Polypharmacy and potential drug-drug interactions for people with HIV in the UK from the Climate-HIV database.

OBJECTIVES: People with HIV (PWHIV) are likely to need therapies for comorbidities as they age. We assessed risk of drug-drug interactions (DDIs) in PWHIV. METHODS: The Climate-HIV electronic recording system was used to cross-sectionally analyse records from PWHIV aged ≥ 18 years attending four UK HIV units with a current antiretroviral (ARV) prescription in February 2018. Antiretroviral and non-ARV medications were categorized by clinical significance of DDIs (University of Liverpool DDI tool). Potential DDIs were predicted using treatment guidelines for commonly recorded comorbidities. RESULTS: Among 4630 PWHIV (44% female), 41% were ≥ 50 years old. The average number of non-ARV comedications increased from < 1 for patients aged ≤ 24 years to > 5 for patients aged ≥ 75 years; 65% were taking one or more non-ARV comedications. The median (interquartile range) number of non-ARVs was 1 (0-2) and 2 (1-5) for those aged < 50 and ≥ 50 years, respectively. Common comorbidities/concurrent health conditions occurred more frequently in patients aged ≥ 50 years vs. < 50 (53% vs. 34%). Boosted protease inhibitors were associated with the highest proportion of contraindicated comedications; dolutegravir and raltegravir had the fewest. For non-ARVs, sildenafil and quetiapine were most likely to result in DDIs. Guideline-recommended treatments for hepatitis C, hepatitis B, and tuberculosis had the highest proportions of contraindications when combined with ARV regimens, while treatments for hepatitis C, malignancy, and mental health conditions had the highest proportion of combinations potentially causing DDIs requiring dose monitoring or adjustment. CONCLUSIONS: Non-ARV use by PWHIV is high and increases with age. Treatment decisions for ageing PWHIV should consider guideline recommendations for comorbidities.

Detection of Hepatitis B Virus DNA among Chronic and potential Occult HBV patients in resource-limited settings by Loop-Mediated Isothermal Amplification assay.

Transmission of Hepatitis B Virus (HBV) usually occurs due to the transfusion of blood or blood products from chronic HBV (CHB) or occult HBV-infected (OBI) patients. Besides serological tests, e.g. HBsAg and anti- HBc (total), detection of HBVDNA is necessary for the diagnosis of OBI patients. Different nucleic acid tests (NATs) including real- time-Polymerase Chain Reaction (qPCR) are used to detect HBV- DNA. The NATs are expensive and require technical expertise which are barriers to introduce them in resource-limited settings. This study was undertaken to evaluate the use of Loop-Mediated Isothermal Amplification (LAMP) assay as an alternative to qPCR for the detection of HBV-DNA in CHB and potential OBI patients in resource-limited settings. Following the published protocols with some modifications, a LAMP assay was developed for detection of HBV-DNA by either using a heat block followed by detection in an agarose gel or using a qPCR thermocycler. The LAMP assay was applied to supernatant prepared from heat-treated serum collected from CHB and potential OBI patients. HBV viral load in serum was measured by qPCR using a single-step HBV-DNA quantification kit. Among 200 samples tested, qPCR was capable to detect HBV-DNA in 25.5% of cases, whereas LAMP assay detected HBV-DNA in 43.5% cases. The qPCR was able to detect 11 (9.16%) potential OBI cases, whereas LAMP assay identified HBV-DNA in 43 (35.83%) cases. In addition to tests for HBsAg and/or anti-HBc (total), detection of HBV-DNA by LAMP assay may aid in preventing post-transfusion HBV infection in resource-limited settings.

A simplified protocol for differentiation of electrophysiologically mature neuronal networks from human induced pluripotent stem cells.

Progress in elucidating the molecular and cellular pathophysiology of neuropsychiatric disorders has been hindered by the limited availability of living human brain tissue. The emergence of induced pluripotent stem cells (iPSCs) has offered a unique alternative strategy using patient-derived functional neuronal networks. However, methods for reliably generating iPSC-derived neurons with mature electrophysiological characteristics have been difficult to develop. Here, we report a simplified differentiation protocol that yields electrophysiologically mature iPSC-derived cortical lineage neuronal networks without the need for astrocyte co-culture or specialized media. This protocol generates a consistent 60:40 ratio of neurons and astrocytes that arise from a common forebrain neural progenitor. Whole-cell patch-clamp recordings of 114 neurons derived from three independent iPSC lines confirmed their electrophysiological maturity, including resting membrane potential (-58.2±1.0 mV), capacitance (49.1±2.9 pF), action potential (AP) threshold (-50.9±0.5 mV) and AP amplitude (66.5±1.3 mV). Nearly 100% of neurons were capable of firing APs, of which 79% had sustained trains of mature APs with minimal accommodation (peak AP frequency: 11.9±0.5 Hz) and 74% exhibited spontaneous synaptic activity (amplitude, 16.03±0.82 pA; frequency, 1.09±0.17 Hz). We expect this protocol to be of broad applicability for implementing iPSC-based neuronal network models of neuropsychiatric disorders.

