Hepatitis B in Heart Transplant Donors and Recipients: A Systematic Review and Meta-Analysis.

INTRODUCTION: Expanding the heart donor pool to include patients with hepatitis B virus (HBV) could help ameliorate the organ shortage in heart transplantation. We performed a systematic review and meta-analysis to evaluate the management and recipient outcomes of D+/R- and D-/R+ heart transplants. METHODS: An electronic search was performed to identify all relevant studies published on heart transplants involving HBV+ donors and/or HBV+ recipients. A comparison was performed between two groups where heart transplants were performed a) D+/R- (n = 98) versus b) D-/R+ (n = 65). RESULTS: Overall, 13 studies were selected, comprising 163 patients. Mean patient age was 55 y (95% CI: 39, 78) and 79% (69, 86) were male. Active post-transplant HBV infection requiring antiviral treatment occurred in 11% (1, 69) of D+/R- recipients and 33% (9, 71) of D-/R+ recipients. Post-transplant antiviral therapy was given to 80% (6, 100) of D+/R- recipients compared to 72% (42, 90) of D-/R+ recipients (P = 0.84). Hepatitis-related mortality was observed in no D+/R- recipients and 7% (2, 27) of D-/R+ recipients. Survival 1-y post-transplant was comparable between both groups at 83% (83, 92) and 81% (61, 92) for D+/R- and D-/R+ transplants, respectively. CONCLUSIONS: Our review found that HBV D+/R- heart transplantation was associated with fewer active hepatitis infections and lower hepatitis-related mortality than D-/R+ transplantation, with comparable survival at 1 y. Additional studies utilizing HBV nucleic acid testing (NAT) to compare outcomes with HBsAg+ and anti-HBc+ donors are crucial to reach more definitive conclusions about the risk of donor-derived infections in this context.

People Living With Human Immunodeficiency Virus During the COVID-19 Pandemic: Experiences With Telemedicine.

Preserving routine primary care for people living with human immunodeficiency virus (PLWH) has been an important challenge during the COVID-19 pandemic. Telemedicine platforms have offered novel means through which care for these individuals may be maintained. Opt-In for Life is a unique mobile health application that contains telemedicine capabilities as well as other features designed specifically for the care of PLWH. Opt-In for Life was implemented early in the pandemic at Hershey Medical Center, although the center is now using a different telemedicine platform across its health care system. Institutional decisions regarding telemedicine platforms are complex. Opt-In for Life contains features that may improve the care of PLWH where telemedicine software alone may be limited.

Acceptability of electronic nicotine delivery systems (ENDS) among HIV positive smokers.

Electronic nicotine delivery systems (ENDS) have the potential to help smokers living with HIV/AIDS (PLWHA) to reduce harms from tobacco use. However, little is known about ENDS use among PLWHA. This study's aim was to evaluate the acceptability of two types of ENDS among PLWHA not planning to quit smoking. The study utilized a cross-over design where participants used two ENDS in a random order as smoking substitutes during two use periods separated by 7 days. Exhaled carbon monoxide (CO) was analyzed and participants reported daily cigarette and ENDS use and completed ratings on ENDS acceptability. Participants (n = 17) were a mean age of 49.1 years (SD = 8.8), were 53% white, and 59% male. All participants had controlled HIV disease status. Participants smoked a mean of 16.9 (SD = 7.9) CPD at baseline. Overall, CPD significantly decreased during both ENDS use periods (p < .01) but there were no differences in reduction between the different devices. CO decreased from baseline to follow-up only during the button-activated ENDS use period (p = .03), but there were no differences between ENDS devices. There were no significant differences in ratings of acceptability between ENDS devices. These results suggest that ENDS could be a harm reduction tool for smokers with HIV.

OPT-In For Life: A Mobile Technology-Based Intervention to Improve HIV Care Continuum for Young Adults Living With HIV.

