Ovarian cancer think tank: An overview of the current status of ovarian cancer screening and recommendations for future directions.

Early diagnosis and screening of ovarian cancer remain significant challenges to improving patient outcomes. There is an urgent need to implement both established and modern strategies to address the "early detection" conundrum, especially as new research continues to uncover the complexities of the disease. The discussion provided is the result of a unique research conference focused on reviewing early detection modalities and providing insight into future approaches.

Are we moving the dial? Canadian health research funding trends for women's health, 2S/LGBTQ + health, sex, or gender considerations.

BACKGROUND: Sex and gender impacts health outcomes and disease risk throughout life. The health of women and members of the Two-Spirit, Lesbian, Gay, Bisexual, Transgender, Queer or Questioning (2S/LGBTQ +) community is often compromised as they experience delays in diagnosis. Distinct knowledge gaps in the health of these populations have prompted funding agencies to mandate incorporation of sex and gender into research. Sex- and gender-informed research perspectives and methodology increases rigor, promotes discovery, and expands the relevance of health research. Thus, the Canadian Institutes of Health Research (CIHR) implemented a sex and gender-based analysis (SGBA) framework recommending the inclusion of SGBA in project proposals in 2010 and then mandating the incorporation of SGBA into grant proposals in 2019. To examine whether this mandate resulted in increased mention of sex or gender in funded research abstracts, we searched the publicly available database of grant abstracts funded by CIHR to analyze the percentage of abstracts that mentioned sex or gender of the population to be studied in the funded research. To better understand broader health equity issues we also examined whether the funded grant abstracts mentioned either female-specific health research or research within the 2S/LGBTQ + community. RESULTS: We categorized a total of 8,964 Project and Operating grant abstracts awarded from 2009 to 2020 based on their study of female-specific or a 2S/LGBTQ + populations or their mention of sex or gender. Overall, under 3% of grant abstracts funded by CIHR explicitly mentioned sex and/or gender, as 1.94% of grant abstracts mentioned sex, and 0.66% mentioned gender. As one of the goals of SGBA is to inform on health equity and understudied populations with respect to SGBA, we also found that 5.92% of grant abstracts mentioned female-specific outcomes, and 0.35% of grant abstracts focused on the 2S/LGBTQ + community. CONCLUSIONS: Although there was an increased number of funded grants with abstracts that mentioned sex and 2S/LGBTQ + health across time, these increases were less than 2% between 2009 and 2020. The percentage of funded grants with abstracts mentioning female-specific health or gender differences did not change significantly over time. The percentage of funding dollars allocated to grants in which the abstracts mentioned sex or gender also did not change substantially from 2009 to 2020, with grant abstracts mentioning sex or female-specific research increasing by 1.26% and 3.47%, respectively, funding allocated to research mentioning gender decreasing by 0.49% and no change for 2S/LGBTQ +-specific health. Our findings suggest more work needs to be done to ensure the public can evaluate what populations will be examined with the funded research with respect to sex and gender to advance awareness and health equity in research.

This paper examined the publicly available database of grant abstracts funded by the Canadian Institute of Health Research (CIHR) from 2009 to 2020 to determine the percentage of abstracts that mentioned sex or gender of the population to be studied. To better understand broader health equity issues we also examined whether the funded grant abstracts mentioned either female-specific health research or research within the 2S/LGBTQ + community. Although there was an increased number of funded grants with abstracts that mentioned sex and 2S/LGBTQ + health across time, these increases were less than 2% between 2009 and 2020. The percentage of funded grants with abstracts mentioning female-specific health or gender differences did not change significantly over time. The percentage of CIHR funding dollars allocated to grants in which the abstracts mentioned sex or female-specific research increased by 1.26% and 3.47%, respectively. However, funding allocated to research mentioning gender decreased by 0.49% and there was no significant change in funding amounts for 2S/LGBTQ +-specific health across time. We outline several recommendations for funding agencies to improve access to information especially on sex, gender and broader health equity populations to ensure the public can evaluate what populations will be examined within the funded research. Our findings suggest that to advance greater health equity in research, different strategies need to be employed to improve researcher utilization of sex and gender-based analysis as well as to advance health equity with respect to 2S/LGBTQ and women's health questions in research.

An effective evidence-based cleaning method for the safe reuse of intermittent urinary catheters: In vitro testing.

