Haemophagocytic Lymphohistiocytosis in an Elderly Patient after Recent Cardiac Surgery.

INTRODUCTION: The underlying pathophysiology of haemophagocytic lymphohistiocytosis (HLH) is characterised by excessive inflammation and tissue destruction secondary to abnormal immune activation. The term primary HLH refers to a genetic abnormality that predisposes to the condition whereas secondary refers to HLH being triggered by an underlying condition such as infection (often Epstein Barr Virus), autoimmune, or neoplastic disease. Its variable clinical presentation poses an obstacle to prompt diagnosis in the elderly patient. CASE: A 70-year-old Caucasian man was admitted to hospital from a convalescence center with symptoms of fatigue, fever, decreased oral intake, and increasing shortness of breath on exertion. The patient was three weeks after coronary artery bypass grafting. Over the next two weeks, the patient continued to deteriorate both clinically and biochemically. The patient met criteria for haemophagocytic lymphohistiocytosis, likely driven by EBV infection. Bone marrow biopsy supported the diagnosis with evidence of active phagocytosis. The patient was commenced on high-dose dexamethasone and reviewed by haematology with further molecular testing confirming the diagnosis. Discussion. LH is becoming more common in older patients. We propose that new guidelines be developed to aid its prompt diagnosis in this age group.

Simvastatin Suppresses Interleukin Iß Release in Human Peripheral Blood Mononuclear Cells Stimulated With Cholesterol Crystals.

Statins are mainstream therapy in the treatment and prevention of cardiovascular disease through inhibitory effects on cholesterol synthesis. However, statins' beneficial effects in cardiovascular disease may also be attributable to their role as anti-inflammatory mediators. Here, we investigated the effects of simvastatin treatment on expression levels of interleukin (IL) 1ß in both patient with hyperlipidemia and healthy human peripheral blood mononuclear cells (PBMCs) using cholesterol crystals (CC), a cardiovascular pathogenic stimulus for activation of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome. Cholesterol crystal-induced NLRP3 inflammasome activation was used to trigger maturation and release of IL-1ß in PBMCs. Specifically, isolated PBMCs from patients with hyperlipidemia at baseline and following 8 weeks of in vivo treatment with simvastatin (10-20 mg) daily were stimulated with lipopolysaccharide (LPS; 100 ng/mL) for 3 hours to induce proIL-Iß expression followed by CC (2 mg/mL) stimulation for further 18 hours to activate the NLRP3 inflammasome complex to induce maturation/activation of IL-1ß. Peripheral blood mononuclear cells were also isolated from healthy donors and stimulated in vitro with simvastatin (50, 25, 5, and 2 µmol/L) prior to stimulation with LPS and CC as described above. The effects of simvastatin treatment on levels of IL-1ß expression were determined by enzyme-linked immunosorbent assay and western blot. Both in vitro and in vivo treatments with simvastatin led to a significant reduction in the levels of expression of IL-1ß in response to stimulation with CC. Simvastatin inhibits the expression and activation of IL-1ß induced by CC in PBMCs, which may contribute to its protective role in patients with cardiovascular disease.

Acute herpes zoster and post herpetic neuralgia in primary care: a study of diagnosis, treatment and cost.

Acute herpes zoster and its complication post herpetic neuralgia represent a significant challenge to primary care physicians in their care of an ageing population of patients. This was a cross-sectional observational study by means of a quantitative survey of 1,000 general practitioners registered in Ireland exploring the frequency of diagnosis, methods of treatment and cost of AHZ and PHN in primary care. We recorded an 18% response rate (n = 184) with an 83% completion rate (n = 152/184). 80% of cases of AHZ occurred in patients aged 50 years or more with 81% of study participants encountering cases at a rate of 1-3 patients per month. Famciclovir (37%) and valaciclovir (36%) were the most commonly prescribed antiviral agents. Mild opioids (32%) were the most common analgesic agents used for first line AHZ pain, and pregabalin (37%) the most commonly prescribed analgesic agent for second line AHZ pain. Pregabalin was also the most commonly prescribed analgesic for both first and second line PHN pain (29% and 24%, respectively). The mean per-case direct cost (medication and GP visits) of treating AHZ and PHN in primary care was €195 (range €153-€236) and €201 (range €140-€313), respectively. Based on national sentinel data the estimated annual direct costs of treating AHZ and PHN in primary care is €2,278,196 (range €1,793,399-€2, 763,445). The treatment of AHZ and PHN represents both a significant care and cost burden on primary care resources in Ireland in keeping with other European based studies.

