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Background: Insertion of a radial head implant that results in radial overlengthening has been associated with altered elbow kinematics, increased radiocapitellar joint forces, capitellar erosions, early-onset arthritis, and loss of elbow flexion. The purpose of this study was to identify clinical and radiographic features that may be used to diagnose overlengthening of the radius intraoperatively and on postoperative radiographs.Methods: Radial head implants of varying thicknesses were inserted into seven cadaver specimens, which were then assessed clinically and radiographically. Eight stages were examined: the intact specimen (stage 1); repair of the lateral collateral ligament (stage 2); radial head resection with repair of the lateral collateral ligament (stage 3); insertion of an implant of the correct thickness (stage 4); and insertion of an implant that resulted in radial overlengthening of 2 mm (stage 5), 4 mm (stage 6), 6 mm (stage 7), or 8 mm (stage 8). The specimens were tested with and without muscle loading to simulate resting muscle tone and surgical paralysis, respectively. At each stage, radiographs were made to measure the ulnohumeral joint space and the lateral ulnohumeral joint was visually assessed.Results: We identified no difference, with regard to medial ulnohumeral joint incongruity as seen radiographically, among stages 1 through 6 during the tests with muscle loading. A significant difference in medial ulnohumeral joint incongruity was found in stages 7 (p = 0.003) and 8 (p < 0.001). The clinical (visually assessed) lateral ulnohumeral joint space gap was negligible in stages 1 through 4 but increased significantly at all stages involving overlengthening (gross gap, 0.9 mm with 2 mm of erlengthening [p = 0.005], 2.3 mm with 4 mm of overlengthening [p < 0.001], 3.4 mm with 6 mm [p < 0.001], and 4.7 mm with 8 mm [p < 0.001]).Conclusions: Incongruity of the medial ulnohumeral joint becomes apparent radiographically only after overlengthening of the radius by ≥6 mm. Intraoperative visualization of a gap in the lateral ulnohumeral joint is a reliable indicator of overlengthening following the insertion of a radial head prosthesis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The R620W (1858C-->T) polymorphism in PTPN22 has been implicated in type 1 diabetes mellitus, rheumatoid arthritis, Graves' disease, Hashimoto thyroiditis, autoimmune thyroid disease, and systemic lupus erythematosus (SLE). The aim of this study was to evaluate this polymorphism in patients with familial SLE and in those with sporadic SLE. METHODS: A total of 4,981 DNA samples were genotyped (from 1,680 SLE patients, 1,834 family members, and 1,467 controls). Both population-based case-control and family-based association designs were used for the analyses. RESULTS: In the European American familial SLE cohort, the minor 1858T allele was more common in randomly selected patients compared with controls (chi(2) = 5.61, P = 0.018, odds ratio [OR] 1.46, 95% confidence interval [95% CI] 1.07-1.99). The heterozygous C/T genotype was also more common in these European American patients compared with controls (OR 1.63, 95% CI 1.15-2.30). Family-based association tests showed preferential transmission of the 1858T allele to affected offspring (chi(2) = 5.87, P = 0.015). In contrast, the frequency of the 1858T minor allele was not significantly increased in the European American patients with sporadic SLE compared with controls, nor did these patients have preferential transmission of the 1858T allele. Indeed, the difference in the 1858T allele frequency between patients with familial SLE and those with sporadic SLE was measurable (allelic chi(2) = 4.22, P = 0.04, OR 1.51, 95% CI 1.02-2.24). Our data also showed that among patients with SLE, the 1858T allele was separately associated with type 1 diabetes mellitus and with autoimmune thyroid disease, confirming the findings of other investigators. CONCLUSION: The 1858T allele of PTPN22 is associated with familial SLE but not with sporadic SLE in European Americans, thereby potentially explaining previous contradictory reports. [ABSTRACT FROM AUTHOR]

Background: There has been a recent increase in the number and complexity of quality improvement (QI) studies in breast reconstruction. To assist with the development of thorough QI reporting practices, with the goal of improving the transferability of these initiatives, the authors conducted a systematic review of studies describing the implementation of QI initiatives in breast reconstruction. The authors used the Standards for Quality Improvement Reporting Excellence (SQUIRE) 2.0 guideline to appraise the quality of reporting of these initiatives., Methods: English language articles published in Embase, MEDLINE, CINAHL, and the Cochrane databases were searched. Quantitative studies evaluating the implementation of QI initiatives in breast reconstruction were included. The primary endpoint of interest in this review was the distribution of studies according to SQUIRE 2.0 criteria scores in proportions. Abstracts and full-text screening, and data extraction were completed independently and in duplicate by the review team., Results: The authors screened 1107 studies, of which 53 full texts were assessed and 35 met inclusion criteria. In our assessment, only three studies (9%) met all 18 SQUIRE 2.0 criteria. SQUIRE 2.0 criteria that were met most frequently were abstract, problem description, rationale, and analysis. The lowest SQUIRE 2.0 scores appeared in the interpretation criteria., Conclusions: Significant opportunity exists to improve QI reporting in breast reconstruction, especially in the realm of costs, strategic tradeoffs, ethical considerations, project sustainability, and potential for spread to other contexts. Improvements in these areas will help to further advance the transferability of QI initiatives in breast reconstruction., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: Alloderm and Dermacell are the two leading human acellular dermal matrices (ADM) in immediate breast reconstruction (IBR). Despite differences in sterility, consistency, thickness and cost, there are no comparative trials to date to compare patient-reported outcome measures (PROM) between the two products. The purpose of this study was to determine if there was a difference in patient-reported outcomes (as measured by the BREAST-Q) between patients reconstructed with Alloderm and Dermacell., Methods: A single center, open-label, randomized control trial of patients undergoing IBR with an implant for breast cancer or breast cancer prophylaxis was performed. Patients were randomized to either Alloderm or Dermacell. Baseline demographic data were compared, and linear mixed models were used to identify associations with BREAST-Q over time., Results: Between June 2016 and October 2018, 62 patients were randomized into two groups, 31(50%) Alloderm and 31(50%) Dermacell. Of these, 23(74%) patients in the Alloderm group and 27(87%) patients of the Dermacell group filled out BREAST-Q questionnaires. Baseline BREAST-Q scores with respect to satisfaction with breasts, psychosocial well-being, sexual well-being, and physical well-being were similar between groups (p>0.05). At 3 months postoperatively, the Alloderm group had a statistically significant improvement with respect to satisfaction with breasts (67 vs 53, p = 0.03), satisfaction with overall results (85 vs 61, p = 0.003), satisfaction with the surgeon (89 vs 67, p = 0.01), and satisfaction with information provided (74 vs 59, p = 0.02). At 12 months postoperatively, there were no statistically significant differences in PROM between groups (p>0.05)., Conclusion: We report the first randomized controlled trial to date comparing patient-reported outcomes of the two most commonly used ADMs in IBR in Canada. Although a short-term analysis favors the use of Alloderm, there does not appear to be any difference in outcomes between the two products in the longer term., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: An understanding of patient expectations predicts better health outcomes following breast reconstruction. No study to date has examined how patient expectations for breast reconstruction and preoperative health-related quality of life vary with time since breast cancer diagnosis., Methods: Women consulting for breast reconstruction to a single surgeon's practice over a 13-month period were enrolled in this cross-sectional study. Patients were asked to prospectively complete the BREAST-Q expectations and preoperative reconstruction modules. A retrospective chart review was then performed on eligible patients, and patient demographics, cancer-related factors, and comorbidities were collected. BREAST-Q scores were transformed using the equivalent Rasch method. Multivariate linear regression models were constructed to assess the association between BREAST-Q scores and time since cancer diagnosis., Results: Sixty-five patients met inclusion criteria for analysis and are characterized by a mean age of 53 ± 11 (34-79) years and a mean body mass index of 28 ± 6 (19-49). Most patients were treated by mastectomy (58%) or lumpectomy (23%). At the time of retrospective chart review, 29 (43%) patients had undergone reconstruction, most of which were delayed (59%). The mean latency from cancer diagnosis to reconstruction was 685 ± 867 days (range: 28-3322 days). Latency from cancer diagnosis to reconstruction was associated with a greater expectation of pain (β = 0.5; standard error [SE] = 0.005; 95% confidence interval [CI]: 0.003-0.027; P < .05), and a slower expectation for recovery (β = -0.5; SE = 0.004; 95% CI: -0.021 to -0.001; P < .05) after breast reconstruction. Latency from cancer diagnosis to reconstruction was associated with an increase in preoperative psychosocial well-being (β = 0.578; SE 0.009; 95% CI: 0.002-0.046; P < .05)., Conclusion: Delaying breast reconstruction may negatively impact patient expectations of postoperative pain and recovery. Educational interventions aimed at understanding and managing patient expectations in the preoperative period may improve health-related quality of life and patient-related outcomes following initial breast cancer surgery., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2019 The Author(s).)

