The prevalence of polypharmacy in older Europeans: A multi-national database study of general practitioner prescribing.

AIMS: The aims of this study were to measure the prevalence of polypharmacy and describe the prescribing of selected medications known for overuse in older people with polypharmacy in primary care. METHODS: This was a multinational retrospective cohort study across six countries: Belgium, France, Germany, Italy, Spain and the UK. We used anonymized longitudinal patient-level information from general practice databases hosted by IQVIA. Patients ≥65 years were included. Polypharmacy was defined as having 5-9 and ≥10 distinct drug classes (ATC Level 3) prescribed during a 6-month period. Selected medications were: opioids, antipsychotics, proton pump inhibitors (PPI), benzodiazepines (ATC Level 5). We included country experts on the healthcare context to interpret findings. RESULTS: Age and gender distribution was similar across the six countries (mean age 75-76 years; 54-56% female). The prevalence of polypharmacy of 5-9 drugs was 22.8% (UK) to 58.3% (Germany); ≥10 drugs from 11.3% (UK) to 28.5% (Germany). In the polypharmacy population prescribed ≥5 drugs, opioid prescribing ranged from 11.5% (France) to 27.5% (Spain). Prescribing of PPI was highest with almost half of patients receiving a PPI, 42.3% (Germany) to 65.5% (Spain). Benzodiazepine prescribing showed a marked variation between countries, 2.7% (UK) to 34.9% (Spain). The healthcare context information explained possible underreporting for selected medications. CONCLUSIONS: We have found a high prevalence of polypharmacy with more than half of the older population being prescribed ≥5 drugs in four of the six countries. Whilst polypharmacy may be appropriate in many patients, worryingly high usage of PPIs and benzodiazepines supports current efforts to improve polypharmacy management across Europe.

Opportunities and Challenges for Decentralized Clinical Trial Approaches: European Health Technology Assessment Perspective.

OBJECTIVES: Decentralized clinical trial (DCT) approaches are clinical trials in which some or all trial activities take place closer to participants' proximities instead of a traditional investigative site. Data from DCTs may be used for clinical and economic evaluations by health technology assessment (HTA) bodies to support reimbursement decision making. This study aimed to explore the opportunities and challenges for DCT approaches from an HTA perspective by interviewing representatives from European HTA bodies. METHODS: We conducted semistructured interviews with 25 European HTA representatives between September 2022 and February 2023, and transcripts were analyzed after thematic analysis. RESULTS: Two main themes were identified from the data relating to (1) DCT approaches in HTA and (2) trial-level acceptance and relevance. Experience with assessing DCTs was limited and a variety of knowledge about DCTs was observed. The respondents recognized the opportunity of DCTs to reduce recall bias when participant-reported outcome data can be collected more frequently and conveniently from home. Concerns were expressed about the data quality when participants become responsible for data collection. Despite this challenge, the respondents recognized the potential of DCTs to increase the generalizability of results because data can be collected in a setting reflective of the everyday situation potentially from a more diverse participant group. CONCLUSIONS: DCTs could generate relevant results for HTA decision making when data are collected in a real-world setting from a diverse participant group. Increased awareness of the opportunities and challenges could help HTA assessors in their appraisal of DCT approaches.

SARS-CoV-2 Transmission among Marine Recruits during Quarantine.

BACKGROUND: The efficacy of public health measures to control the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been well studied in young adults. METHODS: We investigated SARS-CoV-2 infections among U.S. Marine Corps recruits who underwent a 2-week quarantine at home followed by a second supervised 2-week quarantine at a closed college campus that involved mask wearing, social distancing, and daily temperature and symptom monitoring. Study volunteers were tested for SARS-CoV-2 by means of quantitative polymerase-chain-reaction (qPCR) assay of nares swab specimens obtained between the time of arrival and the second day of supervised quarantine and on days 7 and 14. Recruits who did not volunteer for the study underwent qPCR testing only on day 14, at the end of the quarantine period. We performed phylogenetic analysis of viral genomes obtained from infected study volunteers to identify clusters and to assess the epidemiologic features of infections. RESULTS: A total of 1848 recruits volunteered to participate in the study; within 2 days after arrival on campus, 16 (0.9%) tested positive for SARS-CoV-2, 15 of whom were asymptomatic. An additional 35 participants (1.9%) tested positive on day 7 or on day 14. Five of the 51 participants (9.8%) who tested positive at any time had symptoms in the week before a positive qPCR test. Of the recruits who declined to participate in the study, 26 (1.7%) of the 1554 recruits with available qPCR results tested positive on day 14. No SARS-CoV-2 infections were identified through clinical qPCR testing performed as a result of daily symptom monitoring. Analysis of 36 SARS-CoV-2 genomes obtained from 32 participants revealed six transmission clusters among 18 participants. Epidemiologic analysis supported multiple local transmission events, including transmission between roommates and among recruits within the same platoon. CONCLUSIONS: Among Marine Corps recruits, approximately 2% who had previously had negative results for SARS-CoV-2 at the beginning of supervised quarantine, and less than 2% of recruits with unknown previous status, tested positive by day 14. Most recruits who tested positive were asymptomatic, and no infections were detected through daily symptom monitoring. Transmission clusters occurred within platoons. (Funded by the Defense Health Agency and others.).

