Primary-care observational database study of the efficacy of GLP-1 receptor agonists and insulin in the UK.

AIMS: We investigated use and efficacy of glucagon-like peptide-1 (GLP-1) receptor agonists in UK practice. METHODS: People starting a GLP-1 receptor agonist (exenatide, liraglutide) or insulin (glargine, detemir, NPH) after a regimen of two or three oral glucose-lowering agents were identified from The Health Information Network observational primary care database (2007-2011). Mean change in HbA1c and body weight were compared at 1 year between cohorts, adjusting for baseline characteristics. RESULTS: Baseline characteristics of GLP-1 receptor agonist (n = 1123) vs. insulin (n = 1842) users were HbA1c 78 vs. 84 mmol/mol (9.3 vs. 9.8%) and BMI 38.2 vs. 30.9 kg/m². The GLP-1 receptor agonist cohort was younger, had shorter diabetes duration and follow-up, less microvascular disease and heart failure, higher estimated glomerular filtration rate and more use of oral glucose-lowering agents. Lower HbA1c reduction on GLP-1 receptor agonist [7 vs. 13 mmol/mol (0.6 vs. 1.2%) (n = 366 vs. 892)] was not statistically significant [adjusted mean difference -1.4 (95% CI -4.1, 1.2) mmol/mol], except in the highest HbA1c quintile [>96 mmol/mol (>10.9%); adjusted mean difference -17.8 (-28.6, -7.0) mmol/mol]. GLP-1 receptor agonist users lost weight [-4.5 vs. +1.5 kg; adjusted mean difference 4.7 (3.7, 5.8) kg; n = 335 vs. 634]. A UK 6-month target reduction for GLP-1 receptor agonists of 11 mmol/mol (1.0%) HbA1c and 3% weight was reached by 24.9% of those continuing treatment. CONCLUSIONS: Those starting GLP-1 receptor agonists are heavier with better glycaemic control than those starting basal insulin. Subsequently, they have improved weight change, with similar HbA1c reduction unless baseline HbA1c is very high. The UK 6-month GLP-1 receptor agonist target is usually not reached.

A comparison of duration of first prescribed insulin therapy in uncontrolled type 2 diabetes.

AIMS: We investigated whether differences in duration of first insulin use in type 2 diabetes remain after adjustment for potential confounders, and what factors are associated with longer use. METHODS: People prescribed a first insulin (2000-2007) after 2-3 non-insulin glucose lowering treatments (OGLD) were identified from the THIN UK primary care database and grouped by insulin, detemir (n=165), glargine (n=1011) or NPH (n=420). Time from beginning insulin to the prescription of another insulin type or a glucagon-like peptide was compared between insulins in a Cox model adjusting for: demographics, HbA1c, history of vascular complications and cardiovascular risk factors. The strength of association between duration of use and these variables was investigated. RESULTS: The adjusted hazard ratios compared to glargine for treatment change were 1.58 (95% CI 1.25, 2.00) for detemir and 1.49 (1.25, 1.78) for NPH. Lower mean treatment HbA(1c) correlated with longer time to a different insulin regimen (Spearman rank correlation -0.30, p<0.01) as were continuing OGLDs, older age, longer time from diagnosis, lower body mass index, lower HbA(1c), and no heart failure at baseline. CONCLUSIONS: People who began treatment with glargine and those with better on-treatment HbA(1c) remained on their first insulin for longer than those who began detemir or NPH.

Changes and predictors for change to thiazolidinedione prescribing in UK primary care following the rosiglitazone safety warning.