Purpose: Enhanced recovery after surgery (ERAS) protocols improve quality of recovery and decrease length of stay for patients undergoing both alloplastic and autologous breast reconstruction. Their use in latissimus dorsi (LD) flap reconstruction has not been well established. The purpose of this study was to compare postoperative outcomes, length of stay, and total costs in a prospectively enrolled group of patients who underwent LD flap breast reconstruction using an ERAS protocol to those of a retrospective cohort of patients who were treated with a traditional recovery after surgery (TRAS) protocol., Methods: In a prospective cohort study conducted from 2016 to 2019, an ERAS protocol was implemented for patients undergoing LD flap breast reconstruction. The primary outcome was 24-h discharge, and secondary outcomes were readmission rate, complications, and quality of recovery. Outcomes of patients who underwent LD flap reconstruction with the ERAS protocol were compared with those of a retrospective cohort of patients who underwent LD flap reconstruction with TRAS protocols., Results: Twenty patients enrolled in the ERAS group were compared with 58 patients in the TRAS group. Postoperatively, 100% of ERAS patients were discharged within 24 h (60% on the same day) as compared to 21% (9% on the same day) in the TRAS group (p<0.0001). Minor and major complication rates were similar (30% ERAS vs. 33% TRAS and 20% ERAS vs. 10% TRAS, respectively, p > 0.05). There was significant reduction in length of stay and total cost between the two groups (6.4 h vs. 58.5 h (p = 0.003) and $5,666.80 vs. $8890.25 (p = 0.0003), respectively)., Conclusions: Breast reconstruction with the LD flap can be performed safely and effectively in the ambulatory setting. The implementation of an ERAS protocol was successful in discharging all patients home within 24 h, and the expedited discharge was associated with an acceptable complication rate, reduced length of stay, and excellent quality of recovery. Conversion from TRAS to ERAS protocols was associated with $3,223.45 cost savings per patient., (Copyright © 2019 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: The prevalence of cigarette smoking is significantly higher among those living at or below the federal poverty level. Cell phone-based interventions among such populations have the potential to reduce smoking rates and be cost-effective., Methods: We performed a cost-effectiveness analysis of three smoking cessation interventions: Standard Care (SC) (brief advice to quit, nicotine replacement therapy and self-help written materials), Enhanced Care (EC) (SC plus cell phone-delivered messaging) and Intensive Care (IC) (EC plus cell phone-delivered counselling). Quit rates were obtained from Project ACTION (Adult smoking Cessation Treatment through Innovative Outreach to Neighborhoods). We evaluated shorter-term outcomes of cost per quit and long-term outcomes using cost per quality-adjusted life year (QALY)., Results: For men, EC cost an additional $541 per quit vs SC; however, IC cost an additional $5232 per quit vs EC. For women, EC was weakly dominated by IC-IC cost an additional $1092 per quit vs SC. Similarly, for men, EC had incremental cost-effectiveness ratio (ICER) of $426 per QALY gained vs SC; however, IC resulted in ICER of $4127 per QALY gained vs EC. For women, EC was weakly dominated; the ICER of IC vs SC was $1251 per QALY gained. The ICER was below maximum acceptable willingness-to-pay threshold of $50 000 per QALY under all alternative modelling assumptions., Discussion: Cell phone interventions for low socioeconomic groups are a cost-effective use of healthcare resources. Intensive Care was the most cost-effective strategy both for men and women., Trial Registration Number: NCT00948129; Results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Little is known about the mechanisms linking contingency management (CM) treatment with smoking cessation, and recent research suggests that the CM approach is associated with better smoking cessation outcomes among females than males. The current study investigated self-efficacy as a potential mechanism through which CM treatment influences smoking cessation, and explored whether these relationships differed by sex., Methods: Participants (N = 139) were primarily Black (63.3%) and female (57.6%) adults enrolled in a safety-net hospital smoking cessation program. Participants received usual care (UC), which included pharmacotherapy and counseling sessions (n = 66) or a CM intervention (UC + 4 weeks of small, abstinence contingent financial incentives; n = 73). Self-efficacy for quitting was measured on the day after quitting with the Self-Efficacy Scale/Confidence (SESC) questionnaire. Mediation analyses were conducted to evaluate the indirect effects of treatment group on biochemically-verified abstinence (4-weeks post-quit) via self-efficacy, and moderated mediation analyses were conducted to evaluate the moderating role of sex., Results: Self-efficacy was not found to mediate the relations between CM treatment and smoking cessation in the overall sample. However, analyses indicated a significant moderating effect of sex on the indirect effect of treatment group on smoking cessation through self-efficacy (each of the 3 SESC subscales). Specifically, there was a stronger association between CM and greater self-efficacy among females than males., Conclusion: Findings suggest that CM treatment had a differing impact on self-efficacy among males and females, which in turn influenced the likelihood of smoking cessation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Tobacco use among persons living with HIV represents an important risk factor for poor treatment outcomes, morbidity, and mortality. Thus, efforts designed to inform the development of appropriate smoking cessation programs for this population remains a public health priority. To address this need, a study was conducted to longitudinally assess the relationship between intention to quit smoking and cessation over the 12-month period following initiation of HIV care., Methods: Patients initiating HIV care at a large inner city safety net clinic were enrolled (n = 378) in a 12-month prospective study. Audio computer-assisted self-interviews were conducted at baseline, and at 3, 6, 9, and 12 months post-enrollment, and HIV-related clinical data were collected from participants' electronic medical records. Variables of interest included intention to quit smoking, 7-day point prevalence smoking abstinence (biochemically verified), and stage of HIV. Data were collected in Houston, Texas from 2009 to 2015., Results: The sample was 75% male and 62% Black. Findings indicated that intention to quit smoking increased between baseline and 3 months, and subsequently trended downward from 3 to 12 months. Results from linear and generalized linear mixed models indicated that participants with advanced HIV disease (vs. not advanced) reported significantly (p < .05) higher intention to quit smoking at 3, 6, and 12 months post-study enrollment. A similar though nonsignificant pattern was observed in the smoking abstinence outcome., Conclusions: HIV treatment initiation appears to be associated with increases in intention to quit smoking thus serves as a potential teachable moment for smoking cessation intervention., Implications: This study documents significant increases in intention to quit smoking in the 3-month period following HIV care initiation. Moreover, quit intention trended downward following the 3-month follow-up until the 12-month follow-up. In addition, a marked effect for HIV disease stage was observed, whereby participants with advanced HIV disease (vs. those without) experienced a greater increase in intention to quit. HIV treatment initiation appears to be associated with increases in intention to quit smoking, thus serves as a crucial teachable moment for smoking cessation intervention for people living with HIV.

