A method for amending loose smokeless tobacco with menthol for administration in clinical studies.

INTRODUCTION: Menthol has long been incorporated as a flavor additive in tobacco products and can impact use behaviors. Despite its inclusion in some of the most popular flavored smokeless tobacco (ST) products (e.g., "mint" flavored products), few studies have systematically investigated the impact of menthol on ST use behaviors in prospective empirical studies. Rigorous investigation of ST menthol content on behavioral and physiological outcomes requires ST products with stable and precise levels of menthol; however, commercial product composition variability prevents product comparisons when evaluating the effects of systematic changes in menthol content on clinical outcomes. METHODS: We developed amended loose moist snuff ST products by treating commercially available, unflavored loose ST with an ethanol-based menthol spiking solution or a nonmentholated ethanol control solution to develop test products with different levels of menthol: 0, 1, 3, and 5 mg menthol/g tobacco. We evaluated the stability of menthol content in these products over 24 months and evaluated menthol exposure associated with the products through pharmacokinetic analysis of plasma menthol-glucuronide in human participants (n=22). RESULTS: Menthol content of the amended products was on target, homogenous, and stable for up to 24 months. Menthol exposure (menthol-glucuronide Cmax and AUC) significantly differed between each test product. CONCLUSIONS: These data suggest that stable products with nonoverlapping menthol content can be developed using a menthol spiking solution and can be subsequently administered for clinical assessments of mentholated loose ST. IMPLICATIONS: The results from this study suggest that a menthol spiking solution can be used to mentholate unflavored, loose ST to a target menthol content. With this method, the ST menthol content was stable for at least 24 months, and the products exposed users to menthol in a dose-dependent manner. This method yielded loose ST products with precise, stable levels of menthol to allow systematic evaluation of ST menthol content on clinical outcomes. The method may have applications for systematically evaluating changes in other tobacco product ingredients.

E-cigarette Price Impacts legal and Black-Market Cigarette Purchasing Under a Hypothetical Reduced-Nicotine Cigarette Standard.

INTRODUCTION: The Tobacco Control Act gives the U.S. Food and Drug Administration authority to establish a reduced-nicotine content standard in combusted cigarettes. This future potential regulation may pose a significant public health benefit; however, black markets may arise to meet demand for normal-nicotine content cigarettes among smokers unwilling to transition to or use an alternative product. AIMS AND METHODS: We determined the behavioral-economic substitutability of illicit normal-nicotine content cigarettes and e-cigarettes for reduced-nicotine content cigarettes in a hypothetical reduced-nicotine regulatory market. Adult cigarette smokers were recruited online to complete hypothetical cigarette purchasing tasks for usual-brand cigarettes, reduced-nicotine content cigarettes, and illicit normal-nicotine content cigarettes, as well as a cross-commodity task in which reduced-nicotine content cigarettes were available across multiple prices and illicit cigarettes were concurrently available for $12/pack. Participants completed two three-item cross-commodity purchasing tasks in which e-cigarettes were available for $4/pod or $12/pod alongside reduced-nicotine content cigarettes and illicit cigarettes. RESULTS: Usual-brand cigarette purchasing was greater than illicit normal-nicotine content cigarettes and less than reduced-nicotine content cigarettes. In the cross-commodity purchasing tasks, illicit cigarettes and e-cigarettes both served as economic substitutes for reduced-nicotine content cigarettes; however, when e-cigarettes were available for $4/pod, they were purchased at greater levels than illicit cigarettes and resulted in greater reductions in reduced-nicotine content cigarettes purchasing than when available for $12/pod. CONCLUSIONS: These data suggest that some smokers are willing to engage in illicit cigarette purchasing in a reduced-nicotine regulatory environment, but e-cigarette availability at lower prices may reduce black-market engagement and shift behavior away from combusted cigarette use. IMPLICATIONS: E-cigarettes available at low, but not high, prices were stronger substitutes for legal, reduced-nicotine content cigarettes than illegal, normal-nicotine content cigarettes in a hypothetical reduced-nicotine tobacco market. Our findings suggest the availability of relatively inexpensive e-cigarettes may reduce illicit cigarette purchasing and combusted cigarette use under a reduced-nicotine cigarette standard.