Young adults living with HIV (YALH) have lower rates of retention in care and HIV viral suppression. Multiple barriers exist to engage YALH in care. We developed and implemented a multifaceted, mobile application-based intervention, "OPT-In for Life," by targeting YALH to encourage retention in care and eventually viral suppression. The app integrated multiple user-friendly features for YALH to manage their HIV care, including a two-way secure messaging function, HIV-related laboratory results, and appointment or medication reminders. We recruited 92 YALH who were 18 to 34 years old and were newly diagnosed with HIV, had a history of falling out of care, or had a detectable HIV viral load into this intervention. Study participants used the app to manage their HIV care and to communicate and interact with their HIV care team. During the intervention period, the retention rate among our study participants increased from 41.3% at baseline to 78.6% at 6-month follow-up, maintained at 12-month follow-up (79.8%), and slightly decreased to 73.4% at 18-month follow-up but it was still significantly higher than the baseline retention rate (p < .0001). The viral suppression rate (HIV RNA <200 copies/ml) increased from 64.1% at baseline to about 85% at 6-month and at 12-month follow-up and reached 91.4% at 18-month (p = .0002) among participants who were retained in care. Our study demonstrated using a HIPAA-compliant mobile application as an effective intervention to engage YALH in care. This mobile technology-based intervention can be incorporated into routine clinical practice to improve HIV care continuum.

Early Infectious Disease Outpatient Follow-up of Outpatient Parenteral Antimicrobial Therapy Patients Reduces 30-Day Readmission.

We conducted a case-control study to examine the association between outpatient infectious disease (ID) follow-up and risk of 30-day readmission in 384 patients receiving outpatient parenteral antimicrobial therapy. ID outpatient follow-up within 2 weeks was associated with lower risk of all-cause 30-day readmission (adjusted odds ratio, 0.33; P = .0001).

Infectious Diseases Specialty Intervention Is Associated With Better Outcomes Among Privately Insured Individuals Receiving Outpatient Parenteral Antimicrobial Therapy.

BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) can be managed by specialists in infectious diseases (ID) or by other physicians. Better management of OPAT can reduce the likelihood of readmission or emergency department (ED) use. The relative success of ID specialists and other physicians in managing OPAT has received little study. METHODS: We analyzed a national database of insurance claims for privately insured individuals under age 65, locating inpatient acute-care stays in 2013 and 2014 that were followed by OPAT. Through propensity scoring, patients who received outpatient ID intervention (ID-led OPAT) were matched 1-to-1 with those who did not (Other OPAT). We estimated regression models of hospital and ED admissions and of total healthcare payments over the first 30 days after discharge. RESULTS: The final analytic sample of 8200 observations was well balanced on clinical and demographic characteristics. Soft-tissue infection and osteomyelitis were the most common infections in the index event, each affecting more than 40% of individuals. Relative to those with Other OPAT, people with ID-led OPAT had lower odds of an ED admission (odds ratio [OR] 0.449, 95% confidence interval [CI] 0.311-0.645) or hospitalization (OR 0.661, 95% CI 0.557-0.791) over 30 days, and they accumulated $1488 less in total healthcare payments (95% CI -2 688.56--266.58). CONCLUSIONS: Among privately insured individuals below age 65, ID consultations during OPAT are associated with large and significant reductions in the rates of ED admission and hospital admission in the 30 days after index events, as well as lower total healthcare spending.

2018 Infectious Diseases Society of America Clinical Practice Guideline for the Management of Outpatient Parenteral Antimicrobial Therapy.

A panel of experts was convened by the Infectious Diseases Society of America to update the 2004 clinical practice guideline on outpatient parenteral antimicrobial therapy (OPAT) [1]. This guideline is intended to provide insight for healthcare professionals who prescribe and oversee the provision of OPAT. It considers various patient features, infusion catheter issues, monitoring questions, and antimicrobial stewardship concerns. It does not offer recommendations on the treatment of specific infections. The reader is referred to disease- or organism-specific guidelines for such support.