OBJECTIVE: To investigate switching from thiazolidinediones, and predictors for switching treatment, after publication of a meta-analysis reporting an increased risk of myocardial infarction associated with rosiglitazone use. RESEARCH DESIGN AND METHODS: Using the Health Information Network (THIN) UK primary care database, the number of people with type 2 diabetes prescribed either thiazolidinedione, rosiglitazone (n = 10,062) or pioglitazone (n = 4454), and the rate of switching from thiazolidinediones (n = 3301 and 1106, respectively), were computed for each month, May 2006 to January 2008. The probability of switching post-publication, May 2007 to January 2008, was modelled by logistic regression in a forward stepwise model. Variables included demographics, history of ischaemic heart disease (IHD), heart failure (HF) or stroke, risk factors for IHD, glucose-lowering and cardiovascular drug use, HbA(1c) and diabetes duration. RESULTS: There was a sharp increase in switching from both thiazolidinediones in summer 2007; rosiglitazone prescription numbers then decreased while pioglitazone prescribing increased. Switching from rosiglitazone was associated with IHD [adjusted odds ratio (OR) 1.72; 95% confidence intervals (CI) 1.47-2.00], insulin treatment (OR 5.10; 95% CI 3.21-8.10), HF (OR 2.26; 95% CI 1.62-3.18), a recent sulphonylurea prescription (OR 1.33; 95% CI 1.17-1.51) gender (OR men vs. women 0.79; 95% CI 0.70, 0.90) and duration of therapy. Switching from pioglitazone was associated with HF (OR 3.05; 95% CI 1.77-5.26), duration of therapy, and number of glucose-lowering treatments. CONCLUSIONS: Prescribing habits for both thiazolidinediones changed immediately following the safety warning. IHD was associated with switching from rosiglitazone; otherwise reasons for change appear to be complex, not directly related to the findings of the meta-analysis.

Suicide attempts in a prospective cohort of patients with schizophrenia treated with sertindole or risperidone.

The incidence of suicide attempts (fatal and non-fatal) was analysed in a prospective cohort of patients with schizophrenia randomly assigned to sertindole (4905 patients) or risperidone (4904 patients) in a parallel-group open-label study with blinded classification of outcomes (the sertindole cohort prospective study--SCoP). The total exposure was 6978 and 7975 patient-years in the sertindole and risperidone groups, respectively. Suicide mortality in the study was low (0.21 and 0.28 per 100 patients per year with sertindole and risperidone, respectively). The majority (84%) of suicide attempts occurred within the first year of treatment. Cox's proportional hazards model analysis of the time to the first suicide attempt, reported by treating psychiatrists and blindly reviewed by an independent expert group according to the Columbia Classification Algorithm of Suicide Assessment (both defining suicide attempts by association of suicidal act and intent to die), showed a lower risk of suicide attempt for sertindole-treated patients than for risperidone-treated patients. The effect was statistically significant with both evaluation methods during the first year of randomized treatment (hazard ratios [95% CI]: 0.5 [0.31-0.82], p=0.006; and 0.57 [0.35-0.92], p=0.02, respectively). With classification by an independent safety committee using a broader definition including all incidences of intentional self-harm, also those without clear suicidal intent, the results were not significant. A history of previous suicide attempts was significantly associated with attempted suicides in both treatment groups.

Safety of sertindole versus risperidone in schizophrenia: principal results of the sertindole cohort prospective study (SCoP).

OBJECTIVE: To explore whether sertindole increases all-cause mortality or cardiac events requiring hospitalization, compared with risperidone. METHOD: Multinational randomized, open-label, parallel-group study, with blinded classification of outcomes, in 9858 patients with schizophrenia. RESULTS: After 14147 person-years, there was no effect of treatment on overall mortality (sertindole 64, risperidone 61 deaths, Hazard Ratio (HR) = 1.12 (90% CI: 0.83, 1.50)) or cardiac events requiring hospitalization [sertindole 10, risperidone 6, HR = 1.73 (95% CI: 0.63, 4.78)]: Of these, four were considered arrhythmia-related (three sertindole, one risperidone). Cardiac mortality was higher with sertindole (Independent Safety Committee (ISC): 31 vs. 12, HR=2.84 (95% CI: 1.45, 5.55), P = 0.0022; Investigators 17 vs. 8, HR=2.13 (95% CI: 0.91, 4.98), P = 0.081). There was no significant difference in completed suicide, but fewer sertindole recipients attempted suicide (ISC: 68 vs. 78, HR=0.93 (95% CI: 0.66, 1.29), P = 0.65; Investigators: 43 vs. 65, HR=0.67 (95% CI: 0.45, 0.99), P = 0.044). CONCLUSION: Sertindole did not increase all-cause mortality, but cardiac mortality was higher and suicide attempts may be lower with sertindole.

