Failure to Detect Hepatitis A Virus RNA in Factor VIII Concentrates Using the Polymerase Chain Reaction: Results of a Preliminary Study

The transmission of hepatitis A virus (HAV) infection to recipients of some batches of Factor VIII has recently been reported. The polymerase chain reaction (PCR) was used for the detection of HAV RNA in factor VIII concentrates. Primer sequences used were derived from a consensus of published sequences in the 5' non coding region; a nested PCR was used to increase sensitivity and specificity and the resulting fragment was 151 base pairs in length. The PCR was initially validated in clinical samples and only IgM anti-HAV positive patient samples and a sample of liver tissue from a patient who required liver transplantation for fulminant hepatitis A were HAV PCR positive. Other samples tested included those that were IgG anti-HAV positive; these were found to be PCR negative. In an investigation of coagulation factor VIII concentrates by HAV PCR, 40 batches of solvent/detergent-treated high-purity concentrate from four different manufacturers, including one batch of factor VIII possibly implicated in HAV transmission, and a further 3 batches of monoclonal antibody purified factor VIII were all HAV PCR negative. Gel chromatography material, before and after use in factor VIII purification, and eluates from this material were also negative for HAV RNA. Our preliminary results therefore suggest that either the contamination of factor VIII concentrates by HAV RNA is an extremely rare event or that the PCR is insufficiently sensitive to detect an infective HAV dose since each batch of factor VIII concentrate would have been derived from a plasma pool consisting of 10,000 donations, or more and the resulting concentration of virus may be 10² or less.     

Prolonged effectiveness of coronary artery bypass surgery versus drug-eluting stents in diabetics with multi-vessel disease: An updated systematic review and meta-analysis

Background

Currently, the appropriateness of percutaneous coronary intervention (PCI) using drug-eluting stents (DES) versus coronary artery bypass grafting (CABG) for patients with diabetes (DM) and multi-vessel disease (MVD) is uncertain due to limited evidence from few randomised controlled trials (RCTs). We aimed to compare the clinical effectiveness of CABG versus PCI-DES in DM-MVD patients using an evidence-based approach.

Methods

A systematic review and meta-analyses were conducted to compare the risk of all-cause mortality, myocardial infarction (MI), repeat revascularisation, cerebrovascular events (CVE), and major adverse cardiac or cerebrovascular events (MACCE).

Results

A total of 1,837 and 3,052 DM-MVD patients were pooled from four RCTs (FREEDOM, SYNTAX, VA CARDS, and CARDia) and five non-randomised studies. At mean follow-up of 3 years, CABG compared with PCI-DES was associated with a lower risk of all-cause mortality and MI in RCTs. By contrast, no significant differences were observed in the mean 3.5-year risk of all-cause mortality and MI in non-randomised trials. However, the risk of repeat revascularisations following PCI-DES compared with CABG was 2.3 (95% CI = 1.8–2.8) and 3.0 (2.3–4.2)-folds higher in RCTs and non-randomised trials, respectively. Accordingly, the risk of MACCE at 3 years following CABG compared with PCI-DES was lower in both RCTs and non-randomised trials [0.65 (: 0.55–0.77); and 0.77 (0.60–0.98), respectively].

Conclusions

Based on our pooled results, we recommend CABG compared with PCI-DES for patients with DM-MVD. Although non-randomised trials suggest no additional survival-, MI-, and CVE- benefit from CABG over PCI-DES, these results should be interpreted with care.     

Visit-to-visit blood pressure variability as a prognostic marker in patients with cardiovascular and cerebrovascular diseases – Relationships and comparisons with vascular markers of atherosclerosis

Background

Visit-to-visit blood pressure variability (BPV) is a simple surrogate marker for the development of atherosclerotic diseases, cardiovascular and all-cause mortality. Nevertheless, the relative prognostic value of BPV in comparison with other established vascular assessments remain uncertain.

Methods

We prospectively followed-up 656 high-risk patients with diabetes or established cardiovascular or cerebrovascular diseases for the occurrence of major adverse cardiovascular events (MACEs). Baseline brachial endothelial function, carotid intima-media thickness (IMT) and plaque burden, ankle-brachial index and arterial stiffness were determined. Visit-to-visit BPV were recorded during a mean 18 ± 9 outpatient clinic visits.

Results

After a mean 81 ± 12 month's follow-up, 123 patients (19%) developed MACEs. Patients who developed a MACE had significantly higher systolic BPV, more severe endothelial function, arterial stiffness and systemic atherosclerotic burden compared to patients who did not develop a MACE (all P < 0.01). BPV significantly correlated with all of the vascular assessments (P < 0.01). A high carotid IMT had the greatest prognostic value in predicting development of a MACE (area under receiver operating characteristic curve (AUC) 0.69 ± 0.03, P < 0.01). A high BPV also had moderate prognostic value in prediction of MACE (AUC 0.65 ± 0.03, P < 0.01). After adjustment of confounding factors, a high BPV remained a significant independent predictor of MACE (hazards ratio 1.67, 95% confidence interval 1.14-2.43, P < 0.01).