2018 Infectious Diseases Society of America Clinical Practice Guideline for the Management of Outpatient Parenteral Antimicrobial Therapy.

A panel of experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2004 clinical practice guideline on outpatient parenteral antimicrobial therapy (OPAT) [1]. This guideline is intended to provide insight for healthcare professionals who prescribe and oversee the provision of OPAT. It considers various patient features, infusion catheter issues, monitoring questions, and antimicrobial stewardship concerns. It does not offer recommendations on the treatment of specific infections. The reader is referred to disease- or organism-specific guidelines for such support.

Preoperative Anemia Is Associated With Failure of Open Debridement Polyethylene Exchange in Acute and Acute Hematogenous Prosthetic Joint Infection.

BACKGROUND: Acute and acute hematogenous prosthetic joint infections (PJIs) are often treated with open debridement and polyethylene exchange (ODPE) in an effort to save the prosthesis, decrease morbidity, and reduce costs. However, failure of ODPE may compromise a subsequent 2-stage treatment. The purpose of this study is to identify patient factors that impact the success of ODPE for acute and acute hematogenous PJIs. METHODS: A retrospective review examined comorbidities, preoperative laboratory values, and patient history for patients with successful and failed ODPE treatment for acute perioperative or acute hematogenous periprosthetic hip or knee joint infections. Successful treatment was defined as retaining a well-fixed implant without the need for additional surgery for a minimum of 6-month follow-up with or without lifelong oral maintenance antibiotics. RESULTS: Fifty-three of 72 patients (73.6%) underwent successful ODPE. Of the 19 failures, 14 completed 2-stage revision with one subsequent known failure for recurrent infection. Patients with a Staphylococcus aureus infection were more likely to fail ODPE (48.3% vs 11.6%, P = .0012, odds ratio 7.1, 95% confidence interval 2.3-25.3). Patients with a preoperative hematocrit ≤32.1 were also more likely to fail ODPE (55% vs 16%, P = .0013, odds ratio 6.7, 95% confidence interval 2.2-22.4). When neither risk factor was present, 97.1% of PJIs were successfully treated with ODPE. CONCLUSION: S aureus infection and preoperative hematocrit ≤32.1 are independent risk factors for ODPE failure. ODPE is a safe alternative to 2-stage revision in patients without preoperative anemia and without S aureus infection. Two-thirds of patients with a failed ODPE were successfully treated with a 2-stage reimplantation.

HIV transmission risk behaviors among people living with HIV/AIDS: the need to integrate HIV prevention interventions and public health strategies into HIV care.

CONTEXT: People living with human immunodeficiency virus (HIV)/AIDS (PLWHA) who continue high-risk behaviors may represent an important source for transmitting HIV infections. OBJECTIVE: To identify factors associated with high-risk behaviors among PLWHA and to plan better HIV prevention intervention strategies in HIV care. DESIGN: A cross-sectional survey to assess HIV transmission risk behaviors including sexual practices, disclosure of HIV infection status to sexual partner(s), and injection drug use. SETTING: Five HIV outpatient clinics serving diverse PLWHA in south central Pennsylvania. PARTICIPANTS: A total of 519 HIV-infected patients. MAIN OUTCOME MEASURES: Two high-risk behaviors that may increase HIV transmission risk: (1) any unsafe sexual behavior and (2) nondisclosure of HIV infection status to sexual partner(s). An unsafe sexual behavior was defined as inconsistent condom use, sex under the influence of alcohol or drugs, or exchange of sex for money. A subgroup analysis was performed to examine factors related to unprotected anal intercourse among sexually active men who have sex with men. RESULTS: About two-thirds of 519 HIV patients (65.7%) were sexually active, and nearly 50% of sexually active patients reported at least 1 unsafe sexual behavior. Nondisclosure of HIV infection status was reported by about 15% of the patients. Partners' characteristics including HIV infection status and the perceived partner behavior (ie, partner may have sex with other people) were significantly associated with unsafe sexual behaviors and with nondisclosure of HIV infection status. Non-Hispanic black males were more likely to withhold their HIV infection status from their sexual partner(s) (adjusted odds ratio = 4.51) than their white counterparts. In addition, the perceived partner sexual behavior was significantly related to unprotected anal intercourse among men who have sex with men (adjusted odds ratio = 2.00). CONCLUSIONS: High-risk sexual behaviors are commonly reported by PLWHA, and these behaviors may be influenced by their partners' characteristics. HIV prevention interventions and public health strategies need to be incorporated into HIV care.

