A cost-of-illness analysis of the economic burden of obsessive-compulsive disorder in the United Kingdom.

Objectives: Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric condition, with diagnosed patients typically experiencing moderate or severe symptoms. This study evaluated the cost-of-illness (CoI) of OCD in the UK, capturing the annual costs accrued to the National Health Service (NHS) and Personal Social Services (PSS), people with OCD, caregivers and society.

Methods: The UK OCD population was estimated and stratified by age group (children, adults, elderly), symptom severity (mild, moderate, severe) and treatment received (including no treatment).

Neutralization titer biomarker for antibody-mediated prevention of HIV-1 acquisition.

The Antibody Mediated Prevention trials showed that the broadly neutralizing antibody (bnAb) VRC01 prevented acquisition of human immunodeficiency virus-1 (HIV-1) sensitive to VRC01. Using AMP trial data, here we show that the predicted serum neutralization 80% inhibitory dilution titer (PT) biomarker-which quantifies the neutralization potency of antibodies in an individual's serum against an HIV-1 isolate-can be used to predict HIV-1 prevention efficacy. Similar to the results of nonhuman primate studies, an average PT of 200 (meaning a bnAb concentration 200-fold higher than that required to reduce infection by 80% in vitro) against a population of probable exposing viruses was estimated to be required for 90% prevention efficacy against acquisition of these viruses.

Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition.

Background: Whether a broadly neutralizing antibody (bnAb) can be used to prevent human immunodeficiency virus type 1 (HIV-1) acquisition is unclear.

Methods: We enrolled at-risk cisgender men and transgender persons in the Americas and Europe in the HVTN 704/HPTN 085 trial and at-risk women in sub-Saharan Africa in the HVTN 703/HPTN 081 trial. Participants were randomly assigned to receive, every 8 weeks, infusions of a bnAb (VRC01) at a dose of either 10 or 30 mg per kilogram (low-dose group and high-dose group, respectively) or placebo, for 10 infusions in total.

A Phase 2b Study to Evaluate the Safety and Efficacy of VRC01 Broadly Neutralizing Monoclonal Antibody in Reducing Acquisition of HIV-1 Infection in Women in Sub-Saharan Africa: Baseline Findings.

Background: HIV Vaccine Trials Network 703/HIV Prevention Trials Network 081 is a phase 2b randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of passively infused monoclonal antibody VRC01 in preventing HIV acquisition in heterosexual women between the ages of 18 and 50 years at risk of HIV. Participants were enrolled at 20 sites in Botswana, Kenya, Malawi, Mozambique, South Africa, Tanzania, and Zimbabwe. It is one of the 2 Antibody Mediated Prevention efficacy trials, with HIV Vaccine Trials Network 704/HIV Prevention Trials Network 085, evaluating VRC01 for HIV prevention.

Feasibility and Successful Enrollment in a Proof-of-Concept HIV Prevention Trial of VRC01, a Broadly Neutralizing HIV-1 Monoclonal Antibody.

Background: The Antibody-Mediated Prevention trials (HVTN 704/HPTN 085 and HVTN 703/HPTN 081) are the first efficacy trials to evaluate whether VRC01, a broadly neutralizing monoclonal antibody targeting the CD4-binding site of the HIV envelope protein, prevents sexual transmission of HIV-1. HVTN 704/HPTN 085 enrolled 2701 cisgender men and transgender (TG) individuals who have sex with men at 26 sites in Brazil, Peru, Switzerland, and the United States.

Methods: Participants were recruited and retained through early, extensive community engagement.

Safety and tolerability of HIV-1 multiantigen pDNA vaccine given with IL-12 plasmid DNA via electroporation, boosted with a recombinant vesicular stomatitis virus HIV Gag vaccine in healthy volunteers in a randomized, controlled clinical trial.

Background: The addition of plasmid cytokine adjuvants, electroporation, and live attenuated viral vectors may further optimize immune responses to DNA vaccines in heterologous prime-boost combinations. The objective of this study was to test the safety and tolerability of a novel prime-boost vaccine regimen incorporating these strategies with different doses of IL-12 plasmid DNA adjuvant.

Methods: In a phase 1 study, 88 participants received an HIV-1 multiantigen (gag/pol, env, nef/tat/vif) DNA vaccine (HIV-MAG, 3000 μg) co-administered with IL-12 plasmid DNA adjuvant at 0, 250, 1000, or 1500 μg (N = 22/group) given intramuscularly with electroporation (Ichor TriGrid™ Delivery System device) at 0, 1 and 3 months; followed by attenuated recombinant vesicular stomatitis virus, serotype Indiana, expressing HIV-1 Gag (VSV-Gag), 3.

Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials.

Background: Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans.

DNA Priming Increases Frequency of T-Cell Responses to a Vesicular Stomatitis Virus HIV Vaccine with Specific Enhancement of CD8 T-Cell Responses by Interleukin-12 Plasmid DNA.

The HIV Vaccine Trials Network (HVTN) 087 vaccine trial assessed the effect of increasing doses of pIL-12 (interleukin-12 delivered as plasmid DNA) adjuvant on the immunogenicity of an HIV-1 multiantigen (MAG) DNA vaccine delivered by electroporation and boosted with a vaccine comprising an attenuated vesicular stomatitis virus expressing HIV-1 Gag (VSV-Gag). We randomized 100 healthy adults to receive placebo or 3 mg HIV-MAG DNA vaccine (ProfectusVax HIV-1 / or ProfectusVax //, ) coadministered with pIL-12 at 0, 250, 1,000, or 1,500 μg intramuscularly by electroporation at 0, 1, and 3 months followed by intramuscular inoculation with 3.4 × 10 PFU VSV-Gag vaccine at 6 months.

Safety and Immunogenicity of a Recombinant Adenovirus Serotype 35-Vectored HIV-1 Vaccine in Adenovirus Serotype 5 Seronegative and Seropositive Individuals.

Background: Recombinant adenovirus serotype 5 (rAd5)-vectored HIV-1 vaccines have not prevented HIV-1 infection or disease and pre-existing Ad5 neutralizing antibodies may limit the clinical utility of Ad5 vectors globally. Using a rare Ad serotype vector, such as Ad35, may circumvent these issues, but there are few data on the safety and immunogenicity of rAd35 directly compared to rAd5 following human vaccination.

Methods: HVTN 077 randomized 192 healthy, HIV-uninfected participants into one of four HIV-1 vaccine/placebo groups: rAd35/rAd5, DNA/rAd5, and DNA/rAd35 in Ad5-seronegative persons; and DNA/rAd35 in Ad5-seropositive persons.

First-in-Human Evaluation of the Safety and Immunogenicity of a Recombinant Vesicular Stomatitis Virus Human Immunodeficiency Virus-1 gag Vaccine (HVTN 090).

Background.  We report the first-in-human safety and immunogenicity evaluation of a highly attenuated, replication-competent recombinant vesicular stomatitis virus (rVSV) human immunodeficiency virus (HIV)-1 vaccine. Methods.

HIV-specific humoral responses benefit from stronger prime in phase Ib clinical trial.

BACKGROUND. Vector prime-boost immunization strategies induce strong cellular and humoral immune responses. We examined the priming dose and administration order of heterologous vectors in HIV Vaccine Trials Network 078 (HVTN 078), a randomized, double-blind phase Ib clinical trial to evaluate the safety and immunogenicity of heterologous prime-boost regimens, with a New York vaccinia HIV clade B (NYVAC-B) vaccine and a recombinant adenovirus 5-vectored (rAd5-vectored) vaccine.

Timing of plasmid cytokine (IL-2/Ig) administration affects HIV-1 vaccine immunogenicity in HIV-seronegative subjects.

Background: To investigate the potential immunostimulatory effect of interleukin (IL) 2 as a human immunodeficiency virus type 1 (HIV-1) vaccine adjuvant, we conducted a study of a plasmid coding for a fusion protein of IL-2 and immunoglobulin (IL-2/Ig).

Methods: This phase I trial evaluated an HIV-1 DNA vaccine with the plasmid cytokine adjuvant (IL-2/Ig) in 70 HIV-negative adults. Subjects received placebo (group C), adjuvant alone (group A), vaccine alone (group D), increasing doses of adjuvant concurrent with vaccine (groups T1-T4), or adjuvant given 2 days after vaccine (group T5).

Tipsitis: incidence and outcome-a single centre experience.

Introduction: Infection of transjugular intrahepatic portosystemic stent shunt (TIPSS) called 'Tipsitis' has been reported but appears unusual. We report here our experience of patients who were diagnosed to have Tipsitis at our centre.

Methods: Retrospective single centre study.

Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers.

Curcumin is the lipid-soluble antioxidant compound obtained from the rhizome of Curcuma longa Linn, also known as turmeric. Curcumin targets multiple chemotherapeutic and inflammatory pathways and has demonstrated safety and tolerability in humans, supporting its potential as a therapeutic agent; however, the clinical literature lacks conclusive evidence supporting its use as a therapeutic agent due to its low bioavailability in humans. The purpose of this study was to quantify plasma levels of free curcumin after dosing of a solid lipid curcumin particle (SLCP) formulation versus unformulated curcumin in healthy volunteers and to determine its tolerability and dose-plasma concentration relationship in late-stage osteosarcoma patients.