AIMS: To determine a safe bactericidal cleaning method that does not damage urethral catheters used for intermittent catheterization. In some countries, single-use catheters are the norm; in others, the reuse of catheters is common depending on health insurance, personal preference, or individual concerns about the environment. However, no recent study of cleaning methods has been published to provide evidence for the safe reuse of catheters. METHODS: Using advanced microbiological methods, a laboratory study of eight cleaning methods was conducted. Sections of uncoated polyvinylchloride (PVC) catheters were exposed to bacterial uropathogens in physiologically correct artificial urine media then tested with a range of heat, chemical, and mechanical cleaning methods. Analysis of culturable and viable but nonculturable (VBNC) bacteria was done and direct microscopy was used. Descriptive statistics were used to compare values. RESULTS: Heat treatments, although effective, resulted in catheter surface breakdown and damage. Ultrasonic cleaning and vinegar showed evidence of VBNC populations indicating the methods were bacteriostatic. Detergent and water wash followed by immersion in a commercially available 0.6% sodium hypochlorite solution and 16.5% sodium chloride (diluted Milton) gave consistent bactericidal results and no visible catheter damage. CONCLUSIONS: Combined mechanical and chemical treatment of a detergent and water wash followed by immersion in diluted Milton (the "Milton Method") provided consistent and effective cleaning of uncoated PVC catheters, showing bactericidal action for all uropathogens tested after repeated exposure. If found safe in clinical testing, this method could increase the reuse of catheters, reduce plastic waste in the environment, reduce cost, and increase patient choice.

Tissue response to applied loading using different designs of penile compression clamps.

Background: Penile compression devices (PCD) or clamps are applied to compress the urethra and prevent urinary incontinence (UI). PCDs are more secure and less likely to leak than pads, allowing men the opportunity to participate in short-term, vigorous activities. However, they are uncomfortable, can cause pressure ulcers (PU) and affect penile blood flow. No objective assessment of tissue health has been undertaken to assess and compare different PCD designs and to provide guidance on safe use. Objective: This study was designed to evaluate existing PCDs in terms of their physiological response and potential for pressure-induced injury. Design, setting and participants: Six men with post-prostatectomy UI tested four selected PCDs at effective pressures, in a random order, in a controlled laboratory setting. Outcome measurements and statistical analysis: Using objective methods for assessing skin injury, PCDs were measured in situ for their effects on circulatory impedance, interface pressures and inflammatory response. Results and limitations: There was evidence for PCD-induced circulatory impedance in most test conditions. Interface pressures varied considerably between both PCDs and participants, with a mean value of 137.4±69.7 mmHg. In some cases, penile skin was noted to be sensitive to loading with elevated concentration of the cytokine IL-1α after 10 mins wear, indicating an inflammatory response. IL-1α levels were restored to baseline 40 mins following PCD removal. Conclusion: Skin health measures indicated tissue and blood flow compromise during the 50 mins of testing using all PCDs. Although there was an elevation in pro-inflammatory cytokines, PCDs did not cause sustained irritation and skin health measures recovered 40 mins after PCD removal. This research indicates that application of a clamp for one hour with an equal clamp free time before reapplication is likely to be safe. Longer periods are often recommended by manufacturers but have yet to be tested.

Factors affecting continuation of clean intermittent catheterisation in people with multiple sclerosis: Results of the COSMOS mixed-methods study.

BACKGROUND: Clean intermittent catheterisation (CIC) is often recommended for people with multiple sclerosis (MS). OBJECTIVE: To determine the variables that affect continuation or discontinuation of the use of CIC. METHODS: A three-part mixed-method study (prospective longitudinal cohort ( n = 56), longitudinal qualitative interviews ( n = 20) and retrospective survey ( n = 456)) was undertaken, which identified the variables that influenced CIC continuation/discontinuation. The potential explanatory variables investigated in each study were the individual's age, gender, social circumstances, number of urinary tract infections, bladder symptoms, presence of co-morbidity, stage of multiple sclerosis and years since diagnosis, as well as CIC teaching method and intensity. RESULTS: For some people with MS the prospect of undertaking CIC is difficult and may take a period of time to accept before beginning the process of using CIC. Ongoing support from clinicians, support at home and a perceived improvement in symptoms such as nocturia were positive predictors of continuation. In many cases, the development of a urinary tract infection during the early stages of CIC use had a significant detrimental impact on continuation. CONCLUSION: Procedures for reducing the incidence of urinary tract infection during the learning period (i.e. when being taught and becoming competent) should be considered, as well as the development of a tool to aid identification of a person's readiness to try CIC.

