Social media and its relationship with mood, self-esteem and paranoia in psychosis.

OBJECTIVE: An evidence-base is emerging indicating detrimental and beneficial effects of social media. Little is known about the impact of social media use on people who experience psychosis. METHOD: Forty-four participants with and without psychosis completed 1084 assessments of social media use, perceived social rank, mood, self-esteem and paranoia over a 6-day period using an experience sampling method (ESM). RESULTS: Social media use predicted low mood, but did not predict self-esteem and paranoia. Posting about feelings and venting on social media predicted low mood and self-esteem and high paranoia, whilst posting about daily activities predicted increases in positive affect and self-esteem and viewing social media newsfeeds predicted reductions in negative affect and paranoia. Perceptions of low social rank when using social media predicted low mood and self-esteem and high paranoia. The impact of social media use did not differ between participants with and without psychosis; although, experiencing psychosis moderated the relationship between venting and negative affect. Social media use frequency was lower in people with psychosis. CONCLUSION: Findings show the potential detrimental impact of social media use for people with and without psychosis. Despite few between-group differences, overall negative psychological consequences highlight the need to consider use in clinical practice.

In vitro evaluation of the human gingival fibroblast/gingival mesenchymal stem cell dynamics through perforated guided tissue membranes: cell migration, proliferation and membrane stiffness assay.

BACKGROUND: Migration of gingival fibroblasts/gingival mesenchymal stem cells through macro-perforated barrier membranes may allow them to participate positively in periodontal regeneration. The optimal guided tissue membrane perforation diameter that could favor maximum cell migration into the defect area and at the same time act as an occlusive barrier for gingival epithelium and its associated gingival extracellular matrix component is not yet identified. MATERIAL AND METHODS: Cultured human gingival fibroblasts/gingival mesenchymal stem cells were placed in the upper chambers of 12-well collagen-coated polytetrafluoroethylene transwells, which were manually perforated with 0.2, 0.4 and 0.7 mm sized pores. The lower chambers of the transwells received blood clot as an attraction medium. The number of cells that have migrated to the lower chambers was calculated. Proliferation of these cells was evaluated using MTT assay. Scanning electron microscopy images were obtained for the lower surfaces of the transwell membranes. Perforated bovine collagen membranes (Tutopatch® ) were subjected to mechanical testing to determine the tensile strength and modulus of elasticity. RESULTS: Group 3 (0.7 mm) showed significantly higher values for cell migration and proliferation. All groups showed a small degree of extracellular matrix migration through membrane perforations. Scanning electron microscopy evaluation revealed variable numbers of cells in fibrin matrices located mainly around the pore edges. There were non-significant differences between groups regarding mechanical properties. CONCLUSIONS: The present study demonstrated that macro-membrane perforations of 0.2, 0.4 and 0.7 mm are suitable pore diameters that could maintain membrane stiffness and allow for cellular migration. However, these membrane perforation diameters did not allow for total gingival connective tissue isolation.

An audit of the quality of online immunisation information available to Australian parents.

BACKGROUND: The Internet is increasingly a source of health information for parents, who use the Internet alongside health care providers for immunisation information. Concerns have been raised about the reliability of online immunisation information, however to date there has been no audit of the quality or quantity of what is available to Australian parents. The objective of this study was to address this gap by simulating a general online search for immunisation information, and assessing the quality and quantity of the web sites returned by the search. METHODS: We used Google trends to identify the most common immunisation search terms used in Australia. The ten most common terms were entered into five search engines and the first ten non-commercial results from each search collated. A quality assessment tool was developed using the World Health Organization Global Advisory Committee on Vaccine Safety (GACVS) criteria for assessing the quality of vaccine safety web sites, and used to assess and score the quality of the sites. RESULTS: Seven hundred web pages were identified, of which 514 were duplicates, leaving 186 pages from 115 web sites which were audited. Forty sites did not include human immunisation information, or presented personal opinion about individuals, and were not scored. Of the 75 sites quality scored, 65 (87%) were supportive of immunisation, while 10 (13%) were not supportive. The overall mean quality score was 57/100 (range 14/100 to 92/100). When stratified by pro and anti-vaccination stance, the average quality score for pro-vaccine sites was 61/100, while the average score for anti-vaccine sites was 30/100. Pro-vaccine information could be divided into three content groups: generalist overview with little detail; well-articulated and understandable detail; and lengthy and highly technical explanations. The main area found to be lacking in pro-vaccine sites was lack of transparent authorship. CONCLUSION: Our findings suggest a need for information which is easily found, transparently authored, well-referenced, and written in a way that is easily understood.

Heart failure following cancer treatment: characteristics, survival and mortality of a linked health data analysis.