Unintended impact of pharmacovigilance regulatory interventions: A systematic review.

AIMS: Studies assessing the impact of pharmacovigilance regulatory interventions often focus on the expected (or intended) outcomes, while any possible unintended impact may be overlooked. The update of the Good Pharmacovigilance Practice guideline in 2017 elaborated on impact assessment, emphasizing the need also to assess possible unintended impact. This systematic literature review investigated how often the unintended impact of regulatory interventions was considered in publications of studies investigating pharmacovigilance regulatory interventions in Europe. METHODS: We conducted a systematic review of the literature on MEDLINE and EMBASE from 1 January 2012 to 28 February 2022 to identify publications that investigated the impact of regulatory interventions in Europe. The primary outcome of the study was the number of publications reporting assessments of unintended impact. In addition, we studied the characteristics of these publications, including the type of outcomes assessed, the analytical methods applied and the type of data used. RESULTS: In total, 96 publications were included in the analysis. The unintended impact of pharmacovigilance regulatory interventions was investigated in 23 of 96 publications (24%). The drug classes most frequently studied in the publications assessing unintended impact of regulatory interventions were oral glucose-lowering drugs (n = 6, 26%), opioids (n = 4, 17%), antidepressants (n = 4, 17%) and antipsychotics (n = 3, 13%). The reported methods to assess the unintended impact were interrupted time series (n = 10, 43%) and descriptive statistics with or without significance testing (n = 2 [9%] and n = 9 [39%], respectively). The outcomes selected for unintended impact assessments included the use of other drugs (n = 16, 70%), health outcomes (n = 8, 35%) and behavioural changes (n = 4, 17%). Most of the publications reported on the use of electronic health record databases (n = 13, 57%) or claims databases (n = 13, 57%), while registries were used in 4 publications (17%). CONCLUSION: The unintended impact of pharmacovigilance regulatory interventions was reported in only a quarter of identified publications. There was no apparent increase in attention to unintended impact assessments after the update of the Good Pharmacovigilance Practice guidelines.

Direct-to-participant investigational medicinal product supply in clinical trials in Europe: Exploring the experiences of sponsors, site staff and couriers.

AIMS: Insights into the current practice of direct-to-participant (DtP) supply of investigational medicinal product (IMP) in the context of clinical trials conducted in Europe are needed, as regulations are unharmonized. This study is set out to explore how DtP IMP supply has been employed in Europe and what the advantages and disadvantages and barriers and facilitators of its implementation are. METHODS: We conducted semi-structured interviews with representatives from sponsor companies, courier services and site study staff involved in the IMP dispensing and delivery process in Europe. Interviews were conducted between May and November 2021, and data were analysed following thematic analysis. RESULTS: Sixteen respondents participated in one of the 12 interviews. Respondents had experience with different models of DtP IMP supply including shipment from the investigative site, a central pharmacy (a depot under the control of a pharmacist) and a local pharmacy-aiming to reduce trial participation burden. The respondents indicated that investigative site-to-participant shipment is not affected by regulatory barriers, but could burden site staff. Shipment from central locations was considered most efficient, but possible regulatory barriers related to maintaining participants' privacy and investigator oversight were identified. The respondents indicated that the involvement of local pharmacies to dispense IMP can be considered when the IMP is authorized. CONCLUSIONS: Several DtP IMP supply models are implemented in clinical trials conducted in Europe. In this study, three main DtP IMP models were identified, which can be referenced when describing these approaches for regulatory approval.