Reuse of intermittent catheters: a qualitative study of IC users' perspectives.

OBJECTIVES: To explore the views of intermittent catheter (IC) users regarding the advantages and disadvantages of single-use or reuse of catheters. DESIGN: Qualitative study with semi-structured interviews. The interviews were recorded, transcribed and analysed thematically. SETTING: Participant's own homes in Hampshire and Dorset, UK. PARTICIPANTS: A convenience sample of 39 IC users, aged 23-86 years, using IC for at least 3 months. RESULTS: The analysis revealed four main themes: concerns regarding risk of urinary tract infection (UTI); cleaning, preparation and storage; social responsibility; practicalities and location. The main concern was safety, with the fear that reuse could increase risk of UTI compared with single-use sterile catheters. If shown to be safe then around half of participants thought they might consider reusing catheters. The practicalities of cleaning methods (extra products, time and storage) were considered potentially burdensome for reuse; but for single-use, ease of use and instant usability were advantages. Always having a catheter without fear of 'running out' was considered an advantage of reuse. Some participants were concerned about environmental impact (waste) and cost of single-use catheters. The potential for reuse was usually dependent on location. The analysis showed that often the disadvantages of single-use could be off-set by the advantages of reuse and vice versa, for example, the need to take many single-use catheters on holiday could be addressed by reuse, while the burden of cleaning would be obviated by single-use. CONCLUSIONS: If shown to be safe with a practical cleaning method, some participants would find reuse an acceptable option, alongside their current single-use method. The choice to use a mixture of single-use and reuse of catheters for different activities (at home, work or holiday) could optimise the perceived advantages and disadvantages of both. The safety and acceptability of such an approach would require testing in a clinical trial.

Development of a Quantitative LC-MS-MS Assay for Codeine, Morphine, 6-Acetylmorphine, Hydrocodone, Hydromorphone, Oxycodone and Oxymorphone in Neat Oral Fluid.

Recent advances in analytical capabilities allowing for the identification and quantification of drugs and metabolites in small volumes at low concentrations have made oral fluid a viable matrix for drug testing. Oral fluid is an attractive matrix option due to its relative ease of collection, reduced privacy concerns for observed collections and difficulty to adulterate. The work presented here details the development and validation of a liquid chromatography tandem mass spectrometry (LC-MS-MS) method for the quantification of codeine, morphine, 6-acetylmorphine, hydrocodone, hydromorphone, oxycodone and oxymorphone in neat oral fluid. The calibration range is 0.4-150 ng/mL for 6-acetylmorphine and 1.5-350 ng/mL for all other analytes. Within-run and between-run precision were <5% for all analytes except for hydrocodone, which had 6.2 %CV between runs. Matrix effects, while evident, could be controlled using matrix-matched controls and calibrators with deuterated internal standards. The assay was developed in accordance with the proposed mandatory guidelines for opioid confirmation in federally regulated workplace drug testing. The use of neat oral fluid, as opposed to a collection device, enables collection of a single sample that can be split into separate specimens.

The redesigned Forensic Research/Reference on Genetics-knowledge base, FROG-kb.

The Forensic Resource/Reference on Genetics-knowledge base (FROG-kb) web site was introduced in 2011 and in the five years since the previous publication ongoing research into how the database can better serve forensics has resulted in extensive redesign of the database interface and functionality. Originally designed as a prototype to support forensic use of single nucleotide polymorphisms (SNPs), FROG-kb provides a freely accessible web interface that facilitates forensic practice and can be useful for teaching and research. Based on knowledge gained through its use, the web interface has been redesigned for easier navigation through the multiple components. The site also has functional enhancements, extensive new documentation, and new reference panels of SNPs with new curated data. FROG-kb focuses on single nucleotide polymorphisms (SNPs) and provides reference population data for several published panels of individual identification SNPs (IISNPs) and several published panels of ancestry inference SNPs (AISNPs). For each of the various marker panels with reference population data, FROG-kb calculates random match probabilities (RMP) and relative likelihoods of ancestry for a user-entered genotype profile (either completely or partially specified). Example genotype profiles are available and the User's Manual presents interpretation guidelines for the calculations. The extensive documentation along with ongoing updates makes FROG-kb a comprehensive tool in facilitating use of SNPs in forensic practice and education. An overview of the new FROG-kb with examples and material explaining the results of its use are presented here.