Apical periodontitis and autoimmune diseases-should we be screening patients prior to therapy?

DESIGN: A single-centre retrospective case-control study from 2012-2020 comparing the prevalence of apical periodontitis (AP) in patients with autoimmune disorders (AD) against a control group of those without. The different medication groups commonly used for treatment of AD were included for comparison. CASE/CONTROL SELECTION: This study utilised patients' electronic records. These were anonymous. Patient sociodemographic variables were collected and compared. Two cases were removed from selection as they were being treated with dual biologic therapy. DATA ANALYSIS: Both the control group and AP group contained 89 patients. Various additional variables were considered, such as DMFT and a logistical regression analysis was used to correlate between AD and AP. RESULTS: For the autoimmune disease conditions within this study, the authors found a higher prevalence of apical periodontitis than in the control group, 89.9% versus 74.2%, respectively (p = 0.015). Furthermore, those taking conventional disease-modifying drugs such as methotrexate had a lower prevalence than those on biologics. These results were of statistical significance. CONCLUSIONS: Individuals with autoimmune disorders may have increased prevalence of apical periodontitis irrespective of their treatment with biologics or not. A DMFT score can be used to predict the occurrence of AP.

A multicentric, prospective study on oral and maxillofacial trauma in the female population around the world.

BACKGROUND/AIMS: Approximately 20% of patients with maxillofacial trauma are women, but few articles have analysed this. The aim of this multicentric, prospective, epidemiological study was to analyse the characteristics of maxillofacial fractures in the female population managed in 14 maxillofacial surgery departments on five continents over a 1-year period. METHODS: The following data were collected: age (0-18, 19-64, or ≥65 years), cause and mechanism of the maxillofacial fracture, alcohol and/or drug abuse at the time of trauma, fracture site, Facial Injury Severity Scale score, associated injury, day of trauma, timing and type of treatment, and length of hospitalization. RESULTS: Between 30 September 2019 and 4 October 2020, 562 of 2387 patients hospitalized with maxillofacial trauma were females (24%; M: F ratio, 3.2:1) aged between 1 and 96 years (median age, 37 years). Most fractures occurred in patients aged 20-39 years. The main causes were falls (43% [median age, 60.5 years]), which were more common in Australian, European and American units (p < .001). They were followed by road traffic accidents (35% [median age, 29.5 years]). Assaults (15% [median age, 31.5 years]) were statistically associated with alcohol and/or drug abuse (p < .001). Of all patients, 39% underwent open reduction and internal fixation, 36% did not receive surgical treatment, and 25% underwent closed reduction. CONCLUSION: Falls were the main cause of maxillofacial injury in the female population in countries with ageing populations, while road traffic accidents were the main cause in African and some Asian centres, especially in patients ≤65 years. Assaults remain a significant cause of trauma, primarily in patients aged 19-64 years, and they are related to alcohol use.

Aspirin or Rivaroxaban for VTE Prophylaxis after Hip or Knee Arthroplasty.

