority or non-inferiority trials in this environment, a new trial design for treatment-experienced patients, minimizing the risk for drug resistance but allowing full assessment of safety was proposed. The antiviral efficacy of an active investigational drug would be assessed by comparison to placebo as an add-on to a failing regimen in a short, 10–14 day study followed by institution of an optimized background regimen in both arms with investigational drug given to all patients. The follow-on stage would assess dose response, safety, durability of initial response and development of resistance. Additionally, a second safety trial could be conducted comparing patients randomized to the investigational agent plus a new OBR to those on a new OBR plus placebo. Finally, approval decisions could consider other long-term safety endpoints. Exposing treatment-naïve patients to investigational agents remains a controversial issue; stakeholders have different interpretations of risk-benefit for trials in this population which necessitate careful consideration before initiating trials in them.
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