Detection and quantification of codeine-6-glucuronide, hydromorphone-3-glucuronide, oxymorphone-3-glucuronide, morphine 3-glucuronide and morphine-6-glucuronide in human hair from opioid users by LC-MS-MS.

Current hair testing methods that rely solely on quantification of parent drug compounds are unable to definitively distinguish between drug use and external contamination. One possible solution to this problem is to confirm the presence of unique drug metabolites that cannot be present through contamination, such as phase II glucuronide conjugates. This work demonstrates for the first time that codeine-6-glucuronide, hydromorphone-3-glucuronide, oxymorphone-3-glucuronide, morphine-3-glucuronide and morphine-6-glucuronide are present at sufficient concentrations to be quantifiable in hair of opioid users and that their concentrations generally increase as the concentrations of the corresponding parent compounds increase. Here, we present a validated liquid chromatography tandem mass spectrometry method to quantify codeine-6-glucuronide, dihydrocodeine-6-glucuronide, hydromorphone-3-glucuronide, morphine-3-glucuronide, morphine-6-glucuronide, oxymorphone-3-glucuronide, codeine, dihydrocodeine, dihydromorphine, hydrocodone, hydromorphone, morphine, oxycodone, oxymorphone and 6-acetylmorphine in human hair. The method was used to analyze 46 human hair samples from known drug users that were confirmed positive for opioids by an independent laboratory. Glucuronide concentrations in samples positive for parent analytes ranged from ~1 to 25 pg/mg, and most samples had glucuronide concentrations in the range of ~1 to 5 pg/mg. Relative to the parent concentrations, the average concentrations of the four detected glucuronides were as follows: codeine-6-glucuronide, 2.33%; hydromorphone-3-glucuronide, 0.94%; oxymorphone-3-glucuronide, 0.77%; morphine 3-glucuronide, 0.59%; and morphine-6-glucuronide, 0.93%.

Patterns of Marijuana Use in a 6-Month Pain Management Sample in the United States.

This study is a 6-month retrospective analysis of urine drug testing (UDT) data from a pain management population among specimens with clinician-ordered marijuana testing (N = 194 809). Descriptive statistics about the specimen positivity of clinician-ordered marijuana UDT are provided as well as other drug positivity. Specimens from men and adults aged 18 to 34 years had the highest prevalence rates of marijuana positivity. The prevalence of past-month marijuana use among a comparative national population was lower than the prevalence of positive marijuana tests in the UDT specimens by all characteristics. Among the specimens tested for illicit drugs and marijuana, 4.0% were positive for amphetamine, 2.8% were positive for cocaine, and 0.9% were positive for heroin. The most common prescription drugs listed were opioids (64.7%), benzodiazepines (20.5%), and antidepressants (19.9%). In sum, the findings reflect previous research showing high rates of marijuana use, illicit drug use, and prescription drug use in a pain management population.

WITHDRAWN: Intermittent catheterisation for long-term bladder management.

