The Elusive Truth of Cannabinoids for Rheumatic Pain.

PURPOSE OF REVIEW: Medical cannabis (MC) has entered mainstream medicine by a unique route. Regulatory acceptance as a medical product in many jurisdictions has bypassed the traditional evidence-based pathway required for therapies. Easier access to MC, especially related to recreational legalization of cannabis, has led to widespread use by patients for symptom relief of a variety of medical conditions and often without medical oversight. Musculoskeletal pain remains the most common reason for MC use. This review examines real-world issues pertaining to MC and offers some guidance for clinical care of patients with rheumatic diseases being treated with MC. RECENT FINDINGS: Controlled clinical studies of cannabis products in patients with rheumatic diseases have been small and tested a range of compounds, routes of administration, and clinical populations, limiting our ability to generate conclusions on MC's effectiveness in this population. Observational cohort studies and surveys suggest that use of MC and related products in patients with rheumatic diseases improves pain and associated symptoms but is commonly accompanied by mild to moderate side effects. Conflicting evidence contributes to practitioner and patient uncertainty regarding the use of MC for rheumatic disease-related pain. Despite promising preclinical and observational evidence that MC and cannabis-derived compounds are useful in the management of rheumatic disease-related pain, there remains limited high-quality clinical evidence to substantiate these findings. There are a significant number of clinical trials on this topic currently planned or underway, however, suggesting the next decade may yield more clarity. Nevertheless, given that many people with rheumatic diseases are using cannabis products, healthcare professionals must remain apprised of the evidence pertaining to cannabinoids, communicate such evidence to patients in a meaningful way that is free from personal bias and stigma, and maintain strong collaborative clinical care pertaining to MC.

A Prospective Cohort Study of Acute Pain and In-Hospital Opioid Consumption After Cardiac Surgery: Associations With Psychological and Medical Factors and Chronic Postsurgical Pain.

BACKGROUND: Understanding the association of acute pain intensity and opioid consumption after cardiac surgery with chronic postsurgical pain (CPSP) can facilitate implementation of personalized prevention measures to improve outcomes. The objectives were to (1) examine acute pain intensity and daily mg morphine equivalent dose (MME/day) trajectories after cardiac surgery, (2) identify factors associated with pain intensity and opioid consumption trajectories, and (3) assess whether pain intensity and opioid consumption trajectories are risk factors for CPSP. METHODS: Prospective observational cohort study design conducted between August 2012 and June 2020 with 1-year follow-up. A total of 1115 adults undergoing cardiac surgery were recruited from the preoperative clinic. Of the 959 participants included in the analyses, 573 completed the 1-year follow-up. Main outcomes were pain intensity scores and MME/day consumption over the first 6 postoperative days (PODs) analyzed using latent growth mixture modeling (GMM). Secondary outcome was 12-month CPSP status. RESULTS: Participants were mostly male (76%), with a mean age of 61 ± 13 years. Three distinct linear acute postoperative pain intensity trajectories were identified: "initially moderate pain intensity remaining moderate" (n = 62), "initially mild pain intensity remaining mild" (n = 221), and "initially moderate pain intensity decreasing to mild" (n = 251). Age, sex, emotional distress in response to bodily sensations, and sensitivity to pain traumatization were significantly associated with pain intensity trajectories. Three distinct opioid consumption trajectories were identified on the log MME/day: "initially high level of MME/day gradually decreasing" (n = 89), "initially low level of MME/day remaining low" (n = 108), and "initially moderate level of MME/day decreasing to low" (n = 329). Age and emotional distress in response to bodily sensations were associated with trajectory membership. Individuals in the "initially mild pain intensity remaining mild" trajectory were less likely than those in the "initially moderate pain intensity remaining moderate" trajectory to report CPSP (odds ratio [95% confidence interval, CI], 0.23 [0.06-0.88]). No significant associations were observed between opioid consumption trajectory membership and CPSP status (odds ratio [95% CI], 0.84 [0.28-2.54] and 0.95 [0.22-4.13]). CONCLUSIONS: Those with moderate pain intensity right after surgery are more likely to develop CPSP suggesting that those patients should be flagged early on in their postoperative recovery to attempt to alter their trajectory and prevent CPSP. Emotional distress in response to bodily sensations is the only consistent modifiable factor associated with both pain and opioid trajectories.

Postoperative anemia in cardiac surgery patients: a narrative review.