Prevalence of reticular pseudodrusen in newly presenting adult onset foveomacular vitelliform dystrophy.

PurposeTo report the association and prevalence of reticular pseudodrusen (RPD) in eyes with newly presenting adult onset foveomacular vitelliform dystrophy (AFVD). To compare the strength of association with other pathologies resulting from dysfunction of the choroid-Bruch's membrane-retinal pigment epithelium (RPE) complex, including eyes with geographic atrophy (GA) and angioid streaks.MethodsRetrospective single-centre review of all consecutive newly presenting AFVD. Multimodal imaging with spectral domain optical coherence tomography, fundus photographs, red-free/blue light images, and fundus fluorescein angiograms were graded for the presence of RPD. For comparison, all consecutive newly presenting cases of GA and eyes with angioid streaks were studied.ResultsFifteen (15) patients were identified with AFVD (mean age of 77.3 years; 73.3% female). Mean age of patients with AFVD and RPD was 80.5 years (SD 3.7), whereas that of patients with AFVD without RPD was 75.1 years (SD 7.0). This age difference did not reach statistical significance, P=0.1. Six (40%) had identifiable RPD; being a bilateral finding in 100% of patients. No males with AFVD and RPD were identified. A total of 92 eyes presented with GA. Twenty-three (23) of these (25.0%) had RPD. Twelve (12) patients presented with identifiable angioid streaks, with 4 (36.4%) having RPD.ConclusionRPD are a frequent finding in eyes with newly presenting AFVD; not being restricted to AMD, but a finding common among diseases where pathophysiological mechanisms involve damage to Bruch's membrane and the RPE, whether genetic or degenerative. Our study supports the concept that they occur with high but variable frequencies in eyes with various pathologies.

Impaired Cerebrovascular Reactivity Predicts Recurrent Symptoms in Patients with Carotid Artery Occlusion: A Hypercapnia BOLD fMRI Study.

BACKGROUND AND PURPOSE: A key factor in predicting recurrent ischemic episodes in patients with carotid artery occlusion is the presence of hemodynamic impairment. There is, however, no consensus on how to best assess this risk in terms of imaging modalities or thresholds used. Here we investigated whether a predefined threshold of hemispheric asymmetry in hypercapnia fMRI predicts recurrent symptoms in patients with carotid artery occlusion. MATERIALS AND METHODS: We studied 23 patients (2 women) with a mean age of 67.5 ± 9 years. Patients were assessed for recurrent ischemic events until lost to follow-up, study end, death, or recurrent ischemic event. Hypercapnia fMRI was used to assess the cerebrovascular reserve and quantify the percentage signal change in GM in the MCA territory and the hemispheric asymmetry index. Kaplan-Meier survival analysis and log-rank tests were performed to assess differences between patients with normal or abnormal hemispheric indices. RESULTS: The median follow-up was 20 months. During this period, 8 patients experienced recurrent events, and 15 did not. The percentage signal change in GM in the MCA territory was significantly decreased in those patients with recurrent events compared with those without (2.39 ± 0.22 versus 2.70 ± 0.42, P = .032). The normal hemispheric index predicted event-free survival during follow-up (median, 20 months) for both the combined outcome (recurrent events and/or death, log-rank, P = .034) and recurrent retinal or ipsilateral ischemic events only (log-rank, P = .012). CONCLUSIONS: The hemispheric asymmetry index derived from hypercapnia fMRI showed hemodynamic impairment in more than half of the studied patients with carotid occlusion, and those patients showed a higher risk of recurrent ischemic symptoms.

The diagnostic accuracy of spectral-domain optical coherence tomography for neovascular age-related macular degeneration: a comparison with fundus fluorescein angiography.

