HIV medication therapy management services in community pharmacies

ObjectivesTo present a rationale and a proposed structure to support pharmacist-delivered medication therapy management (MTM) for human immunodeficiency virus (HIV ) diseaseand to outline challenges to implementing and sustaining the service.Data sourcesProfessional literature.SummaryHistorically, the effect of pharmacy services for HIV-infected persons has been demonstrated in inpatient and clinic-based settings. Developing similar programs adapted for community pharmacists could be a model of care to improve patient adherence to antiretroviral therapy and retention in care. Initiation of antiretroviral therapy and regular monitoring of CD4+ cell count, HIV RNA viral load, adverse drug events, and adherence form the backbone of successful medical management of HIV infection. Support for these services can be provided to HIV-infected patients through pharmacist-managed HIV MTM programs in community pharmacy settings in collaboration with primary providers and other health care professionals.ConclusionCommunity pharmacists can help meet the growing need for HIV care through provision of MTM services. Although resources have been developed, including the general MTM framework, challenges of adequate training, education, and support of community pharmacists need to be addressed in order for HIV MTM to be a successful model.     

Response to atomoxetine in boys with high-functioning autism spectrum disorders and attention deficit/hyperactivity disorder

Aim: To study the efficacy and tolerability of atomoxetine in high‐functioning boys with autism spectrum disorders (ASD) and comorbid attention deficit/hyperactivity disorder (AD/HD). Methods: Fourteen boys (age 7–17) participated in a 10‐week open‐label study. Atomoxetine doses were 0.5 mg/kg/day in week 1 and 1.2–1.4 mg/kg/day in weeks 2–10. Changes in AD/HD symptoms were measured by the AD/HD Rating Scale, and global improvements by the Clinical Global Improvement Scale. Both measures were used to assess drug response. Assessments were done at baseline and at weeks 2, 4, 6 and 10. Teacher ratings were done at baseline and 10 weeks. Results: There were significant reductions in AD/HD symptoms rated by parents (p < 0.005) and by teachers (p < 0.05). One participant was rated as ‘Much improved’, five as ‘Moderately improved’, seven as ‘Minimally improved’, and one as ‘Unchanged or worse’. Seven subjects were classified as clinical responders. The most common adverse events were nausea and headache. Two participants discontinued treatment. Conclusion: Seven out of 14 boys with high‐functioning ASD and comorbid AD/HD showed significant reductions in AD/HD symptoms and were classified as responders to atomoxetine. Most children tolerated the drug well.     

Short-term safety and tolerability of didanosine combined with high- versus low-dose tenofovir disproxil fumarate in ambulatory HIV-1-infected persons

Coadministration of didanosine (ddI) and tenofovir (TDF) results in increased ddI serum concentrations, which may lead to increased risk of ddI-associated toxicities. To evaluate the safety and tolerability of ddI/TDF, we performed a retrospective cohort analysis of patients seen in the HIV Outpatient Study, an ongoing dynamic cohort study of HIV-infected persons in clinical care. Study subjects were those who received at least 14 days of combined ddI/TDF before October 2003. Of 260 subjects who received ddI/TDF-based antiretroviral therapy, 155 (60%) received high-dose ddI (400 mg daily dose) and 105 (40%) received low-dose ddI (100-250 mg daily). Forty-two of the high-dose ddI recipients were later switched to low-dose ddI. The median time of observation for those on high-dose ddI only was 5 months, high-dose ddI switched to low-dose ddI was 16 months, and low-dose ddI only was 5 months (p < 0.05). Discontinuations because of toxicity were more frequent on high-dose ddI regimens (34/155, 22%) than on low-dose ddI regimens (9/105, 9%) (unadjusted odds ratio [OR(unadj)] 3.0, 95% confidence interval [95% CI] 1.30-7.09; p = 0.007). Among subjects without preexisting peripheral neuropathy, 12 (12%) of 101 subjects ever on high-dose ddI regimens had treatment-emergent peripheral neuropathy compared to 2 (4%) of 55 subjects on low-dose ddI regimens (OR(unadj) 3.57; 95% CI, 0.72-24.1; p = 0.14). Among patients without a history of pancreatitis, 6 (4%) of 153 subjects developed pancreatitis after starting high-dose ddI regimens, compared to none of the 103 subjects on low-dose ddI regimens (OR(adj) and 95% CIs undefined; p = 0.08). Severe laboratory abnormalities of creatinine, phosphorous, and bicarbonate were not different between the groups. A summary variable for any event--discontinuation for toxicity, treatment- emergent adverse event or abnormal laboratory values--indicated that 44 (28%) of 155 of those on high-dose ddI versus 13 (12%) of 105 on low-dose ddI developed any event (OR(unadj) 2.81; 95% CI, 1.36-5.86; p = 0.004). In conclusion, high-dose ddI/TDF-based therapy was more frequently associated with drug-related toxicity, adverse events, and treatment discontinuation than low-dose ddI/TDF regimens; low-dose ddI with TDF was generally well tolerated in these HIV-infected persons.     