PURPOSE: Anemia reduces the blood's ability to carry and deliver oxygen. Following cardiac surgery, anemia is very common and affects up to 90% of patients. Nevertheless, there is a paucity of data examining the prognostic value of postoperative anemia. In this narrative review, we present findings from the relevant literature on postoperative anemia in cardiac surgery patients, focusing on the incidence, risk factors, and prognostic value of postoperative anemia. We also explore the potential utility of postoperative anemia as a therapeutic target to improve clinical outcomes. SOURCE: We conducted a targeted search of MEDLINE, Embase, and the Cochrane Database of Systematic Reviews up to September 2022, using a combination of search terms including postoperative (post-operative), perioperative (peri-operative), anemia (anaemia), and cardiac surgery. PRINCIPAL FINDINGS: The reported incidence of postoperative anemia varied from 29% to 94% across the studies, likely because of variations in patient inclusion criteria and classification of postoperative anemia. Nonetheless, the weight of the evidence suggests that postoperative anemia is common and is an independent risk factor for adverse postoperative outcomes such as acute kidney injury, stroke, mortality, and functional outcomes. CONCLUSIONS: In cardiac surgery patients, postoperative anemia is a common and prognostically important risk factor for postoperative morbidity and mortality. Nevertheless, there is a lack of data on whether active management of postoperative anemia is feasible or effective in improving patient outcomes.

RéSUMé: OBJECTIF: L'anémie réduit la capacité du sang à transporter et à fournir de l'oxygène. Suite à une chirurgie cardiaque, l'anémie est très fréquente et touche jusqu'à 90 % des patient·es. Néanmoins, il existe peu de données examinant la valeur pronostique de l'anémie postopératoire. Dans ce compte rendu narratif, nous présentons les résultats de la littérature pertinente sur l'anémie postopératoire chez les patient·es ayant bénéficié d'une chirurgie cardiaque, en mettant l'accent sur l'incidence, les facteurs de risque et la valeur pronostique de l'anémie postopératoire chez les personnes ayant bénéficié d'une chirurgie cardiaque. Nous explorons également l'utilité potentielle de l'anémie postopératoire en tant que cible thérapeutique pour améliorer les devenirs cliniques. SOURCES: Nous avons réalisé une recherche ciblée dans MEDLINE, Embase et la base de données des revues systématiques Cochrane jusqu'en septembre 2022, en utilisant une combinaison de termes de recherche, notamment postopératoire (postoperative/post-operative), périopératoire (perioperative/peri-operative), anémie (anemia/anaemia) et chirurgie cardiaque (cardiac surgery). CONSTATATIONS PRINCIPALES: L'incidence rapportée de l'anémie postopératoire variait de 29 % à 94 % d'une étude à l'autre, probablement en raison des variations dans les critères d'inclusion des patient·es et la classification de l'anémie postopératoire. Néanmoins, le poids de la preuve suggère que l'anémie postopératoire est courante et constitue un facteur de risque indépendant pour les devenirs postopératoires indésirables tels que l'insuffisance rénale aiguë, les accidents vasculaires cérébraux, la mortalité et les devenirs fonctionnels. CONCLUSION: Chez la patientèle en chirurgie cardiaque, l'anémie postopératoire est un facteur de risque commun et pronostiquement important de morbidité et de mortalité postopératoires. Néanmoins, il y a un manque de données sur la faisabilité ou l'efficacité de la prise en charge active de l'anémie postopératoire pour améliorer les devenirs des patient·es.

Australian rural service learning student placements: a national survey.

This preliminary national study is the first of its kind to investigate how service learning placements are implemented in real world settings in rural Australia and what factors enable or hinder their implementation. An anonymous survey was distributed to 17 University Departments of Rural Health (UDRH) in Australia. Numerical data were analysed descriptively. Textual data were analysed using a hybrid content analysis approach. Thirty seven respondents provided data representing 12 UDRHs. Responding UDRHs reported facilitating service learning programs, with experience in this context ranging from 3 months to 21 years. Service learning placements predominantly occurred in schools and aged care facilities. Occupational therapy, physiotherapy, and speech pathology were the most frequently involved professions in service learning. Enablers and barriers identified were categorised into: People, Partnerships, and Place and Space. This national-scale study provides a springboard for more in-depth investigation and implementation research focused on development of a conceptual model to support service learning across rural and remote Australia.

An integrative review of the impact of allied health student placements on current staff's knowledge and procedural skills in acute and primary care settings.

