Estimating the critical immunity threshold for preventing hepatitis A outbreaks in men who have sex with men.

Several outbreaks of hepatitis A in men who have sex with men (MSM) were reported in the 1980s and 1990s in Australia and other countries. An effective hepatitis A virus (HAV) vaccine has been available in Australia since 1994 and is recommended for high-risk groups including MSM. No outbreaks of hepatitis A in Australian MSM have been reported since 1996. In this study, we aimed to estimate HAV transmissibility in MSM populations in order to inform targets for vaccine coverage in such populations. We used mathematical models of HAV transmission in a MSM population to estimate the basic reproduction number (R 0) and the probability of an HAV epidemic occurring as a function of the immune proportion. We estimated a plausible range for R 0 of 1·71-3·67 for HAV in MSM and that sustained epidemics cannot occur once the proportion immune to HAV is greater than ~70%. To our knowledge this is the first estimate of R 0 and the critical population immunity threshold for HAV transmission in MSM. As HAV is no longer endemic in Australia or in most other developed countries, vaccination is the only means of maintaining population immunity >70%. Our findings provide impetus to promote HAV vaccination in high-risk groups such as MSM.

Evaluation of Potential Pharmacokinetic Drug-Drug Interaction between Armodafinil and Aripiprazole in Healthy Adults.

INTRODUCTION: Armodafinil, a moderate inducer of cytochrome P450 (CYP) 3A4, has been studied as adjunctive therapy to maintenance medications for major depressive episodes associated with bipolar I disorder. We evaluated the effect of daily dosing with armodafinil on the pharmacokinetics and safety of the CYP3A4 substrate aripiprazole, an atypical antipsychotic used to treat bipolar I disorder. METHODS: Healthy adults received 15 mg aripiprazole alone and after armodafinil (250 mg/day) pretreatment. Pharmacokinetic parameters were derived from plasma concentrations of aripiprazole and its active metabolite, dehydro-aripiprazole, obtained over 16 days after each aripiprazole administration. Steady-state pharmacokinetics of armodafinil and its 2 circulating metabolites was assessed. RESULTS: Of 36 subjects enrolled, 24 were evaluable for pharmacokinetic analysis. Armodafinil reduced systemic exposure to aripiprazole (Cmax, - 8%; AUC0-∞, -34%) and dehydro-aripiprazole, which is both formed and eliminated in part via CYP3A4 (Cmax, - 10%; AUC0-∞, - 32%). Adverse events were generally consistent with known safety profiles of each agent. DISCUSSION: Systemic exposure to aripiprazole and dehydro-aripiprazole was moderately reduced following armodafinil pretreatment. The combination was generally well tolerated under the conditions studied.

Automating sequence-based detection and genotyping of SNPs from diploid samples.

The detection of sequence variation, for which DNA sequencing has emerged as the most sensitive and automated approach, forms the basis of all genetic analysis. Here we describe and illustrate an algorithm that accurately detects and genotypes SNPs from fluorescence-based sequence data. Because the algorithm focuses particularly on detecting SNPs through the identification of heterozygous individuals, it is especially well suited to the detection of SNPs in diploid samples obtained after DNA amplification. It is substantially more accurate than existing approaches and, notably, provides a useful quantitative measure of its confidence in each potential SNP detected and in each genotype called. Calls assigned the highest confidence are sufficiently reliable to remove the need for manual review in several contexts. For example, for sequence data from 47-90 individuals sequenced on both the forward and reverse strands, the highest-confidence calls from our algorithm detected 93% of all SNPs and 100% of high-frequency SNPs, with no false positive SNPs identified and 99.9% genotyping accuracy. This algorithm is implemented in a software package, PolyPhred version 5.0, which is freely available for academic use.

Improved serological response to H1N1 monovalent vaccine associated with viral suppression among HIV-1-infected patients during the 2009 influenza (H1N1) pandemic in the Southern Hemisphere.

