Pilot study of a community pharmacist led program to treat hepatitis C virus among people who inject drugs.

Background: People who inject drugs (PWID) are a key population for treatment with direct-acting antiviral medications (DAAs) to eliminate hepatitis C virus (HCV). We developed a Pharmacist, Physician, and Patient Navigator Collaborative Care Model (PPP-CCM) for delivery of HCV treatment; this study describes clinical outcomes related to HCV treatment (initial evaluation, treatment initiation, completion, and cure), as well as patient satisfaction. Methods: We conducted a single-arm prospective pilot study of adult PWID living with HCV. Participants completed baseline and six-month follow-up surveys, and treatment and outcomes were abstracted from electronic health records. Primary outcome was linkage to pharmacist for HCV evaluation; secondary outcomes included DAA initiation, completion, and cure, as well as patient-reported satisfaction. Results: Of the 40 PWID enrolled, mean age was 43.6 years, 12 (30 %) were female, 20 (50 %) were non-white, and 15 (38 %) were unhoused. Thirty-eight (95 %) were successfully linked to the pharmacist for initial evaluation. Of those, 21/38 (55 %) initiated DAAs, and 16/21 (76 %) completed treatment. Among those completing treatment who had viral load data to document whether they achieved "sustained virologic response", i.e. cure, 10/11 (91 %) were found to be cured. There was high satisfaction with 100 % responding "agree or strongly agree" that they had a positive experience with the pharmacist. Conclusion: Nearly all participants in this pilot were successfully linked to the pharmacist for evaluation, and more than half were started on DAAs; results provide preliminary evidence of feasibility of pharmacist-led models of HCV treatment for PWID. Clinicaltrialsgov registration number: NCT04698629.

Rates and predictors of response to anti-viral treatment for hepatitis C virus in HIV/HCV co-infection in a nationwide study of 619 patients.

BACKGROUND: The effectiveness of anti-viral treatment for hepatitis C virus (HCV) in HIV/HCV co-infected patients in 'real world', clinical practice is unclear. AIMS: To determine the rates and predictors of sustained virological response (SVR) to anti-viral treatment for HCV with pegylated interferon (PEG-IFN) and ribavirin in HIV/HCV co-infected patients. METHODS: We identified all HIV/HCV co-infected patients who received anti-viral treatment with PEG-IFN and ribavirin in the Veterans Affairs healthcare system nationally between 2002 and 2009 (n = 665). RESULTS: Sustained virological response was achieved in 21.6% overall, 16.7% among patients with genotype 1 HCV (n = 491) and 44% among patients with genotype 2 or 3 HCV (n = 116). Among genotype 1-infected patients, characteristics that were negatively associated with SVR independently included baseline HCV viral load >2 million IU/mL [adjusted odds ratio (AOR) 0.41, 95% CI 0.2-0.7], Black race [AOR 0.56 (0.3-0.96)], diabetes [AOR 0.42 (0.2-0.9)], baseline anaemia [AOR 0.42 (0.2-0.97)], serum aspartate aminotransferase/alanine aminotransferase ratio ≥1.2 [AOR 0.48 (0.2-0.97)] and use of zidovudine [AOR 0.41 (0.2-0.9)]; characteristics positively associated with SVR included a starting dose of ribavirin ≥1000-1200 mg/day [AOR 2.0 (1.1-3.7)] and erythropoietin use during treatment [AOR 2.9 (1.6-5.0)]. Among genotype 2 or 3 infected patients, only erythropoietin use was an independent predictor of SVR [AOR 3.1 (1.2-7.8)], while a starting dose of ribavirin >800 mg/day was not associated with SVR. CONCLUSIONS: Sustained virological response rates achieved with PEG-IFN and ribavirin in HIV/HCV co-infected patients are low in clinical practice. The use of erythropoietin was the most important, modifiable factor associated with SVR.

Risk factors for late-onset cytomegalovirus disease in donor seropositive/recipient seronegative kidney transplant recipients who receive antiviral prophylaxis.