Background: Smartphone apps can provide real-time, tailored interventions for smoking cessation. The current study examines the effectiveness of a smartphone-based smoking cessation application that assessed risk for imminent smoking lapse multiple times per day and provided messages tailored to current smoking lapse risk and specific lapse triggers., Methods: Participants (N=59) recruited from a safety-net hospital smoking cessation clinic completed phone-based ecological momentary assessments (EMAs) 5 times/day for 3 consecutive weeks (1week pre-quit, 2weeks post-quit). Risk for smoking lapse was estimated in real-time using a novel weighted lapse risk estimator. With each EMA, participants received messages tailored to current level of risk for imminent smoking lapse and self-reported presence of smoking urge, stress, cigarette availability, and motivation to quit. Generalized linear mixed model analyses determined whether messages tailored to specific lapse risk factors were associated with greater reductions in these triggers than messages not tailored to specific triggers., Results: Overall, messages tailored to smoking urge, cigarette availability, or stress corresponded with greater reductions in those triggers than messages that were not tailored to specific triggers (p's=0.02 to <0.001). Although messages tailored to stress were associated with greater reductions in stress than messages not tailored to stress, the association was non-significant (p=0.892) when only moments of high stress were included in the analysis., Conclusions: Mobile technology can be used to conduct real-time smoking lapse risk assessment and provide tailored treatment content. Findings provide initial evidence that tailored content may impact users' urge to smoke, stress, and cigarette availability., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Efforts are needed to ensure that smokers with lower health literacy are provided with understandable and impactful information about the health consequences of smoking and benefits of quitting., Purpose: To test the influence of health literacy on smokers' responses to health risk messages manipulated on framing (gain vs. loss) and emotionality (factual vs. emotional)., Methods: Participants (N = 402) were randomized to evaluate one of four sets of smoking risk messages (factual gain-framed, factual loss-framed, emotional gain-framed, or emotional loss-framed). Multiple linear regressions examined main effects of health literacy, message emotionality, and message framing on: (a) risk perceptions, (b) behavioral expectations (i.e. cut down, limit, quit), and (c) risk knowledge. Two-way interactions of health literacy with emotionality and framing were examined for these outcomes. Analyses were based on theory-driven, a priori hypotheses., Results: As hypothesized, main effects emerged such that smokers with higher health literacy reported stronger risk perceptions and knowledge retention regardless of message type. Additionally, emotional (vs. factual) and gain- (vs. loss-) framed messages were associated with certain lower risk perceptions regardless of health literacy level. Consistent with hypotheses, two-way crossover interactions emerged between health literacy and emotionality. Among smokers with higher health literacy, factual messages produced higher perceived risk and stronger expectations for quitting. Among smokers with lower health literacy, emotional messages produced higher perceived risk and stronger expectations for quitting., Conclusions: Health literacy plays an important role in influencing how smokers respond to different risk messages. One's health literacy should be considered when determining whether risk communications emphasize factual or emotional content.