BACKGROUND: Clinical trials and meta-analyses have suggested that aspirin may be effective for the prevention of venous thromboembolism (proximal deep-vein thrombosis or pulmonary embolism) after total hip or total knee arthroplasty, but comparisons with direct oral anticoagulants are lacking for prophylaxis beyond hospital discharge. METHODS: We performed a multicenter, double-blind, randomized, controlled trial involving patients who were undergoing total hip or knee arthroplasty. All the patients received once-daily oral rivaroxaban (10 mg) until postoperative day 5 and then were randomly assigned to continue rivaroxaban or switch to aspirin (81 mg daily) for an additional 9 days after total knee arthroplasty or for 30 days after total hip arthroplasty. Patients were followed for 90 days for symptomatic venous thromboembolism (the primary effectiveness outcome) and bleeding complications, including major or clinically relevant nonmajor bleeding (the primary safety outcome). RESULTS: A total of 3424 patients (1804 undergoing total hip arthroplasty and 1620 undergoing total knee arthroplasty) were enrolled in the trial. Venous thromboembolism occurred in 11 of 1707 patients (0.64%) in the aspirin group and in 12 of 1717 patients (0.70%) in the rivaroxaban group (difference, 0.06 percentage points; 95% confidence interval [CI], -0.55 to 0.66; P<0.001 for noninferiority and P=0.84 for superiority). Major bleeding complications occurred in 8 patients (0.47%) in the aspirin group and in 5 (0.29%) in the rivaroxaban group (difference, 0.18 percentage points; 95% CI, -0.65 to 0.29; P=0.42). Clinically important bleeding occurred in 22 patients (1.29%) in the aspirin group and in 17 (0.99%) in the rivaroxaban group (difference, 0.30 percentage points; 95% CI, -1.07 to 0.47; P=0.43). CONCLUSIONS: Among patients who received 5 days of rivaroxaban prophylaxis after total hip or total knee arthroplasty, extended prophylaxis with aspirin was not significantly different from rivaroxaban in the prevention of symptomatic venous thromboembolism. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT01720108 .).

Weekly carfilzomib plus cyclophosphamide and dexamethasone in the treatment of relapsed/refractory multiple myeloma: Final results from the MCRN-003/MYX.1 single arm phase II trial.

The MCRN-003/CCTGMYX.1 is a single arm phase II trial of weekly carfilzomib, cyclophosphamide and dexamethasone (wKCd), exploring a convenient immunomodulator (IMiD)-free regimen in relapsed myeloma. Weekly carfilzomib (20/70 mg/m2 ), dexamethasone 40 mg and cyclophosphamide 300 mg/m2 was delivered over 28-day cycles. The primary endpoint was overall response after four cycles. Secondary endpoints included toxicity, response depth, PFS and OS. Exploratory endpoints included the impact of cytogenetics, prior therapy exposure and serum free light chain (sFLC) escape; 76 patients were accrued. The ORR was 85% (68% ≥very good partial response [VGPR] and 29% ≥complete response [CR]). The median OS and PFS were 27 and 17 months respectively. High-risk cytogenetics conferred a worse ORR (75% vs. 97%, p = .013) and median OS (18 months vs. NR, p = .002) with a trend toward a worse median PFS (14 vs. 22 months, p = .06). Prior proteasome inhibitor (PI) or lenalidomide did not influence OS or PFS. The sFLC was noted in 15% of patients with a median PFS of 17 months when included as a progression event. The most common ≥ grade 3 non-hematologic adverse events were infectious (40%), vascular (17%) and cardiac (15%). The wKCD is a safe and effective regimen in relapse, especially for patients ineligible for lenalidomide-based therapies.

Attention-Deficit/Hyperactivity Disorder Symptoms Are Associated with Greater Delay Discounting of Condom-Protected Sex and Money.