Clinician perspectives on technology-enhanced in vivo exposures during prolonged exposure therapy for PTSD.

OBJECTIVE: To investigate clinicians' perceptions regarding the use of mobile technology tools during prolonged exposure (PE) therapy to allow for monitoring and enhancing in-vivo exposures (IVEs). METHODS: Clinicians with training in PE therapy (N = 32; average of 9 years of practice) completed surveys asking about their perspectives on the utility of virtually attending IVEs with patients while simultaneously having access to real-time subjective and physiological data (i.e., heart rate, galvanic skin conductance) to guide exposure exercises and assure optimal stimulus engagement. RESULTS: Findings showed clinicians to have a favorable view of applying technology devices and systems to enhance IVEs of PE therapy. Most clinicians (93.8%) believed that real-time monitoring of IVEs-particularly monitoring patients' subjective distress and completion of and duration of time in the IVE-would be useful and significantly enhance PE therapy. CONCLUSION: The positive perceptions toward integrating technology into IVEs in this study have important implications for the development and implementation of technology-enhanced PE therapy. A mobile technology system that incorporates real-time indicators of engagement (i.e., both subjective and physiological) during IVEs and allows clinicians to review recordings of, or virtually accompany, patients during IVEs has the potential to innovate and transform PE and other exposure-based treatments. Clinicians also believed that technology-enhanced IVEs may help reduce early termination from PE.

SARS-CoV-2 Outbreak Dynamics in an Isolated US Military Recruit Training Center With Rigorous Prevention Measures.

BACKGROUND: Marine recruits training at Parris Island experienced an unexpectedly high rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, despite preventive measures including a supervised, 2-week, pre-entry quarantine. We characterize SARS-CoV-2 transmission in this cohort. METHODS: Between May and November 2020, we monitored 2,469 unvaccinated, mostly male, Marine recruits prospectively during basic training. If participants tested negative for SARS-CoV-2 by quantitative polymerase chain reaction (qPCR) at the end of quarantine, they were transferred to the training site in segregated companies and underwent biweekly testing for 6 weeks. We assessed the effects of coronavirus disease 2019 (COVID-19) prevention measures on other respiratory infections with passive surveillance data, performed phylogenetic analysis, and modeled transmission dynamics and testing regimens. RESULTS: Preventive measures were associated with drastically lower rates of other respiratory illnesses. However, among the trainees, 1,107 (44.8%) tested SARS-CoV-2-positive, with either mild or no symptoms. Phylogenetic analysis of viral genomes from 580 participants revealed that all cases but one were linked to five independent introductions, each characterized by accumulation of mutations across and within companies, and similar viral isolates in individuals from the same company. Variation in company transmission rates (mean reproduction number R 0 ; 5.5 [95% confidence interval [CI], 5.0, 6.1]) could be accounted for by multiple initial cases within a company and superspreader events. Simulations indicate that frequent rapid-report testing with case isolation may minimize outbreaks. CONCLUSIONS: Transmission of wild-type SARS-CoV-2 among Marine recruits was approximately twice that seen in the community. Insights from SARS-CoV-2 outbreak dynamics and mutations spread in a remote, congregate setting may inform effective mitigation strategies.

Data sources for drug utilization research in Latin American countries-A cross-national study: DASDUR-LATAM study.

PURPOSE: Drug utilization research (DUR) contributes to inform policymaking and to strengthen health systems. The availability of data sources is the first step for conducting DUR. However, documents that systematize these data sources in Latin American (LatAm) countries are not known. We compiled the potential data sources for DUR in the LatAm region. METHODS: A network of DUR experts from nine LatAm countries was assembled and experts conducted: (i) a website search of the government, academic, and private health institutions; (ii) screening of eligible data sources, and (iii) liaising with national experts in pharmacoepidemiology (via an online survey). The data sources were characterized by accessibility, geographic granularity, setting, sector of the data, sources and type of the data. Descriptive analyses were performed. RESULTS: We identified 125 data sources for DUR in nine LatAm countries. Thirty-eight (30%) of them were publicly and conveniently available; 89 (71%) were accessible with limitations, and 18 (14%) were not accessible or lacked clear rules for data access. From the 125 data sources, 76 (61%) were from the public sector only; 46 (37%) were from pharmacy records; 43 (34%) came from ambulatory settings and; 85 (68%) gave access to individual patient-level data. CONCLUSIONS: Although multiple sources for DUR are available in LatAm countries, the accessibility is a major challenge. The procedures for accessing DUR data should be transparent, feasible, affordable, and protocol-driven. This inventory could permit a comparison of drug utilization between countries identifying potential medication-related problems that need further exploration.