Background: Financial strain has an adverse impact on smoking cessation. However, the mechanisms through which financial strain influences cessation remain unclear. The purpose of the current study was to determine whether financial strain indirectly influenced smoking cessation through withdrawal symptom severity., Methods: Participants (N=139) were primarily Black (63.3%) and female (57.6%) adults enrolled in a smoking cessation program at a safety-net hospital. A self-report financial strain questionnaire was completed one week prior to the scheduled quit date, and the Wisconsin Smoking Withdrawal Scale (WSWS) was completed on the day after the scheduled quit date. Biochemically-verified 7-day point prevalence abstinence was assessed four weeks after the scheduled quit date. Adjusted mediation analyses were conducted using the PROCESS macro for SPSS to evaluate the indirect effects of financial strain on smoking cessation via post-quit withdrawal symptom severity., Results: Analyses indicated a significant indirect effect of financial strain on smoking cessation through total withdrawal symptom severity, B=0.027; 95% CI (0.003, 0.066); and specifically anger, B=0.035; 95% CI (0.008, 0.074), anxiety, B=0.021; 95% CI (0.001, 0.051), and sleep symptoms, B=0.015; 95% CI (0.005, 0.043). Greater pre-quit financial strain was associated with greater post-quit withdrawal symptom severity, which increased the likelihood of non-abstinence 4 weeks after the scheduled quit attempt. The direct effect of financial strain on smoking cessation was not significant in any of the mediation models., Conclusions: Findings: suggest that withdrawal severity is an underlying mechanism through which financial strain influences smoking cessation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Electronic cigarettes' (e-cigarettes) viability as a public health strategy to end smoking will likely be determined by their ability to mimic the pharmacokinetic profile of a cigarette while also exposing users to significantly lower levels of harmful/potentially harmful constituents (HPHCs). The present study examined the nicotine delivery profile of third- (G3) versus second-generation (G2) e-cigarette devices and their users' exposure to nicotine and select HPHCs compared with cigarette smokers., Methods: 30 participants (10 smokers, 9 G2 and 11 G3 users) completed baseline questionnaires and provided exhaled carbon monoxide (eCO), saliva and urine samples. Following a 12-hour nicotine abstinence, G2 and G3 users completed a 2-hour vaping session (ie, 5 min, 10-puff bout followed by ad libitum puffing for 115 min). Blood samples, subjective effects, device characteristics and e-liquid consumption were assessed., Results: Smokers, G2 and G3 users had similar baseline levels of cotinine, but smokers had 4 and 7 times higher levels of eCO (p<0.0001) and total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (i.e., NNAL, p<0.01), respectively, than G2 or G3 users. Compared with G2s, G3 devices delivered significantly higher power to the atomiser, but G3 users vaped e-cigarette liquids with significantly lower nicotine concentrations. During the vaping session, G3 users achieved significantly higher plasma nicotine concentrations than G2 users following the first 10 puffs (17.5 vs 7.3 ng/mL, respectively) and at 25 and 40 min of ad libitum use. G3 users consumed significantly more e-liquid than G2 users. Vaping urges/withdrawal were reduced following 10 puffs, with no significant differences between device groups., Discussion: Under normal use conditions, both G2 and G3 devices deliver cigarette-like amounts of nicotine, but G3 devices matched the amount and speed of nicotine delivery of a conventional cigarette. Compared with cigarettes, G2 and G3 e-cigarettes resulted in significantly lower levels of exposure to a potent lung carcinogen and cardiovascular toxicant. These findings have significant implications for understanding the addiction potential of these devices and their viability/suitability as aids to smoking cessation., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: The current study evaluated the feasibility and effectiveness of a diet and physical activity intervention for homeless adults., Methods: Shelter residents (N = 32) were randomly assigned to a 4-week diet and physical activity intervention (n = 17) or an assessment-only control group (n = 15). Intervention participants received tailored educational newsletters, pedometers with step goals, and twice daily fruit/vegetable snacks. Key measures included 24-hour dietary recall interviews and accelerometer-measured moderate-to-vigorous intensity physical activity (MVPA)., Results: At baseline, 68.8% of participants were overweight or obese, 93.8% reported food insecurity, and 43.8% reported activity levels below physical activity guidelines. Baseline dietary recall interviews indicated low fruit/vegetable consumption, and elevated intake of added sugar, saturated fat, and sodium relative to current dietary recommendations. During the 4-week study period, intervention participants engaged in significantly greater accelerometer-measured daily MVPA (P < .001) than controls (median = 60 daily minutes p vs. 41 daily minutes). Between groups differences in fruit/vegetable consumption at the end of treatment did not reach statistical significance. Most participants reported that the intervention was helpful for increasing fruit/vegetable intake and physical activity., Conclusions: Findings highlight the potential to improve dietary quality and increase physical activity among sheltered homeless adults.

Background: Despite substantial public health progress in reducing the prevalence of smoking in the United States overall, smoking among socioeconomically disadvantaged adults remains high., Objective: To determine the feasibility and preliminary effectiveness of a novel smartphone-based smoking cessation app designed for socioeconomically disadvantaged smokers., Methods: Participants were recruited from a safety-net hospital smoking cessation clinic in Dallas, Texas, and were followed for 13 weeks. All participants received standard smoking cessation clinic care (ie, group counseling and cessation pharmacotherapy) and a smartphone with a novel smoking cessation app (ie, Smart-T). The Smart-T app prompted 5 daily ecological momentary assessments (EMAs) for 3 weeks (ie, 1 week before cessation and 2 weeks after cessation). During the precessation period, EMAs were followed by messages that focused on planning and preparing for the quit attempt. During the postcessation period, participant responses to EMAs drove an algorithm that tailored messages to the current level of smoking lapse risk and currently present lapse triggers (eg, urge to smoke, stress). Smart-T offered additional intervention features on demand (eg, one-click access to the tobacco cessation quitline; "Quit Tips" on coping with urges to smoke, mood, and stress)., Results: Participants (N=59) were 52.0 (SD 7.0) years old, 54% (32/59) female, and 53% (31/59) African American, and 70% (40/57) had annual household income less than US $16,000. Participants smoked 20.3 (SD 11.6) cigarettes per day and had been smoking for 31.6 (SD 10.9) years. Twelve weeks after the scheduled quit date, 20% (12/59) of all participants were biochemically confirmed abstinent. Participants responded to 87% of all prompted EMAs and received approximately 102 treatment messages over the 3-week EMA period. Most participants (83%, 49/59) used the on-demand app features. Individuals with greater nicotine dependence and minority race used the Quit Tips feature more than their counterparts. Greater use of the Quit Tips feature was linked to nonabstinence at the 2 (P=.02), 4 (P<.01), and 12 (P=.03) week follow-up visits. Most participants reported that they actually used or implemented the tailored app-generated messages and suggestions (83%, 49/59); the app-generated messages were helpful (97%, 57/59); they would like to use the app in the future if they were to lapse (97%, 57/59); and they would like to refer friends who smoke to use the Smart-T app (85%, 50/59). A minority of participants (15%, 9/59) reported that the number of daily assessments (ie, 5) was "too high.", Conclusions: This novel just-in-time adaptive intervention delivered an intensive intervention (ie, 102 messages over a 3-week period), was well-liked, and was perceived as helpful and useful by socioeconomically disadvantaged adults who were seeking smoking cessation treatment. Smartphone apps may be used to increase treatment exposure and may ultimately reduce tobacco-related health disparities among socioeconomically disadvantaged adults., Competing Interests: Conflicts of Interest: None declared., (©Michael S Businelle, Ping Ma, Darla E Kendzor, Summer G Frank, Damon J Vidrine, David W Wetter. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 12.12.2016.)