Validation of the quality of The National Pain Database for pain management services in the United Kingdom.

Data on specialist pain management is scarce. We evaluated PainDB, a database which aggregates this information from UK pain clinics. PainDB entries for 1120 patients (2648 consultations) were compared to records at 30 pain clinics. Staff were surveyed about normal practice at 28 sites. First consultations (17 135) on the aggregated PainDB were analysed for 2003 for omissions. Those consultations included on PainDB (54.6%) showed good concurrence with written notes (88.1%), with no pattern for the missing visits. Questionnaire responses were often absent from notes (56%) and diagnosis was most frequently omitted from PainDB (12.4-18.4%). Clinic staff overestimated completeness. Despite commitment, PainDB is currently unsuitable for research or audit. As routine hospital data should provide information on activity, specific questions on severity and outcome could be answered by short-term recording of predefined variables.

Cardiovascular outcomes among sildenafil users: results of the International Men's Health Study.

AIM: To assess the incidence of serious cardiovascular disease (CVD) events [i.e. myocardial infarction (MI) and stroke] and all-cause mortality in men with erectile dysfunction (ED) who received prescriptions for sildenafil. METHODS: The International Men's Health Study (IMHS) was a prospective, observational cohort study of patients with ED and a new or existing prescription for sildenafil. Baseline and follow-up questionnaires provided information on demographics, CVD risk factors and ED. Postevent questionnaires were mailed to patients following possible nonfatal CVD events to collect information related to exposure to sildenafil/ED treatments before the event. RESULTS: Thirty-five CVD events were reported in 30 patients in the analysis set (n = 3813). The incidence of all-cause mortality, MI and stroke was 0.4, 0.6 and 0.1 per 100 patient-years of observation respectively. Among the six men who reported using sildenafil in the month before a nonfatal CVD event, two reported use in the 24 h before the event. CONCLUSION: The results of the IMHS support previous reports that ED and CVD are often comorbid and share risk factors.

Effectiveness of wet and dry mercury vapour suppressant systems in a faculty of dentistry clinic.

The objective of this study was to determine the effectiveness of a liquid and a dry commercial mercury vapour suppressant system. Measurements were made in a student dental clinic, using a mercury vapour detector for periods up to 76 weeks. The two products examined were Mercon vap liquid in a stock jar and the Mercon tainer dry jar system. Amalgam scrap jars were removed from the study when the mercury vapour concentration in the jars exceeded the arbitrary cut-off criterion of 0.05 mg Hg m(-3). Results showed that the mercury vapour concentration in the liquid system exceeded the cut-off criterion in 44 weeks or less, whereas the dry system remained below the detection limit (0.01 mg Hg m(-3)) for the maximum measurement period of 76 weeks. It was concluded that the dry system is more effective and reliable than the liquid system. The reliability of the liquid system may be influenced by contact of amalgam scrap with the portion of the inner wall of the jar that is not covered by liquid. It is proposed that amalgam scrap contaminates the wall with mercury during its insertion.

Psychotherapy research with ethnic minorities: empirical, ethical, and conceptual issues.

There is an increasing demand for psychotherapy among ethnic minority populations. Yet, there is not adequate evidence that empirically supported therapies (ESTs) are effective with ethnic minorities. Ethical guidelines suggest that psychotherapies be modified to become culturally appropriate for ethnic minority persons. Conceptual approaches have identified interdependence, spirituality, and discrimination as considerations for culturally sensitive therapy (CST). However, there is no more empirical support for the efficacy of CSTs than there is for the efficacy of ESTs with ethnic minority populations. The chasm between EST and CST research is a function of differences between methods and researchers in these 2 traditions. Specific recommendations for research collaboration between CST and EST researchers are offered.

In search of cultural diversity: recent literature in cross-cultural and ethnic minority psychology.