Clinical outcomes of nonvitamin K oral anticoagulants and acenocoumarol for stroke prevention in contemporary practice: A population-based propensity-weighted cohort study.

AIMS: Acenocoumarol is a vitamin-K antagonist (VKA) primarily used in certain countries (e.g. India, Netherlands, Spain). The half-life of acenocoumarol is similar to that of non-VKA oral anticoagulants (NOAC), unlike warfarin, and this could affect comparative effectiveness and safety (CES). However, data on CES for NOAC come almost exclusively from studies using warfarin as the comparator. We aimed to assess outcomes of NOAC and acenocoumarol in people with non-valvular atrial fibrillation (NVAF) in real-world clinical practice. METHODS: This is a population-based retrospective cohort study. All new users of oral anticoagulants from November 2011 to December 2015 with NVAF were included (n = 41,560). Data were obtained by linking several health electronic records of the Valencia region, Spain. Incidence rates were estimated. We used the inverse probability of treatment weighted Cox analysis to control for indication bias when assessing the risk of effectiveness and safety outcomes for each NOAC compared with acenocoumarol. Several sensitivity analyses were performed. RESULTS: We did not find differences in the risk of mortality, ischaemic stroke or any gastrointestinal bleeding. However, we did find a decreased risk of intracranial haemorrhage for dabigatran (HR: 0.34, 95% CI 0.20-0.56) and rivaroxaban (HR: 0.55, 95% CI 0.35-0.85) as compared to acenocoumarol. In subanalyses, apixaban showed a higher risk of ischaemic stroke in high-risk persons (≥75 years and CHA2DS2-VASC score ≥ 2). CONCLUSIONS: No differences in clinical outcomes were found between NOAC and acenocoumarol overall, although dabigatran and rivaroxaban showed a lower risk of intracranial haemorrhage. Findings on the potential inferiority of specific NOAC in high-risk subgroups should be studied further.

Group-based Trajectory Models to Assess Quality of INR Control and Its Association With Clinical Outcomes.

BACKGROUND: The Time in Therapeutic Range (TTR) is the gold-standard measure used to assess the quality of oral anticoagulation with vitamin K antagonists. However, TTR is a static measure, and International Normalized Ratio (INR) control is a dynamic process. Group-based Trajectory Models (GBTM) can address this dynamic nature by classifying patients into different trajectories of INR control over time. OBJECTIVES: The objective of this study was to assess the quality of INR control in a population-based cohort of new users of vitamin K antagonist with a diagnosis of atrial fibrillation using GBTM. METHODS: We classified patients into different trajectories according to their propensity for being adequately anticoagulated over their first year of treatment using GBTM, and we evaluated the association between trajectories and relevant clinical outcomes over the following year. RESULTS: We included 8024 patients in the cohort who fulfilled the inclusion criteria; the mean number of INR determinations over the first year of treatment was 13.9. We identified 4 differential trajectories of INR control: Optimal (9.7% of patients, TTR: 83.8%), Improving (27.4% of patients, TTR: 61.2%), Worsening (28%; TTR: 69.1%), and Poor control (34.9%; TTR: 41.5%). In adjusted analysis, Poor and Worsening control patients had a higher risk of death than Optimal control patients (hazard ratio: 1.79; IC 95%, 1.36-2.36 and hazard ratio: 1.36; IC 95%, 1.02-1.81, respectively). Differences in other outcomes did not achieve statistical significance, except for a reduced risk of transient ischemic attack in the Improving Control group. CONCLUSIONS: GBTM may contribute to a better understanding and assessment of the quality of oral anticoagulation and may be used in addition to traditional, well-established measures such as TTR.

Rural-urban disparities in the distribution of dental caries among children in south-eastern Louisiana: a cross-sectional study.