Background: Mobile phone‒based real-time ecological momentary assessments (EMAs) have been used to record health risk behaviors, and antecedents to those behaviors, as they occur in near real time., Objective: The objective of this study was to determine if intensive longitudinal data, collected via mobile phone, could be used to identify imminent risk for smoking lapse among socioeconomically disadvantaged smokers seeking smoking cessation treatment., Methods: Participants were recruited into a randomized controlled smoking cessation trial at an urban safety-net hospital tobacco cessation clinic. All participants completed in-person EMAs on mobile phones provided by the study. The presence of six commonly cited lapse risk variables (ie, urge to smoke, stress, recent alcohol consumption, interaction with someone smoking, cessation motivation, and cigarette availability) collected during 2152 prompted or self-initiated postcessation EMAs was examined to determine whether the number of lapse risk factors was greater when lapse was imminent (ie, within 4 hours) than when lapse was not imminent. Various strategies were used to weight variables in efforts to improve the predictive utility of the lapse risk estimator., Results: Participants (N=92) were mostly female (52/92, 57%), minority (65/92, 71%), 51.9 (SD 7.4) years old, and smoked 18.0 (SD 8.5) cigarettes per day. EMA data indicated significantly higher urges (P=.01), stress (P=.002), alcohol consumption (P<.001), interaction with someone smoking (P<.001), and lower cessation motivation (P=.03) within 4 hours of the first lapse compared with EMAs collected when lapse was not imminent. Further, the total number of lapse risk factors present within 4 hours of lapse (mean 2.43, SD 1.37) was significantly higher than the number of lapse risk factors present during periods when lapse was not imminent (mean 1.35, SD 1.04), P<.001. Overall, 62% (32/52) of all participants who lapsed completed at least one EMA wherein they reported ≥3 lapse risk factors within 4 hours of their first lapse. Differentially weighting lapse risk variables resulted in an improved risk estimator (weighted area=0.76 vs unweighted area=0.72, P<.004). Specifically, 80% (42/52) of all participants who lapsed had at least one EMA with a lapse risk score above the cut-off within 4 hours of their first lapse., Conclusions: Real-time estimation of smoking lapse risk is feasible and may pave the way for development of mobile phone‒based smoking cessation treatments that automatically tailor treatment content in real time based on presence of specific lapse triggers. Interventions that identify risk for lapse and automatically deliver tailored messages or other treatment components in real time could offer effective, low cost, and highly disseminable treatments to individuals who do not have access to other more standard cessation treatments., Competing Interests: Conflicts of Interest: None declared.

Breast reconstruction can be performed using a variety of techniques, most commonly categorized into an alloplastic approach or an autologous tissue method. Both strategies have certain risk factors that influence reconstructive outcomes and complication rates. In alloplastic breast reconstruction, surgical outcomes and complication rates are negatively impacted by radiation, smoking, increased body mass index (BMI), hypertension, and prior breast conserving therapy. Surgical factors such as the type of implant material, undergoing immediate breast reconstruction, and the use of fat grafting can improve patient satisfaction and aesthetic outcomes. In autologous breast reconstruction, radiation, increased BMI, certain previous abdominal surgery, smoking, and delayed reconstruction are associated with higher complication rates. Though a pedicled transverse rectus abdominis myocutaneous (TRAM) flap is the most common type of flap used for autologous breast reconstruction, pedicled TRAMs are more likely to be associated with fat necrosis than a free TRAM or deep inferior epigastric perforator (DIEP) flap. Fat grafting can also be used to improve aesthetic outcomes in autologous reconstruction. This article focuses on factors, both patient and surgical, that are predictors of complications and outcomes in breast reconstruction.

Background: The infiltration of local anesthetics can be painful, which is likely due, in part, to their acidity. In spite of a Cochrane study that recommended neutralizing lidocaine with bicarbonate to decrease the pain of injection, not many surgeons have adopted the practice, and there are many 'recipes' for how much bicarbonate one should add., Objective: To determine the acidity of lidocaine and the correct ratio of bicarbonate that should be added to neutralize lidocaine to achieve body pH., Methods: Fifty samples each of commonly used anesthetics (lidocaine 1% and 2%, with and without epinephrine 1:100,000) were obtained and tested for pH. Data were also analyzed according to whether the vials had been previously opened. Ten additional samples of lidocaine 1% with 1:100,000 epinephrine were titrated against sodium bicarbonate 8.4% and tested for pH and the presence of precipitate., Results: A solution of 1% lidocaine with 1:100,000 epinephrine had a mean (± SD) pH of 4.24±0.42, and 2% lidocaine with 1:100,000 epinephrine had a mean pH of 3.93±0.43. Plain 1% lidocaine had a pH of 6.09±0.16, and plain 2% lidocaine had a pH of 6.00±0.27. Epinephrine-containing solutions were more acidic when they had been previously opened. One per cent lidocaine with epinephrine required 8.4% sodium bicarbonate at a ratio of 1.1 mL:10 mL to 1.8 mL:10 mL to achieve the target tissue pH of 7.38 to 7.62., Conclusion: Lidocaine with epinephrine was approximately 1000 times more acidic than subcutaneous tissue. The addition of bicarbonate to the local anesthetic solution is simple to perform and is inexpensive. The proper volume ratio of 8.4% sodium bicarbonate to 1% lidocaine with 1:100,000 epinephrine is approximately 1 mL:10 mL. Surgeons should be more aware of the simplicity and value of buffering with bicarbonate to decrease the pain of injection.

Objective: To evaluate the anti-inflammatory and analgesic activities of leaf extract of Melanthera scandens (M. scandens)., Methods: The crude leaf extract (39-111 mg/kg) of M. scandens was investigated for anti-inflammatory and analgesic activities using various experimental models. The anti-inflammatory activity was investigated using carragenin, egg-albumin induced oedema models, while acetic acid, formalin-induced paw licking and thermal-induced pain models were used to evaluate the antinociceptive property., Results: The extract caused a significant (P<0.05 - 0.001) dose-dependent reduction of inflammation and pains induced by different agents used., Conclusions: The leaf extract possesses anti-inflammatory and analgesic effects which may be mediated through the phytochemical constituents of the plant.