BACKGROUND: Intermittent catheterisation is a commonly recommended procedure for people with incomplete bladder emptying. There are now several designs of intermittent catheter (e.g. different lengths, 'ready to use' presentation) with different materials (e.g. PVC-free) and coatings (e.g. hydrophilic). The most frequent complication of intermittent catheterisation is urinary tract infection (UTI), but satisfaction, preference and ease of use are also important to users. It is unclear which catheter designs, techniques or strategies affect the incidence of UTI, which are preferable to users and which are most cost effective. OBJECTIVES: To compare one type of catheter design versus another, one type of catheter material versus another, aseptic catheterisation technique versus clean technique, single-use (sterile) catheters versus multiple-use (clean) catheters, self-catheterisation versus catheterisation by others and any other strategies designed to reduce UTI and other complications or improve user-reported outcomes (user satisfaction, preference, ease of use) and cost effectiveness in adults and children using intermittent catheterisation for incomplete bladder emptying. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE in process, and handsearching of journals and conference proceedings (searched 30 September 2013), the reference lists of relevant articles and conference proceedings, and we attempted to contact other investigators for unpublished data or for clarification. SELECTION CRITERIA: Randomised controlled trials (RCTs) or randomised cross-over trials comparing at least two different catheter designs, catheterisation techniques or strategies. DATA COLLECTION AND ANALYSIS: Two review authors assessed the methodological quality of trials and abstracted data. For dichotomous variables, risk ratios and 95% confidence intervals were derived for each outcome where possible. For continuous variables, mean differences and 95% confidence intervals were calculated for each outcome. Because of trial heterogeneity, it was not always possible to combine data to give an overall estimate of treatment effect. MAIN RESULTS: Thirty-one trials met the inclusion criteria, including 13 RCTs and 18 cross-over trials. Most were small (less than 60 participants completed), although five trials had more than 100 participants. There was considerable variation in length of follow-up and definitions of UTI. Participant dropout was a problem for several trials, particularly where there was long-term follow-up to measure incidence of UTI. Fifteen trials were more than 10 years old and focused mainly on comparing different catheterisation techniques (e.g. single versus multiple-use) on clinical outcomes whereas, several more recent trials have focused on comparing different types of catheter designs or materials, especially coatings, and user preference. It was not possible to combine data from some trials owing to variations in the catheters tested and in particular the catheter coatings. Where there were data, confidence intervals around estimates were wide and hence clinically important differences in UTI and other outcomes could neither be identified nor reliably ruled out. No study assessed cost-effectiveness. AUTHORS' CONCLUSIONS: Despite a total of 31 trials, there is still no convincing evidence that the incidence of UTI is affected by use of aseptic or clean technique, coated or uncoated catheters, single (sterile) or multiple-use (clean) catheters, self-catheterisation or catheterisation by others, or by any other strategy. Results from user-reported outcomes varied. The current research evidence is weak and design issues are significant. More well-designed trials are strongly recommended. Such trials should include analysis of cost-effectiveness because there are likely to be substantial differences associated with the use of different catheter designs, catheterisation techniques and strategies.

Identification of Eight Synthetic Cannabinoids, Including 5F-AKB48 in Seized Herbal Products Using DART-TOF-MS and LC-QTOF-MS as Nontargeted Screening Methods.

Synthetic cannabinoids are sprayed onto plant material and smoked for their marijuana-like effects. Clandestine manufacturers modify synthetic cannabinoid structures by creating closely related analogs. Forensic laboratories are tasked with detection of these analog compounds, but targeted analytical methods are often thwarted by the structural modifications. Here, direct analysis in real time coupled to accurate mass time-of-flight mass spectrometry (DART-TOF-MS) in combination with liquid chromatography quadruple time-of-flight mass spectrometry (LC-QTOF-MS) are presented as a screening and nontargeted confirmation method, respectively. Methanol extracts of herbal material were run using both methods. Spectral data from four different herbal products were evaluated by comparing fragmentation pattern, accurate mass and retention time to available reference standards. JWH-018, JWH-019, AM2201, JWH-122, 5F-AKB48, AKB48-N-(4-pentenyl) analog, UR144, and XLR11 were identified in the products. Results demonstrate that DART-TOF-MS affords a useful approach for rapid screening of herbal products for the presence and identification of synthetic cannabinoids.

Evaluation of first generation synthetic cannabinoids on binding at non-cannabinoid receptors and in a battery of in vivo assays in mice.

Anecdotal reports suggest that abused synthetic cannabinoids produce cannabis-like "highs," but some of their effects may also differ from traditional cannabinoids such as Δ(9)-tetrahydrocannabinol (THC). This study examined the binding affinities of first-generation indole-derived synthetic cannabinoids at cannabinoid and noncannabinoid receptors and their effects in a functional observational battery (FOB) and drug discrimination in mice. All seven compounds, except JWH-391, had favorable affinity (≤159 nM) for both cannabinoid receptors. In contrast, binding at noncannabinoid receptors was absent or weak. In the FOB, THC and the six active compounds disrupted behaviors in CNS activation and muscle tone/equilibrium domains. Unlike THC, however, synthetic cannabinoids impaired behavior across a wider dose and domain range, producing autonomic effects and signs of CNS excitability and sensorimotor reactivity. In addition, mice acquired JWH-018 discrimination, and THC and JWH-073 produced full substitution whereas the 5-HT2B antagonist mianserin did not substitute in mice trained to discriminate JWH-018 or THC. Urinary metabolite analysis showed that the compounds were extensively metabolized, with metabolites that could contribute to their in vivo effects. Together, these results show that, while first-generation synthetic cannabinoids shared some effects that were similar to those of THC, they also possessed effects that differed from traditional cannabinoids. The high nanomolar (or absent) affinities of these compounds at receptors for most major neurotransmitters suggests that these divergent effects may be related to the greater potencies and/or efficacies at CB1 receptors; however, action(s) at noncannabinoid receptors yet to be assessed or via different signaling pathways cannot be ruled out.