INTRODUCTION: The purpose of this cross-sectional study was to assess the prevalence of dental caries among elementary school-aged children in rural compared to urban communities within south-eastern Louisiana that have participated in a school-based dental screening and sealant program. METHODS: The authors utilized de-identified Sealant Efficiency Assessment for Locals and States screening data for 2007-2014 provided by The Health Enrichment Network oral health program. The screening was conducted throughout 46 elementary schools in Louisiana. Screening forms recorded decayed, missing, and filled permanent teeth (DMFT). Descriptive statistics including demographic characteristics and oral health conditions were calculated. Univariate and multivariable logistic regression analyses were performed to assess the burden of caries in schools. RESULTS: Of 963 children screened, 32% had dental caries. There was an increased risk of having any DMFT among children who attended rural schools as compared to those who attended urban schools (prevalence odds ratio (POR)=2.17, 95% confidence interval (CI)=1.61-2.93). This study found that non-Hispanic black children had reduced odds of DMFT as compared to the children from other reported ethnicities (POR=0.695, 95%CI=0.503-0.960). CONCLUSION: A higher prevalence of dental caries was found in rural compared to urban communities. Further research is needed to assess the extent of geographic differences to improve oral health outcomes.

Steatorrhea and Hyperoxaluria in Severely Obese Patients Before and After Roux-en-Y Gastric Bypass.

BACKGROUND AND AIMS: Hyperoxaluria after Roux-en-Y gastric bypass (RYGB) is generally attributed to fat malabsorption. If hyperoxaluria is indeed caused by fat malabsorption, magnitudes of hyperoxaluria and steatorrhea should correlate. Severely obese patients, prior to bypass, ingest excess dietary fat that can produce hyperphagic steatorrhea. The primary objective of the study was to determine whether urine oxalate excretion correlates with elements of fat balance in severely obese patients before and after RYGB. METHODS: Fat balance and urine oxalate excretion were measured simultaneously in 26 severely obese patients before and 1 year after RYGB, while patients consumed their usual diet. At these time points, stool and urine samples were collected. Steatorrhea and hyperoxaluria were defined as fecal fat >7 g/day and urine oxalate >40 mg/day. Differences were evaluated using paired 2-tailed t tests. RESULTS: Prior to RYGB, 12 of 26 patients had mild to moderate steatorrhea. Average urine oxalate excretion was 61 mg/day; there was no correlation between fecal fat and urine oxalate excretion. After RYGB, 24 of 26 patients had steatorrhea and urine oxalate excretion averaged 69 mg/day, with a positive correlation between fecal fat and urine oxalate excretions (r = 0.71, P < .001). For each 10 g/day increase in fecal fat output, fecal water excretion increased only 46 mL/day. CONCLUSIONS: Steatorrhea and hyperoxaluria were common in obese patients before bypass, but hyperoxaluria was not caused by excess unabsorbed fatty acids. Hyperphagia, obesity, or metabolic syndrome could have produced this previously unrecognized hyperoxaluric state by stimulating absorption or endogenous synthesis of oxalate. Hyperoxaluria after RYGB correlated with steatorrhea and was presumably caused by excess fatty acids in the intestinal lumen. Because post-bypass steatorrhea caused little increase in fecal water excretion, most patients with steatorrhea did not consider themselves to have diarrhea. Before and after RYGB, high oxalate intake contributed to the severity of hyperoxaluria.

Concurrent treatment of PTSD and alcohol use disorder via telehealth in a female Iraq veteran.

BACKGROUND AND OBJECTIVES: A growing literature provides evidence for the use of integrated treatments (e.g., Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure; COPE); however, no known studies have applied COPE via telehealth. METHOD: COPE was delivered via telehealth to treat one black female veteran with combat trauma and alcohol use disorder. RESULTS: The patient demonstrated significant reductions in alcohol consumption and PTSD and depressive symptoms. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Although preliminary, findings demonstrate that integrated treatment via telehealth is feasible and effective, and may be useful for female veterans reluctant to seek services at male-dominated VAMCs. (Am J Addict 2017;26:112-114).

Impact of the introduction of mandatory generic substitution in South Africa: private sector sales of generic and originator medicines for chronic diseases.

