Comparison of Clinical Interventions between Student Pharmacists on Advanced Pharmacy Practice Experiences in Indianapolis, Indiana versus Eldoret, Kenya.

Student pharmacists can have a positive impact on patient care. The objective of this research was to compare clinical interventions made by Purdue University College of Pharmacy (PUCOP) student pharmacists completing internal medicine Advanced Pharmacy Practice Experiences (APPE) in Kenya and the US. A retrospective analysis of interventions made by PUCOP student pharmacists participating in either the 8-week global health APPE at Moi Teaching and Referral Hospital (MTRH-Kenya) or the 4-week adult medicine APPE at the Sydney & Lois Eskenazi Hospital (SLEH-US) was completed. Twenty-nine students (94%) documented interventions from the MTRH-Kenya cohort and 23 (82%) from the SLEH-US cohort. The median number of patients cared for per day was similar between the MTRH-Kenya (6.98 patients per day, interquartile range [IQR] = 5.75 to 8.15) and SLEH-US students (6.47 patients per day, IQR = 5.58 to 7.83). MTRH-Kenya students made a median number of 25.44 interventions per day (IQR = 20.80 to 28.95), while SLEH-US students made 14.77 (IQR = 9.80 to 17.72). The most common interventions were medication reconciliation/t-sheet rewrite and patient chart reviews for MTRH-Kenya and the SLEH-US, respectively. This research highlights how student pharmacists, supported in a well-designed, location-appropriate learning environment, can positively impact patient care.

How to phase II: Timelines, perceptions, and suggestions from PGY-1 residency program directors.

BACKGROUND: Phase II was implemented in 2016 to provide structure for applicants and unmatched residency pharmacy programs to interact. Previous literature has provided some approaches for this process; however, clarification on navigating the phase II process to successfully match for applicants and their mentors is still needed. In addition, with phase II occurring for >6 years, there is a need for continual evaluation. OBJECTIVES: The objectives were to describe (1) program phase II structure and timelines, (2) program personnel demand, and (3) perceptions of and suggestions for phase II from postgraduate year (PGY)1 residency program directors (RPDs) to provide clarity to applicants, mentors, and residency stakeholders. METHODS: A 31-item survey was developed including 9 demographic items, 13 program-specific timeline-based items, 5 skip-logic items on screening interviews, and 4 qualitative questions on the benefits, drawbacks, and suggested changes to phase II. The survey was disseminated to PGY-1 RPDs participating in phase II with available contact information in June 2021 and May 2022, with 3 weekly reminders. RESULTS: The survey was completed by 180 of the 484 RPDs participating in phase II (37.2% response rate). Programs participating in the survey had an average of 1.4 positions (± 0.7) open in phase II and 31 applicants (± 31) per open position. The timelines for screening applications, contacting applicants, and conducting interviews were variable. For qualitative data, RPDs appreciated the structured process and noted high-quality and geographic diversity of applicants in phase II. However, challenges reported were the quantity of applications, lack of time to fully review applications, and technical issues. Suggested changes included an extended phase II timeline, universal application deadline, and technical improvements. CONCLUSION: The structured approach of phase II was an improvement compared with historical approaches; however, variability exists in timelines for programs. Respondents identified further opportunities to refine phase II to benefit residency stakeholders.

Understanding the role of community pharmacies in current medication for opioid use disorder care practices.