Attention-deficit/hyperactivity disorder (ADHD) is associated with increased risk of detrimental life outcomes. Recent research also indicates that ADHD is associated with sexual risk behavior, such as unprotected sex. Some risky sexual behaviors may be driven, in part, by preference for immediate rewards, referred to as delay discounting, which is prominent in etiological models of ADHD. Therefore, the present study examined the effect of delay on preference for both monetary and sexual outcomes in adults with many ADHD symptoms (both on and off medication) and with fewer ADHD symptoms. Online participants (N = 275; n = 161 males, n = 114 females) completed a monetary delay discounting task, assessing preference for smaller sooner versus larger delayed hypothetical money, and the Sexual Delay Discounting Task, assessing preference for condom use in hypothetical casual sex scenarios based on delay until condom availability. Those with greater ADHD symptoms discounted delayed monetary outcomes as well as delayed condom-protected sex (i.e., preferred sooner money rewards and immediate unprotected sex) significantly more than those with fewer symptoms; however, no effect of current medication use was found across monetary or sexual delay discounting among those with greater ADHD symptoms. This study is the first to demonstrate the relation between ADHD symptoms and reduced condom-use likelihood. Increased discounting of delayed condom-protected sex might constitute one mechanism of risky sexual behavior among individuals with ADHD symptoms. Interventions geared toward increasing condom use in situations in which condoms may otherwise be unavailable, may mitigate risky sexual behaviors and their associated harms in this population.

A quadripartite model of passion for marijuana use: Associations with consumption, consequences, craving, and satisfaction with life.

BACKGROUND: Identifying factors that can be targeted in intervention/prevention programs aimed at reducing marijuana-(MJ) related consequences is of critical concern due to the changing legislative landscape of MJ. The dualistic model of passion for MJ has indicated that two factors, obsessive passion (OP) and harmonious passion (HP), have unique effects associated with MJ use outcomes. New research suggests that a quadripartite approach could provide a more nuanced method to interpret risk and protective factors associated with MJ use. Therefore, we used moderation to investigate the associations among OP, HP, and MJ use outcomes. METHOD: A community sample of frequent MJ users was recruited using internet-based advertisements and completed web-based surveys (n=161; M age=27.3, SD=8.9; Male=87%; White/Caucasian=86%; M past30-dayMJuse=22.3, SD=9.9). HP was tested as the moderator between OP, and MJ related outcomes and conditional effects (+/-1 SD) were examined when interaction effects were significant. RESULTS: Only main effects for OP had a relation to quantity/frequency of MJ use and MJ intoxication, while main effects for OP and HP were associated with reduction attempts. Interaction effects were significant for MJ consequences, craving, and life satisfaction. Neither OP nor HP were significantly associated with substance use outcomes. CONCLUSIONS: Findings demonstrate that Pure OP and Mixed Passion are associated with greater risk. Mixed Passion may be a precursor to Pure OP and experiencing MJ-related consequences. Furthermore, Mixed Passion and Pure OP may be important targets for intervention/prevention programs designed to reduce negative outcomes.

What are the implications of flap design on post-operative complications when carrying out third molar surgery?

Data sources The review carried out electronic searches using several online databases through November 2018, namely PubMed, Virtual Health Library, Cochrane Library and Scopus. Terms searched for on these databases included third molar, flap and variations thereof. A grey literature search was also conducted.Study selection In total, 2,455 articles were identified,1,449 being duplicates. Additionally, 1,006 articles remained for assessment which, with clear exclusion criteria listed, was reduced to 20. From the 20 incorporated into the review, 18 articles were utilised for meta-analysis. Three of the researchers were involved in assessing the articles after research management software was used to remove the aforementioned duplicates. A Cohen's kappa index was calculated to confirm inter-rater consistency using 10% of the articles.Data extraction and synthesis Data extraction followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidance.Results From their systematic review and meta-analyses, the authors found that flap design had no effect on common post-operative complications including pain, trismus, dehiscence, or osteitis. The triangular flap did, however, have greater post-operative ecchymosis but reduced periodontal probing depth on day seven when compared to the envelope flap in mandibular third molar surgeries.Conclusions Third molar surgery is carried out across all facets of dentistry, including general and specialised. Further studies must be carried out that look specifically at these variables utilising randomised controlled trials so a consensus can be achieved across the profession of which flap is of superior design.

Methylenedioxymethamphetamine-like discriminative stimulus effects of seven cathinones in rats.