Background: Heat shock proteins (Hsps) play a role in the delivery and presentation of antigenic peptides and are thought to be involved in the pathogenesis of multifactorial diseases., Objective: To investigate genes encoding cytosolic Hsp70 proteins for associations of allelic variants with systemic lupus erythematosus (SLE)., Methods: Case-control studies of two independent Caucasian SLE cohorts were performed. In a haplotype-tagging single-nucleotide polymorphism approach, common variants of HspA1L, HspA1A and HspA1B were genotyped and principal component analyses were performed for the cohort from the Oklahoma Medical Research Foundation (OMRF). Relative quantification of mRNA was carried out for each Hsp70 gene in healthy controls. Conditional regression analysis was performed to determine if allelic variants in Hsp70 act independently of HLA-DR3., Results: On analysis of common genetic variants of HspA1L, HspA1A and HspA1B, a haplotype significantly associated with SLE in the Erlangen-SLE cohort was identified, which was confirmed in the OMRF cohort. Depending on the cohorts, OR ranging from 1.43 to 1.88 and 2.64 to 3.16 was observed for individuals heterozygous and homozygous for the associated haplotype, respectively. Patients carrying the risk haplotype or the risk allele more often displayed autoantibodies to Ro and La in both cohorts. In healthy controls bearing this haplotype, the amount of HspA1A mRNA was significantly increased, whereas total Hsp70 protein concentration was not altered., Conclusions: Allelic variants of the Hsp70 genes are significantly associated with SLE in Caucasians, independently of HLA-DR3, and correlate with the presence of autoantibodies to Ro and La. Hence, the Hsp70 gene locus appears to be involved in SLE pathogenesis.

Background: Insertion of a radial head implant that results in radial overlengthening has been associated with altered elbow kinematics, increased radiocapitellar joint forces, capitellar erosions, early-onset arthritis, and loss of elbow flexion. The purpose of this study was to identify clinical and radiographic features that may be used to diagnose overlengthening of the radius intraoperatively and on postoperative radiographs., Methods: Radial head implants of varying thicknesses were inserted into seven cadaver specimens, which were then assessed clinically and radiographically. Eight stages were examined: the intact specimen (stage 1); repair of the lateral collateral ligament (stage 2); radial head resection with repair of the lateral collateral ligament (stage 3); insertion of an implant of the correct thickness (stage 4); and insertion of an implant that resulted in radial overlengthening of 2 mm (stage 5), 4 mm (stage 6), 6 mm (stage 7), or 8 mm (stage 8). The specimens were tested with and without muscle loading to simulate resting muscle tone and surgical paralysis, respectively. At each stage, radiographs were made to measure the ulnohumeral joint space and the lateral ulnohumeral joint was visually assessed., Results: We identified no difference, with regard to medial ulnohumeral joint incongruity as seen radiographically, among stages 1 through 6 during the tests with muscle loading. A significant difference in medial ulnohumeral joint incongruity was found in stages 7 (p = 0.003) and 8 (p < 0.001). The clinical (visually assessed) lateral ulnohumeral joint space gap was negligible in stages 1 through 4 but increased significantly at all stages involving overlengthening (gross gap, 0.9 mm with 2 mm of overlengthening [p = 0.005], 2.3 mm with 4 mm of overlengthening [p < 0.001], 3.4 mm with 6 mm [p < 0.001], and 4.7 mm with 8 mm [p < 0.001])., Conclusions: Incongruity of the medial ulnohumeral joint becomes apparent radiographically only after overlengthening of the radius by >or=6 mm. Intraoperative visualization of a gap in the lateral ulnohumeral joint is a reliable indicator of overlengthening following the insertion of a radial head prosthesis.

A set of PharmD program curricular outcomes form the foundation of a doctor of pharmacy (PharmD) curriculum and are critical to the development of both the structure/courses of the curriculum and the assessment plan for the program. A goal for developing these outcomes is to craft a set of clear, concise, assessable statements that accurately reflect competencies of the generalist entry-level pharmacist or graduate of the first-professional doctor of pharmacy degree. This article will provide a review of one specific type of outcome, ability-based outcomes, and present a case study of how one college revised their PharmD program-level outcomes. A discussion of key elements for the successful adoption of these outcomes is also presented.

Curricular maps can be used to link ability-based outcomes (ABOs) and content to courses in PharmD curricula as one component of an overall assessment plan. Curricular maps can also be used to meet some of the requirements delineated by Accreditation Council for Pharmacy Education, Standards 2007. Five steps can be followed to help ensure the successful production of a curricular map that both meets accreditation requirements and helps to inform curricular improvements. A case study is presented detailing how one college implemented a curricular mapping process that was subsequently used as data to inform curricular revisions.

The pentraxin C-reactive protein (CRP), an innate immune system opsonin which binds nuclear debris and apoptotic bodies, may protect against autoimmunity. A relative deficiency of CRP levels in patients with systemic lupus erythematosus (SLE) might contribute to altered handling of self-antigens. We report that the proximal 5' promoter region of CRP contains several polymorphisms that exhibit association with SLE in multiple populations. Strongest association was observed at the proximal promoter single nucleotide polymorphism (SNP) rs3093061 (CRP-707) (P = 6.41 x 10(-7) and P = 2.13 x 10(-6) in African-American and Caucasian case-control samples respectively). This association remains after adjustment for admixture. Linkage disequilibrium exists between SNPs in the proximal promoter and association of functional haplotypes containing rs3091244/rs3093062 (CRP-409/-390) appear to be driven by the rs3093061 (CRP-707) association. These data demonstrate that rs3093061 at the -707 site within the CRP gene is an SLE susceptibility locus.

Increased expression of interferon (IFN)-inducible genes is implicated in the pathogenesis of systemic lupus erythematosus (SLE). One transcription factor responsible for regulating IFN, interferon regulatory factor-5 (IRF5), has been associated with SLE in genetic studies of Asian, Caucasian and Hispanic populations. We genotyped up to seven polymorphic loci in or near IRF5 in a total of 4870 African-American and Caucasian subjects (1829 SLE sporadic cases and 3041 controls) from two independent studies. Population-based case-control comparisons were performed using the Pearson's chi(2)-test statistics and haplotypes were inferred using HaploView. We observed significant novel associations with the IRF5 variants rs2004640 and rs3807306 in African Americans and replicated previously reported associations in Caucasians. While we identified risk haplotypes, the majority of haplotypic effects were accounted for by one SNP (rs3807306) in conditional analyses. We conclude that genetic variants of IRF5 associate with SLE in multiple populations, providing evidence that IRF5 is likely to be a crucial component in SLE pathogenesis among multiple ethnic groups.

Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with complex etiology but strong clustering in families (lambda(S) = approximately 30). We performed a genome-wide association scan using 317,501 SNPs in 720 women of European ancestry with SLE and in 2,337 controls, and we genotyped consistently associated SNPs in two additional independent sample sets totaling 1,846 affected women and 1,825 controls. Aside from the expected strong association between SLE and the HLA region on chromosome 6p21 and the previously confirmed non-HLA locus IRF5 on chromosome 7q32, we found evidence of association with replication (1.1 x 10(-7) < P(overall) < 1.6 x 10(-23); odds ratio = 0.82-1.62) in four regions: 16p11.2 (ITGAM), 11p15.5 (KIAA1542), 3p14.3 (PXK) and 1q25.1 (rs10798269). We also found evidence for association (P < 1 x 10(-5)) at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases, as well as at > or =9 other loci (P < 2 x 10(-7)). Our results show that numerous genes, some with known immune-related functions, predispose to SLE.

Supersaturated and crystallized lidocaine (LC)/pressure sensitive adhesive (PSA) systems have been studied by differential scanning calorimetry (DSC) and FT-IR with the objective of characterizing the thermodynamic states and compatibility of the two-component systems. Analysis of the phase behavior of LC/DT2287 systems indicates that LC and DT2287 are thermodynamically miscible within the composition range containing less than approximately 20% w/w LC, beyond which LC may crystallize from the blends forming a separated crystalline phase. The composition dependence of the glass transition temperature (T(g)) was used to characterize the physical and thermodynamic states of the supersaturated systems. The Fox, Gordon-Taylor, Kwei, Kovacs, and Brekner, Schneider and Cantow (BSC) equations were employed to conduct the analysis. It was found that the PSA in the supersaturated LC/PSA systems underwent significant entropic relaxation upon mixing. LC in the miscible systems is absorbed into and swells the polymer network of the PSA, thereby exhibiting reduced molecular mobility, while the PSA attains significant molecular conformation relaxation and entropy increase. It was also found that LC molecules extensively participate in molecular relaxation of the PSA throughout the composition range studied. The molecular mobility of LC is inhibited as the volume fraction of DT2287 increases, suggesting that the PSA molecular network reduces the molecular mobility of LC by closely involving LC molecules in its relaxation, and thereby may enhancing the physical stability of the systems. No strong intermolecular interactions between the two components were found based upon the results of T(g)-composition analysis, and was confirmed by FT-IR studies. This indicates that the analysis based on the BSC equation provides more precise characterization of polymer systems than the T(g) -composition analysis based on other equations cited., (Copyright 2006 Wiley-Liss, Inc. and the American Pharmacists Association.)

Isothermal crystallization of lidocaine (LC) in supersaturated LC/Duro-Tak 87-2287 (DT2287) polyacrylate pressure sensitive adhesive (PSA) systems has been studied by differential scanning calorimetry (DSC). It was found that crystallization of LC in supersaturated LC/DT2287 systems was governed by the nucleation process, which in turn was dependent on temperature and composition of the systems. A critical temperature T(crit) was found at approximately 26 degrees C, above which the crystallization of LC in LC/DT2287 systems becomes slow. The lack of dependence of T(crit) on the composition of the mixtures indicates that the presence of the PSA affected the kinetics (diffusion) rather than the thermodynamics of the nucleation process. A critical degree of saturation S(crit) of approximately 4 was also found, above which the nucleation rate sharply increases. Kinetic analysis based on the classical theory of nucleation indicates that nucleation of LC in the PSA medium is a diffusion-controlled process. The activation energy of crystallization had a two-phase dependence on temperature suggesting that the mechanism of crystallization may change at the transition temperatures. As the weight fraction of LC increased in the systems, the activation energy of crystallization, DeltaG(c), was minimal at approximately 15 degrees C, indicating that the nucleation of LC in the LC/DT2287 systems is at its fastest rate around this temperature. These fundamental analyses of nucleation and crystallization mechanisms are of practical significance in the design of supersaturated drug delivery systems.

To evaluate pluronic polyol F-127 (PF-127) as a vitreous substitute and an intraocular drug delivery system, a total vitrectomy was performed on 18 New Zealand rabbits (18 eyes). The vitreous was replaced with either PF-127 (9 eyes) or balanced salt solution (9 eyes). There was little difference clinically between the eyes containing PF-127 and the control eyes. Both groups showed mild postoperative inflammation, with no differences in intraocular pressures. Histopathologic findings for the control group showed no significant retinal alteration, and serial ERG findings were within normal limits. In contrast, the eyes containing PF-127 showed marked destruction of the retina by 2 weeks after surgery. The ERG amplitudes decreased dramatically to a flat tracing by 24 hours after surgery. Although it is attractive as a potential vitreous substitute, PF-127 is not safe for human use, at least at the concentration used.

The distribution conditions in oil-water emulsions prepared by emulsifying a 1:1 eutectic mixture of lidocaine and prilocaine with a nonionic surfactant in water were studied by membrane and gel filtration methods. In this system, the local anesthetics are considered to be freely dissolved, surfactant solubilized, and emulsified in three separate phases. The dispersity of the oil phase was investigated by light microscopy and light-scatter spectroscopy. The majority of drops in the lidocaine-prilocaine emulsions were less than 1 micron in size. The concentration of freely dissolved drug in the aqueous phase of the emulsions was equal to the aqueous solubility of lidocaine-prilocaine in a 1:1 ratio. At constant lidocaine/prilocaine/surfactant ratio, increasing the total drug concentration in the emulsion resulted in an increase of the emulsified fraction of lidocaine-prilocaine, whereas the surfactant-solubilized fraction remained constant.

The amount and size of particulate contamination in three commercially available cephalosporin injections and a new product, anophilized cephalothin sodium injection, were studied. Particles in reconstituted cephalothin sodium (commercially available and anophilized), cephapirin sodium, and cephradine injections were counted using two methods: (1) modified USP membrane-filtration technique and (2) Elzone computerized particle analyzer. The amount of particulate contamination in the ranges of 10-24 and greater than or equal to 25 microns was determined by both methods. In the 10-24-microns range, the cephalothin, cephapirin, and cephradine products had significantly greater particle counts than the anophilized cephalothin product. The greater than or equal to 25-microns particle counts showed that the cephapirin and cephradine products had particle counts greater than the anophilized cephalothin product, while total particle counts showed the same results as the 10-24-microns particle counts. A comparison of counting methods showed that the only significant difference between the number of particulates obtained using the modified USP and Elzone computer methods was with the cephalothin product. Anophilized cephalothin sodium injection has significantly fewer particles in the size ranges studied. No conclusion could be reached as to the more accurate method for counting particles.