BACKGROUND: Cytomegalovirus (CMV) disease occurs frequently after cessation of antiviral prophylaxis in CMV-seronegative kidney transplant recipients from seropositive donors (D+R-), and the risk factors are incompletely defined. METHOD: We retrospectively assessed the incidence, clinical features, and risk factors for CMV disease in a cohort of D+R- kidney transplant recipients who received antiviral prophylaxis at a single US transplant center using descriptive statistics and Cox proportional hazards models. RESULTS: CMV disease developed in 29 of 113 (26%) D+R- patients at a median of 185 days (interquartile range 116-231 days) post transplant, including CMV syndrome (66%) and tissue invasive disease (34%). The incidence of CMV disease was higher in patients who underwent re-transplantation (57% vs. 24%) and this factor was independently associated with a higher risk of CMV disease in multivariable analysis (hazard ratio, 4.02; 95% confidence interval, 1.3-13; P = 0.016). Other demographic and transplant variables were not independently associated with a risk of late-onset CMV disease. CONCLUSIONS: Despite a comprehensive analysis of patient and transplant variables, only re-transplantation was identified as a risk factor for CMV disease in D+R- kidney transplant recipients who received antiviral prophylaxis, but had limited clinical predictive value. The development of novel laboratory markers to identify patients at greatest risk for CMV disease should be a priority for future studies.

HIV clinicalpharmacists – the USperspective

Clinical pharmacists have been involved in treating people with HIV and AIDS since the epidemic began. Their roles have evolved from inpatient infectious diseases training clinical pharmacists offering treatment regimens for the serious opportunistic infections seen in the hospital, to clinical pharmacists who received specialized training in the treatment of people with HIV in the ambulatory care setting. Their roles and benefits have been documented in the literature, but not to a large extent. Improvements in adherence and cost savings have been seen, but significant improvements in clinical outcomes (changes in viral load and CD4 cell counts) are quite complex and often difficult to identify in the small studies that have been published. This manuscript will review the published data on this topic, and provide examples of clinically trained pharmacists in the US who focus on the treatment of people with HIV infection. The pharmacists discussed here practice in a variety of settings (privately managed free-clinics and government managed clinics), take care of a variety of types of patients (children, adults, military veterans, lower socio-economic groups, etc.), and are employed by a variety of institutions (academic, pharmaceutical company, large healthcare systems and small healthcare systems). These pharmacists were chosen to be representative of the wide variety of individuals, positions and roles of clinical pharmacists involved in the treatment of HIV in the US (AU)

Los farmacéuticos clínicos se han involucrado en el tratamiento de los pacientes con VIH y sida desde el comienzo de la epidemia. Sus papeles han evolucionado desde farmacéuticos con formación en enfermedades infecciosas que requieren hospitalización, aquellos que ofrecen regímenes de tratamiento para las infecciones oportunistas graves que aparecen en el hospital, hasta farmacéuticos con formación especializada para el tratamiento ambulatorio de pacientes con VIH. Sus funciones y beneficios se han documentado en la literatura, pero no de forma exhaustiva. Asimismo, se han demostrado las mejoras en la adherencia al tratamiento y el ahorro en costes, sin embargo las mejoras significativas en los resultados clínicos (cambios en la carga viral y recuentos celulares CD4) son muy complejas y a menudo difíciles de identificar en los escasos estudios publicados. En este documento se revisarán los datos publicados sobre este tema, y se mostrarán ejemplos de farmacéuticos con formación clínica en los Estados Unidos especializados en el tratamiento de personas infectadas con VIH. Además, los farmacéuticos incluidos ejercen en diferentes entornos (clínicas privadas y clínicas públicas), asisten a distintos tipos de pacientes (niños, adultos, veteranos de guerra, grupos de orígenes humildes, etc.), y pertenecen a diferentes instituciones (académicas, farmacéuticas, sistemas sanitarios de gran envergadura y de pequeña envergadura). Estos farmacéuticos se han elegido como representantes de una gran variedad de individuos, puestos y funciones que conforma el grupo de farmacéuticos clínicos involucrados en el tratamiento del VIH en los Estados Unidos (AU)

HIV clinical pharmacists--the US perspective.

Clinical pharmacists have been involved in treating people with HIV and AIDS since the epidemic began. Their roles have evolved from inpatient infectious diseases training clinical pharmacists offering treatment regimens for the serious opportunistic infections seen in the hospital, to clinical pharmacists who received specialized training in the treatment of people with HIV in the ambulatory care setting. Their roles and benefits have been documented in the literature, but not to a large extent. Improvements in adherence and cost savings have been seen, but significant improvements in clinical outcomes (changes in viral load and CD4 cell counts) are quite complex and often difficult to identify in the small studies that have been published. This manuscript will review the published data on this topic, and provide examples of clinically trained pharmacists in the US who focus on the treatment of people with HIV infection. The pharmacists discussed here practice in a variety of settings (privately managed free-clinics and government managed clinics), take care of a variety of types of patients (children, adults, military veterans, lower socio-economic groups, etc.), and are employed by a variety of institutions (academic, pharmaceutical company, large healthcare systems and small healthcare systems). These pharmacists were chosen to be representative of the wide variety of individuals, positions and roles of clinical pharmacists involved in the treatment of HIV in the US.