Onychomycosis in a premature infant caused by Candida tropicalis

We report a case of onychomycosis caused by Candida tropicalis in a 107-day-old infant.     

Very low birthweight infants: outcome in a sub-Arctic population

Objective : To evaluate the outcome for very low birthweight (VLBW) infants in northern Norway. Subjects and methods: All live born infants ( n = 536) with birthweight ≤1500g born during 1978–89 to women residing in the northern health region of Norway were studied retrospectively. Data were from the Medical Birth Registry (MBR), hospital records and from follow-up recordings to 4 y of age at maternal and child health centres. Stillborn infants ( n = 269) with birthweight ≤1500g during the same period were also registered. Results : The annual incidence of live born VLBW infants (7.1/1000 live births) did not change, but the proportion of infants born alive before 26 weeks'gestation increased and the stillborn part decreased significantly. The Caesarean section (CS) rate, antenatal transfer and the use of a neonatal transport team increased significantly. Four hundred and seventy-five infants (89%) were considered viable at birth, 347 (65%) survived to 1 y and 343 (64%) to 4y. The likelihood of survival was independently related to female gender. The trend for survival to 4y of age did not increase significantly. Thirty children suffered from cerebral palsy (8.7% of survivors, 5.6% of live births) and the cerebral palsy rate for infants with birthweight 751-1000 g decreased. The proportion of survivors considered to be normal or mild disabled increased and the part suffering from moderate or severe disability decreased significantly. Conclusions : In spite of long distances and unfavourable climatic conditions VLBW infants can be adequately cared for in this sparsely populated region of Norway.     

The costs of HIV antiretroviral therapy adherence programs and impact on health care utilization

From a trial comparing interventions to improve adherence to antiretroviral therapy-directly administered antiretroviral therapy (DAART) or an intensive adherence case management (IACM)-to standard of care (SOC), for HIV-infected participants at public HIV clinics in Los Angeles County, California, we examined the cost of adherence programs and associated health care utilization. We assessed differences between DAART, IACM, and SOC in the rate of hospitalizations, hospital days, and outpatient and emergency department visits during an average of 1.7 years from study enrollment, beginning November 2001. We assigned costs to health care utilization and program delivery. We calculated incremental costs of DAART or IACM v SOC, and compared those costs with savings in health care utilization among participants in the adherence programs. IACM participants experienced fewer hospital days compared with SOC (2.3 versus 6.7 days/1000 person-days, incidence rate ratio [IRR]: 0.34, 97.5% confidence interval [CI]: 0.13-0.87). DAART participants had more outpatient visits than SOC (44.2 versus 31.5/1000 person-days, IRR: 1.4; 97.5% CI: 1.01-1.95). Average per-participant health care utilization costs were $13,127, $8,988, and $14,416 for DAART, IACM, and SOC, respectively. Incremental 6-month program costs were $2,120 and $1,653 for DAART and IACM participants, respectively. Subtracting savings in health care utilization from program costs resulted in an average net program cost of $831 per DAART participant; and savings of $3,775 per IACM participant. IACM was associated with a significant decrease in hospital days compared to SOC and was cost saving when program costs were compared to savings in health care utilization.     

HIV/AIDS treatment and HIV vaccines for Africa

Increased support from the global HIV/AIDS community is driving advances in HIV treatment and vaccine development in the developing world. Care of patients with AIDS includes many biomedical, nutritional, psychosocial, and behavioural interventions. In resource-poor settings, antiretroviral drugs should be given with use of standardised treatment regimens and streamlined algorithms for monitoring use. A safe and effective HIV vaccine will supplement prevention efforts to protect uninfected people against infection, or might possibly be able to modify the course of HIV infection. Advances have been made in understanding the immune response and immunisation to HIV, and new ideas for candidate vaccines have been developed, including several based on HIV-1 strains prevalent in Africa. HIV vaccine efficacy trials are needed in Africa to determine whether these advances can be translated into clinical and public health benefits. In this review, we discuss the prospects for use of treatment and vaccines in resource-poor settings.     

Drug-Induced Extrapyramidal Symptoms Scale of the Norwegian version: inter-rater and test–retest reliability

Abstract

Background: The Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) is a multidimensional rating scale designed for the fast, easy and reliable assessment of extrapyramidal symptoms (EPSs) induced by antipsychotics.

Aim: The aim of this study was to validate the level of inter-rater and test–retest reliability of the Norwegian translation of this scale.