Synthetic cathinone derivatives are commonly considered quasi-legal alternatives for stimulant drugs, such as cocaine and methamphetamine, but some derivatives are increasingly being detected in club drug formulations of Ecstasy or 'Molly' as substitutes for methylenedioxymethamphetamine (±-MDMA). Although several studies have evaluated the psychostimulant-like effects of synthetic cathinones, few cathinone compounds have been assessed for MDMA-like activity. In order to determine their likelihood of interchangeability with entactogenic club drugs, the discriminative stimulus effects of methcathinone, 4-fluoromethcathinone, 4-methylmethcathinone, 4-methylethcathinone, 3-fluoromethcathinone, pentedrone, and ethylone were assessed in Sprague-Dawley rats trained to discriminate 1.5 mg/kg racemic methylenedioxymethamphetamine (±-MDMA) from vehicle. Methamphetamine and the cathinones 4-fluoromethcathinone, 4-methylmethcathinone, 4-methylethcathinone, 3-fluoromethcathinone, pentedrone, and ethylone fully substituted for the discriminative stimulus effects of ±-MDMA. In contrast, methcathinone produced a maximum of only 43% ±-MDMA-appropriate responding and higher doses suppressed responding. Most, but not all of the cathinone compounds tested have discriminative stimulus effects similar to those of MDMA as well as psychostimulant-like effects; however, the potency of MDMA versus psychostimulant substitution varies substantially among the compounds, suggesting that a subset of synthetic cathinones are more MDMA-like than psychostimulant-like. These findings further highlight the highly-variable pharmacology of this class of compounds and suggest that those cathinones with MDMA-like effects may also have increased use as club drugs.

The Hotel Room Purchase Task: Effects of Gender and Partner Desirability on Demand for Hypothetical Sex in Individuals with Disordered Cocaine Use and Controls.

Hypothetical purchase tasks allow for rapid assessment of behavioral economic demand for numerous commodities and are useful in evaluating reinforcer pathologies, such as substance and behavioral addiction. Currently, there is not a task for evaluating demand for sex without requiring implicit engagement in sex work. The current study used a novel purchase task with hotel rooms for sex as the hypothetical commodity to assess demand for sex in individuals with disordered cocaine use, a population that frequently engages in risky sexual behavior. Adults meeting criteria for cocaine abuse or dependence (13 males, ten females) and noncocaine-using controls (eight males, three females) chose hypothetical sexual partners from a series of photographs and endorsed two partners with whom they would most and least like to have sex. Participants then completed the hotel purchase task for both partners, wherein they reported how many nights at a hotel room, at prices from $10 to $1280 per night, they would purchase in a year. Demand intensity was significantly greater and demand elasticity was significantly lower for the most preferred relative to the less preferred partner. Males demonstrated significantly greater intensity and lesser elasticity for sex than females. Demand metrics did not differ between the cocaine and control group. This task may serve as a useful measure of demand for sex without requiring implicit hypothetical engagement in sex work. Future studies exploring the relation between task performance and other characteristics such as sexual dysfunction, in addition to acute substance administration effects, may further determine the task's clinical utility.

What is the impact of COVID-19 on head and neck squamous cell carcinoma patients?

Data sources It is not made clear in this review the different databases selected or how they conducted their search. The studies used are from 1975-2020Study selection The authors have performed a scoping review using 84 studies ranging from 1975-2020. The majority of these are from before the 2019-2020 COVID-19 outbreak period. This is indicative of the lack of evidence on this topic and exemplifies why a scoping review was carried out rather than a systematic review. The studies that were reviewed were predominately cohort and case studies. With regards to previous treatment outcomes, a few systematic reviews were included, but again, the novel nature of this outbreak means that largely, there are only cohort or case studies available for review.Data extraction and synthesis There are ten authors, with no indication of how many performed the literature review or if a mediator was involved in the final decision making on what papers would be reviewed.Results Excessive consumption of alcohol, history of tobacco use, an ageing population, and comorbidities such as cardiopulmonary issues are substantial risk factors for episodes of unfavourable respiratory outcomes. The risk of these outcomes is increased by some of the toxic effects of treatments such as chemotherapy or radiotherapy.Conclusions The COVID-19 outbreak has a potentially disproportionate impact on the cohort of head and neck cancer patients, and the respiratory effects this has on these patients may increase morbidity and mortality. It is important to include alcohol and smoking cessation, along with good oral hygiene instruction in the care of these patients.