BACKGROUND: Staff shortages limit access to health services. The bidirectional benefits of allied health clinical placements are understood in the domains of student learning, health service delivery, and future workforce development. Still, the benefits to current workforce outcomes remain unknown. This review provides insights into the effects of allied health student placements in acute and primary care settings, particularly on healthcare staff's knowledge and procedural skills. METHODS: This search was based on the integrative review process established by Whittemore and Knafl in 2005. In October 2023, the first author (MH) searched five major electronic databases: Medline-EBSCO, PubMed, CINAHL, Embase, and Scopus. The CLUSTER model was used to track additional references. The first three authors (MH, SM, and SC) were involved in screening, quality appraisal, and synthesis of the studies. Data were thematically synthesised and analysed. RESULTS: MeSH headings and keywords were used in key search areas: health education, health professional training, clinical placements, and allied health professions. The systematic search yielded 12 papers on allied health student placements across various healthcare settings in rural and metropolitan areas, with no high-quality methodologies measuring student placements' impact on staff knowledge and skills. Four main themes were identified from the analysis: meaningful student integration in service delivery, targeted educational support to healthcare staff, development of staff procedural skills and confidence, and the mechanisms of why student placements work in this aspect. CONCLUSIONS: This review suggests that offering allied health student placement could be a promising approach to supporting rural healthcare staff in performing patient assessments and treatments proficiently and collaboratively. However, this requires further investigation to confirm.

Use of injections for chronic pain from 2010 to 2019 in Ontario, Canada.

PURPOSE: The management of chronic pain often involves interventional procedures such as injections. Nevertheless, there have been concerns raised regarding the frequency with which these injections are being performed. We conducted a descriptive study to examine trends in the use of pain injections over a ten-year time period in Ontario, Canada. METHODS: We used provincial administrative data to conduct a retrospective observational study of the most common pain injections performed from 2010 to 2019 in Ontario. We determined the frequency of pain injections and their associated physician billings from physician billing data. RESULTS: A total of 18,050,058 pain injections were included in this study with an associated total cost of CAD 865,431,605. There was a threefold increase in the number of blocks performed annually and associated costs, rising from 1,009,324 blocks (CAD 50,026,678) in 2010 to 3,198,679 blocks (CAD 156,809,081) in 2019. The majority of injections were performed by general practioners (70.8%), followed by anesthesiologists (8.3%). CONCLUSION: This descriptive study revealed a rapid increase in the frequency of pain injections performed in Ontario from 2010 to 2019. Given the associated costs and potential risks, this warrants further investigation to ensure that these interventions are being administered appropriately.

RéSUMé: OBJECTIF: La prise en charge de la douleur chronique implique souvent des procédures interventionnelles telles que des injections. Néanmoins, des préoccupations ont été soulevées quant à la fréquence à laquelle ces injections sont administrées. Nous avons réalisé une étude descriptive pour examiner les tendances dans l'utilisation d'injections pour soulager la douleur sur une période de dix ans en Ontario, au Canada. MéTHODE: Nous avons utilisé les données administratives provinciales pour réaliser une étude observationnelle rétrospective des injections pour soulager la douleur les plus courantes effectuées de 2010 à 2019 en Ontario. Nous avons déterminé la fréquence des injections pour soulager la douleur et les facturations des médecins associées à partir des données de facturation des médecins. RéSULTATS: Au total, 18 050 058 injections pour soulager la douleur ont été incluses dans cette étude, avec un coût total associé de 865 431 605 CAD. Le nombre de blocs exécutés chaque année et les coûts associés ont triplé, passant de 1 009 324 blocs (50 026 678 CAD) en 2010 à 3 198 679 blocs (156 809 081 CAD) en 2019. La majorité des injections ont été administrées par des médecins généralistes (70,8 %), suivis par des anesthésiologistes (8,3 %). CONCLUSION: Cette étude descriptive a révélé une augmentation rapide de la fréquence des injections pour soulager la douleur et administrées en Ontario de 2010 à 2019. Compte tenu des coûts associés et des risques potentiels, cela justifie une enquête plus approfondie pour s'assurer que ces interventions sont administrées de manière appropriée.

Interventional pain blocks in Ontario: a population-based cross-sectional study on 2019 procedural volumes, clustering, and physician billings.

PURPOSE: Multidisciplinary chronic pain management includes pharmacologic, psychological, and interventional strategies. In Canada, the use of interventional pain blocks (PBs) has increased in recent years. We sought to determine the distribution and clustering of PBs among physicians in Ontario, and to examine differences in the patient and physician characteristics by volume of PBs administered. METHODS: We conducted a population-based cross-sectional study of PBs administered for chronic pain to Ontario residents between 1 January and 31 December 2019. Our primary outcome was the total number of PBs administered in an outpatient setting for chronic pain by eligible physicians. We used Lorenz curves, overall and stratified by PB type and physician specialty, to examine clustering of PBs among physicians, and compared patient and physician characteristics using standardized differences. RESULTS: Among physicians who provided PBs, provision was highly clustered, with the top 1% of physicians providing 39% of blocks. In these high-volume PB providers, the majority of whom were general practitioners (88.4%), PBs made up the vast majority (median [interquartile range (IQR)], 87% [84-89]) of their billings, with the majority of the patients in their practices (63.0%) receiving at least one PB in 2019. Patients who received a PB from a high-volume provider had a higher annual frequency of visit for PBs (median [IQR], 10 [3-23]) and number of PBs administered per visit (median [IQR], 5 [4-6]). CONCLUSION: Pain block administration is highly clustered in Ontario, with many patients receiving PBs in ways that are not supported by best evidence. Further research is required to determine whether the Ontario fee-for-service model of billing has created a suboptimal use of these health care resources.