Methods: A total of 125 video clips showing a variety of or no signs of EPSs were used in the present study. The participants recorded were Japanese psychiatric patients receiving first- and/or second-generation antipsychotics. A total of 103 patients (47 males and 56 females), diagnosed with schizophrenia (n?=?68) or mood disorders (n?=?35) appeared in the video clips. Their mean age was 48.7?±?16.3 years (range 18–80) at the time of video recording. Inter-rater agreement was assessed with five raters and test–retest reliability with three.

Results: Inter-rater reliability analyses showed interclass correlation coefficients (ICCs) ranging from 0.74 to 0.93 for each individual item. Test–retest reliability analysed independently for each rater ranged from 0.71 to 0.96.

Conclusions: Inter-rater and test–retest agreement exhibited satisfactory ICC levels above 0.70. The Norwegian version of the DIEPSS is a reliable instrument for the assessment of drug-induced EPSs.     

Recombinant human interleukin-1 receptor antagonist protects early myeloid progenitors in a murine model of cyclophosphamide-induced myelotoxicity

Expression of hematoregulatory cytokines such as interleukin-1 (IL-1) in response to cytotoxic chemotherapy hastens hematopoietic recovery, but may also potentiate myelotoxicity if myeloid progenitors enter cell cycle before drug clearance. In the present study, the ability of recombinant human IL-1 receptor antagonist (IL-1ra) to protect hematopoietic progenitors was studied in a murine model of cyclophosphamide (CPA)-induced myelotoxicity. CF-1 female mice received 200 mg/kg CPA and either 10 mg/kg IL-1ra or an equal volume of 0.05% human serum albumin (HSA) intraperitoneally (i.p.), followed 12 hours later by IL-1ra or HSA. CPA and IL-1ra increased absolute neutrophil counts (ANCs) at days 2 (P = .001) and 14 (P = .0025) after CPA. In IL- 1ra-treated mice, colony-forming units granulocyte-macrophage (CFU- GM)/tibia were increased twofold and threefold at days 2 (P = .0047) and 7 (P = .023), respectively, whereas high proliferative potential colony-forming cells (HPP-CFC)/tibia were decreased twofold to threefold at 8 hours (P = .039) and 24 hours (P = .0033), but were approximately threefold higher than HSA-treated mice at day 7 after CPA. Coadministration of CPA and IL-1 enhanced myelotoxicity compared with mice injected with CPA and IL-1ra or HSA. In vivo, IL-1ra protected HPP-CFC, but not CFU-GM, from hydroxyurea suicide after a single dose of CPA, suggesting that IL-1ra inhibited cycling of HPP- CFC. In vitro, IL-1ra did not alter proliferation of CFU-GM, but inhibited IL-1-enhanced proliferation of HPP-CFC. These data suggest that IL-1ra acts as an indirect negative regulator of hematopoiesis and protects HPP-CFC from CPA, possibly by inhibiting IL-1-enhanced proliferation of early myeloid progenitors.     

Benzimidazolones enhance the function of epithelial Na+ transport

Background and Purpose

Pharmacological enhancement of vectorial Na⁺ transport may be useful to increase alveolar fluid clearance. Herein, we investigated the influence of the benzimidazolones 1-ethyl-1,3-dihydro-2-benzimidazolone (1-EBIO), 5,6-dichloro-1-EBIO (DC-EBIO) and chlorzoxazone on vectorial epithelial Na⁺ transport.

Experimental Approach

Effects on vectorial Na⁺ transport and amiloride-sensitive apical membrane Na⁺ permeability were determined by measuring short-circuit currents (I_SC) in rat fetal distal lung epithelial (FDLE) monolayers. Furthermore, amiloride-sensitive membrane conductance and the open probability of epithelial Na⁺ channels (ENaC) were determined by patch clamp experiments using A549 cells.

Key Results

I_SC was increased by approximately 50% after addition of 1-EBIO, DC-EBIO and chlorzoxazone. With permeabilized basolateral membranes in the presence of a 145:5 apical to basolateral Na⁺ gradient, the benzimidazolones markedly increased amiloride-sensitive I_SC. 5-(N-Ethyl-N-isopropyl)amiloride-induced inhibition of I_SC was not affected. The benzamil-sensitive I_SC was increased in benzimidazolone-stimulated monolayers. Pretreating the apical membrane with amiloride, which inhibits ENaC, completely prevented the stimulating effects of benzimidazolones on I_SC. Furthermore, 1-EBIO (1 mM) and DC-EBIO (0.1 mM) significantly increased (threefold) the open probability of ENaC without influencing current amplitude. Whole cell measurements showed that DC-EBIO (0.1 mM) induced an amiloride-sensitive increase in membrane conductance.

Conclusion and Implications

Benzimidazolones have a stimulating effect on vectorial Na⁺ transport. The antagonist sensitivity of this effect suggests the benzimidazolones elicit this action by activating the highly selective ENaC currents. Thus, the results demonstrate a possible new strategy for directly enhancing epithelial Na⁺ transport.