The formation of an inclusion compound by beta-cyclodextrin with hydrocortisone has been studied by proton magnetic resonance (1H-NMR) and phase solubility analysis. The magnitude of the chemical shifts of the interior and exterior beta-cyclodextrin protons in the presence of hydrocortisone indicated that hydrocortisone is included within the beta-cyclodextrin cavity and probably interacts with protons on the edge of the torus. The overall stoichiometry of the inclusion compound was not a single, simple relationship, but was unusual in that it was variable and apparently dependent on the relative amounts of hydrocortisone and beta-cyclodextrin in the system.

The mechanism of inclusion compound formation by dinoprostone (prostaglandin E2) with beta-cyclodextrin was studied by phase solubility analysis and PMR spectroscopy. As indicated by the linear increase of aqueous solubility of dinoprostone with beta-cyclodextrin concentration, some types of molecular interactions definitely exist between dinoprostone and the complexing ligands. The temperature dependence of a 1:1 complex formation constant yielded the following thermodynamic data at 20 degrees : deltaG degrees = -4.11 kcal/mole, deltaH degrees = 7.20 kcal/mole, and deltaS degrees = 10.5 e.u. Since water was the solvent system, these parameters appear to be largely determined by solvent reorganization through hydrogen bonding rather than solely by the binding of desolvated free dinoprostone and beta-cyclodextrin entities. PMR data indicate that dinoprostone is included within the cavity and also interacts with protons on the exterior of the beta-cyclodextrin molecule. A model consisting of a 1:1 complex, in which a dinoprostone molecule is partially included within the cavity and the remainder of the molecule extends around the edge of the opening of the cavity to the exterior of the beta-cyclodextrin molecule, is proposed as the most probable structure of this inclusion compound.

Reduction of naltrexone and naloxone with sodium borohydride gave a mixture (85:15) of the 6alpha- and 6beta-hydroxy epimers, alpha- and beta-naltrexol and alpha- and beta-naloxol, respectively. Each pair of epimers was separated by preparative thin-layer chromatography and the physical and spectral properties of each compound were determined. Previous assignments for the configuration of the epimers were verified. A semi-quantitative electron capture gas-liquid chromatographic method was devised for distinguishing either alpha- or beta-naltrexol in the presence of the other and in the presence of large amounts (at least 10-fold greater) of naltrexone. The method was used to determine the approximate weight ratio of beta-naltrexol to naltrexone present in enzymatically hydrolyzed urine samples. It was found that substantially greater quantities of beta-naltrexol and/or its conjugates were excreted in the urine of man, monkey, guinea pig and rabbit after administration of naltrexone, whereas very small quantities were excreted by the mouse, rat and dog. In contrast, just trace amounts of the 6alpha-hydroxy epimer, alpha-naltrexol, were detected in the urine of only 2 of the 7 species that had received naltrexone, i.e., monkey and guinea pig. After administration of 3H-15,16-naltrexone, 1 mg/kg, i.v. to the guinea pig, 25% of the radioactivity found following thin-layer chromatography of the extract of acid-hydrolyzed urine corresponded to beta-naltrexol. In gall bladder bile from the guinea pig, only conjugates of naltrexone and beta-naltrexol were found 2 hours after administration of naltrexone. Following administration of beta-naltrexol, 1 mg/kg, i.v. to guinea pigs only beta-naltrexol and/or its conjugates were detected in urine or bile. However, urine collected after administration of alpha-naltrexol, 1 mg/kg, i.v. to guinea pigs contained alpha-naltrexol and its conjugates, as well as a yet unidentified metabolite.

In the context of the potential usefulness of clays in retarding the rate of release of adsorbed drugs, dissolution dialysis studies of the release of metronidazole from montmorillonite adsorbates have been conducted. The goal was to develop a means for improving local gastrointestinal therapy of amebiasis while concurrently maintaining efficacy in treating hepatic amebiasis. At acidic pH, the clay was in a flocculated state and the rate of drug release was inhibited. This effect was apparently due to slow diffusion of the drug throughout the clay flocculate. A physical admixture of montmorillonite and metronidazole was also effective in inhibiting the rate of release of metronidazole. Upon increasing the pH to 7, the clay particles progressively deflocculated and the rate of release increased significantly.

The binding of 15,16,-3H-naltrexone in human, monkey, dog, guinea pig, rat, and mouse plasma was investigated over a range of concentrations, including predicted therapeutic levels. Studies using equilibrium dialysis at 37 degrees indicate that the extent of binding is independent of naltrexone concentration over the concentration range of 1-500 ng/ml for dog plasma and of 0.1-500 ng/ml for human, monkey, guinea pig, rat, and mouse plasma. The extent of naltrexone binding in plasma is similar in the six species studied, the range being from 20% bound in rat plasma to 26% in plasma from beagle and mongrel dogs. This relatively low extent of naltrexone binding in plasma is consistent with previous findings of a large apparent volume of distribution of this drug in the dog. To investigate further the distribution of tritiated naltrexone, the tissue levels of radioactivity in mice at 1, 5, and 15 min after intravenous administration of 8-3H-naltrexone were determined. Naltrexone was rapidly distributed from plasma to tissues, with less than 4% of the dose being present in plasma at 1 min after injection.

The in vitro drug release properties of a topical anesthetic formulation known to be effective on intact skin, based on a 1:1 eutectic mixture of lidocaine and prilocaine emulsified in water, were investigated with a poly(dimethylsiloxane) membrane partition model. Aqueous solutions and solubilized systems of lidocaine and prilocaine in a 1:1 ratio by weight were also included in the study as well as the eutectic mixture itself. Two identical sets of samples were used, one of which was gelled with carbomer 934 P. Drug solubilities in the membrane, partition coefficients between membrane and water, and diffusion coefficients in the membrane and the formulations were determined. As in the case of an aqueous medium, lidocaine and prilocaine in combination had lower solubilities in the membrane than they did separately. However, in the aqueous phase or in the membrane, the diffusion coefficients were mutually independent. Carbomer 934P, when neutralized totally with sodium hydroxide, did not decrease the aqueous diffusivities of the local anesthetic bases. The major advantages of using the emulsion formulation based on a eutectic mixture rather than more conventional formulations are: (a) the local anesthetic bases are present in their permeable uncharged forms; (b) the use of a poor solvent, water, as the vehicle provides a saturated system at low concentrations; (c) lipophilic solvent is absent in the dispersed phase, the presence of which would decrease the effective distribution coefficients of the active substances between the skin and the formulation; (d) the droplets consist of dissolvable drug and act as reservoirs to obtain steady-state release; and (e) the fluid state of the excess drug provides a higher dissolution rate than from a solid state.