Locomotor and discriminative stimulus effects of four novel hallucinogens in rodents.

There has been increasing use of novel synthetic hallucinogenic compounds, 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25B-NBOMe), 2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25C-NBOMe), 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine hydrochloride (25I-NBOMe), and N,N-diallyl-5-methoxy tryptamine (5-MeO-DALT), which have been associated with severe toxicities. These four compounds were tested for discriminative stimulus effects similar to a prototypical hallucinogen (-)-2,5-dimethoxy-4-methylamphetamine (DOM) and the entactogen (±)-3,4-methylenedioxymethamphetamine (MDMA). Locomotor activity in mice was tested to obtain dose range and time-course information. 25B-NBOMe, 25C-NBOMe, and 25I-NBOMe decreased locomotor activity. 5-MeO-DALT dose dependently increased locomotor activity, with a peak at 10 mg/kg. A higher dose (25 mg/kg) suppressed activity. 25B-NBOMe fully substituted (≥80%) in both DOM-trained and MDMA-trained rats at 0.5 mg/kg. However, higher doses produced much lower levels of drug-appropriate responding in both DOM-trained and MDMA-trained rats. 25C-NBOMe fully substituted in DOM-trained rats, but produced only 67% drug-appropriate responding in MDMA-trained rats at doses that suppressed responding. 25I-NBOMe produced 74-78% drug-appropriate responding in DOM-trained and MDMA-trained rats at doses that suppressed responding. 5-MeO-DALT fully substituted for DOM, but produced few or no MDMA-like effects. All of the compounds, except 25I-NBOMe, fully substituted for DOM, whereas only 25B-NBOMe fully substituted for MDMA. However, the failure of 25I-NBOMe to fully substitute for either MDMA or DOM was more likely because of its substantial rate-depressant effects than weak discriminative stimulus effects. All of the compounds are likely to attract recreational users for their hallucinogenic properties, but probably of much less interest as substitutes for MDMA. Although no acute adverse effects were observed at the doses tested, the substantial toxicities reported in humans, coupled with the high likelihood for illicit use, suggests that these compounds have the same potential for abuse as other, currently scheduled compounds.

Functional and patient-reported outcomes of the Swanson metacarpo-phalangeal arthroplasty in the rheumatoid hand.

INTRODUCTION: Replacement of the metacarpo-phalangeal joints (MCPJ) with silastic Swanson's implants can help decrease pain, stiffness and allow for improved function in rheumatoid arthritis (RA). There is a lack of patient reported outcome measure (PROM) studies assessing the efficacy of this procedure in RA. The aim of this study was to report any change in function, pain, stiffness and satisfaction following the Swanson MCPJ replacement using patient reported outcomes in a rheumatoid population. METHODS: The combined results of 64 RA patients (71 hands) with 284 Swanson MCPJ arthroplasties (mean follow-up: 75.85 months) were assessed using the validated M-SACRAH questionnaire and a separate satisfaction questionnaire. Radiographic evaluation was performed to insure correct alignment of the hinged prosthesis postoperatively. No attempt was made to identify other predictors, radiologically or clinically. Data analysed in the study was interpreted in the context of the number of hands and survivorship was defined as implant fracture, loosening or revision. RESULTS: The mean total functional outcome score improved by 46.2% and the total pain outcome improved by 60.2%. The total stiffness outcome improved by 56.9% postoperatively and the results obtained from the satisfaction questions revealed that 73.2% of patients would retrospectively elect to have the procedure again. We report two postoperative complications in this group of superficial wound infections. Radiographically, all MCPJs showed improved alignment, however five patients reported worsening pain, four patients reported increased stiffness and four reported reduced function postoperatively. There was one re-operation of a 5th MCPJ Swanson's, which did not require implant exchange and one implant was revised. Implant survivorship was 98.6%. CONCLUSIONS: Patient satisfaction and functional surrogate markers were overall favourable. Our results support the continued use of Swanson silastic arthoplasty in advanced RA.