Securement of the Indwelling Urinary Catheter: A Prevalence Study.

PURPOSE: The aims of this study were 4-fold: (1) to examine the proportion of indwelling urinary catheters that were secured in an acute care setting; (2) to determine the proportion of secured catheters that were secured correctly; (3) to examine the association of catheter securement with type of unit, age, sex, and location of insertion; and (4) to determine the proportion of units with catheter securement products available on the unit. DESIGN: Descriptive prevalence study. SUBJECTS AND SETTING: All medical and surgical units (n = 21) were surveyed for inpatients with indwelling urinary catheters in 1 urban tertiary care hospital in Western Canada. Critical care and pediatric units were excluded. METHODS: During a 6-hour period, 6 RNs data collectors recorded presence and accuracy of catheter securement, area where the participant was catheterized, and availability of securement products on unit. Data were collected using a data form designed for the study. RESULTS: Seventy-two of 370 inpatients had indwelling catheters on the day of the study. Of these, 61% (44/72) participated. The overall prevalence of catheter securement was 18% (8/44). Seven of the 8 secured catheters were secured correctly. The primary method of securement was a commercial adhesive device (6/8; 75%). Securement products were stocked on 47% of medicine units and 92% of surgical units. CONCLUSION: Findings are consistent with other studies and indicate that catheter securement practices are inadequate despite several guidelines published on catheter care.

AB-CHMINACA, AB-PINACA, and FUBIMINA: Affinity and Potency of Novel Synthetic Cannabinoids in Producing Δ9-Tetrahydrocannabinol-Like Effects in Mice.

Diversion of synthetic cannabinoids for abuse began in the early 2000s. Despite legislation banning compounds currently on the drug market, illicit manufacturers continue to release new compounds for recreational use. This study examined new synthetic cannabinoids, AB-CHMINACA (N-[1-amino-3-methyl-oxobutan-2-yl]-1-[cyclohexylmethyl]-1H-indazole-3-carboxamide), AB-PINACA [N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide], and FUBIMINA [(1-(5-fluoropentyl)-1H-benzo[d]imadazol-2-yl)(naphthalen-1-yl)methanone], with the hypothesis that these compounds, like those before them, would be highly susceptible to abuse. Cannabinoids were examined in vitro for binding and activation of CB1 receptors, and in vivo for pharmacological effects in mice and in Δ(9)-tetrahydrocannabinol (Δ(9)-THC) discrimination. AB-CHMINACA, AB-PINACA, and FUBIMINA bound to and activated CB1 and CB2 receptors, and produced locomotor suppression, antinociception, hypothermia, and catalepsy. Furthermore, these compounds, along with JWH-018 [1-pentyl-3-(1-naphthoyl)indole], CP47,497 [rel-5-(1,1-dimethylheptyl)-2-[(1R,3S)-3-hydroxycyclohexyl]-phenol], and WIN55,212-2 ([(3R)-2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenyl-methanone, monomethanesulfonate), substituted for Δ(9)-THC in Δ(9)-THC discrimination. Rank order of potency correlated with CB1 receptor-binding affinity, and all three compounds were full agonists in [(35)S]GTPγS binding, as compared with the partial agonist Δ(9)-THC. Indeed, AB-CHMINACA and AB-PINACA exhibited higher efficacy than most known full agonists of the CB1 receptor. Preliminary analysis of urinary metabolites of the compounds revealed the expected hydroxylation. AB-PINACA and AB-CHMINACA are of potential interest as research tools due to their unique chemical structures and high CB1 receptor efficacies. Further studies on these chemicals are likely to include research on understanding cannabinoid receptors and other components of the endocannabinoid system that underlie the abuse of synthetic cannabinoids.