Management of complications after laparoscopic Roux-en-Y gastric bypass.

Obesity has become an increasing problem in developed countries and laparoscopic Roux-en-Y gastric bypass (LRYGB) is one of the leading treatments for this disease. Although studies show that it is effective in reducing weight and lessening comorbidities, both early and late complications can occur. Early complications include venous thromboembolism, anastomotic leak, and hemorrhage. Late complications include obstruction, anastomotic stenosis, fistula, ulcer, cholelithiasis and nutritional deficiencies. Diagnosis of these complications is often challenging due to the lack of specificity of the presenting signs and symptoms. A high index of suspicion for detecting these complications is universally advocated. Fortunately, mortality from this procedure is rare. Management of the complications is generally consistent with basic surgical principles and surgical reinterventions can often be performed either endoscopically or laparoscopically depending on the situation and the surgeon's expertise. The available literature is confounded by mixing of results between open and laparoscopic techniques as well as the substantial differences in technique between authors reporting their outcomes. Although there is no consensus for managing the reported complications of LRYGB surgery, this article reviews the current literature and describes the presentation, diagnosis, and management of each of the early and late complications associated with the procedure.

Prevention and control of proliferative vitreoretinopathy: primary retinal detachment surgery using silicone oil as a planned two-stage procedure in high-risk cases.

AIMS: For rhegmatogenous retinal detachment, reattachment with a single procedure is associated with better visual outcomes. In the past, silicone oil has been used mostly as a last resort following failed primary surgery. This study evaluates a novel approach to patients at high risk of primary failure, using silicone tamponade as the primary stage of a planned two-stage procedure. METHODS: We report a series of 140 eyes that underwent primary surgery for rhegmatogenous retinal detachment. Patients at higher risk of surgical failure (eg giant retinal tear, inability to posture, poor view, uncertainty of location of primary break, primary proliferative vitreoretinopathy (PVR), multiple tears with rolled posterior edges, retinoschisis/detachment, staphyloma with macular hole) were managed by a planned staged procedure using primary silicone oil tamponade. This was followed by silicone removal at a later date. RESULTS: Fifty-four eyes underwent scleral buckling alone, with primary success in 52/54 (96%). Fifty-three eyes underwent vitrectomy and gas, achieving primary success in 50/53 (94%). Thirty-three eyes were classified high risk and managed with primary silicone. Silicone was safely removed in 22/25. In eight eyes, silicone was retained without attempt at removal. In total, primary retinal reattachment was achieved in 128 of 140 eyes (91.4%). Of these, 124 (97%) did not require long-term tamponade. Only four eyes (2.9%) developed PVR. DISCUSSION: A planned two-stage approach to highrisk cases of retinal detachment using primary silicone oil tamponade followed by silicone removal can achieve a high primary reattachment rate with less than 3% incidence of PVR.

Distribution and characterization of Borrelia burgdorferi isolates from Ixodes scapularis and presence in mammalian hosts in Ontario, Canada.

The blacklegged tick, Ixodes scapularis Say (Acari: Ixodidae), has a wide geographical distribution in Ontario, Canada, with a detected range extending at least as far north as the 50th parallel. Our data of 591 adult I. scapularis submissions collected from domestic animals (canines, felines, and equines) and humans during a 10-yr period (1993-2002) discloses a monthly questing activity in Ontario that peaks in May and October. The Lyme disease spirochete Borrelia burgdorferi Johnson, Schmidt, Hyde, Steigerwalt & Brenner was detected in 12.9% of I. scapularis adults collected from domestic hosts with no history of out-of-province travel or exposure at a Lyme disease endemic area. Fifty-three isolates of B. burgdorferi were confirmed positive with polymerase chain reaction by targeting the rrf (5S)-rrl (23S) gene. Using DNA sequencing of the ribosomal species-specific rrf (5S) -rrl (23S) intergenic spacer region, all isolates belong to the pathogenic genospecies B. burgdorferi sensu stricto (s.s.). Nucleotide sequence analysis of a 218- to 220-bp amplicon fragment exhibits six cluster patterns and, collectively, these isolates branch into four phylogenetic cluster groups for both untraveled, mammalian hosts and those with travel to the northeastern United States (New Jersey and New York). Four of five geographic regions in Ontario had strain variants consisting of three different genomic cluster groups. Overall, our molecular characterization of B. burgdorferi s.s. shows genetic heterogeneity within Ontario and displays a connecting link to common strains from Lyme disease endemic areas in the northeastern United States. Moreover, our findings of B. burgdorferi in I. scapularis reveal that people and domestic animals may be exposed to Lyme disease vector ticks, which have wide-ranging distribution in eastern and central Canada.