OBJECTIVE: To assess the impact of mandatory offer of generic substitution, introduced in South Africa in May 2003, on private sector sales of generic and originator medicines for chronic diseases. METHODS: Private sector sales data (June 2001 to May 2005) were obtained from IMS Health for proton pump inhibitors (PPIs; ATC code A02BC), HMG-CoA reductase inhibitors (statins; C10AA), dihydropyridine calcium antagonists (C08CA), angiotensin-converting enzyme inhibitors (ACE-I; C09AA) and selective serotonin reuptake inhibitors (SSRIs; N06AB). Monthly sales were expressed as defined daily doses per 1000 insured population per month (DDD/TIM). Interrupted time-series models were used to estimate the changes in slope and level of medicines use after the policy change. ARIMA models were used to correct for autocorrelation and stationarity. RESULTS: Only the SSRIs saw a significant rise in level of generic utilisation (0.2 DDD/TIM; P < 0.001) and a fall in originator usage (-0.1 DDD/TIM; P < 0.001) after the policy change. Utilisation of generic PPIs fell (level 0.06 DDD/TIM, P = 0.048; slope 0.01 DDD/TIM, P = 0.043), but utilisation of originator products also grew (level 0.05 DDD/TIM, P < 0.001; slope 0.003, P = 0.001). Generic calcium antagonists and ACE-I showed an increase in slope (0.01 DDD/TIM, P = 0.016; 0.02 DDD/TIM, P < 0.001), while the originators showed a decrease in slope (-0.003 DDD/TIM, P = 0.046; -0.01 DDD/TIM, P < 0.001). There were insufficient data on generic statin use before the policy change to allow for analysis. CONCLUSION: The mandatory offer of generic substitution appeared to have had a quantifiable effect on utilisation patterns in the 2 years after May 2003. Managed care interventions that were already in place before the intervention may have blunted the extent of the changes seen in this period. Generic policies are an important enabling provision for cost-containment efforts. However, decisions taken outside of official policy may anticipate or differ from that policy, with important consequences.

Impact of group motivational interviewing on enhancing treatment engagement for homeless Veterans with nicotine dependence and other substance use disorders: A pilot investigation.

BACKGROUND: Prior studies have shown that Group Motivational Interviewing (GMI) for dually diagnosed patients holds promise for increasing treatment engagement. OBJECTIVES: The current study evaluated the impact of a novel GMI protocol that included tobacco-specific components (referred to as "Tobacco GMI or T-GMI") targeting enhanced engagement in smoking cessation treatment. METHODS: Thirty-seven primary alcohol and nicotine-dependent cigarette smoking homeless Veterans with co-morbid psychiatric conditions were recruited to receive four GMI sessions over 4 consecutive days. The first 16 participants received standard GMI, aimed at enhancing engagement in substance abuse treatment and for reducing substance use, while the remaining 21 participants received a modified "tobacco-specific" GMI protocol (T-GMI) that included additional content specific to cessation of tobacco use and enhancing smoking cessation treatment, in addition to the standard substance abuse content of GMI. RESULTS: Participants in T-GMI were more likely to attend tobacco cessation programming (p = .05), as well as to attend combined tobacco cessation programming with prescribed nicotine replacement therapy (p = .03), compared to those in standard GMI. Differences between treatment conditions with respect to alcohol and illicit drug use outcomes were not significant, although overall substance use declined over time in both groups. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Results suggest that inclusion of tobacco-specific components in the context of GMI for substance abuse may enhance treatment engagement for tobacco cessation behaviors among dually diagnosed nicotine dependent homeless patients, a highly vulnerable population for which interventional resources targeting engagement in smoking cessation treatment has historically been lacking. (Am J Addict 2016;25:533-541).

Seasonal variation in penicillin use in Mexico and Brazil: analysis of the impact of over-the-counter restrictions.

During 2010, Mexico and Brazil implemented policies to enforce existing laws of restricting over-the-counter sales of antibiotics. We determined if the enforcement led to more appropriate antibiotic use by measuring changes in seasonal variation of penicillin use. We used retail quarterly sales data in defined daily doses per 1,000 inhabitant-days (DDD/TID) from IMS Health from the private sector in Mexico and Brazil from the first quarter of 2007 to the first quarter of 2013. This database contains information on volume of antibiotics sold in retail pharmacies using information from wholesalers. We used interrupted time-series models controlling for external factors with the use of antihypertensives with interaction terms to assess changes in trend, level, and variation in use between quarters for total penicillin use and by active substance. The most used penicillin was amoxicillin, followed by amoxicillin-clavulanic acid and ampicillin (minimal use in Brazil). Before the restrictions, the seasonal variation in penicillin use was 1.1 DDD/TID in Mexico and 0.8 DDD/TID in Brazil. In Mexico, we estimated a significant decrease in the seasonal variation of 0.4 DDD/TID after the restriction, mainly due to changes in seasonal variation of amoxicillin and ampicillin. In Brazil, the seasonal variation did not change significantly, overall and in the breakdown by individual active substances. For Mexico, inappropriate penicillin use may have diminished after the restrictions were enforced. For Brazil, increasing use and no change in seasonal variation suggest that further efforts are needed to reduce inappropriate penicillin use.