The purpose of this study was to identify where the most work on cross-cultural and ethnic minority psychology is being published and who the most productive authors are. The journals that published the most articles on cross-cultural and ethnic minority issues from 1993 to 1999 and the most prolific authors on these issues were identified by PsycINFO. Cross-cultural research is cross-national, whereas ethnic minority research involves groups of color within the United States. The citation impact of these journals and authors was determined from the 1997 Social Sciences Citation Index. The results suggest that there is very limited overlap between the literatures in cross-cultural and ethnic minority psychology. Most of the research in these areas is published in specialty journals, and there is a paucity of this research in prestigious journals. Perceived or actual barriers to publication in prestigious journals may cause some to seek specialty journals as outlets for research on cultural diversity. The top scholars in cross-cultural psychology are primarily men of European ancestry, whereas most of the top scholars in ethnic minority psychology are ethnic minority men and women. Strategies to increase the prominence of cultural diversity in the psychology literature include combining cross-cultural and ethnic minority psychology, increasing the number of editorial board members of prestigious journals having expertise in cultural diversity, and increasing the quality of specialty journals. Psychology will remain ill-equipped to face the challenges of the new millennium without increased attention to cultural diversity.

Considerations in measuring the electrical potentials of metallic restorations in vivo.

Many variables are believed to affect the accurate measuring of metallic restoration electrical potentials. This study examined the effects of intra- versus extra-oral location of the reference electrode, the type of metallic probe used to make contact with the restoration, and scratching and brushing of the restoration surface. Dental amalgam restorations were measured in 40 human subjects. Results showed that only the location of the reference electrode affected the central tendency of the potential. The study discusses the significance of some experimental variables in the accurate measuring of metallic potentials and the need to consider individual subject differences when statistically analysing for the central tendency of a sample.

Culture-specific models of men's sexual aggression: intra- and interpersonal determinants.

The role of intra- and interpersonal variables was examined in samples of Asian American (N = 91) and European American (N = 377) men. A path model for Asian American men suggested 2 interpersonal paths and 1 intrapersonal path to sexual aggression. For Asian Americans, concern about social standing is a risk factor among those who hold misogynous beliefs and who use alcohol before sex. Concern about the negative reputational impact of sexual aggression is a protective factor among Asian Americans who do not hold these negative attitudes. A European American model suggested only an intrapersonal path to sexual aggression consisting of misogynous beliefs, with interpersonal variables not being predictive of sexual aggression. These results suggest both individualist and collectivist determinants of Asian American sexual aggression, whereas only individualist determinants were found for European American sexual aggression.

Effect of stepped light exposure on the volumetric polymerization shrinkage and bulk modulus of dental composites and an unfilled resin.

PURPOSE: To compare the volumetric polymerization shrinkage and dynamic bulk modulus of five resins and an experimental unfilled resin polymerized with a stepped power light and with a conventional one step curing light. MATERIALS AND METHODS: Parallel sided glass rings 5 mm in diameter and 2 mm high were etched for 5 min with hydrofluoric acid and silanated. The density and volume of the rings were calculated before they were filled with either SureFil, AEliteflo, Pertac II, Z100, or an experimental unfilled resin. When cured, the resin was bonded to the glass ring which produced a mold with a configuration C-factor of approximately 0.8. The resin was cured for 40 s on each side using either a one step curing light or a stepped power curing light. After curing, the specimens were weighed in air and in water to calculate their final density and volumetric shrinkage. Ten samples were made using each light system and for each resin (total of 100 samples). The bulk modulus was determined for each resin using an ultrasonic method, and the percentage filler contents were determined by thermogravimetric analysis. RESULTS: The mean +/- SD volumetric polymerization shrinkage values ranged from 3.10 +/- 1.19% for SureFil using the one step light to 12.35 +/- 1.38% for the unfilled resin using the stepped power curing light. Student-Newman-Keuls post hoc test separated the 10 different materials into three significant groups at P= 0.05. The unfilled resin exhibited the highest volumetric shrinkage followed by the flowable composite (AEliteflo). For all materials tested, there was no significant difference in the volumetric shrinkage values when the resin was cured with the one step or the stepped power curing light. There was no significant difference in the volumetric shrinkage values for the hybrid composites (Pertac II, Z100, and SureFil). The volumetric shrinkage values were highly sensitive to filler weight (P < 0.001). Except for Z100, there was no difference in the specific gravity values and velocities of the longitudinal and shear waves and bulk modulus when the one step and stepped power curing lights were used. The bulk modulus values ranged from 6.30 +/- 0.19 GPa for unfilled resin, to 17.10 +/- 1.09 GPa for Z100. Curing with the one step or the stepped curing light had no significant effect on the modulus values for any resin with the exception of Z100, P = 0.05. The bulk modulus values were highly sensitive to filler weight, and higher modulus values were associated with increased filler weight (P < 0.001). There was no significant difference between the bulk modulus of Pertac II and SureFil (P = 0.05).