RéSUMé: OBJECTIF: La prise en charge multidisciplinaire de la douleur chronique comprend des stratégies pharmacologiques, psychologiques et interventionnelles. Au Canada, l'utilisation de blocs interventionnels pour la douleur (PB pour 'pain block') a augmenté au cours des dernières années. Nous avons cherché à déterminer la répartition et le regroupement des PB parmi les médecins en Ontario, et à examiner les différences dans les caractéristiques de la patientèle et des médecins selon le volume de blocs administrés. MéTHODE: Nous avons mené une étude transversale basée sur la population des PB administrés pour traiter la douleur chronique aux personnes résidant en Ontario entre le 1er janvier et le 31 décembre 2019. Notre critère d'évaluation principal était le nombre total de blocs pour la douleur administrés en ambulatoire pour la douleur chronique par des médecins éligibles. Nous avons utilisé les courbes de Lorenz, globalement et stratifiées par type de blocs pour la douleur et par spécialité médicale, pour examiner le regroupement des PB parmi les médecins, et comparé les caractéristiques de la patientèle et des médecins en utilisant des différences standardisées. RéSULTATS: Parmi les médecins qui réalisaient des PB, l'offre était fortement regroupée, le 1 % supérieur des médecins réalisant 39 % des blocs. Parmi ces médecins réalisant un volume élevé de PB, dont la majorité étaient des médecins généralistes (88,4 %), les PB représentaient la grande majorité ([écart interquartile (ÉIQ)] médian, 87 % [84-89]) de leur facturation, la majorité (63,0 %) des patient·es de leur cabinet recevant au moins un bloc pour la douleur en 2019. Les patient·es qui ont reçu un PB d'un prestataire à volume élevé avaient une fréquence annuelle de visite plus élevée pour les PB (médiane [ÉIQ], 10 [3-23]) et un nombre plus élevé de PB administrés par visite (médiane [ÉIQ], 5 [4-6]). CONCLUSION: L'administration de blocs pour la douleur est fortement concentrée en Ontario, bon nombre de patient·es recevant des PB d'une manière qui n'est pas appuyée par les meilleures données probantes. D'autres recherches sont nécessaires pour déterminer si le modèle de facturation à l'acte de l'Ontario a créé une utilisation sous-optimale de ces ressources en soins de santé.

Trichodermin Induces G0/G1 Cell Cycle Arrest by Inhibiting c-Myc in Ovarian Cancer Cells and Tumor Xenograft-Bearing Mice.

Ovarian cancer is a fatal gynecological cancer because of a lack of early diagnosis, which often relapses as chemoresistant. Trichodermin, a trichothecene first isolated from Trichoderma viride, is an inhibitor of eukaryotic protein synthesis. However, whether trichodermin is able to suppress ovarian cancer or not was unclear. In this study, trichodermin (0.5 µM or greater) significantly decreased the proliferation of two ovarian cancer cell lines A2780/CP70 and OVCAR-3. Normal ovarian IOSE 346 cells were much less susceptible to trichodermin than the cancer cell lines. Trichodermin predominantly inhibited ovarian cancer cells by inducing G0/G1 cell cycle arrest rather than apoptosis. Trichodermin decreased the expression of cyclin D1, CDK4, CDK2, retinoblastoma protein, Cdc25A, and c-Myc but showed little effect on the expression of p21Waf1/Cip1, p27Kip1, or p16Ink4a. c-Myc was a key target of trichodermin. Trichodermin regulated the expression of Cdc25A and its downstream proteins via c-Myc. Overexpression of c-Myc attenuated trichodermin's anti-ovarian cancer activity. In addition, trichodermin decelerated tumor growth in BALB/c nude mice, proving its effectiveness in vivo. These findings suggested that trichodermin has the potential to contribute to the treatment of ovarian cancer.

Anticancer Activity of Natural and Synthetic Capsaicin Analogs.