Locomotor, discriminative stimulus, and place conditioning effects of MDAI in rodents.

5,6-Methylenedioxy-2-aminoindane (MDAI) has become a common substitute for (±)-3,4-methylenedioxymethamphetamine (MDMA) in Ecstasy. MDAI is known to produce MDMA-like discriminative stimulus effects, but it is not known whether MDAI has psychostimulant or hallucinogen-like effects. MDAI was tested for locomotor stimulant effects in mice and subsequently for discriminative stimulus effects in rats trained to discriminate cocaine (10 mg/kg, intraperitoneally), methamphetamine (1 mg/kg, intraperitoneally), ±MDMA (1.5 mg/kg, intraperitoneally), or (-)-2,5-dimethoxy-4-methylamphetamine hydrochloride (0.5 mg/kg, intraperitoneally) from saline. The ability of MDAI to produce conditioned place preference was also tested in mice. MDAI (3 to 30 mg/kg) depressed locomotor activity from 10 to 60 min. A rebound stimulant effect was observed at 1 to 3.5 h following 30 mg/kg. Lethality occurred in 8/8 mice following 100 mg/kg MDAI. Similarly, MDMA depressed locomotor activity immediately following the administration of 0.25 mg/kg and stimulant effects were observed 50-70 min following the administration of 0.5 and 1 mg/kg. MDAI fully substituted for the discriminative stimulus effects of MDMA (2.5 mg/kg), (-)-2,5-dimethoxy-4-methylamphetamine hydrochloride (5 mg/kg), and cocaine (7.5 mg/kg), but produced only 73% methamphetamine-appropriate responding at a dose that suppressed responding (7.5 mg/kg). MDAI produced tremors at 10 mg/kg in one methamphetamine-trained rat. MDAI produced conditioned place preference from 0.3 to 10 mg/kg. The effects of MDAI on locomotor activity and drug discrimination were similar to those produced by MDMA, having both psychostimulant-like and hallucinogen-like effects; thus, MDAI may have similar abuse potential as MDMA.

Management of Labour and Delivery in a Patient With Acquired Factor VII Deficiency With Inhibitor: A Case Report.

BACKGROUND: Acquired factor VII (FVII) deficiency with inhibitor increases the risk of hemorrhage during pregnancy. However, there are no published reports guiding its management in the peripartum period. CASE: A 24-year-old woman with inhibitory antibodies to FVII delivered at 34 weeks of gestation. The patient was administered recombinant factor VIIa (rFVIIa) and tranexamic acid. There were no bleeding-related complications; however, the FVII level was supratherapeutic. The patient returned during a second pregnancy. A reduced dose of rFVIIa was administered. The delivery was complicated by postpartum hemorrhage, which resolved with the addition of uterotonic agents. CONCLUSION: Recombinant FVIIa and tranexamic acid offer an effective peripartum treatment in women with inhibitory antibody to FVII. Further research should delineate the optimal time of administration.

Patient rated outcomes study into the surgical interventions available for the rheumatoid hand and wrist.