Intermittent catheterisation for long-term bladder management (abridged cochrane review).

AIMS: To review the evidence on strategies to reduce UTI, other complications or improve satisfaction in intermittent catheter (IC) users by comparing: (1) one catheter design, material or technique versus another; (2) sterile technique versus clean; or (3) single-use (sterile) or multiple-use (clean) catheters. METHODS: We searched Cochrane Incontinence Group Specialised Trials Register, MEDLINE, EMBASE, CINAHL, ERIC, reference lists, and conference proceedings to November 2013. We contacted other investigators for unpublished data or clarification. Trial screening, assessment and data abstraction were all in accordance with the Cochrane handbook. RESULTS: Thirty one trials (13 RCTs and 18 randomized crossover trials), addressed the inclusion criteria comparing method or design and UTI/bacteriuria, other complications or participant assessed outcomes. Studies varied widely in follow-up, UTI definition and attrition; in some, data could not be combined. Where there were data, confidence intervals were wide and hence clinically important differences could neither be reliably identified nor ruled out. CONCLUSIONS: Current research evidence is weak and design issues are significant. It has not yet been established whether incidence of UTI, other complications such as haematuria, or user satisfaction are affected by sterile or clean technique, coated or uncoated catheters, single or multiple-use catheters or by any other strategy. For people using IC, choice of catheter will depend on personal preference, cost, portability, and ease of use. Individuals should discuss the catheter options with their healthcare practitioner. Cost-effectiveness analysis and use of the standard definition of UTI are essential in any proposed clinical trial.

Randomized Crossover Trial of Single Use Hydrophilic Coated vs Multiple Use Polyvinylchloride Catheters for Intermittent Catheterization to Determine Incidence of Urinary Infection.

PURPOSE: Urinary tract infection is a key issue for long-term intermittent catheterization users. Various catheter designs and methods have evolved to decrease the risk but the evidence remains unclear regarding whether product type improves outcomes. We determined whether single use hydrophilic coated catheters reduced urinary tract infections compared to multiple use polyvinylchloride catheters for children with neurogenic bladder due to spina bifida. MATERIALS AND METHODS: This was a randomized crossover 4-center trial with 2 treatment periods of 24 weeks each, consisting of single use hydrophilic coated catheter and multiple use polyvinylchloride catheter (washed with soap and water, and air dried after each use). Each week participants recorded symptoms and urine results (Multistix® 8SG reagent strip). Primary outcome was person-weeks of urinary tract infection, defined as positive leukocytes plus fever, flank pain, increased incontinence, malaise, or cloudy or odorous urine requiring antibiotic treatment. Individuals were included if they were a child or young adult with spina bifida and used intermittent catheterization as the primary method of bladder emptying. RESULTS: Calculated sample size was 97. More than 120 patients were screened, of whom 66 were randomized and 45 completed both trial arms. Mean age was 10.6 years. Of the patients 21 were male and 24 were female. Mean ± SD person-weeks of urinary tract infection was 3.42 ± 4.67 in the single use hydrophilic coated catheter group and 2.20 ± 3.23 in the multiple use polyvinylchloride catheter group (p <0.001). There were no statistical differences in weeks of febrile urinary tract infection or antibiotic use. CONCLUSIONS: Results are consistent with the Cochrane Review in that single use hydrophilic coated catheters may not decrease the incidence of symptomatic urinary tract infection in community dwelling chronic intermittent catheterization users when compared to clean multiple use polyvinylchloride catheters.

A trial of devices for urinary incontinence after treatment for prostate cancer.