The nutritional compound capsaicin is the major spicy ingredient of chili peppers. Although traditionally associated with analgesic activity, recent studies have shown that capsaicin has profound antineoplastic effects in several types of human cancers. However, the applications of capsaicin as a clinically viable drug are limited by its unpleasant side effects, such as gastric irritation, stomach cramps, and burning sensation. This has led to extensive research focused on the identification and rational design of second-generation capsaicin analogs, which possess greater bioactivity than capsaicin. A majority of these natural capsaicinoids and synthetic capsaicin analogs have been studied for their pain-relieving activity. Only a few of these capsaicin analogs have been investigated for their anticancer activity in cell culture and animal models. The present review summarizes the current knowledge of the growth-inhibitory activity of natural capsaicinoids and synthetic capsaicin analogs. Future studies that examine the anticancer activity of a greater number of capsaicin analogs represent novel strategies in the treatment of human cancers.

Silencing HIF-1α induces TET2 expression and augments ascorbic acid induced 5-hydroxymethylation of DNA in human metastatic melanoma cells.

Expression and function of Ten-eleven translocation (TET) enzymes, which initiate DNA demethylation by catalyzing the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine (5 hmC) on methylated DNA, are frequently lost in malignant tissue. This ultimately results in lost expression of methylated tumor suppressor genes. Many malignancies, including melanoma, also aberrantly overexpress the oncogenic hypoxia inducible factor-1α (HIF-1α) transcription factor, however the association between HIF-1α and TET enzyme expression is largely uninvestigated. Interestingly, ascorbic acid, a critical cofactor for optimal TET enzyme function and normoxic regulation of HIF-1α protein stability, is frequently depleted in malignant tissue, and may further contribute to the malignant phenotype. In our studies, we found supplementation of WM9 human metastatic melanoma cells with ascorbic acid significantly increased 5 hmC content, which was abrogated by TET2 knockdown. Moreover, knockdown of HIF-1α increased TET2 gene and protein expression, and further augmented ascorbic acid-induced TET2 dependent 5-hydroxymethylation in both WM9 and T98G glioblastoma cells. Our data provides novel evidence that HIF-1α is involved in regulating TET expression and 5 hmC status of malignant cells. Furthermore, therapeutic intervention to inhibit HIF-1α in conjunction with adjuvant ascorbic acid may promote DNA demethylation and reexpression of critical tumor suppressor genes in malignant cells and warrants further investigation.

Outcome of Intensive Cognitive Behaviour Therapy in a Residential Setting for People with Severe Obsessive Compulsive Disorder: A Large Open Case Series.

BACKGROUND: There is little data to inform the treatment of severe obsessive compulsive disorder (OCD) in an inpatient or residential setting. AIMS: This paper aimed to: a) describe treatment outcomes at a residential unit over 11 years; b) investigate whether treatment was successful for a subset of severe treatment refractory residents; c) compare an intensive treatment programme to a "standard" treatment programme; and d) find predictors of self or early discharge from the unit. METHOD: We compared treatment outcomes for (i) a minimum 12-week treatment (hereafter "standard") programme versus a 2-week intensive programme and (ii) for severe treatment refractory cases on the standard programme. We identified 472 residents with OCD admitted to the Anxiety Disorders Residential Unit at the Bethlem Royal Hospital between 2001 and 2012. Outcomes were measured with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Obsessive Compulsive Inventory (OCI), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) obtained throughout treatment and up to one year after discharge. RESULTS: Although residents had very severe OCD on admission, sequential assessment with the Y-BOCS, OCI, BAI and BDI demonstrated that scores on all outcome measures significantly decreased from pre to posttreatment and were generally maintained at follow-up. There was no significant difference between those on the standard or the 2-week intensive programme. Sixty-nine per cent of residents with OCD made significant improvements, with at least a 25% reduction on the Y-BOCS. There were predictors of self or early discharge but none for outcome on the Y-BOCS. CONCLUSIONS: The data support the principle of stepped care for severe OCD.

Ascorbic acid and ascorbate-2-phosphate decrease HIF activity and malignant properties of human melanoma cells.