BACKGROUND: Many barriers for patient access to medications for opioid use disorder (MOUD) exist in current care practices. Previous literature has evaluated subsets of pharmacists, patients, and prescribers; however, few have collectively evaluated the perspectives of all 3 groups. OBJECTIVE: The objective of the study was to identify barriers, facilitators, and opportunities for improvement in Indiana community pharmacy MOUD care practices from the perspectives of peer recovery coaches, community pharmacists, and prescribers to optimize patient care. METHODS: Individual semistructured interviews were conducted with each participant. Interviews explored stakeholders' perspectives on their current role in MOUD care practices and how current pharmacy practices could be improved. Data were analyzed using preconceived deductive and iterative inductive codes. The first author analyzed all transcripts, of which 3 were also analyzed separately by the last author to confirm consistent utilization of codes. All transcripts were coded once, followed by a second coding to ensure inductive codes were thoroughly applied. RESULTS: Ten peer recovery coaches, 10 pharmacists, and 6 prescribers were included. Interviews identified barriers, facilitators, and opportunities for improvement in current MOUD care practices. Stigma was a major barrier identified by all groups. Other barriers identified included limited patient engagement at pharmacies and lack of access to patient-specific health information in community pharmacy settings. Pharmacists also identified additional barriers including Drug Enforcement Administration regulations and difficulties balancing patient care with external factors like insurance and legal policies. Positive prescriber/pharmacist relationships were identified as a facilitator of care. Opportunities for improvement included having community MOUD resource information available at pharmacies, further education on MOUD for pharmacists, and increased collaboration between pharmacists and prescribers. CONCLUSION: Many barriers exist in current MOUD care practices. Additional pharmacist MOUD education and intentional collaboration between pharmacists, peer recovery coaches, and prescribers would facilitate better care and leverage the accessibility of pharmacists within their communities.

Community-based medication delivery program for antihypertensive medications improves adherence and reduces blood pressure.

Non-adherence to antihypertensive medications is a major cause of uncontrolled hypertension, leading to cardiovascular morbidity and mortality. Ensuring consistent medication possession is crucial in addressing non-adherence. Community-based medication delivery is a strategy that may improve medication possession, adherence, and blood pressure (BP) reduction. Our program in Kenya piloted a community medication delivery program, coupled with blood pressure monitoring and adherence evaluation. Between September 2019 and March 2020, patients who received hypertension care from our chronic disease management program also received community-based delivery of antihypertensive medications. We calculated number of days during which each patient had possession of medications and analyzed the relationship between successful medication delivery and self-reported medication adherence and BP. A total of 128 patient records (80.5% female) were reviewed. At baseline, mean systolic blood pressure (SBP) was 155.7 mmHg and mean self-reported adherence score was 2.7. Sixty-eight (53.1%) patients received at least 1 successful medication delivery. Our pharmacy dispensing records demonstrated that medication possession was greater among patients receiving medication deliveries. Change in self-reported medication adherence from baseline worsened in patients who did not receive any medication delivery (+0.5), but improved in patients receiving 1 delivery (-0.3) and 2 or more deliveries (-0.8). There was an SBP reduction of 1.9, 6.1, and 15.5 mmHg among patients who did not receive any deliveries, those who received 1 delivery, and those who received 2 or more medication deliveries, respectively. Adjusted mixed-effect model estimates revealed that mean SBP reduction and self-reported medication adherence were improved among individuals who successfully received medication deliveries, compared to those who did not. A community medication delivery program in western Kenya was shown to be implementable and enhanced medication possession, reduced SBP, and significantly improved self-reported adherence. This is a promising strategy to improve health outcomes for patients with uncontrolled hypertension that warrants further investigation.

Compression Therapy for HIV-Associated Kaposi Sarcoma Leg Lymphedema: Results of the Kenyan Improvised Compression for Kaposi Sarcoma Randomized Controlled Trial.

PURPOSE: Evaluate the effectiveness of compression while receiving chemotherapy compared with chemotherapy alone in the treatment of HIV-associated Kaposi sarcoma (KS) lymphedema. METHODS: A randomized controlled trial was conducted in a single oncology clinic in western Kenya (NCT03404297). A computer-generated randomization schedule was used to allocate treatment arms. Randomized block design was used for stratification by lymphedema stage. Participants were HIV positive adults age ≥ 18 years on antiretroviral therapy with biopsy-proven KS associated with leg lymphedema and being initiated on chemotherapy. The intervention was 10 weeks of weekly clinic-based application of two-component paste compression bandages. The primary outcome was change in the Lower Extremity Lymphedema Index (LELI) score from week 0 to week 14. The secondary outcomes were change in the Lymphedema Quality of Life measure (LYMQOL) and change in the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 score from week 0 to week 14. Blinded outcome assessments were conducted. RESULTS: Of 30 participants randomly assigned, 25 eligible patients (chemotherapy [control], n = 13; compression plus chemotherapy [intervention], n = 12) returned at week 14. Change in LELI, LYMQOL, and EORTC QLQ-C30 scores between week 14 and week 0 did not significantly differ by arm. The mean (standard deviation) change in LELI score was -25.9 (34.6) for the control arm compared with -13.3 (29.5) for the intervention arm, P = .340. The difference (95% CI) in the change in LELI score was -12.6 (-39.3 to 14.1). CONCLUSION: Future studies evaluating a 14-week change in LELI for KS lymphedema should assume a standard deviation of approximately 30. Lessons learned from this pilot trial should inform the development of a larger, multicenter trial to evaluate the effectiveness of compression for KS lymphedema.