OBJECTIVES: Patients infected with HIV-1 were targeted for vaccination against H1N1 influenza because of their anticipated increased risk of mortality associated with H1N1 infection. Reports regarding the efficacy of vaccination in HIV-1-infected patients have suggested a reduced immunogenic response compared with the general population. Hence, the study aimed to determine the serological response to pandemic H1N1 influenza vaccine in HIV-1-infected patients in a clinical setting. METHODS: A retrospective review of all HIV-1-infected patients who attended mass H1N1 vaccination between October 2009 and March 2010 at an Australian HIV clinic was carried out. Pre- and post-vaccination H1N1 antibody titres were measured. The main outcome measure was response to the vaccination, which was defined as an H1N1 antibody titre of ≥ 1:40 using a haemagglutination inhibition (HI) assay. RESULTS: Baseline blood samples were collected from 199 patients, of whom 154 agreed to receive vaccination; of these, 126 had pre- and post-vaccination HI titres measured. Seventy-seven of 199 patients (38.7%) showed a baseline antibody titre of ≥ 1:40. Eighty-five (67.4%) showed a fourfold or greater increase in titre and 109 of 126 (86.5%) achieved an antibody titre of ≥ 1:40 after vaccination. The serum HI H1N1 antibody geometric mean titre (GMT) for the 126 paired samples was 39.32 ± 3.46 pre-vaccination and increased to 237.36 ± 3.94 [standard deviation (SD)] post-vaccination (P<0.001). In a binary logistic regression analysis, HIV viral load and baseline HI antibody titre were significantly associated with post-vaccination increase in HI H1N1 antibody titre. CONCLUSIONS: A high prevalence of HI H1N1 antibodies was found before vaccination in the cohort, consistent with previous exposure to H1N1 influenza virus. The response to vaccination was considered adequate, as more than two-thirds of patients achieved a fourfold or more increase in antibody titre after vaccination. The response to vaccination was significantly greater in those patients who were aviraemic for HIV, suggesting that antiretroviral therapy improves the humoral response, which is important in optimizing vaccine effectiveness.

Adaptations in Visual Search Behaviour as a Function of Expertise in Rugby Union Players Completing Attacking Scenarios.

The current study investigated the adaptations which occur in visual search behaviour as a function of expertise in rugby union players when completing attacking scenarios. Ten experienced players (EP) and ten novice players (NP) completed 2 vs. 1 attacking game scenarios. Starting with the ball in hand and wearing a mobile eye tracker throughout, participants were required to score a try against a defender. The scenarios allowed for a pass to their supporting player (Spin Pass or Switch) or trying to run past the defender (Take-Player-On or Dummy Switch). No between group differences were found in fixating on the supporting attacking player (p > 0.05). However, EP increased the length (p = 0.008) and frequency (p = 0.004) looking at the area immediately ahead of the supporting player, particularly when executing a spin pass. NP fixated longer (p = 0.005) and more frequently (p = 0.032) at the defender, whilst EP fixated more frequently in the space the supporting player would run into in Switch and Dummy Switch scenarios (p = 0.025). More successful passes were completed and tries scored by EP compared to NP (p = 0.001). Differences in visual search behaviour between experienced and NP suggest that the experts extract information from areas directly related to guiding the motor action; the space immediately ahead of the support player to pass the ball in. Contrastingly, novices use a more allocentric perspective where the actions from the defender are used to guide their motor actions.

Perioperative care: a survey of New Zealand and Australian colorectal surgeons.

AIM: Recent surveys in Europe and North America have demonstrated significant challenges in the implementation of evidence-based surgical practice. METHOD: A survey of New Zealand and Australian colorectal surgeons was conducted to help understand current practice and perceived barriers to interventions in this region. Questions were based around elective colorectal resection care. RESULTS: There were 152 eligible participants identified. Over a 60-day period, 82 (54%) surgeons responded but only 76 (50%) of the questionnaires were complete; they were used for data analysis. The majority of surgeons indicated a preference for laparoscopic techniques. Barriers to laparoscopy include lack of operating time, lack of adequate training and institutional pressures. Only 28 (37%) indicated that they cared for patients in a formalized enhanced recovery programme (ERAS). Barriers to implementing ERAS included lack of support from institutions and other specialities. Routine oral 'mechanical' bowel preparation for colon and rectal resection was preferred by 28% and 63%, respectively. Drainage after routine colon and rectal resection was not used by 62 (83%) and 39 (53%). Prophylactic nasogastric intubation afterwards was not used by 66 (87%) responders. The preferred mode of analgesia was patient-controlled opioid analgesia (PCA) for 52%. A 'restrictive' intravenous fluid therapy was preferred by 34 (49%) while 33 (48%) preferred no fluid restriction. A prolonged 'nil by mouth' status was preferred by 28%. CONCLUSION: There appears to be a high rate of evidence in agreement with some interventions but not others. The systemic barriers to implementing evidence-based perioperative care need attention.