Incidence and predictors of vancomycin-associated nephrotoxicity.

OBJECTIVES: Earlier studies reported a low incidence of vancomycin-associated nephrotoxicity (VAN); however, recent studies have reported higher incidences exceeding 30%. Predictors of nephrotoxicity are not well defined. In this study we aimed to better estimate the incidence and evaluate predictors of VAN in a cohort of patients predominated by long treatment courses. METHODS: We conducted a retrospective study on patients treated with vancomycin while in the hospital and who were observed closely through the Outpatient Parenteral Antibiotic Therapy program. Nephrotoxicity was defined as an increase in the serum creatinine level of 0.5 mg/dL or 50% from baseline on at least two consecutive readings while taking vancomycin. We compared the patients who developed nephrotoxicity with those who did not with regard to vancomycin dosing, trough levels, baseline serum creatinine, underlying infection, residence in the critical care unit, comorbid conditions, concurrent nephrotoxic treatments, and baseline characteristics. RESULTS: Of 579 patients, 154 (26.6%) developed nephrotoxicity. Ninety patients developed VAN within the first 14 days of treatment, whereas 64 patients developed nephrotoxicity after 14 days of treatment. The median time to development of nephrotoxicity was 9 days. Admission to the intensive care unit, concurrent use of loop diuretics, and comorbidity with cirrhosis were independently associated with nephrotoxicity. A higher baseline creatinine value was unexpectedly associated with a lower incidence of nephrotoxicity (P = 0.0016). CONCLUSIONS: VAN is not an uncommon outcome in both short- and long-term treatment courses. Admission to the intensive care unit while receiving treatment, concurrent treatment with a loop diuretic, an underlying diagnosis of cirrhosis, and the initial trough level appear to be the main risk factors for nephrotoxicity. Unexpectedly, elevated baseline creatinine levels appeared to be protective and this could be the result of careful use of vancomycin among individuals with relatively higher baseline creatinine values.

Infective endocarditis following heart transplantation: A systematic review.

PURPOSE: Infective endocarditis (IE) is a rare but potentially fatal complication following heart transplantation (HTx). There is a lack of literature regarding the patterns and clinical course of IE development following HTx. We sought to pool the existing data in regards to defining characteristics, management options, and outcomes of IE following HTx. METHODS: An electronic search of Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Ovid Medline, and the Scopus databases were performed to identify all articles in the English literature that report IE following HTx in adult patients. Patient-level data were extracted and analyzed. RESULTS: Systematic search yielded 57 patients from 32 articles. Median patient age was 52 [IQR 43, 59] and 75% of patients (43/57) were male. Median time to IE presentation post-HTx was 8.4 [IQR 3.0, 35.8] months. IE of the mitral valve was observed in 36.8% (21/57) of patients, followed by mural IE in 24.6% (14/57), and tricuspid valve IE in 21.1% (12/57). The most common organisms were Staphylococcus aureus in 26.3% (15/57), Aspergillus fumigatus in 19.3% (11/57), Enterococcus faecalis in 12.3% (7/57), and an undetermined or unspecified organism in 14.0% (8/57) patients. Overall case fatality was 44.6% (25/56). Fungal IE was associated with a significantly higher case fatality 75.0% (9/12) than that of bacterial IE 36.1% (13/36) (p = 0.02). Surgical management of post-HTx IE was observed in 35.1% (20/57) of patients. This included valve surgery for 70.0% (14/20), including the mitral valve in 50.0% (7/14), aortic valve in 35.7% (5/14), and the tricuspid valve in 14.3% (2/14) of patients. CONCLUSION: In addition to bacterial organisms, fungi also represent a frequent cause of IE in post-HTx patients. Overall HTx patient survival in the setting of IE is poor and may be worse if caused by A. fumigatus.