PURPOSE: To evaluate the diagnostic accuracy of spectral-domain optical coherence tomography (SD-OCT) for neovascular age-related macular degeneration (nAMD): a comparison against fundus fluorescein angiography (FFA). METHODS: A retrospective review of SD-OCT, colour fundus photographs (FP), and FFA of 411 consecutive patients referred to a rapid access Macular Clinic over a 4-year period was performed. FFA images were reviewed non-stereoscopically. SD-OCT images were acquired using the Topcon 3D OCT-1000 instrument. All FFA and OCT images were graded by at least two ophthalmologists independently. Side-by-side grading took place with immediate open discussion and adjudication. If there was disagreement between the two grading ophthalmologists or they were not 90% confident of their assigned grade, then adjudication by a third ophthalmologist was performed. RESULTS: A total of 278 eyes were graded as having choroidal neovascularisation (CNV) with SD-OCT and 231 diagnosed with FFA. The main diagnostic CNV classifications on FFA were: classic no occult in 27 eyes, predominantly classic in 16, minimally classic in 50, occult in 129, and 9 peripapillary membranes. There were a total of 47 false positives with SD-OCT: a rate of 16.9%. The sensitivity and specificity of SD-OCT alone for detecting CNV was 100 and 80.8%, respectively. CONCLUSION: Our study confirms SD-OCT in comparison to the reference standard of non-stereoscopic FFA is highly sensitive at detecting newly presenting nAMD in the setting of a specialist AMD clinic where the investigations are interpreted by trained specialists. However, it does not seem accurate enough to replace FFA in the diagnosis on nAMD in current practice.

Acute myocardial infarction--an unusual presentation of non-specific aortoarteritis.

A 42 year old man presented with classical presentation of Acute ST elevation MI of 2 hours duration. His CAG revealed a spared LMCA with a totally occluded LAD in proximal segment, for which he underwent a successful PAMI with DES to LAD. 2 days later he developed high grade fever, elevated inflammatory markers (ESR/CRP) with a dull aching pain in root of neck. On evaluation of brachiocephalic vessels, CT Aortogram suggested a diagnosis of acute onset Non-Specific Aortoarteritis. Nonspecific Aortoarteritis in young males is an uncommon presentation, though associated coronary artery involvement is known, but its presentation as an Acute MI is a rare phenomenon.

Don't neglect 'neglect'- an update on post stroke neglect.

OBJECTIVES: Post-stroke neglect is common and an independent predictor of functional outcome. Assessment of neglect is very demanding, the treatment extremely difficult and the literature vast; we performed a literature search for all aspects of this difficult subject. METHODS: We searched the PubMed, EMBASE databases and historical manuals for authoritative studies on post stroke neglect between 1951 and 2011. FINDINGS: There is a great dearth of randomised controlled data on neglect because standardised assessment does not occur frequently. Eighty-eight manuscripts were identified in the literature, which were quite heterogeneous in their content and addressing diverse aspects of this clinical entity. INTERPRETATION AND IMPLICATIONS: The most important historical papers were selected along with the most widely accepted and proven strategies for assessment and treatment. Standardised assessment of neglect does not always occur, but several useful strategies are available and are described in the following sections.

Microbial contamination in herbal medicines available in Bangladesh.

Plants have long been used as herbal medicines in many countries. However, microbial contamination of these medicines may affect human health. Present study was performed to assess the pathogenic proliferation in the locally available commercial herbal oral medicines. The pathogenic load was compared with the microbiological standard given by the British Pharmacopoeia. Out of 85 oral liquid samples, 2 were found to be highly contaminated with a total aerobic bacterial load of 1.24 x 10(5) cfu/ml, 10 samples were contaminated with fungi (1.2 x 10(4)-6.3 x 10(4) cfu/ml). Tests for specific pathogens were carried out. One sample showed contamination by coliforms but none of the samples were contaminated by Salmonella spp. and Shigella spp. Among 40 semisolid samples, one showed to be contaminated with bacteria (1.93 x 10(5) cfu/g) and 5 samples consisted of fungal load ranging between 1.5 x 10(4)-2.2 x 10(4) cfu/g. The presence of bacteria and fungi in these samples thus suggest the fact that aseptic handling is necessary during processing of oral herbal medicines.

Advances in spontaneous intracerebral haemorrhage.

OBJECTIVES: To assess the evidence and available literature on the clinical, pathogenetic, prognostic and therapeutic aspects of intracerebral haemorrhage. METHODS: The most important manuscripts and reviews on the subject were considered. Information was collected from Medline, Embase & National Library of Medicine over the last 40 years up to Oct 2011. The bibliographies of relevant articles were searched for additional references. The most up to date and randomised trials were given preference. Clinical guidelines including AHA/ASA, Royal college of Physicians, NICE, Scottish Intercollegiate guidelines and several others were taken into consideration. FINDINGS: There are numerous advances in the understanding of the pathogenesis and management, but hardly any change in the overall mortality in the last few decades. There is a poor understanding of the results of surgical trials that has resulted in a large drop in surgical intervention since 2007. INTERPRETATIONS AND IMPLICATIONS: Advances in neuroimaging and neurophysiology have improved our understanding of the mechanisms of neuronal injury and existence of perihaematomal 'tissue at risk'. Numerous new therapeutic targets have been identified. There is a lot of misunderstanding of the results of the newer surgical trials which need to be clarified. The importance of cerebral amyloid angiopathy and microbleeds in older patients is increasingly recognised. Control of hypertension is the most important public health measure. Stroke units provide the best outcomes for the patients.