Can sterilization of disposable face masks be an alternative for imported face masks? A nationwide field study including 19 sterilization departments and 471 imported brand types during COVID-19 shortages.

BACKGROUND: Face masks, also referred to as half masks, are essential to protect healthcare professionals working in close contact with patients with COVID-19-related symptoms. Because of the Corona material shortages, healthcare institutions sought an approach to reuse face masks or to purchase new, imported masks. The filter quality of these masks remained unclear. Therefore, the aim of this study was to assess the quality of sterilized and imported FFP2/KN95 face masks. METHODS: A 48-minute steam sterilization process of single-use FFP2/KN95 face masks with a 15 minute holding time at 121°C was developed, validated and implemented in the Central Sterilization Departments (CSSD) of 19 different hospitals. Masks sterilized by steam and H2O2 plasma as well as new, imported masks were tested for particle filtration efficiency (PFE) and pressure drop in a custom-made test setup. RESULTS: The results of 84 masks tested on the PFE dry particle test setup showed differences of 2.3±2% (mean±SD). Test data showed that the mean PFE values of 444 sterilized FFP2 face masks from the 19 CSSDs were 90±11% (mean±SD), and those of 474 new, imported KN95/FFP2 face masks were 83±16% (mean±SD). Differences in PFE of masks received from different sterilization departments were found. CONCLUSION: Face masks can be reprocessed with 121 °C steam or H2O2 plasma sterilization with a minimal reduction in PFE. PFE comparison between filter material of sterilized masks and new, imported masks indicates that the filter material of most reprocessed masks of high quality brands can outperform new, imported face masks of unknown brands. Although the PFE of tested face masks from different sterilization departments remained efficient, using different types of sterilization equipment, can result in different PFE outcomes.

Radiotherapy without tattoos: Could this work?

INTRODUCTION: An evaluation to compare the traditional tattoo based set up procedure with a surface guided method to assess the possibility of eliminating permanent tattoos in breast cancer patents who are undergoing radiotherapy to the breast/chest wall. METHODS: Forty-three patients that were having radiotherapy to the breast or chest wall were included in this evaluation. The patients were divided into two groups and further divided into 2 sub-groups. The first group received standard dark ink tattoos and were positioned by aligning these tattoos with lasers. The second group had no tattoo's and were positioned using the Surface-Guided technology (SGRT). Within each group the patients were split into 2 sub-group; right and left sided treatment areas. The right side were treated using a Free-Breathing (FB) technique and the left sided were treated using a Deep-Inspiration Breath-Hold (DIBH) technique. RESULTS: For the patients having right sided breast radiotherapy, the mean shift using the standard tattoos and laser set up was 0.52 cm, compared with using the SGRT method where the mean shift was 0.47 cm. (p-value 0.04) For patients having left sided breast radiotherapy with DIBH the mean shift using the standard tattoo's and laser set up was 0.76 cm, compared with a mean shift of 0.45 cm using SGRT alone (p-value < 0.001). CONCLUSION: The elimination of tattoos together with SGRT offers a comparable set-up for right sided breast treatments against the traditional tattoo method. A significant set-up improvement was observed for the left sided breast DIBH treatments. IMPLICATIONS FOR PRACTICE: To set up patients having breast Radiotherapy, with no tattoo's.

Scotin, a novel p53-inducible proapoptotic protein located in the ER and the nuclear membrane.

p53 is a transcription factor that induces growth arrest or apoptosis in response to cellular stress. To identify new p53-inducible proapoptotic genes, we compared, by differential display, the expression of genes in spleen or thymus of normal and p53 nullizygote mice after gamma-irradiation of whole animals. We report the identification and characterization of human and mouse Scotin homologues, a novel gene directly transactivated by p53. The Scotin protein is localized to the ER and the nuclear membrane. Scotin can induce apoptosis in a caspase-dependent manner. Inhibition of endogenous Scotin expression increases resistance to p53-dependent apoptosis induced by DNA damage, suggesting that Scotin plays a role in p53-dependent apoptosis. The discovery of Scotin brings to light a role of the ER in p53-dependent apoptosis.