Effect of stepped vs. continuous light curing exposure on bond strengths to dentin.

PURPOSE: To compare the 10-min and 24-hr shear bond strengths of three dentin bonding systems, polymerized with either a standard (Optilux 401) light for 60 s, or a stepped curing light (Elipar Highlight) that delivered a low light intensity for 10 s followed by high intensity for 50 s. MATERIALS AND METHODS: Three bonding systems were used to bond two resin-based composites (RBC) to dentin at 34 degrees +/- 2C using the two curing lights. Single Bond (SB) and Prime & Bond 2.1 (P&B) were used with Z100 RBC, and EBS bonding system was used with Pertac II RBC. Ten specimens from each combination were debonded at 37 degrees +/- 1C 10 min after starting to light cure the bonding system. Ten other specimens were stored in water at 37 degrees +/- 1C for 24 hrs before debonding at 37 degrees +/- 1C (total 120 teeth). RESULTS: The 10-min mean shear bond strengths were: Standard Cure; EBS 11.9 +/- 2.9 MPa, SB 14.6 +/- 2.2 MPa, P&B 14.7 +/- 4.2 MPa: Stepped Curing; EBS 7.4 +/- 2.1 MPa, SB 13.0 +/- 3.6 MPa, P&B 15.6 +/- 4.8 MPa. The 24-hr mean shear bond strengths were: Standard Cure; EBS 14.8 +/- 5.1 MPa, SB 25.1 +/- 3.3 MPa, P&B 25.2 +/- 8.8 MPa: Stepped Curing; EBS 15.1 +/- 4.6 MPa, SB 21.9 +/- 5.9 MPa, P&B 17.3 +/- 9.2 MPa. Three way ANOVA showed significant main effects for light, bonding system and time and no 2- or 3-way interaction effects at P = 0.01. The Least-Squares Means test with Sidak's adjustment for Multiple Comparisons showed that the bond strengths obtained using the standard light were significantly greater than the bond strengths obtained using the stepped curing light (P < 0.01). The 24-hr bond strengths were significantly greater (P < 0.01) than the 10-min bond strengths. The bond strengths obtained with EBS were significantly less than SB and P&B (P < 0.01), but there were no significant differences between SB and PB (P = 0.9752).

In vitro comparison of 10-minute versus 24-hour shear bond strengths of six dentin bonding systems.

OBJECTIVE: Early bond strengths produced by dentin bonding systems should be sufficient to resist the polymerization shrinkage of resin composite. This study compared the 10-minute and 24-hour shear bond strengths of six dentin bonding systems: One-Step (OS), PermaQuik (PQ), Prime & Bond 2.1 (PB), Scotchbond Multi-Purpose (SBMP), Single Bond (SB), and Tenure Quik with Fluoride (TQ). METHOD AND MATERIALS: Each bonding system was used to bond composite to visibly moist dentin at 34 degrees C +/- 2 degrees C. The specimens were debonded at 37 degrees C +/- 1 degree C 10 minutes after the start of light curing of the bonding system, and the results were compared with the 24-hour bond strengths. The mode of failure was recorded. RESULTS: The 10-minute mean shear bond strengths were: OS, 16.4; PQ, 14.3; SB, 14.0; PB, 12.7; TQ, 10.7; and SBMP, 9.3 MPa. The 24-hour mean shear bond strengths were OS, 23.3; PB, 20.8; SB, 20.3; PQ, 19.4; TQ, 11.2; and SBMP, 10.0 MPa. The 10-minute mean shear bond strengths of OS, PQ, PB, and SB bonding systems were significantly less than the 24-hour values. More dentinal fractures and mixed failures were observed with OS, PQ, and PB. Systems with higher bond strengths had more resin penetration into the lateral dentinal branches. CONCLUSION: The 10-minute mean shear bond strengths were all less than 17 MPa, and the 10-minute bond strengths were less than the 24-hour values.