Metabonomic analysis of hepatitis E patients shows deregulated metabolic cycles and abnormalities in amino acid metabolism.

Hepatitis E, which is endemic to resource-poor regions of the world, is largely an acute and self-limiting disease, but some patients have an increased susceptibility to develop fulminant hepatitis. The pathogenesis of hepatitis E in humans is poorly characterized. To understand the metabolic pathways involved in the pathophysiology of hepatitis E, we have used (1) H nuclear magnetic resonance spectroscopy to quantify various metabolites in the plasma and urine of the patients with hepatitis E. These were compared with specimens from patients with acute hepatitis B as disease controls and healthy volunteers. Data were analysed using chemometric statistical methods and metabolite databases. The main metabonomic changes found in patients with hepatitis E, but not in those with hepatitis B, included increased plasma levels of L-isoleucine, acetone, and glycerol, reduced plasma levels of glycine, and reduced urinary levels of imidazole, 3-aminoisobutanoic acid, 1-methylnicotinamide, biopterin, adenosine, 1-methylhistidine, and salicyluric acid. Patients with hepatitis E or B both showed increased levels of plasma and urinary L-proline and decreased levels of various other metabolites. Pathway analysis tools suggest the involvement of glycolysis, tricarboxylic acid cycle, urea cycle, and amino acid metabolism in patients with acute hepatitis E. These findings may help better understand the clinical and biochemical manifestations in this disease and the underlying pathophysiologic processes. Based on our findings, it would be worthwhile determining whether patients with hepatitis E are more prone to develop lactic acidosis and ketosis compared with other forms of viral hepatitis.

High prevalence of hepatitis A virus antibody among Bangladeshi children and young adults warrants pre-immunization screening of antibody in HAV vaccination strategy.

Serum samples from 465 subjects aged between 1 and 25 years were tested for antibody against hepatitis A virus (HAV) [anti-HAV IgG and IgM] to determine the seroprevalence of HAV antibody and do a cost-benefit analysis for decision making about vaccination against HAV among the general population of Bangladesh. A high prevalence of anti-HAV (74.8%) was observed in the study population; the whole study population was found positive for anti-HAV by the age of 25 years. On performing the cost-benefit analysis, it was found that the cost for vaccination with screening for anti-HAV was almost three times cheaper than vaccination without screening. Thus, in the present socioeconomic condition of Bangladesh, a policy based on screening for HAV antibody before vaccination is recommended.

Effect of biotin supplementation on hoof health and ceramide composition in dairy cattle.

The effect of biotin supplementation on various foot lesions and hoof ceramide composition of toe (wall) and sole portions of hooves was studied in crossbred dairy cattle. Biotin supplementation was done for five months in 14 cattle at a farm and the other 14 animals kept as control. A significant decline was observed in heel erosions and sole avulsions along with total disappearance of white line fissures and double soles in the biotin supplemented cattle resulting in decrease in the overall disease score. Thin layer chromatographs of the hoof lipids revealed 11 types of ceramides in sole lipids and 6 types of ceramides in toe (wall) lipids. The ceramides were typed and identified according to their Rf values. A qualitative increase in the density of thin layer chromatographs of sole lipids was observed in biotin supplemented cattle whereas a non-significant difference in density of thin layer chromatographs of toe lipids was observed after supplementation of biotin.

Carotid and vertebral artery dissection syndromes.

Cervicocerebral arterial dissections (CAD) are an important cause of strokes in younger patients accounting for nearly 20% of strokes in patients under the age of 45 years. Extracranial internal carotid artery dissections comprise 70%-80% and extracranial vertebral dissections account for about 15% of all CAD. Aetiopathogenesis of CAD is incompletely understood, though trauma, respiratory infections, and underlying arteriopathy are considered important. A typical picture of local pain, headache, and ipsilateral Horner's syndrome followed after several hours by cerebral or retinal ischaemia is rare. Doppler ultrasound, MRI/MRA, and CT angiography are useful non-invasive diagnostic tests. The treatment of extracranial CAD is mainly medical using anticoagulants or antiplatelet agents although controlled studies to show their effectiveness are lacking. The prognosis of extracranial CAD is generally much better than that of the intracranial CAD. Recurrences are rare in CAD.