Fission-track dating of haughton astrobleme and included biota, devon island, Canada.

Haughton Astrobleme is a major extraterrestrial impact structure located on Devon Island in the Canadian Arctic Archipelago, Northwest Territories. Apatite grains separated from shocked Precambrian gneiss contained in a polymict breccia from the center of the astrobleme yielded a fission-track date of 22.4 million +/- 1.4 million years before the present or early Miocene (Aquitanian). This provides a date for the impact event and an upper limit on the age of crater-filling lake sediments and a flora and vertebrate fauna occurring in them. A geologically precise date for these fossils provides an important biostratigraphic reference point for interpreting the biotic evolution of the Arctic.

Collagenase: localization in polymorphonuclear leukocyte granules in the rabbit.

Polymorphonuclear leukocyte granules were submitted to zonal fractionation through a discontinuous sucrose gradient. Azurophilic and specific granules were enzymatically characterized by peroxidase and alkaline phosphatase activity, respectively. The enzymes formed modal distributions like those reported by others. Collagenase activity was consistently associated with the specific granules containing alkaline phosphatase.

Falls in older people: comparing older and younger fallers in a developing country.

PURPOSE: While falls are common in older people, causing significant mortality and morbidity, this phenomenon has not been extensively studied in the Caribbean. This study aimed to compare falls in older and younger people in this setting. METHODS: We conducted a prospective observational study of older trauma patients in Trinidad, comparing older and younger patients sustaining falls. RESULTS: 1432 adult trauma patients were included (1141 aged 18-64 years and 291 aged 65 years and older). Older fallers were more likely to be female (66.7 vs 47.2%; p < 0.001), suffer from multiple pre-existing diseases (24.7 vs 2.4%; p < 0.001) and take multiple medications (16.1 vs 0.8%; p < 0.001). They also sustained more severe injuries and presented with higher acuity than younger fallers. Admission rates were higher among older fallers (29.9 vs 13.1%; p < 0.001). CONCLUSIONS: In our study, older patients who fell were a distinct group from younger falls victims, with unique demographic, clinical and injury related characteristics. Their increased risk of injury within the home, coupled with their propensity for more severe injuries made them a high risk patient group. More research is needed to better understand this patient group and plan specific preventive interventions.

Anti-streptococcal antibodies in the diagnosis of acute and post-streptococcal disease: streptokinase versus streptolysin O and deoxyribonuclease B.

AIMS: To establish population normal values and compare the diagnostic value of antibodies against streptokinase (ASK), streptolysin O (ASO) and deoxyribonuclease B (ADNaseB) singularly and in combinations in acute and post-streptococcal disease. METHODS: A retrospective analysis of serological results was performed to define population norms. Subjects with acute culture-confirmed infection and post-streptococcal disease were assessed using population norms, as were matched controls. The sensitivity and specificity of each antibody assay and of combinations of the different assays were calculated. RESULTS: Age specific population normal values were derived from 2,321 specimens. None of the three antibodies alone or in combination was a reliable marker of acute streptococcal infection. The sensitivity and specificity of a single antibody titre in post-streptococcal disease ranged from 70.5 to 72.7% and 86.4 to 93.2%, respectively. The combination of ASO and ADNaseB was the most sensitive and specific combination for identifying post-streptococcal disease (sensitivity 95.5%, specificity 88.6%). CONCLUSIONS: In the diagnosis of acute and post-streptococcal disease, the addition of ASK does not increase the sensitivity or specificity of serological testing. A combination of ASO and ADNaseB is required in post-streptococcal disease to achieve maximum sensitivity and specificity.

Diffusion magnetic resonance imaging: an early surrogate marker of therapeutic efficacy in brain tumors.