Implementing a Locally Made Low-Cost Intervention for Wound and Lymphedema Care in Western Kenya.

In Western Kenya, the burden of chronic wounds and lymphedema has a significant impact on functionality and quality of life. Major barriers to provision of care include availability, affordability, and accessibility of bandages. At the Academic Model Providing Access to Healthcare, dermatologists and pharmacists collaborated to develop a 2-component compression bandage modeled after the Unna boot, using locally available materials, that is distributed through a revolving fund pharmacy network. In partnership with nursing, use of these bandages at a national referral hospital and a few county facilities has increased, but increasing utilization to an expanded catchment area is needed.

An ethics-based approach to global health research part 1: Building partnerships in global health.

Global health partnerships (GHPs) can be the cornerstone for advancing research and public health. The steps to build a global research partnership focus on sharing a common research agenda, identifying key partners in the community, and establishing goals and expectations for partnerships. Moreover, upholding important values, such as communication, trust, and transparency is essential for building successful partnerships. Ethical dilemmas can propose challenges to researchers in global health. These challenges can be overcome by creating a shared vision for a research agenda, maintaining communication, and providing bidirectional training.

Framework and case study for establishing impactful global health programs through academia - biopharmaceutical industry partnerships.

BACKGROUND: The field of global health has grown with multiple different public and private stakeholders engaging in the effort to improve health outcomes for underserved populations around the world. There is, however, only limited published guidance on how to promote successful partnerships between academia and the biopharmaceutical industry. OBJECTIVE: This analysis will provide a framework for developing successful partnerships around five central principles. This framework will then be applied to two representative pharmacy collaboration case studies focused on training and donations. FRAMEWORK DESCRIPTION AND CASE STUDY FINDINGS: Within the Academic Model Providing Access to Healthcare (AMPATH), successful collaborations between the biopharmaceutical industry philanthropic entities and academic partners have consistently prioritized 1) contextualization, 2) collaboration, 3) local priorities, 4) institutional commitment, and 5) integration. In the first case study, the application of this framework to clinical pharmacy training activities sponsored by Celgene and implemented by the Purdue Kenya Partnership has helped the program transition from an entirely donor dependent training program to a revenue generating, locally administered program which is now recognized and accredited by the Kenyan government. In the second case study, medication donations from Eli Lilly and Company have been converted from a traditional donation program in one Kenyan health facility to a replicable and sustainable supply chain model which has been expanded to more than 70 public sector facilities across western Kenya. CONCLUSION: Adherence to the five core principles of the proposed framework can help guide partnerships between academic institutions and the biopharmaceutical industry to advance healthcare services for underserved populations around the world. As large-scale government-based development agencies continue to primarily focus on specific disease states, biopharmaceutical industry-based collaborations can help initiate activities in underfunded therapeutic areas such as non-communicable diseases.

Randomized controlled trial to evaluate locally sourced two-component compression bandages for HIV-associated Kaposi sarcoma leg lymphedema in western Kenya: The Kenyan Improvised Compression for Kaposi Sarcoma (KICKS) study protocol.