OBJECTIVE: To compare the performance of three continence management devices and absorbent pads used by men with persistent urinary incontinence (>1 year) after treatment for prostate cancer. PATIENTS AND METHODS: Randomised, controlled trial of 56 men with 1-year follow-up. Three devices were tested for 3 weeks each: sheath drainage system, body-worn urinal (BWU) and penile clamp. Device and pad performance were assessed. Quality of life (QoL) was measured at baseline and follow-up with the King's Health Questionnaire. Stated (intended use) and revealed (actual use) preference for products were assessed. Value-for-money was gathered. RESULTS: Substantial and significant differences in performance were found. The sheath was rated as 'good' for extended use (e.g. golf and travel) when pad changing is difficult; for keeping skin dry, not leaking, not smelling and convenient for storage and travel. The BWU was generally rated worse than the sheath and was mainly used for similar activities but by men who could not use a sheath (e.g. retracted penis) and was not good for seated activities. The clamp was good for short vigorous activities like swimming/exercise; it was the most secure, least likely to leak, most discreet but almost all men described it as uncomfortable or painful. The pads were good for everyday activities and best for night-time use; most easy to use, comfortable when dry but most likely to leak and most uncomfortable when wet. There was a preference for having a mixture of products to meet daytime needs; around two-thirds of men were using a combination of pads and devices after testing compared with baseline. CONCLUSIONS: This is the first trial to systematically compare different continence management devices for men. Pads and devices have different strengths, which make them particularly suited to certain circumstances and activities. Most men prefer to use pads at night but would choose a mixture of pads and devices during the day. Device limitations were important but may be overcome by better design.

Effects of α-pyrrolidinopentiophenone and 4-methyl-N-ethylcathinone, two synthetic cathinones commonly found in second-generation "bath salts," on intracranial self-stimulation thresholds in rats.

BACKGROUND: Use of synthetic cathinones, which are designer stimulants found in "bath salts," has increased dramatically in recent years. Following governmental bans of methylenedioxypyrovalerone, mephedrone, and methylone, a second generation of synthetic cathinones with unknown abuse liability has emerged as replacements. METHODS: Using a discrete trials current intensity threshold intracranial self-stimulation procedure, the present study assessed the effects of 2 common second-generation synthetic cathinones, α-pyrrolidinopentiophenone (0.1-5 mg/kg) and 4-methyl-N-ethcathinone (1-100 mg/kg) on brain reward function. Methamphetamine (0.1-3 mg/kg) was also tested for comparison purposes. RESULTS: Results revealed both α-pyrrolidinopentiophenone and 4-methyl-N-ethcathinone produced significant intracranial self-stimulation threshold reductions similar to that of methamphetamine. α-Pyrrolidinopentiophenone (1 mg/kg) produced a significant maximal reduction in intracranial self-stimulation thresholds (~19%) most similar to maximal reductions produced by methamphetamine (1 mg/kg, ~20%). Maximal reductions in intracranial self-stimulation thresholds produced by 4-methyl-N-ethcathinone were observed at 30 mg/kg (~15%) and were comparable with those observed with methamphetamine and α-pyrrolidinopentiophenone tested at the 0.3-mg/kg dose (~14%). Additional analysis of the ED50 values from log-transformed data revealed the rank order potency of these drugs as methamphetamine ≈ α-pyrrolidinopentiophenone>4-methyl-N-ethcathinone. CONCLUSIONS: These data suggest that the newer second-generation synthetic cathinones activate the brain reward circuitry and thus may possess a similar degree of abuse potential as prototypical illicit psychostimulants such as methamphetamine as well as the first generation synthetic cathinone methylenedioxypyrovalerone, as previously reported.

Evaluation of laser diode thermal desorption-tandem mass spectrometry (LDTD-MS-MS) in forensic toxicology.

Many forensic laboratories experience backlogs due to increased drug-related cases. Laser diode thermal desorption (LDTD) has demonstrated its applicability in other scientific areas by providing data comparable with instrumentation, such as liquid chromatography-tandem mass spectrometry, in less time. LDTD-MS-MS was used to validate 48 compounds in drug-free human urine and blood for screening or quantitative analysis. Carryover, interference, limit of detection, limit of quantitation, matrix effect, linearity, precision and accuracy and stability were evaluated. Quantitative analysis indicated that LDTD-MS-MS produced precise and accurate results with the average overall within-run precision in urine and blood represented by a %CV <14.0 and <7.0, respectively. The accuracy for all drugs in urine ranged from 88.9 to 104.5% and 91.9 to 107.1% in blood. Overall, LDTD has the potential for use in forensic toxicology but before it can be successfully implemented that there are some challenges that must be addressed. Although the advantages of the LDTD system include minimal maintenance and rapid analysis (∼10 s per sample) which makes it ideal for high-throughput forensic laboratories, a major disadvantage is its inability or difficulty analyzing isomers and isobars due to the lack of chromatography without the use of high-resolution MS; therefore, it would be best implemented as a screening technique.