BACKGROUND: A surrogate marker for treatment response that can be observed earlier than comparison of sequential magnetic resonance imaging (MRI) scans, which depends on relatively slow changes in tumor volume, may improve survival of brain tumor patients by providing more time for secondary therapeutic interventions. Previous studies in animals with the use of diffusion MRI revealed rapid changes in tumor water diffusion values after successful therapeutic intervention. METHODS: The present study examined the sensitivity of diffusion MRI measurements in orthotopic rat brain tumors derived from implanted rat 9L glioma cells. The effectiveness of therapy for individual brain cancer patients was evaluated by measuring changes in tumor volume on neuroimaging studies conducted 6--8 weeks after the conclusion of a treatment cycle. RESULTS: Diffusion MRI could detect water diffusion changes in orthotopic 9L gliomas after doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU or carmustine) that resulted in as little as 0.2 log cell kill, a measure of tumor cell death. Mean apparent diffusion coefficients in tumors were found to be correlated with and highly sensitive to changes in tumor cellularity (r =.78; two-sided P =.041). The feasibility of serial diffusion MRI in the clinical management of primary brain tumor patients was also demonstrated. Increased diffusion values could be detected in human brain tumors shortly after treatment initiation. The magnitude of the diffusion changes corresponded with clinical outcome. CONCLUSIONS: These results suggest that diffusion MRI will provide an early surrogate marker for quantification of treatment response in patients with brain tumors.

Exogenous genistein in late gestation: effects on fetal development and sow and piglet performance.

Due to their functional similarity to estradiol, phytoestrogens could prove to be beneficial in late gestating sows. The goal of this study was to determine the impact of providing the phytoestrogen genistein during late pregnancy on the performance of sows and their litters. In total, 56 gilts were equally divided into the two following groups on day 90 of gestation: (1) controls (CTL); and (2) two daily i.m. injections of 220 mg of genistein (GEN). Treatments were carried out until farrowing. Jugular blood samples were collected from 16 gilts/treatment on days 89 and 110 of gestation, and on days 3 and 21 of lactation. Milk samples were also obtained from those sows on day 3 of lactation. A male piglet from 16 CTL and 15 GEN litters was slaughtered at 24 h postpartum and a blood sample was obtained. The liver, heart and visceral organs were weighed and the semitendinosus (ST) muscle was collected and carcass composition was determined. The treatment increased (P0.1) on weight or backfat loss of sows during lactation, milk composition or weights of piglets. The pre-weaning mortality rate of piglets was very low (0.1). However, carcasses from GEN litters contained more fat than those from CTL litters (9.63% v. 8.34%, P0.1). In conclusion, injecting gilts with 440 mg/day of genistein in late gestation increased IGF1 concentrations in gilts and carcass fat in neonatal piglets, but had minimal effect on muscle development of piglets at birth and on the performance of lactating sows and their litters.

Congenitally corrected transposition of the great arteries in the adult: functional status and complications.

OBJECTIVES: We sought to assess the clinical outcome, functional status and complications of adult patients with congenitally corrected transposition of the great arteries. BACKGROUND: Congenitally corrected transposition is a rare form of congenital heart disease, although survival into adult life may be expected. Little information is available on the long-term prognosis of these patients once they have reached adulthood. This study focuses exclusively on patients >18 years old followed up at a single tertiary referral center. METHODS: The charts of all patients with a diagnosis of congenitally corrected transposition of the great arteries from the Toronto Congenital Cardiac Centre for Adults since 1985 were reviewed. Data were available for 52 patients, 26 of whom had undergone radionuclide angiography. Mortality, clinical and functional status, surgical procedures and complications were reviewed. RESULTS: Thirteen patients (25%) died; age at death was 38.5 +/- 12.5 years (mean +/- SD). The current age of survivors is 32.7 years (range 18.2 to 54.3). Of the survivors, 17 had palliative procedures, and 25 had definitive repair, 11 of whom required reoperation. Left ventricle to pulmonary artery conduit replacement was necessary in seven patients. Eighteen patients have permanent pacemakers, nine of whom developed complete heart block perioperatively. Nine patients developed progressive atrioventricular (AV) block unrelated to operation. Supraventricular arrhythmias occurred in 15 patients. Progressive systemic AV valve regurgitation developed in 10 patients and endocarditis in 6. CONCLUSIONS: Congenitally corrected transposition in the adult patient is not a benign condition. Late complications are common and warrant careful, long-term follow-up.

A phase I study of high-dose tamoxifen for the treatment of refractory malignant gliomas of childhood.