BACKGROUND: HIV-associated Kaposi sarcoma (KS), among the most frequent cancers seen in sub-Saharan Africa, is associated with a high prevalence of lymphedema. Lymphedema causes progressive functional impairment marked by swelling, physical discomfort, disfiguring changes, skin hardening from fibrosis, poor wound healing, and recurrent skin infection. While compression therapy is considered a major component of lymphedema management, this intervention has never been evaluated in HIV-associated KS lymphedema. METHODS/DESIGN: The Kenyan Improvised Compression for Kaposi Sarcoma (KICKS) study is a randomized, controlled trial. Due to variable lymphedema stage, we will use block randomization with a 1:1 allocation to assign participants to one of two groups: "Immediate compression" or "Delayed compression." Those randomized to "Immediate compression" intervention arm will receive weekly two-component compression bandages while receiving chemotherapy, whereas those in the "Delayed compression" control arm will be followed during chemotherapy and then receive compression after chemotherapy is completed. The primary outcome is change in Lower Extremity Lymphedema Index from enrollment at Week 0 to blinded outcome assessment at Week 14 between intervention and control arms. Secondary outcomes are change in leg lymphedema-specific quality of life (LYMQOL) and change in overall health quality of life in cancer (EORTC QLQ C30). DISCUSSION: This represents the first study in sub-Saharan Africa to assess a lymphedema-directed intervention for KS, and the intervention-locally sourced two-component compression bandages-is affordable and available. Thus, the KICKS study is an important step towards developing an evidence-based path for regionally relevant management of HIV-associated KS lymphedema. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov on January 19, 2018: identifier NCT03404297.

Development of Low-Cost Locally Sourced Two-Component Compression Bandages in Western Kenya.

INTRODUCTION: Compression therapy is well-established standard of care for chronic leg ulcers from venous disease and lymphedema. Chronic leg ulcers and lymphedema have a significant impact on quality of life, driven by pain, foul odor, and restricted mobility. Provision of layered compression therapy in resource-limited settings, as in Western Kenya and other regions of sub-Saharan Africa, is a major challenge due to several barriers: availability, affordability, and access to healthcare facilities. When wound care providers from an Academic Model Providing Access to Healthcare (AMPATH) health center in Western Kenya noted that a donated, finite supply of two-component compression bandages was helping to heal chronic leg ulcers, they began to explore the potential of finding a local, sustainable solution. Dermatology and pharmacy teams from AMPATH collaborated with health center providers to address this need. METHODS: Following a literature review and examination of ingredients in prepackaged brand-name kits, essential components were identified: elastic crepe, gauze, and zinc oxide paste. All of these materials are locally available and routinely used for wound care. Two-component compression bandages were made by applying zinc oxide to dry gauze for the inner layer and using elastic crepe as the outer layer. Feedback from wound clinic providers was utilized to optimize the compression bandages for ease of use. RESULTS: Adjustments to assembly of the paste bandage included use of zinc oxide paste instead of zinc oxide ointment for easier gauze impregnation and cutting the inner layer gauze in half lengthwise to facilitate easier bandaging of the leg, such that there were two rolls of zinc-impregnated gauze each measuring 5 inches × 2 m. Adjustments to use of the compression bandage have included increasing the frequency of bandage changes from 7 to 3 days during the rainy seasons, when it is difficult to keep the bandage dry. Continuous local acquisition of all components led to lower price quotes for bulk materials, driving down the production cost and enabling a cost to the patient of 200 KSh (2 USD) per two-component compression bandage kit. Wound care providers have provided anecdotal reports of healed chronic leg ulcers (from venous stasis, trauma), improved lymphedema, and patient tolerance of compression. CONCLUSIONS: Low-cost locally sourced two-component compression bandages have been developed for use in Western Kenya. Their use has been initiated at an AMPATH health center and is poised to meet the need for affordable compression therapy options in Western Kenya. Studies evaluating their efficacy in chronic leg ulcers and Kaposi sarcoma lymphedema are ongoing. Future work should address adaptation of compression bandages for optimal use in Western Kenya and evaluate reproducibility of these bandages in similar settings, as well as consider home- or community-based care delivery models to mitigate transportation costs associated with accessing healthcare facilities.

Leveraging peer-based support to facilitate HIV care in Kenya.

Rakhi Karwa and colleagues discuss a program in which peer navigators support care for people with HIV at a Kenyan hospital.