Usage of unscheduled hospital care by homeless individuals in Dublin, Ireland: a cross-sectional study.

OBJECTIVES: Homeless people lack a secure, stable place to live and experience higher rates of serious illness than the housed population. Studies, mainly from the USA, have reported increased use of unscheduled healthcare by homeless individuals.We sought to compare the use of unscheduled emergency department (ED) and inpatient care between housed and homeless hospital patients in a high-income European setting in Dublin, Ireland. SETTING: A large university teaching hospital serving the south inner city in Dublin, Ireland. Patient data are collected on an electronic patient record within the hospital. PARTICIPANTS: We carried out an observational cross-sectional study using data on all ED visits (n=47 174) and all unscheduled admissions under the general medical take (n=7031) in 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: The address field of the hospital's electronic patient record was used to identify patients living in emergency accommodation or rough sleeping (hereafter referred to as homeless). Data on demographic details, length of stay and diagnoses were extracted. RESULTS: In comparison with housed individuals in the hospital catchment area, homeless individuals had higher rates of ED attendance (0.16 attendances per person/annum vs 3.0 attendances per person/annum, respectively) and inpatient bed days (0.3 vs 4.4 bed days/person/annum). The rate of leaving ED before assessment was higher in homeless individuals (40% of ED attendances vs 15% of ED attendances in housed individuals). The mean age of homeless medical inpatients was 44.19 years (95% CI 42.98 to 45.40), whereas that of housed patients was 61.20 years (95% CI 60.72 to 61.68). Homeless patients were more likely to terminate an inpatient admission against medical advice (15% of admissions vs 2% of admissions in homeless individuals). CONCLUSION: Homeless patients represent a significant proportion of ED attendees and medical inpatients. In contrast to housed patients, the bulk of usage of unscheduled care by homeless people occurs in individuals aged 25-65 years.

Generic substitution of antiretrovirals: patients' and health care providers' opinions.

There is interest in introducing generic antiretroviral drugs (ARVs) into high-income countries in order to maximise efficiency in health care budgets. Studies examining patients' and providers' knowledge and attitudes to generic substitution in HIV are few. This was a cross-sectional, observational study with a convenience sample of adult HIV-infected patients and health care providers (HCPs). Data on demographics, knowledge of generic medicine and facilitators of generic substitution were collected. Descriptive and univariate analysis was performed using SPSS V.23™. Questionnaires were completed by 66 patients. Seventy-one per cent would have no concerns with the introduction of generic ARVs. An increase in frequency of administration (61%) or pill burden (53%) would make patients less likely to accept generic ARVs. There were 30 respondents to the HCP survey. Concerns included the supply chain of generics, loss of fixed dose combinations, adherence and use of older medications. An increase in dosing frequency (76%) or an increase in pill burden (50%) would make HCPs less likely to prescribe a generic ARV. The main perceived advantage was financial. Generic substitution of ARVs would be acceptable to the majority of patients and HCPs. Reinvesting savings back into HIV services would facilitate the success of such a programme.

Evaluating the neonatal BCG vaccination programme in Ireland.

BACKGROUND: The aim of this study was to compare the cost effectiveness of the current Irish programme of universal BCG vaccination of infants versus a programme which considered selectively vaccinating high risk infants using decision analytical modelling. METHODS: The efficacy of the BCG vaccine was re-evaluated to inform a decision analytical model constructed to follow a birth cohort of vaccinated and unvaccinated infants over a 15 year time horizon. The number of life years gained (LYG) was the primary outcome measure and this was compared to the net cost of the vaccination strategies. RESULTS: In the base case analysis, the incremental cost effectiveness ratios (ICERs) for the universal strategy and selective strategy vs no vaccination were €204,373/LYG and €143,233/LYG respectively. When comparing the incremental difference in moving from the universal to the selective strategy, the selective strategy costs €1,055,692 less per 4.8 life years lost per birth cohort. One way sensitivity analyses highlighted that a move from the universal to the selective strategy was particularly sensitive to the estimate of vaccine efficacy against deaths, the cost of administering the vaccine and the multiplier used to apportion risk of contracting tuberculosis. Probabilistic analysis suggested that a move from a universal based strategy to a selective based strategy could be deemed cost effective (probability of cost effectiveness is 76.8 %). CONCLUSION: The results of the study support the protective effect of the BCG vaccine in infants and quantified the cost effectiveness of the current BCG vaccination strategy and the decremental difference in moving to a selective strategy. This analysis highlights that the additional protection offered by the universal vaccination strategy is small compared to that of the selective strategy. Consideration should therefore be given to the implementation of a selective vaccination strategy, and diverting resources to improve TB case management and control.