BACKGROUND: Hypoxia inducible factor-1 alpha (HIF-1α) is thought to play a role in melanoma carcinogenesis. Posttranslational regulation of HIF-1α is dependent on Prolyl hydroxylase (PHD 1-3) and Factor Inhibiting HIF (FIH) hydroxylase enzymes, which require ascorbic acid as a co-factor for optimal function. Depleted intra-tumoral ascorbic acid may thus play a role in the loss of HIF-1α regulation in melanoma. These studies assess the ability of ascorbic acid to reduce HIF-1α protein and transcriptional activity in metastatic melanoma and reduce its invasive potential. METHODS: HIF-1α protein was evaluated by western blot, while transcriptional activity was measured by HIF-1 HRE-luciferase reporter gene activity. Melanoma cells were treated with ascorbic acid (AA) and ascorbate 2-phosphate (A2P) to assess their ability to reduce HIF-1α accumulation and activity. siRNA was used to deplete cellular PHD2 in order to evaluate this effect on AA's ability to lower HIF-1α levels. A2P's effect on invasive activity was measured by the Matrigel invasion assay. Data was analyzed by One-way ANOVA with Tukey's multiple comparisons test, or Student-T test as appropriate, with p < .05 considered significant. RESULTS: Supplementation with both AA and A2P antagonized normoxic as well as cobalt chloride- and PHD inhibitor ethyl 3, 4-dihydroxybenzoate induced HIF-1α protein stabilization and transcriptional activity. Knockdown of the PHD2 isoform with siRNA did not impede the ability of AA to reduce normoxic HIF-1α protein. Additionally, reducing HIF-1α levels with A2P resulted in a significant reduction in the ability of the melanoma cells to invade through Matrigel. CONCLUSION: These studies suggest a positive role for AA in regulating HIF-1α in melanoma by demonstrating that supplementation with either AA, or its oxidation-resistant analog A2P, effectively reduces HIF-1α protein and transcriptional activity in metastatic melanoma cells. Our data, while supporting the function of AA as a necessary cofactor for PHD and likely FIH activity, also suggests a potential non-PHD/FIH role for AA in HIF-1α regulation by its continued ability to reduce HIF-1α in the presence of PHD inhibition. The use of the oxidation-resistant AA analog, A2P, to reduce the ability of HIF-1α to promote malignant progression in melanoma cells and enhance their response to therapy warrants further investigation.

Am I normal? A systematic review and construction of nomograms for flaccid and erect penis length and circumference in up to 15,521 men.

OBJECTIVE: To systematically review and create nomograms of flaccid and erect penile size measurements. METHODS: Study key eligibility criteria: measurement of penis size by a health professional using a standard procedure; a minimum of 50 participants per sample. EXCLUSION CRITERIA: samples with a congenital or acquired penile abnormality, previous surgery, complaint of small penis size or erectile dysfunction. Synthesis methods: calculation of a weighted mean and pooled standard deviation (SD) and simulation of 20,000 observations from the normal distribution to generate nomograms of penis size. RESULTS: Nomograms for flaccid pendulous [n = 10,704, mean (SD) 9.16 (1.57) cm] and stretched length [n = 14,160, mean (SD) 13.24 (1.89) cm], erect length [n = 692, mean (SD) 13.12 (1.66) cm], flaccid circumference [n = 9407, mean (SD) 9.31 (0.90) cm], and erect circumference [n = 381, mean (SD) 11.66 (1.10) cm] were constructed. Consistent and strongest significant correlation was between flaccid stretched or erect length and height, which ranged from r = 0.2 to 0.6. LIMITATIONS: relatively few erect measurements were conducted in a clinical setting and the greatest variability between studies was seen with flaccid stretched length. CONCLUSIONS: Penis size nomograms may be useful in clinical and therapeutic settings to counsel men and for academic research.

Penile Dysmorphic Disorder: Development of a Screening Scale.

Penile dysmorphic disorder (PDD) is shorthand for men diagnosed with body dysmorphic disorder, in whom the size or shape of the penis is their main, if not their exclusive, preoccupation causing significant shame or handicap. There are no specific measures for identifying men with PDD compared to men who are anxious about the size of their penis but do not have PDD. Such a measure might be helpful for treatment planning, reducing unrealistic expectations, and measuring outcome after any psychological or physical intervention. Our aim was, therefore, to validate a specific measure, termed the Cosmetic Procedure Screening Scale for PDD (COPS-P). Eighty-one male participants were divided into three groups: a PDD group (n = 21), a small penis anxiety group (n = 37), and a control group (n = 23). All participants completed the COPS-P as well as standardized measures of depression, anxiety, social phobia, body image, quality of life, and erectile function. Penis size was also measured. The final COPS-P was based on nine items. The scale had good internal reliability and significant convergent validity with measures of related constructs. It discriminated between the PDD group, the small penis anxiety group, and the control group. This is the first study to develop a scale able to discriminate between those with PDD and men anxious about their size who did not have PDD. Clinicians and researchers may use the scale as part of an assessment for men presenting with anxiety about penis size and as an audit or outcome measure after any intervention for this population.

Learning categories via rules and similarity: comparing adults and children.