Venous Thromboembolism Requiring Extended Anticoagulation Among HIV-Infected Patients in a Rural, Resource-Constrained Setting in Western Kenya.

BACKGROUND: HIV-infected patients are at an increased risk of developing venous thromboembolism (VTE), and minimal data are available to describe the need for extended treatment. OBJECTIVE: To evaluate the frequency of and determine predictive risk factors for extended anticoagulation of VTE in HIV-infected patients in rural, western Kenya. METHODS: A retrospective chart review was conducted at the Anticoagulation Monitoring Service affiliated with Moi Teaching and Referral Hospital and the Academic Model Providing Access to Healthcare. Data were collected on patients who were HIV-infected and receiving anticoagulation for lower-limb deep vein thrombosis. The need for extended anticoagulation, defined as receiving ≥7 months of warfarin therapy, was established based on patient symptoms or Doppler ultrasound-confirmed diagnosis. Evaluation of the secondary outcomes utilized a univariate analysis to identify risk factors associated with extended anticoagulation. RESULTS: A total of 71 patients were included in the analysis; 27 patients (38%) required extended anticoagulation. The univariate analysis showed a statistically significant association between the need for extended anticoagulation and achieving a therapeutic international normalized ratio within 21 days in both the unadjusted and adjusted analysis. Patients with a history of opportunistic infections required an extended duration of anticoagulation in the adjusted analysis: odds ratio = 3.42; 95% CI = 1.04-11.32; P = 0.04. CONCLUSIONS: This study shows that there may be a need for increased duration of anticoagulation in HIV-infected patients, with a need to address the issue of long-term management. Guideline recommendations are needed to address the complexity of treatment issues in this population.

Infective Endocarditis in Low- and Middle-Income Countries.

Infective endocarditis (IE) is a rare, life-threatening disease with a mortality rate of 25% and significant debilitating morbidities. Although much has been reported on contemporary IE in high-income countries, conclusions on the state of IE in low- and middle-income countries (LMICs) are based on studies conducted before the year 2000. Furthermore, unique challenges in the diagnosis and management of IE persist in LMICs. This article reviews IE studies conducted in LMICs documenting clinical experiences from the year 2000 to 2016. Presented are the causes of IE, management of patients with IE, and prevailing challenges in diagnosis and treatment of IE in LMICs.

Targeted Spontaneous Reporting: Assessing Opportunities to Conduct Routine Pharmacovigilance for Antiretroviral Treatment on an International Scale.

INTRODUCTION: Targeted spontaneous reporting (TSR) is a pharmacovigilance method that can enhance reporting of adverse drug reactions related to antiretroviral therapy (ART). Minimal data exist on the needs or capacity of facilities to conduct TSR. OBJECTIVES: Using data from the International epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium, the present study had two objectives: (1) to develop a list of facility characteristics that could constitute key assets in the conduct of TSR; (2) to use this list as a starting point to describe the existing capacity of IeDEA-participating facilities to conduct pharmacovigilance through TSR. METHODS: We generated our facility characteristics list using an iterative approach, through a review of relevant World Health Organization (WHO) and Uppsala Monitoring Centre documents focused on pharmacovigilance activities related to HIV and ART and consultation with expert stakeholders. IeDEA facility data were drawn from a 2009/2010 IeDEA site assessment that included reported characteristics of adult and pediatric HIV care programs, including outreach, staffing, laboratory capacity, adverse event monitoring, and non-HIV care. RESULTS: A total of 137 facilities were included: East Africa (43); Asia-Pacific (28); West Africa (21); Southern Africa (19); Central Africa (12); Caribbean, Central, and South America (7); and North America (7). Key facility characteristics were grouped as follows: outcome ascertainment and follow-up; laboratory monitoring; documentation-sources and management of data; and human resources. Facility characteristics ranged by facility and region. The majority of facilities reported that patients were assigned a unique identification number (n = 114; 83.2 %) and most sites recorded adverse drug reactions (n = 101; 73.7 %), while 82 facilities (59.9 %) reported having an electronic database on site. CONCLUSION: We found minimal information is available about facility characteristics that may contribute to pharmacovigilance activities. Our findings, therefore, are a first step that can potentially assist implementers and facility staff to identify opportunities and leverage their existing capacities to incorporate TSR into their routine clinical programs.