Human immunodeficiency virus testing behaviors among US adults: the roles of individual factors, legislative status, and public health resources.

BACKGROUND: The Centers for Disease Control and Prevention recommended an "opt-out" human immunodeficiency virus (HIV) testing strategy in 2006 for all persons aged 13 to 64 years at healthcare settings. We conducted this study to identify individual, health, and policy factors that may be associated with HIV testing in US adults. METHODS: The 2008 Behavioral Risk Factors Surveillance System data were utilized. Individuals' residency states were classified into 4 categories based on the legislation status to HIV testing laws in 2007 and HIV/acquired immune deficiency syndrome morbidity. A multivariate logistic regression adjusting for survey designs was performed to examine factors associated with HIV testing. RESULTS: A total of 281,826 adults aged 18 to 64 years answered HIV testing questions in 2008. The proportions of US adults who had ever been tested for HIV increased from 35.9% in 2006 to 39.9% in 2008. HIV testing varied across the individual's characteristics including sociodemographics, access to regular health care, and risk for HIV infection. Compared with residents of "high morbidity-opt out" states, those living in "high morbidity-opt in" states with legislative restrictions for HIV testing had a slightly lower odds of being tested for HIV (adjusted odds ratio = 0.96; 95% confidence interval = 0.92, 1.01). Adults living in "low morbidity" states were significantly less likely to be tested for HIV, regardless of legislative status. CONCLUSIONS: To implement routine HIV testing in the general population, the role of public health resources should be emphasized and legislative barriers should be further reduced. Strategies need to be developed to reach people who do not have regular access to health care.

COVID-19 treatment combinations and associations with mortality in a large multi-site healthcare system.

INTRODUCTION: During the early months of the COVID-19 pandemic, mortality associated with the disease declined in the United States. The standard of care for pharmacological interventions evolved during this period as new and repurposed treatments were used alone and in combination. Though these medications have been studied individually, data are limited regarding the relative impact of different medication combinations. The objectives of this study were to evaluate the association of COVID-19-related mortality and observed medication combinations and to determine whether changes in medication-related practice patterns and measured patient characteristics, alone, explain the decline in mortality seen early in the COVID-19 pandemic. METHODS: A retrospective cohort study was conducted at a multi-hospital healthcare system exploring the association of mortality and combinations of remdesivir, corticosteroids, anticoagulants, tocilizumab, and hydroxychloroquine. Multivariable logistic regression was used to identify predictors of mortality for both the overall population and the population stratified by intensive care and non-intensive care unit admissions. A separate model was created to control for the change in unmeasured variables over time. RESULTS: For all patients, four treatment combinations were associated with lower mortality: Anticoagulation Only (OR 0.24, p < 0.0001), Anticoagulation and Remdesivir (OR 0.25, p = 0.0031), Anticoagulation and Corticosteroids (OR 0.53, p = 0.0263), and Anticoagulation, Corticosteroids and Remdesivir (OR 0.42, p = 0.026). For non-intensive care unit patients, the same combinations were significantly associated with lower mortality. For patients admitted to the intensive care unit, Anticoagulation Only was the sole treatment category associated with decreased mortality. When adjusted for demographics, clinical characteristics, and all treatment combinations there was an absolute decrease in the mortality rate by 2.5% between early and late periods of the study. However, when including an additional control for changes in unmeasured variables overtime, the absolute mortality rate decreased by 5.4%. CONCLUSIONS: This study found that anticoagulation was the most significant treatment for the reduction of COVID-related mortality. Anticoagulation Only was the sole treatment category associated with a significant decrease in mortality for both intensive care and non-intensive care patients. Treatment combinations that additionally included corticosteroids and/or remdesivir were also associated with decreased mortality, though only in the non-intensive care stratum. Further, we found that factors other than measured changes in demographics, clinical characteristics or pharmacological interventions accounted for an additional decrease in the COVID-19-related mortality rate over time.