Compartmentalized cAMP signalling: a personal perspective.

Scaffolding proteins create order out of chaos. Multifunctional binding proteins such as the AKAPs (A-kinase-anchoring proteins) oversee the dynamic organization of signalling events by clustering activator proteins with kinases, phosphatases and phosphodiesterases and directing them toward their downstream effectors. This article will focus on the role of AKAPs in the spatial and temporal control of cAMP signalling events.

WAVE signalling: from biochemistry to biology.

The small GTPases Rho, Rac and Cdc42 (cell-division cycle 42) function as molecular switches to modulate the actin cytoskeleton. They achieve this by modulating the activity of downstream cellular targets. One group of Rho GTPase effectors, WAVE (Wiskott-Aldrich syndrome protein verprolin homologous)-1, WAVE-2 and WAVE-3, function as scaffolds for actin-based signalling complexes. The present review highlights current knowledge regarding the biochemistry of the WAVE signalling complexes and their biological significance.

A rationale for membrane peeling in the repair of stage 4 macular holes.

AIM: To examine the histological and immunocytochemical characteristics of epiretinal membranes (ERM) associated with stage 4 macular holes (MH) so as to establish a vitreoretinal rationale for surgery in stage 4 MH. METHOD: Consecutive patients with stage 4 MH undergoing vitrectomy and membrane peeling were recruited. Preoperatively, the eyes were examined for ERM formation over the macula and completeness of posterior hyaloid membrane (PHM) separation from the retina. ERM peel specimens obtained during surgery were sent for histological and immunocytochemical studies and were compared with the PHM specimens taken from a previous post-mortem study of eyes with physiological posterior vitreous detachment but without macular holes. RESULT: A total of 13 patients with stage 4 MH fulfilled the inclusion criteria and were recruited. Preoperatively, all eyes had an ERM over the macula and incomplete separation of the PHM seen as a defect in the PHM on specular biomicroscopy. Histologically, the ERM specimens had very similar morphological characteristics to PHM, consisting of an eosinophilic membrane of varying thickness with scattered spindle-shaped cells. The membranes stained positively for type IV collagen while the cells were glial fibrillary acidic protein positive. Postoperatively, successful closure of MH was achieved in all cases. CONCLUSION: Stage 4 MH is characterised by incomplete separation of the PHM from the retina with remnants overlying the macula manifesting as ERM. Removal of the ERM is required during vitrectomy in order to relieve the tangential forces involved in the development of MH.

Clinical features and surgical management of retinal detachment secondary to round retinal holes.

AIMS: The majority of rhegmatogenous retinal detachments result from pathological posterior vitreous detachment (PVD) and secondary horseshoe or giant retinal tears. Retinal detachment without PVD is usually associated with either retinal dialysis or round retinal holes. This study characterises the features, surgical outcome, and incidence of bilateral involvement of detachment associated with round retinal holes. METHODS: In all, 110 retinal detachments from 96 consecutive patients with retinal detachment secondary to round retinal holes were studied. Analysis of patient age, sex, refraction, preoperative visual acuity, presented symptoms, position and extent of detachment, number and distribution of holes present, posterior hyaloid membrane status, surgical management, outcome of surgery, and postoperative visual acuity were studied. RESULTS: The mean age for patients was 34 years with a marked female preponderance (64%) and myopia (83%). The posterior hyaloid membrane remained attached in 95 eyes (86%). In all, 45% patients had bilateral pathology, of which 33% had 'mirror image' distribution. Detachments were predominantly shallow (93%) and slow in progression (17%). A total of 100 detachments were repaired with cryotherapy and scleral buckling, eight with cryotherapy alone, and one with laser retinopexy. In all, 99% detachments were successfully reattached with a single procedure. The mean follow-up period was 2 years. There were no instances of redetachment. CONCLUSIONS: Round hole detachments are slowly evolving detachments with attached vitreous gel in young, predominantly female myopes. Examination of the fellow eye should be mandatory as there is a high incidence of bilateral pathology. Scleral buckling procedures remained highly effective in this selected group of patients.