Two experiments explored the different strategies used by children and adults when learning new perceptual categories. Participants were asked to learn a set of categories for which both a single-feature rule and overall similarity would allow for perfect performance. Other rules allowed for suboptimal performance. Transfer stimuli (Experiments 1 and 2) and single features (Experiment 2) were presented after training to help determine how the categories were learned. In both experiments, we found that adults made significantly more optimal rule-based responses to the test stimuli than children. Children showed a variety of categorization styles, with a few relying on the optimal rules, many relying on suboptimal single-feature rules, and only a few relying on overall family resemblance. We interpret these results within a multiple systems framework, and we argue that children show the pattern they do because they lack the necessary cognitive resources to fully engage in hypothesis testing, rule selection, and verbally mediated category learning.

Beliefs about penis size: validation of a scale for men ashamed about their penis size.

INTRODUCTION: No measures are available for understanding beliefs in men who experience shame about the perceived size of their penis. Such a measure might be helpful for treatment planning, and measuring outcome after any psychological or physical intervention. AIM: Our aim was to validate a newly developed measure called the Beliefs about Penis Size Scale (BAPS). METHOD: One hundred seventy-three male participants completed a new questionnaire consisting of 18 items to be validated and developed into the BAPS, as well as various other standardized measures. A urologist also measured actual penis size. MAIN OUTCOME MEASURES: The BAPS was validated against six psychosexual self-report questionnaires as well as penile size measurements. RESULTS: Exploratory factor analysis reduced the number of items in the BAPS from 18 to 10, which was best explained by one factor. The 10-item BAPS had good internal consistency and correlated significantly with measures of depression, anxiety, body image quality of life, social anxiety, erectile function, overall satisfaction, and the importance attached to penis size. The BAPS was not found to correlate with actual penis size. It was able to discriminate between those who had concerns or were dissatisfied about their penis size and those who were not. CONCLUSIONS: This is the first study to develop a scale for measurement of beliefs about penis size. It may be used as part of an assessment for men who experience shame about the perceived size of their penis and as an outcome measure after treatment. The BAPS measures various manifestations of masculinity and shame about their perceived penis size including internal self-evaluative beliefs; negative evaluation by others; anticipated consequences of a perceived small penis, and extreme self-consciousness.

Efficacy of cognitive behaviour therapy versus anxiety management for body dysmorphic disorder: a randomised controlled trial.

BACKGROUND: The evidence base for the efficacy of cognitive behaviour therapy (CBT) for treating body dysmorphic disorder (BDD) is weak. AIMS: To determine whether CBT is more effective than anxiety management (AM) in an outpatient setting. METHOD: This was a single-blind stratified parallel-group randomised controlled trial. The primary endpoint was at 12 weeks, and the Yale-Brown Obsessive Compulsive Scale for BDD (BDD-YBOCS) was the primary outcome measure. Secondary measures for BDD included the Brown Assessment of Beliefs Scale (BABS), the Appearance Anxiety Inventory (AAI) and the Body Image Quality of Life Inventory (BIQLI). The outcome measures were collected at baseline and week 12. The CBT group, unlike the AM group, had 4 further weekly sessions that were analysed for their added value. Both groups then completed measures at their 1-month follow-up. Forty-six participants with a DSM-IV diagnosis of BDD, including those with delusional BDD, were randomly allocated to either CBT or AM. RESULTS: At 12 weeks, CBT was found to be significantly superior to AM on the BDD-YBOCS [ß = -7.19; SE (ß) = 2.61; p < 0.01; 95% CI = -12.31 to -2.07; d = 0.99] as well as the secondary outcome measures of the BABS, AAI and BIQLI. Further benefits occurred by week 16 within the CBT group. There were no differences in outcome for those with delusional BDD or depression. CONCLUSIONS: CBT is an effective intervention for people with BDD even with delusional beliefs or depression and is more effective than AM over 12 weeks.

Atypical antipsychotic augmentation in SSRI treatment refractory obsessive-compulsive disorder: a systematic review and meta-analysis.