Tocilizumab in the Management of COVID-19: A Preliminary Report.

IMPORTANCE: Pneumonia due to COVID-19 can lead to respiratory failure and death due to the development of the acute respiratory distress syndrome. Tocilizumab, a monoclonal antibody targeting the interleukin-6 receptor, is being administered off-label to some patients with COVID-19, and although early small studies suggested a benefit, there are no conclusive data proving its usefulness. OBJECTIVE: To evaluate outcomes in hospitalized patients with COVID-19 with or without treatment with Tocilizumab. DESIGN, SETTING, PARTICIPANTS: Retrospective study of 1938 patients with confirmed COVID-19 pneumonia admitted to hospitals within the Jefferson Health system in Philadelphia, Pennsylvania, between March 25, 2020 and June 17, 2020, of which 307 received Tocilizumab. EXPOSURES: Confirmed COVID-19 pneumonia. MAIN OUTCOMES AND MEASURES: Outcomes data related to length of stay, admission to intensive care unit (ICU), requirement of mechanical ventilation, and mortality were collected and analyzed. RESULTS: The average age was 65.2, with 47% women; 36.4% were African-American. The average length of stay was 22 days with 26.3% of patients requiring admission to the ICU and 14.9% requiring mechanical ventilation. The overall mortality was 15.3%. Older age, admission to an ICU, and requirement for mechanical ventilation were associated with higher mortality. Treatment with Tocilizumab was also associated with higher mortality, which was mainly observed in subjects not requiring care in an ICU with estimated odds ratio (OR) of 2.9 (p = 0.0004). Tocilizumab treatment was also associated with higher likelihood of admission to an ICU (OR = 4.8, p < 0.0001), progression to requiring mechanical ventilation (OR = 6.6, p < 0.0001), and increased length of stay (OR = 16.2, p < 0.0001). CONCLUSION AND RELEVANCE: Our retrospective analysis revealed an association between Tocilizumab administration and increased mortality, ICU admission, mechanical ventilation, and length of stay in subjects with COVID-19. Prospective trials are needed to evaluate the true effect of Tocilizumab in this condition.

The roles of social domains, behavioral risk, health care resources, and chlamydia in spatial clusters of US cervical cancer mortality: not all the clusters are the same.

BACKGROUND: While high-risk geographic clusters of cervical cancer mortality have previously been assessed, factors associated with this geographic patterning have not been well studied. Once these factors are identified, etiologic hypotheses and targeted population-based interventions may be developed and lead to a reduction in geographic disparities in cervical cancer mortality. METHODS: The authors linked multiple data sets at the county level to assess the effects of social domains, behavioral risk factors, local physician and hospital availability, and Chlamydia trachomatis infection on overall spatial clustering and on individual clusters of cervical cancer mortality rates in 2000-2004 among 3,105 US counties in the 48 states and the District of Columbia. RESULTS: During the study period, a total of 19,898 cervical cancer deaths occurred in women aged 20 and older. The distributions of county-level characteristics indicated wide ranges in social domains measured by demographics and socioeconomic status, local health care resources, and the rate of chlamydial infection. We found that overall geographic clustering of increased cervical cancer mortality was related to the high proportion of black population, low socioeconomic status, low Papanicolaou test rate, low health care coverage, and the high chlamydia rate; however, unique characteristics existed for each individual cluster, and the Appalachian cluster was not related to a high proportion of black population or to chlamydia rates. DISCUSSION: This study indicates that local social domains, behavioral risk, and health care sources are associated with geographic disparities in cervical cancer mortality rates. The association between the chlamydia rate and the cervical cancer mortality rate may be confounded by other factors known to be a risk for cervical cancer mortality, such as the infection with human papillomavirus. The findings will help cancer researchers examine etiologic hypotheses and develop tailored, cluster-specific interventions to reduce cervical cancer disparities.