Meeting the Needs of Underserved Patients in Western Kenya by Creating the Next Generation of Global Health Pharmacists.

Objective. To describe a novel training model used to create a sustainable public health-focused pharmacy residency based in Kenya and to describe the outcomes of this training program on underserved populations. Design. The postgraduate year 2 residency was designed to expose trainees to the unique public health facets of inpatient, outpatient, and community-based care delivery in low and middle-income countries. Public health areas of focus included supply chain management, reproductive health, pediatrics, HIV, chronic disease management, and teaching. Assessment. The outcomes of the residency were assessed based on the number of new clinical programs developed by residents, articles and abstracts written by residents, and resident participation in grant writing. To date, six residents from the United States and eight Kenyan residents have completed the residency. Eleven sustainable patient care services have been implemented as a result of the residency program. Conclusion. This pharmacy residency training model developed accomplished pharmacists in public health pharmacy, with each residency class expanding funding and clinical programming, contributing to curriculum development, and creating jobs.

Describing the profile of patients on concurrent rifampin and warfarin therapy in western Kenya: a case series.

BACKGROUND: Rifampicin's ability to induce hepatic enzymes is responsible for causing a clinically significant drug interaction with warfarin. Little data exists to guide clinicians on managing this interaction, especially in Sub-Saharan Africa where many patients are exposed to this combination due to a higher burden of tuberculosis. OBJECTIVE: The objective of the case series is to provide insight to practicing clinicians of the unique dynamics of this drug interaction in resource-constrained settings. The case series will provide details on commonly encountered scenarios and the dosage adjustments required to maintain a therapeutic INR. METHODS: A retrospective chart review was conducted of patients attending the Moi Teaching and Referral Hospital anticoagulation clinic in Eldoret, Kenya. Patients were included if they had a history of concurrent rifampicin and warfarin therapy and a minimum follow up of 2 months. Descriptive statistics were used to explain the demographic characteristics, time to therapeutic INR and average weekly warfarin dose. The inference on proportions test was conducted to compare the time in the therapeutic range (TTR) for patients on concurrent rifampicin to the rest of the patients not receiving rifampicin in the clinic. RESULTS: Of the 350 patient charts evaluated, 10 met the inclusion criteria. The median percentage increase of the weekly warfarin dose from baseline was 15.7%. For the patients in this analysis, the median TTR was 47%. DISCUSSION: Patients on concurrent therapy should be rigorously monitored with regular INR checks and warfarin dosage adjustments. Empiric dosage adjustments of warfarin should be avoided but patient characteristics can aid in understanding the alterations seen in INR.

The evolution of diabetes care in the rural, resource-constrained setting of western Kenya.

BACKGROUND: The initial focused effort on addressing the HIV pandemic in sub-Saharan Africa has helped set the groundwork for addressing many of the other areas of the health-care system requiring support in resource-constrained settings. With the growing prevalence of diabetes in this setting, the US Agency for International Development-Academic Model Providing Access to Healthcare Partnership (USAID-AMPATH) has begun developing infrastructure to meet the growing need for diabetes care. OBJECTIVE: To describe the evolution of diabetes care in the rural, resource-constrained setting of western Kenya and to analyze preliminary data on the current status of glucose control of patients. METHODS: Through partnerships, USAID-AMPATH has facilitated the provision of basic modalities of diabetes care, including reliable stocks of insulin, hemoglobin A(1c) (A1C) testing, and point-of-care glucose-testing supplies. RESULTS: Through the introduction of A1C testing, the poor quality of diabetes care was revealed, as the average A1C for the clinic population was 10.4%, with insulin-dependent patients constituting the majority of individuals with markedly elevated A1C levels. To address this, a contextualized electronic medical record and a cell phone-based home glucose monitoring program were created to improve glycemic control, which has led to significant reductions in A1C levels. CONCLUSIONS: Through the inclusion of clinical data within the electronic medical record, there is an ongoing effort to research various aspects of diabetes care in this understudied population, with the goal of addressing many of the unanswered questions surrounding diabetes care in sub-Saharan Africa. The lessons learned from this pilot program will be used to create sustainable infrastructure for diabetes care in partnership with the Kenyan government and will serve as a model for similar programs.