INTRODUCTION: A multitude of surgical interventions are recognised for the treatment of the rheumatoid hand and wrist, however there seems to be a distinct lack of patient rated outcome measures (PROMs) studies reporting on the efficacy of these procedures. The aim of this study was to assess the PROMs related to hand and wrist surgery in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: A single surgeon series identified 94 patients (133 hands) with RA who had undergone one of eight surgical procedures (Swanson's arthroplasty, finger joint or wrist arthrodesis, carpal tunnel decompression, posterior interosseous nerve denervation, RA nodule excision, synovectomy/tenosynovectomy and tendon repair/release) with a mean follow-up period of 3 years. The primary outcome measures were the same for all patients and comprised the validated modified score for the assessment and quantification of chronic rheumatoid affections of the hand (M-SACRAH) and a separate satisfaction questionnaire. RESULTS: Highly significant improvements in both function and pain scores are reported across the cohort as a whole following hand surgery, with this pattern replicated within all of the operative subgroups. In keeping with these favourable results very high levels of overall satisfaction were reported with 93 % of patients reporting themselves to be very or fairly satisfied with their procedure. CONCLUSIONS: Overall, patient reported outcomes in functional, stiffness and pain domains of the M-SACRAH questionnaire appear very favourable across the range of surgical procedures that can be performed in the rheumatoid hand. We believe this data supports the use of all the procedures explored, and will be helpful in patient guidance.

Comparative Behavioral Pharmacology of Three Pyrrolidine-Containing Synthetic Cathinone Derivatives.

Synthetic cathinones, often sold as "bath salts," are a popular class of recreational drugs used as quasi-legal alternatives to cocaine, methamphetamine, and methylenedioxymethamphetamine. The increased prevalence and health consequences of synthetic cathinone use has prompted regulatory agencies to control a number of these compounds; however, a broad class of analogous compounds known as the second-generation cathinones has been brought to the market to take the place of the banned synthetic cathinone derivatives. The current study aims to characterize the behavioral pharmacology of three pyrrolidinylated second-generation cathinones: 4-methyl-α-pyrrolidinopropiophenone (4'-MePPP), α-pyrrolidinopropiobutiophenone (α-PBP), and α-pyrrolidinopentiophenone (α-PVP). Locomotor activity was tested in mice over an 8-hour period. The discriminative stimulus effects of these compounds were tested in rats trained to discriminate either cocaine or methamphetamine. The rewarding effects of these drugs were assessed in mice using conditioned place preference. Both α-PBP and α-PVP produced long-lasting increases in locomotor activity across a wide range of doses, whereas 4'-MePPP produced locomotor stimulation only at 30 mg/kg. Both α-PBP and α-PVP fully substituted for the discriminative stimulus effects of both cocaine and methamphetamine, whereas 4'-MePPP substituted fully for the discriminative stimulus effects of methamphetamine only. Both α-PBP and α-PVP produced conditioned place preference in an inverted U-shaped dose effect, whereas 4'-MePPP did not produce conditioned place preference. These findings suggest that α-PBP and α-PVP are likely to be recreationally used and have potential for addiction and abuse, but 4'-MePPP may not.

Restorative dentistry clinical decision-making for hypodontia: peg and missing lateral incisor teeth.

Peg-shaped and missing lateral incisor teeth are common features for patients affected by hypodontia. While improvements in dental appearance may be a strong motivating factor for these patients, providing dental treatment to improve the clinical condition and achieve an acceptable and stable outcome can be complex and lengthy.For patients affected by hypodontia, discussion and consideration of various approaches to their individual treatment are best achieved in a multidisciplinary team environment. This allows debate of options and joint agreement between at least orthodontic and restorative dentistry specialist colleagues, based largely on clinical factors, towards a treatment plan that is acceptable to the patient. As most patients with this lateral incisor form of hypodontia are initially treated as teenagers and young adults, there is also an understanding that treatment outcomes will have lifelong maintenance and resource implications to consider.This paper identifies and discusses the key clinical features that influence the treatment planning process for a patient with either missing or peg lateral incisor teeth. These will often involve consideration of whether to open or close the lateral incisor spaces and whether to restore or replace a peg lateral incisor tooth. The process should be patient-centred, evidence-based, and aim to minimise the lifelong treatment burden, retaining options for future maintenance and retreatment.