BACKGROUND: In 2006, the National Institute of Clinical and Health Excellence (NICE) guidelines for Obsessive Compulsive Disorder (OCD) recommended anti-psychotics as a class for SSRI treatment resistant OCD. The article aims to systematically review and conduct a meta-analysis on the clinical effectiveness of atypical anti-psychotics augmenting an SSRI. METHODS: Studies that were double-blind randomized controlled trials of an atypical antipsychotic against a placebo, for a minimum of 4 weeks, in adults with OCD, were included. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores were the primary outcome measure. Inclusion criteria included Y-BOCS score of 16 or more and at least one adequate trial of a SSRI or clomipramine for at least 8 weeks prior to randomization. Data sources included Medline, Embase, PsycINFO, Cochrane Database of Systematic Reviews (CDSR), trial registries and pharmaceutical databases and manufacturers up to September 2013. Forest-plots were drawn to display differences between drug and placebo on the Y-BOCS. RESULTS: Two studies found aripiprazole to be effective in the short-term. There was a small effect-size for risperidone or anti-psychotics in general in the short-term. We found no evidence for the effectiveness of quetiapine or olanzapine in comparison to placebo. CONCLUSIONS: Risperidone and aripiprazole can be used cautiously at a low dose as an augmentation agent in non-responders to SSRIs and CBT but should be monitored at 4 weeks to determine efficacy.

A multi-step approach: Coupling of biodegradation and UV photocatalytic oxidation TiO2 for the treatment of naphthenic acid fraction compounds in oil sands process-affected water.

Bitumen extraction in Alberta's oil sands region uses large volumes of water, leading to an abundance of oil sands process-affected water (OSPW). OSPW contains naphthenic acid fraction compounds (NAFCs) which have been found to contribute to OSPW toxicity. This study utilized a multistep treatment, coupling biological degradation with UV photocatalytic oxidation, and nutrient addition to boost the native microbial community's degradation capacity. OSPW initially contained 40-42 mg/L NAFCs with a toxicity of 3.8-3.9 TU. Initial biodegradation (Step 1) was used to remove the easily biodegradable NAFCs (11-25% removal), followed by a light or heavy dose of oxidation (Step 2) to breakdown the recalcitrant NAFCs (66-82% removal). Lastly, post-oxidation biodegradation with nutrients (Step 3) removed the residual bioavailable NAFCs (16-31% removal). By the end of the multistep treatment, the final NAFC concentrations and toxicity ranged from 5.3 to 6.8 mg/L and 1.1-1.2 TU. Analysis showed that OPSW was limited in phosphorus (below detection limit), and the addition of nutrients improved the degradation of NAFCs. Two treatments throughout the multistep treatment never received nutrients and showed minimal NAFC degradation post-oxidation. The native microbial community survived the stress from UV photocatalytic oxidation as seen by the post-oxidation NAFC biodegradation. Microbial community diversity was reduced considerably following oxidation, but increased with nutrient addition. The microbial community consisted predominately of Proteobacteria (Gammaproteobacteria and Alphaproteobacteria), and the composition shifted depending on the level of oxidation received. Possible NAFC-degrading microbes identified after a light oxidation dose included Pseudomonas, Acinetobacter and Xanthomonadales, while Xanthobacteracea and Rhodococcus were the dominant microbes after heavy oxidation. This experiment confirms that the microbial community is capable of degrading NAFCs and withstanding oxidative stress, and that degradation is further enhanced with the addition of nutrients.

An Experimental Protocol for the Boyden Chamber Invasion Assay With Absorbance Readout.

The phenomenon of cell invasion is an essential step in angiogenesis, embryonic development, immune responses, and cancer metastasis. In the course of cancer progression, the ability of neoplastic cells to degrade the basement membrane and penetrate neighboring tissue (or blood vessels and lymph nodes) is an early event of the metastatic cascade. The Boyden chamber assay is one of the most prevalent methods implemented to measure the pro- or anti-invasive effects of drugs, investigate signaling pathways that modulate cell invasion, and characterize the role of extracellular matrix proteins in metastasis. However, the traditional protocol of the Boyden chamber assay has some technical challenges and limitations. One such challenge is that the endpoint of the assay involves photographing and counting stained cells (in multiple fields) on porous filters. This process is very arduous, requires multiple observers, and is very time-consuming. Our improved protocol for the Boyden chamber assay involves lysis of the dye-stained cells and reading the absorbance using an ELISA reader to mitigate this challenge. We believe that our improved Boyden chamber methodology offers a standardized, high-throughput format to evaluate the efficacy of various drugs and test compounds in influencing cellular invasion in normal and diseased states. We believe that our protocol will be useful for researchers working in the fields of immunology, vascular biology, drug discovery, cancer biology, and developmental biology. Key features • Measurement of tumor invasion using human cancer cells. • Ability to measure the pro-invasive/anti-invasive activity of small molecules and biological modifiers. • Measurement of chemotaxis, chemokines, trafficking of immune cells, and proteolytic activity of matrix metalloproteinases, lysosomal hydrolysates, collagenases, and plasminogen activators in physiological and pathological conditions. • Investigation of the role of extracellular matrix proteins in the crosstalk between endothelial, epithelial, muscle, or neuronal cells and their adjacent stroma.