Conclusions

Compared with established surrogate markers of atherosclerosis, visit-to-visit BPV provides similar prognostic information and may represent a new and simple marker for adverse outcomes in patients with vascular diseases.     

COVID-19 and ischemic stroke: a systematic review and meta-summary of the literature

Journal of Thrombosis and Thrombolysis - Acute ischemic stroke (AIS) is a life-threatening complication of coronavirus disease 2019 (COVID-19) infection. Increasing reports suggest an association...     

Co-administration of non-carrier nanoparticles boosts antigen immune response without requiring protein conjugation

Nanotechnology promises a revolution in medicine including through new vaccine approaches. The use of nanoparticles in vaccination has, to date, focused on attaching antigen directly to or within nanoparticle structures to enhance antigen uptake by immune cells. Here we question whether antigen incorporation with the nanoparticle is actually necessary to boost vaccine effectiveness. We show that the immunogenicity of a sub-unit protein antigen was significantly boosted by formulation with silica nanoparticles even without specific conjugation of antigen to the nanoparticle. We further show that this effect was observed only for virus-sized nanoparticles (50 nm) but not for larger (1000 nm) particles, demonstrating a pronounced effect of nanoparticle size. This non-attachment approach has potential to radically simplify the development and application of nanoparticle-based formulations, leading to safer and simpler nanoparticle applications in vaccine development.     

Evaluation of a parenting program for children with behavioural problems: Signposts in Singapore

Abstract

Background The Signposts for Building Better Behaviour program, developed by the Parenting Research Centre, Victoria, Australia, was conducted at a public hospital facility in Singapore.

Method More than 1,000 parents completed the program, and filled in questionnaires about their child's behaviours.

Results Parents rated themselves in the questionnaires as being significantly less hassled, stressed, depressed, and anxious after attending the program. They were more confident and satisfied with managing their child, and rated their children's behaviours as having improved. Effect sizes ranged from 0.12 to 0.59. The findings were maintained 3 months after completion of the program.

Conclusions The study provides evidence of the cross-cultural applicability of the principles underlying the Signposts program. As there are long-term repercussions when children's behaviour problems are not dealt with appropriately, such behaviour management programs should be made more available to parents and caregivers.     

IgG4- Related Disease as a Rare Cause of Tubulointerstitial Nephritis

Isolated IgG4 tubulointerstitial nephritis (TIN) is a rare disorder characterized by raised serum IgG4 levels and histological findings of dense lymphoplasmacytic infiltrates rich in IgG4 positive plasma cells. We report a case of isolated IgG4 TIN that presented with acute kidney injury in an 84 year old man with a polyclonal increase in his total IgG and a raised IgE of 381 kUA/L but without evidence of systemic autoimmunity. We draw a parallel with IgG4-related autoimmune pancreatitis and show raised levels of circulating regulatory T cells. Importantly the plasma levels of the T regulatory cell cytokine, IL10, the TH1 cytokines IL12 and IFNγ, the proinflammatory TNF α and immune regulatory IL27 were all highly raised. Furthermore, the level of IL21 that promotes IgG4 production was also very significantly elevated. These results suggest efforts of the immune system to reduce inflammation and suppress an exaggerated Th2 response. A raised serum IgG in the setting of acute kidney injury and in the absence of autoimmunity and chronic infection should encourage an assessment of the IgG subclasses. Prompt steroid treatment of those with a raised IgG4 may reduce ongoing renal damage.     

Gastrointestinal parasites in rural dogs and cats in Selangor and Pahang states in Peninsular Malaysia

To estimate the current prevalence of gastrointestinal (GI) parasites in dogs and cats, a total of 105 fresh faecal samples were collected from rural areas in Peninsular Malaysia. Each faecal sample was examined for the presence of GI parasites by microscopic examination after formalin-ether concentration technique and for protozoa, trichrome and Ziehl-Neelsen staining were employed. The overall prevalence of GI parasitic infection was 88.6% (95% CI = 82.5–94.7) in which 88.3% of dogs and 89.3% of cats were infected with at least one parasites species, respectively. There were 14 different GI parasites species (nematodes, cestodes and protozoa) detected, including Ancylostoma spp. (62.9%), Toxocara spp. (32.4%), Trichuris vulpis (21.0%), Spirometra spp. (9.5%), Toxascaris leonina (5.7%), Dipylidium caninum (4.8%), Ascaris spp. (2.9%), Hymenolepis diminuta (1.0%) and others. General prevalence of GI parasites showed a significant difference between helminth (84.4%) and protozoa (34.3%) infections. Monoparasitism (38.1%) was less frequent than polyparasitism (46.7%). As several of these GI parasites are recognized as zoonotic agents, the results of this investigation revealed that local populations may be exposed to a broad spectrum of zoonotic agents by means of environmental contamination with dogs and cats faeces and this information should be used to mitigate public health risks. Prevention and control measures have to be taken in order to reduce the prevalence rates especially in socioeconomically disadvantaged communities where animals live in close proximity to people, poor levels of hygiene and overcrowding together with a lack in veterinary attention and zoonotic awareness.