Efungumab: a novel agent in the treatment of invasive candidiasis.

OBJECTIVE: To review the use of efungumab as an adjunctive agent in the treatment of invasive candidiasis (IC) and to provide guidance on formulary placement. DATA SOURCES: Searches of MEDLINE (1966-June 2009) and EMBASE (1974-June 2009) were conducted using the terms efungumab, Mycograb, heat shock protein 90, and invasive candidiasis. Other resources included www.clinicaltrials.gov and article bibliographies. STUDY SELECTION AND DATA EXTRACTION: All studies and case reports evaluating efungumab use in IC were included. Literature review was limited to the English language. DATA SYNTHESIS: Efungumab is a monoclonal antibody targeted against heat shock protein 90 (HSP 90). It binds to HSP 90, preventing a conformational change needed for fungal viability. In vitro data show that HSP 90 inhibition may decrease resistance against antifungal agents and increase antifungal activity. Efungumab shows activity against Candida spp. when used alone and synergism when combined with fluconazole, caspofungin, and amphotericin B. A randomized controlled trial evaluated combination therapy of efungumab 1 mg/kg twice daily and liposomal amphotericin B versus amphotericin B therapy alone. At day 10, a favorable response was seen in 84% of patients in the efungumab group compared with 48% of patients in the placebo group (OR 5.76; 95% CI 2.4 to 13.8). Mortality at day 33 was also lower in the efungumab group, 4% versus 18%, respectively (OR 0.168; 95% CI 0.036 to 0.797). Although adverse effects were similar in this trial (10% vs 7%), case reports revealed an increased incidence of blood pressure fluctuations. Cytokine release syndrome has also been linked to efungumab use, warranting further exploration of its safety. CONCLUSIONS: Efungumab is a new antifungal agent with a novel mechanism of action. Available clinical data and synergy studies support the use of efungumab in combination with other antifungal agents for the treatment of IC. Further safety data are needed before formulary recommendations can be made.

Midodrine and octreotide in treatment of cirrhosis-related hemodynamic complications.

OBJECTIVE: To review studies evaluating the use of midodrine and octreotide in hemodynamic complications of cirrhosis, including ascites and hepatorenal syndrome. DATA SOURCES: Searches of MEDLINE (1966-September 2008) and EMBASE (1974-September 2008) were conducted using the terms midodrine, octreotide, hepatorenal syndrome, ascites, cirrhosis, and paracentesis-induced circulatory dysfunction. Literature review was limited to English-language, human studies. STUDY SELECTION AND DATA EXTRACTION: Studies identified from data sources were considered for review. Studies were excluded if primary therapy involved any of the following: transjugular intrahepatic portosystemic shunt procedure, medications other than midodrine or octreotide, or patients included for treatment or prevention of portal hypertension and/or variceal bleeding. Pharmacokinetic/pharmacodynamic studies and studies using retrospective data collection were excluded. Seven studies were included in this review. DATA SYNTHESIS: Midodrine and octreotide in combination or alone have shown conflicting results for systemic and renal hemodynamics and renal function in patients with cirrhosis-related complications. Patients with ascites being treated with midodrine, alone or in combination with octreotide, showed significant changes in systemic hemodynamics, without a correlating change in renal perfusion. Studies comparing the use of midodrine with use of albumin for the prevention of paracentesis-induced circulatory dysfunction (PICD) showed no incidence of PICD in either treatment group. In hepatorenal syndrome, patients using midodrine with octreotide showed significant changes in systemic hemodynamics and improvements in renal perfusion. This regimen's effect on survival is yet to be determined. CONCLUSIONS: Available evidence shows inconsistent results for the effectiveness and safety of midodrine and octreotide use in cirrhotic patients. Because of the contradictory results, longer treatment duration and increased number of study participants are necessary to determine the proper use of midodrine and octreotide in these patients.