Hepatitis C in the era of direct-acting antivirals: real-world costs of untreated chronic hepatitis C; a cross-sectional study.

BACKGROUND: Recent advances in Hepatitis C therapeutics offer the possibility of cure but will be expensive. The cost of treatment may be partially offset by the avoidance of advanced liver disease. We performed a micro-costing study of the ambulatory healthcare utilisation of patients with Hepatitis C supplemented with inpatient diagnosis related group costs. METHODS: The staff utilisation costs associated with a Hepatitis C ambulatory visit were measured and combined with the costs of investigations to establish a mean cost per consultation. An annualised estimate of cost was produced by multiplying this by the number of consultations accessed, stratified by degree of liver impairment. Inpatient costs were established by identifying the number of inpatient episodes and multiplying by Irish diagnosis related group costs. Non-parametric bootstrapping was performed to derive mean and 95%CI values. RESULTS: Two hundred and twenty-five patients were identified. The cost of an outpatient medical review was €136 (€3.60 SD). The cost of a Hepatitis C nursing review was €128 (€7.30 SD). The annual mean costs of care were as follows (95%CI): Mild €398 (€336, €482), Moderate €417(€335, €503), Compensated cirrhosis €1790 (€990, €3164), Decompensated cirrhosis €8302 (€3945, €14,637), Transplantation Year 1 €137,176 (€136,024, €138,306), Transplantation after Year 1 €5337 (€4942, €5799), Hepatocellular carcinoma €21,992 (€15,222, €29,467), Sustained virological response €44 (€16, €73). CONCLUSIONS: The direct medical cost associated with Hepatitis C care in Ireland is substantial and increases exponentially with progression of liver disease. The follow-up costs of patients with a sustained virological response in this cohort were low in comparison to patients with chronic infection.

The relative efficacy of boceprevir and telaprevir in the treatment of hepatitis C virus genotype 1.

BACKGROUND: The licensing of direct-acting antivirals heralds a new era in the treatment of hepatitis C virus (HCV) genotype 1. We undertook a mixed treatment comparison to examine the relative efficacy among current treatments for HCV. METHODS: A systematic literature review identified relevant studies. Meta-analyses were planned in treatment-naive and treatment-experienced patients. Study arms that evaluated telaprevir or boceprevir for unlicensed durations or without both pegylated interferon and ribavirin at standard doses were excluded. A Bayesian mixed treatment comparison model was fitted for each patient population. RESULTS: Four hundred ninety-nine studies were identified. Ten met inclusion criteria. In the subgroup of prior treatment "relapsers," telaprevir had greater relative efficacy than boceprevir (odds ratio [OR], 2.61 [95% confidence interval {CI}, 1.24-5.52]). There were no statistically significant differences detected in relative efficacy for other patient categories. Treatment-naive patients: boceprevir vs standard of care (n = 1417) (OR, 3.06 [95% CI, 2.43-3.87]); telaprevir vs standard of care (n = 1309) (OR, 3.24 [95% CI, 2.56-4.10]); telaprevir vs boceprevir (OR, 1.06 [95% CI, 0.75-1.47]). Total treatment-experienced population: boceprevir vs standard of care (n = 604) (OR, 6.53 [95% CI, 4.20-10.32]); telaprevir vs standard of care (n = 891) (OR, 8.32 [5.69-12.36]); telaprevir vs boceprevir (OR, 1.27 [95% CI, .71-2.30]). CONCLUSIONS: Telaprevir had greater relative efficacy than boceprevir in patients who had previously relapsed. There was insufficient evidence to detect a difference in treatment outcomes between the 2 agents in the overall population. It was not possible to determine relative efficacy for subgroups such as patients with cirrhosis owing to small numbers.

Ritonavir-boosted atazanavir, methadone, and ventricular tachycardia: 2 case reports.

We describe 2 cases of symptomatic ventricular tachycardia associated with prolonged QT interval. Both patients were infected with the human immunodeficiency virus and were receiving treatment with ritonavir-boosted atazanavir and methadone. Discontinuation of atazanavir in both cases resulted in a reduction in the QT interval and cessation of arrhythmia. We concluded that atazanavir contributed to prolonged corrected QT interval and subsequent ventricular tachycardia.