Corrosion and cytotoxicity evaluation of thermafil endodontic obturator carriers.

The purpose of this study was to evaluate the in vitro cytotoxicity of two metallic and two plastic Thermafil carrier materials, and to separately evaluate the in vitro corrosion behavior of the two metallic carriers. Stainless-steel, Ti-6AI-4V, Polysulfone, and Vectra carriers were evaluated for cytotoxicity using the ISO-recommended agar overlay test. The two metallic carriers were additionally corrosion tested in 0.9% NaCl solution for 174 wk, at 37 degrees C. Elemental analyses of the corrosion solutions were periodically conducted using inductively coupled plasma-mass spectroscopy. Agar overlay results showed that the four carrier materials were not cytotoxic to L929 fibroblasts. Inductively coupled plasma-mass spectroscopy results showed that the metallic materials had small mass loss rates. Scanning electron microscopy showed no evidence of pitting or crevice corrosion.

Sexual aggression among Asian Americans: risk and protective factors.

Rates of sexual aggression among Asian Americans are relatively low. It is possible that these low rates are because Asian Americans are less likely than other groups to develop developmental, motivational, and situational risk factors associated with sexual aggression. Moreover, an emphasis in Asian cultures on self-control of sexual and aggressive behavior may serve as a protective factor. Nevertheless, patriarchal aspects of Asian cultures may place some Asian Americans at risk for sexual victimization or perpetration of sexually aggressive behavior. Although Asian Americans may be at less risk for sexual aggression than other groups, interventions that counteract the patriarchal aspects of Asian cultures may further reduce risk.

Prevention of sexual aggression: Sociocultural risk and protective factors.

Physiological, cognitive, affective, and developmental sociocultural risk factors for perpetrating sexual aggression are identified. Feminine and multicultural socialization may serve as protective factors against these risk factors because both forms of socialization emphasize empathy and sexuality in the context of committed relationships. It is proposed that feminist and multicultural education across the developmental span may constitute methods of reducing and preventing the development of sexually aggressive behavior. However, feminist and multicultural approaches may have limited impact without greater acceptance within societal power structures, including psychology. The authors call for psychologists interested in reducing sexually aggressive behavior to become better informed and experienced with feminist and multicultural approaches. They also suggest that it may be time for all persons in society to become competent in multiple domains.

Crystallization of experimental bioactive glass compositions.

Crystallization kinetics studies for six experimental glass formulations in the system Na2O-CaO-SiO2-P2O5 synthesized by wet chemistry were conducted by means of differential thermal analysis. These glasses had CaO/P2O5 and SiO2/ (CaO + Na2O) ratios ranging from 8.74-3.38 and 0.92-3.03, respectively. Samples of each glass (n = 30 were heated from 23 to 1250 degrees C under N2 atmosphere at heating rates ranging from 10 to 50 degrees C/min. Glass-ceramics were obtained after heat treating the initial glasses at temperatures determined from their DTA exotherms. The activation energy of crystallization for each glass composition was calculated from an expression-relating log-heating rate and the reciprocal of the exothermic peak temperature. The compositions of the six glasses were significantly different (p = 0.05). The activation energy of crystallization (Q) values ranged from 196 to 782 kJ/mole. A correlation was obtained between Q and CaO/P2O5 and between Q and the Young's modulus (P < 0.001). Two of the six glasses exhibited bulk crystallization. X-ray diffraction studies showed that four of the six glasses exhibited different proportions of crystalline phases following heat treatment. These phases were wollastonite (CaSiO3), Na2CaSi3O9, combeite [Na4Ca3SI6O16(OH)2], and some unidentifiable phases. Two of the six bioceramic materials had a mixture of unknown crystalline phases.