Recent studies have indicated that the proliferation of malignant gliomas is in part dependent on excessive activation of protein kinase C (PKC)-mediated pathways. Conversely, inhibiting PKC may provide a novel approach for blocking glioma growth. The antiestrogen tamoxifen, a moderately potent PKC inhibitor, has been shown in vitro to block the proliferation of malignant glioma cell lines at concentrations several-fold higher than those typically attained during the treatment of breast cancer; such serum concentrations may be achieved with doses > 40 mg/m2 b.i.d. The safety and efficacy of these high doses for producing disease control in patients with malignant gliomas has recently been noted anecdotally, although a rigorous study of this agent has been lacking. To address this issue, we examined the safety and efficacy of high-dose tamoxifen in a series of children with malignant gliomas that had progressed after conventional therapy. An initial group was treated with 60 mg/m2 p.o. b.i.d. and a second group with 100 mg/m2 b.i.d. Steady-state serum tamoxifen and metabolite levels were measured in most patients. Toxicity with the regimen was minimal; two patients treated at the higher dose required reduction to the lower dose because of asymptomatic prolongation of the QT interval on an electrocardiogram. Although none of the patients exhibited clear-cut tumor regression, 4 of 14 patients had stabilization of previously progressive disease for at least 3 months; the longest survivor lived for 17 months after beginning tamoxifen. The moderate efficacy of this agent in otherwise end-stage disease coupled with its low toxicity and the relative ease of oral administration provides a rationale for proceeding with larger studies of this agent in patients with malignant gliomas, possibly as a means for potentiating the effects of conventional chemotherapeutic agents, which to date have shown limited efficacy in the treatment of these tumors.

A care pathway for chlamydia, what's happening in primary care 12 months on?

Primary care is seen as central to the future provision of sexual health services, including chlamydia screening. The aim of this study was to establish levels of awareness and application of a chlamydia care pathway among practice nurses in primary care 12 months after its launch and present knowledge and practice of testing. Questionnaires were sent to 46 practice nurses at 22 general practitioner practices within the care pathway pilot site. Response rate was 33/46 (72%), with 30 (94%) practice nurses aware of the care pathway and 19 (62%) routinely using it. Endocervical swabbing was performed by 29 (90%) respondents, no endourethral swabs were taken from men and 85% nurses did not perceive partner notification as being part of their role. Practice nurses identified the need for training in using the care pathway and in identification of infection to optimize the provision of effective sexual health care in primary care.

Risk-assessment-based approach to patients exposed to endoscopes contaminated with Pseudomonas spp.

Patients exposed to bronchoscopes contaminated with Pseudomonas aeruginosa are at increased risk of pseudomonal infection. The optimal methods for management and mitigation of risk following exposure are controversial. This article describes a two-phase risk assessment following pseudomonal contamination of a family of 75 endoscopes, detected through routine surveillance and attributed to one endoscope washer-disinfector. An initial risk assessment identified 18 endoscopes as high risk, based on the presence of lumens used for irrigation or biopsy. Exposure was communicated to the patients' clinical teams and a further clinical risk assessment of the exposed patients was performed. No patients developed complications due to pseudomonal infection.

Cervicomedullary tumors in children: a distinct subset of brainstem gliomas.

We reviewed the clinical course of 17 children who underwent surgical resection of an intra-axial cervicomedullary tumor between 1980 and 1992. The clinical symptoms, which reflected medullary dysfunction in nine children and cervical cord deficits in eight, were present for a mean of 2.1 years before diagnosis (range, 2 months to 7.5 years), and for at least 1 year in 80% of the patients. Neurodiagnostic imaging (MRI in 14, CT in 3) showed the tumor epicenter in the medulla in 11 and in the upper cervical cord in six. Surgery was performed for newly diagnosed tumor in 11 children, and for progressive disease in six who had received prior radiotherapy. The surgical resection was gross total in two and partial (60 to 95%) in fifteen. Fifteen patients had low-grade glial tumors (10 astrocytomas, four gangliogliomas, and one mixed glioma), and two had anaplastic gangliogliomas. Four-year progression-free and total survival rates after surgery for patients who had surgery as initial therapy were 70 and 100%; for those who had surgery at the time of progression, these were 41 and 62%. Postsurgical neurologic complications occurred in five children. Four of these children had received prior radiotherapy. Two of them already had severe preoperative deficits and three had moderate deficits that worsened after surgery. Twelve patients with mild deficits were unchanged or improved postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)