Epstein Barré virus-negative diffuse large B-cell lymphoma in an HIV-infected man with a durable complete remission on highly active antiretroviral therapy alone.

We report a unique case of a human immunodeficiency virus (HIV)-infected man with Epstein-Barré virus (EBV) negative diffuse large B-cell lymphoma (DLBCL) that responded solely to highly active antiretroviral therapy (HAART). Our patient presented with a retroperitoneal mass, high viral load, CD4 288 and began therapy with HAART with marked improvement of symptoms. The patient declined chemotherapy since he felt better after HAART, and rescanning at that time demonstrated marked improvement of the lymphoma on HAART alone. Viral load became undetectable, CD4 450 by 8 weeks. By 6 months, the patient had a complete remission verified by positron emission tomography/computed tomography (PET/CT) and has remained in remission to date on HAART alone. We postulate that HIV infection directly precipitated the lymphoma.

Small bowel diverticulitis: an often overlooked cause of acute abdomen.

We present 3 cases of small bowel diverticulitis ultimately presenting to our Emergency Department over a span of 2 years. Though the final diagnosis was the same, each patient's symptomatology was different, mimicking more common pathologies. Thus, it is important to consider this entity when confronted with signs and symptoms of acute abdomen, especially in the elderly. A missed or delayed diagnosis can lead to costly erroneous studies, incorrect treatments and delay in proper management, resulting in significant morbidity and even mortality. The variety of presentations can often be misleading; therefore, a high index of suspicion is needed on the part of the Emergency Department physician and Radiologist.

Transdermal Delivery of Enfuvirtide in a Porcine Model Using a Low-Frequency, Low-Power Ultrasound Transducer Patch.

Ultrasound-mediated transdermal delivery is a promising parenteral administration method for large-molecule or unstable medications. This study evaluated skin health and systemic delivery when administering enfuvirtide, an injectable anti-retroviral medication, over a 1-mo period in a porcine model using a low-frequency cymbal transducer. Three groups received twice-daily treatments: (i) enfuvirtide injection control (n = 12); (ii) saline ultrasound control (n = 6); and (iii) enfuvirtide ultrasound treatment (n = 13). Ultrasound parameters were as follows: 30-min exposure, 90 mW/cm², 24-26 kHz and 15% duty cycle. No statistical difference in trans-epidermal water loss, a measure of skin health and function, was seen between ultrasound-treated and control skin sites for either saline (p = 0.50) or enfuvirtide (p = 0.29) groups. Average trough plasma concentrations of enfuvirtide were 0.6 ± 0.2 and 2.8 ± 0.8 µg/mL for ultrasound and injection, respectively. Tolerability and efficacy results indicate that chronic, low-frequency ultrasound exposure can be a practical means for transdermal delivery of medications such as enfuvirtide.

Trimethoprim-sulfamethoxazole revisited.

During the past 3 decades, the combination of trimethoprim and sulfamethoxazole has occupied a central role in the treatment of various commonly encountered infections and has also been particularly useful for several specific clinical conditions. However, changing resistance patterns and the introduction of newer broad-spectrum antibiotics have led to the need to carefully redefine the appropriate use of this agent in clinical practice. While trimethoprim-sulfamethoxazole's traditional role as empirical therapy for several infections has been modified by increasing resistance, it remains a highly useful alternative to the new generation of expanded-spectrum agents if resistance patterns and other clinical variables are carefully considered. It also seems to have an increasing role as a cost-effective pathogen-directed therapy with the potential to decrease or delay development of resistance to newer antibiotics used for empirical treatment. In addition, trimethoprim-sulfamethoxazole continues to be the drug of choice for several clinical indications.