BACKGROUND: Cardiotoxicity resulting in heart failure is a devastating complication of cancer therapy. A patient may survive cancer only to develop heart failure (HF), which has a higher mortality rate than some cancers. AIM: This study aimed to describe the characteristics and outcomes of HF in patients with blood or breast cancer after chemotherapy treatment. METHODS: Queensland Cancer Registry, Death Registry and Hospital Administration records were linked (1996-2009). Patients were categorised as those with an index HF admission (that occurred after cancer diagnosis) and those without an index HF admission (non-HF). RESULTS: A total of 15 987 patients was included, and 1062 (6.6%) had an index HF admission. Median age of HF patients was 67 years (interquartile range 58-75) versus 54 years (interquartile range 44-64) for non-HF patients. More men than women developed HF (48.6% vs 29.5%), and a greater proportion in the HF group had haematological cancer (83.1%) compared with breast cancer (16.9%). After covariate adjustment, HF patients had increased mortality risk compared with non-HF patients (hazard ratios 1.67 (95% confidence interval, 1.54-1.81)), and 47% of the index HF admission occurred within 1 year from cancer diagnosis and 70% within 3 years. CONCLUSION: Cancer treatment may place patients at a greater risk of developing HF. The onset of HF occurred soon after chemotherapy, and those who developed HF had a greater mortality risk.

Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure.

BACKGROUND AND AIMS: Flow-mediated dilatation of the brachial artery (FMD) is a biomarker of endothelial function and cardiovascular health. Impaired FMD is associated with several cardiovascular risk factors including hypertension and obesity. Various food ingredients such as polyphenols have been shown to improve FMD. We investigated whether consuming resveratrol, a polyphenol found in red wine, can enhance FMD acutely and whether there is a dose-response relationship for this effect. METHODS AND RESULTS: 19 overweight/obese (BMI 25-35 kg m(-2)) men or post-menopausal women with untreated borderline hypertension (systolic BP: 130-160 mmHg or diastolic BP: 85-100 mmHg) consumed three doses of resveratrol (resVida™ 30, 90 and 270 mg) and a placebo at weekly intervals in a double-blind, randomized crossover comparison. One hour after consumption of the supplement, plasma resveratrol and FMD were measured. Data were analyzed by linear regression versus log(10) dose of resveratrol. 14 men and 5 women (age 55 ± 2 years, BMI 28.7 ± 0.5 kg m(-2), BP 141 ± 2/89 ± 1 mmHg) completed this study. There was a significant dose effect of resveratrol on plasma resveratrol concentration (P < 0.001) and on FMD (P < 0.01), which increased from 4.1 ± 0.8% (placebo) to 7.7 ± 1.5% after 270 mg resveratrol. FMD was also linearly related to log(10) plasma resveratrol concentration (P < 0.01). CONCLUSION: Acute resveratrol consumption increased plasma resveratrol concentrations and FMD in a dose-related manner. This effect may contribute to the purported cardiovascular health benefits of grapes and red wine.

Effectiveness of the 2009 seasonal influenza vaccine against pandemic influenza A(H1N1)2009 in healthcare workers in New Zealand, June-August 2009.

There is uncertainty whether the 2009 seasonal influenza vaccination influences the risk of infection with the 2009 pandemic influenza A(H1N1) virus. This issue was investigated in 548 healthcare workers from Capital and Coast District Health Board, Wellington, New Zealand, presenting with influenza-like illness during the influenza pandemic between June and August 2009. All workers completed an assessment sheet and had a nasopharyngeal swab tested by real-time RT-PCR. The risk of pandemic influenza A(H1N1) infection associated with the 2009 seasonal inactivated trivalent influenza vaccine was determined by logistic regression, with adjustment for potential confounding variables. In 96 workers pandemic influenza A(H1N1) RNA was detected and 452 tested negative. The multivariate analysis did not show any effect of vaccination on PCR-confirmed influenza A(H1N1)2009 infection (odds ratio 1.2, 95% confidence interval 0.7­1.9, p=0.48). We conclude that 2009 seasonal influenza vaccination had no protective effect against influenza A(H1N1)2009 infection amongst healthcare workers. To protect against further waves of the current pandemic influenza or future pandemics in which the influenza virus is antigenically distinct from contemporary seasonal influenza viruses, it would be necessary to vaccinate with a specific pandemic influenza vaccine, or a seasonal influenza vaccine that includes the pandemic influenza serotype.

Population pharmacokinetic simulation of varied Immune Globulin Subcutaneous (Human), 20% solution (Ig20Gly) loading and maintenance dosing regimens in immunoglobulin-naïve patients with primary immunodeficiency diseases.