Beneficial effects of L-arginine against diabetes-induced oxidative stress in gastrointestinal tissues in rats.

Oxidative stress occurs in diabetic patients and experimental models of diabetes. The ability of L-arginine to ameliorate oxidative stress after treatment with alloxan was investigated in rats. Adult male rats were injected intraperitoneally with multiple doses of alloxan to produce experimental oxidative stress characteristic of diabetes mellitus.

Randomized controlled trial of carvedilol versus variceal band ligation for the prevention of the first variceal bleed.

Unlabelled: Current therapy for preventing the first variceal bleed includes beta-blocker and variceal band ligation (VBL). VBL has lower bleeding rates, with no differences in survival, whereas beta-blocker therapy can be limited by side effects. Carvedilol, a non-cardioselective vasodilating beta-blocker, is more effective in reducing portal pressure than propranolol; however, there have been no clinical studies assessing the efficacy of carvedilol in primary prophylaxis.

Phase angle of entrainment in morning- and evening-types under naturalistic conditions.

Differences in morningness-eveningness among humans are commonly ascribed to circadian parameters, such as circadian period and responsivity to environmental time cues, as well as homeostatic sleep drive. Light is the primary synchronizer of the human biological clock, and if circadian differences exist between morning and evening types, they should have different phase angles of entrainment to the light/dark cycle; that is, morning and evening types should have different patterns of light exposure relative to endogenous circadian phase (ECP). When phase angle of entrainment is strictly defined as the relationship between a marker of ECP and the timing of light exposure, such differences have been demonstrated in the laboratory under controlled light/dark cycles and have recently been shown under conditions of spring and summer light exposure outside the laboratory, taking into account the variable intensity of light.

Bleeding ectopic varices in cirrhosis: the role of transjugular intrahepatic portosystemic stent shunts.

Background: Bleeding from ectopic varices is uncommon but can be difficult to manage.

Aim: To report our experience of the use of transjugular intrahepatic portosystemic stent shunts (TIPSS) in the management of uncontrolled bleeding from ectopic varices.

Methods: A retrospective study of patients who had TIPSS for bleeding ectopic varices.

Gastrointestinal dysfunction in diabetic rats relates with a decline in tissue L-arginine content and consequent low levels of nitric oxide.

Diabetic subjects exhibit low levels of nitric oxide (NO), its precursor L-arginine, and nitric oxide synthase (NOS) in tissues like endothelium and kidney. In view of this, we speculated that gastrointestinal (GI) dysfunction in diabetes could be related to similar changes in NO turnover in GI tissues. Hence, the studies were carried out in rats after eight weeks of streptozotocin-induced hyperglycemia, wherein the GI functions were assessed in terms of gastric emptying and intestinal transit using barium sulfate semisolid test meal, and the levels of L-arginine and NO in pylorus and ileum were estimated, respectively, by HPLC and amperometry.

Prevalence of coronary artery calcification in patients undergoing assessment for orthotopic liver transplantation.

Patients with advanced liver disease are at increased risk of cardiovascular events, especially following orthotopic liver transplantation (OLT). Coronary artery calcification (CAC) is a novel and independent predictor of cardiovascular risk, but its prevalence and utility in patients with cirrhosis are unknown. The aim of this study was to define the prevalence of CAC and its association with markers of disease severity and standard measures of cardiovascular risk in a large cohort of patients undergoing OLT assessment.

Transjugular intrahepatic portosystemic stent shunt (TIPSS) modification in the management of post-TIPSS refractory hepatic encephalopathy.

Background: Post-transjugular intrahepatic portosystemic stent shunt (TIPSS) hepatic encephalopathy (HE) can occur in up to one third of patients. In 5%, this can be refractory to optimal medical treatment and may require shunt modification. The efficacy of shunt modification has been poorly studied.

Evaluation of a modified medium for the one hour urease test for Helicobacter pylori infection.

The biopsy urease test is a simple and rapid method for the diagnosis of Helicobacter pylori infection; results are obtained within 4 h to 24 h. Various modifications of the media used in this test have been tried, to improve the accuracy and speed of the test. We compared the yield obtained with two media: the standard Christensen's urea medium and a modified plain urea medium (without the nutrients glucose and peptone); the result was read upto 1 h.

Lactobacillus acidophilus inhibits growth of Campylobacter pylori in vitro.

Campylobacter pylori has been implicated as a causative factor in acid-peptic disease. Lactobacillus acidophilus is known to inhibit the growth of pathogens in the human gastrointestinal tract. We recovered C.