Hyperconvolution of the inner limiting membrane in vitreomaculopathies.

BACKGROUND: This study investigates the similarities and differences between epiretinal membranes in four clinically distinct types of vitreomaculopathy. We propose a hypothesis on the origin of the predominant cell type and its potential role in causing these conditions. METHODS: Epiretinal membranes (ERMs) surgically removed from a prospective, consecutive series of vitrectomies for macular pucker associated with an untreated peripheral horseshoe tear (MP), cellophane maculopathy (CM), stage 4 macular hole (MH) and vitreomacular traction syndrome (VMT) were examined by light microscopy and by immunocytochemistry (ICC) using antibodies marking type IV collagen, type II collagen, glial fibrillary acidic protein (GFAP), and low- and high-molecular-weight cytokeratin (MNF116). These specimens were compared with post-mortem control eyes with and without physiological posterior vitreous detachment (PVD). Light microscopy was carried out on 5-microm-thick sections cut from formalin-fixed, paraffin-embedded tissue blocks. Appropriate autoclave or enzyme pre-digestion steps were deployed to retrieve antigens for ICC. No patient had undergone previous vitreoretinal surgery or peripheral retinopexy. RESULTS: From a series of 38 patients, (13 CM, 8 MP, 16 MH and 1 VMT) a total of 20 specimens contained sufficient tissue for histology and immunocytochemistry. All specimens contained portions of inner limiting membrane (ILM) coated by GFAP-positive cells. Specimens from patients with MP and CM exhibited hyperconvolution of the ILM, which was not found in the specimens from patients with MH or VMT or in the control eyes. Hyperconvolution was associated with increased glial cell density, GFAP staining intensity and duplication of ILM basement membrane. Three cases of ERMs from the MP group contained, in addition, cytokeratin-positive cells. In the control group; post-mortem eyes with PVDs showed patchy staining of the posterior hyaloid membrane for GFAP and type 4 collagen. Post-mortem eyes with attached gel showed weak positivity of the ILM for type 4 collagen, and a monolayer of GFAP-positive cells lined the vitreous aspect of the ILM. CONCLUSIONS: These results indicate that glial cells are fundamentally important in the formation of ERMs found in this group of vitreomaculopathies. The hyperconvolution and duplication of the ILM in CM and MP were striking and distinctive features and suggest a mechanism by which these membranes exert tractional forces on the retina. Post-mortem control eyes contained a similar (but more dispersed) population of GFAP-positive cells in the region of the ILM, suggesting the primary aetiology for CM and MP may originate within the ILM. ERMs from MP cases may, in addition, contain cytokeratin-positive cells, of probable RPE origin.

A-kinase-anchoring proteins and cytoskeletal signalling events.

Targeting of protein kinases and phosphatases to the cytoskeleton enhances the regulation of many signalling events. Cytoskeletal signalling complexes facilitate this process by optimizing the relay of messages from membrane receptors to specific sites on the actin cytoskeleton. These signals influence fundamental cell properties such as shape, movement and division. Targeting of the cAMP-dependent kinase (protein kinase A) and other enzymes to this compartment is achieved through interaction with A-kinase-anchoring proteins (AKAPs). The present paper discusses recent progress on dissecting the biological role of WAVE1 (Wiskott-Alrich syndrome protein family verprolin homology protein 1), an AKAP that assembles a cytoskeletal transduction complex in response to signals that emanate from the low-molecular-mass GTPase, Rac.

Molecular genetics of rhegmatogenous retinal detachment.

Rhegmatogenous retinal detachment (RRD) most commonly occurs as a spontaneous event resulting from posterior vitreous detachment, typically between the ages of 40-70 yrs. It is also a feature in some inherited disorders, most commonly Stickler syndrome. The relationship between these inherited disorders and the spontaneous cases is unclear. Here in particular we review Stickler syndrome, and discuss the differential diagnosis of Stickler, Wagner and Marshall syndromes. Other rare inherited disorders associated with RRD are also briefly reviewed.