BACKGROUND: The pharmacokinetics of Ig20Gly, a 20% subcutaneous immunoglobulin (IG) therapy, is well characterized in IG-experienced patients with primary immunodeficiency diseases (PID). Data from IG-naïve patients are limited. OBJECTIVE: Simulate serum total immunoglobulin G (IgG) pharmacokinetic profiles in IG-naïve patients with PID for different Ig20Gly initiation and maintenance dosing regimens. METHODS: A population pharmacokinetic model developed with data from pivotal phase 2/3 trials of weekly Ig20Gly in PID (NCT01412385, NCT01218438) was used to simulate pharmacokinetic profiles of IgG in various scenarios with 400- or 800-mg/kg total loading doses (administered as split doses over 1-2 weeks) and corresponding 100- or 200-mg/kg weekly maintenance doses, respectively. Endogenous baseline IgG levels (1.5, 2.0, 4.0, 6.0 g/L) were evaluated for each scenario; time to putative therapeutic target IgG trough level (7 g/L) was determined. RESULTS: Serum IgG levels reached steady-state by approximately Week 12 for all scenarios and baseline endogenous IgG levels. Time to target trough level generally occurred sooner with 1-week versus 2-week loading schemes. Endogenous baseline IgG levels <4 g/L required a 1-week 800-mg/kg total loading dose to achieve target levels within 2 weeks. Both maintenance regimens sustained serum IgG above target level. CONCLUSIONS: Simulations indicated IG-naïve patients with PID can achieve protective serum IgG levels within 1-3 weeks using appropriate Ig20Gly loading regimens. Patients with low endogenous IgG may benefit most from an 800-mg/kg/month loading dose. 400- or 800-mg/kg/month Ig20Gly maintenance regimens appeared adequate to maintain stable IgG levels. Serum IgG monitoring and clinical status can guide dosing parameters.

Population Pharmacokinetic Model Development and Simulation for Recombinant Erwinia Asparaginase Produced in Pseudomonas fluorescens (JZP-458).

JZP-458 is a recombinant Erwinia asparaginase produced using a novel Pseudomonas fluorescens expression platform that yields an enzyme expected to lack immunologic cross-reactivity to Escherichia coli-derived asparaginases. It is being developed as part of a multiagent chemotherapeutic regimen to treat acute lymphoblastic leukemia or lymphoblastic lymphoma patients who develop E coli-derived asparaginase hypersensitivity. A population pharmacokinetic (PopPK) model was developed for JZP-458 using serum asparaginase activity (SAA) data from a phase 1, single-dose study (JZP458-101) in healthy adults. Effects of intrinsic covariates (body weight, body surface area, age, sex, and race) on JZP-458 PK were evaluated. The model included SAA data from 24 healthy adult participants from the phase 1 study who received JZP-458: intramuscular (IM) data at 12.5 mg/m2 (N = 6) and 25 mg/m2 (N = 6), and intravenous (IV) data at 25 mg/m2 (N = 6) and 37.5 mg/m2 (N = 6). Model simulations of adult and pediatric SAA profiles were performed to explore the likelihood of achieving a therapeutic target nadir SAA (NSAA) level ≥0.1 IU/mL based on different administration strategies. PopPK modeling and simulation suggest JZP-458 is expected to achieve 72-hour NSAA levels ≥0.1 IU/mL in 100% of adult or pediatric populations receiving IM administration at 25 mg/m2 , and in 80.9% of adult and 94.5% of pediatric populations receiving IV administration at 37.5 mg/m2 on a Monday/Wednesday/Friday (M/W/F) dosing schedule. Based on these results, the recommended starting dose for the phase 2/3 pivotal study is 25 mg/m2 IM or 37.5 mg/m2 IV on a M/W/F dosing schedule in pediatric and adult patients.

Mhc haplotype M3 is associated with early control of SHIVsbg infection in Mauritian cynomolgus macaques.

The restricted major histocompatibilty complex of Mauritian cynomolgus macaques confers exceptional potential on this species in human immunodeficiency virus (HIV) vaccine development. However, knowledge of the effects of Mhc genetics on commonly used simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) stocks is incomplete. We determined the effect of Mhc haplotypes on SHIVsbg replication kinetics in a cohort of 25 naïve cynomolgus macaques. Haplotype M3 was associated with a 1.58log(10) reduction in viraemia at day 28 post infection (p.i.). Haplotype M6 was associated with elevated SHIVsbg viraemia at days 28 and 56. No significant effect of Mhc class II haplotypes on viral replication was observed. These data emphasise the importance of genetic characterisation of experimental macaques and advance our understanding of host genetic effects in SIV/SHIV models of HIV infection.

Predicting the safety of medicines in pregnancy: A workshop report.

The framework for developmental toxicity testing has remained largely unchanged for over 50 years and although it remains invaluable in assessing potential risks in pregnancy, knowledge gaps exist, and some outcomes do not necessarily correlate with clinical experience. Advances in omics, in silico approaches and alternative assays are providing opportunities to enhance our understanding of embryo-fetal development and the prediction of potential risks associated with the use of medicines in pregnancy. A workshop organised by the Medicines and Healthcare products Regulatory Agency (MHRA), "Predicting the Safety of Medicines in Pregnancy - a New Era?", was attended by delegates representing regulatory authorities, academia, industry, patients, funding bodies and software developers to consider how to improve the quality of and access to nonclinical developmental toxicity data and how to use this data to better predict the safety of medicines in human pregnancy. The workshop delegates concluded that based on comparative data to date alternative methodologies are currently no more predictive than conventional methods and not qualified for use in regulatory submissions. To advance the development and qualification of alternative methodologies, there is a requirement for better coordinated multidisciplinary cross-sector interactions coupled with data sharing. Furthermore, a better understanding of human developmental biology and the incorporation of this knowledge into the development of alternative methodologies is essential to enhance the prediction of adverse outcomes for human development. The output of the workshop was a series of recommendations aimed at supporting multidisciplinary efforts to develop and validate these alternative methodologies.