D-cycloserine combined with cue exposure therapy fails to attenuate subjective and physiological craving in cocaine dependence.

BACKGROUND: Based on preclinical studies showing that the partial N-methyl-D-aspartate (NMDA) agonist D-cycloserine (DCS) facilitates extinction of cocaine self-administration and cocaine-induced conditioned place preference, we evaluated whether 50 mg of DCS would reduce craving to cocaine cues when combined with cue exposure (CE) in cocaine dependent humans. METHODS: In this double-blind placebo-controlled pilot study, 47 cocaine dependent participants were randomized to DCS or placebo (PBO), plus CE. Participants received DCS or PBO 30 minutes prior to two CE sessions, conducted one day apart. Craving and heart rate was assessed prior to CE sessions, during CE trials, and after CE trials. These measures were assessed again at a 1-week follow-up (session 3) after the second CE session. RESULTS: DCS failed to significantly attenuate cocaine cue reactivity based on subjective craving and physiological reactivity (heart rate) compared to PBO. The CE protocol, consisting of repeated exposure to drug cues combined with skills training, resulted in extinction to cocaine cues as suggested by decreased craving within and between sessions in both treatment conditions. All participants exhibited elevated heart rate with repeated exposures, demonstrating a potentiation in heart rate between sessions. CONCLUSIONS: 50 mg of DCS may not be effective for extinguishing reactivity to drug cues for individuals with cocaine dependence. SCIENTIFIC SIGNIFICANCE: Future studies examining the effect of DCS on facilitating extinction to drug cues should examine variations in cue exposure length, number of CE presentations, and timing of DCS dose administration prior to cue exposures, which may differentially impact drug cue reactivity.

Rectal pre-treatment with ozonized oxygen (O3) aggravates clinic status in septic rats treated with amoxicillin/clavulanate.

INTRODUCTION: Despite the advanced antibiotic therapies, sepsis continues being a clinical entity with high morbidity and mortality. The ozone/oxygen mixture (O3/O2) has been reported to exhibit positive effects on immunity. The aim of our study was to analyze whether (O3/O2) combined with amoxicillin/clavulanate has any influence on the morbidity and mortality of septic rats. METHODS: We used 48 Sprague-Dawley rats randomly allocated to 6 groups (n=8): healthy (C), septic (I), healthy+ozone therapy (O3), septic+amoxicillin/clavulanate (AMC), septic+amoxicillin/clavulanate+ozone therapy (AMC/O3) and septic+ozone therapy (I/O3). O3/O2 was administered rectally at increasing O3 concentrations during 10 days prior to the onset of sepsis model (intraperitoneally injection of fecal material) or saline administration in healthy control rats. Later (post-inoculation), 3 days per week, O3 was also administered. Vital signs were recorded, and microbiological, hematological and histopathological studies were performed. RESULTS: The number of surviving animal/total was higher in AMC (8/8) than in AMC/O3 (4/8) p=0.077. The percentage of surviving animals with pneumonia was higher in AMC/O3 than in AMC (100% vs 37.5%). In dead animals, AMC/O3 rats had a significantly higher percentage of lesions: Cardiac lesions, pulmonary hemorrhages and pleuritis (100%) and serositis/peritonitis (75%). Only Escherichia coli (2 different biotypes) was isolated from blood and/or peritoneal fluid from all infected groups. A significant decrease in the percentage of band neutrophils from the surviviors belonging to AMC/O3vs AMC was observed (p<0.05). CONCLUSION: Rectal pre-treatment with O3/O2 aggravates clinic status in septic rats treated with amoxicillin/clavulanate.

Atmospheric corrosion of carbon steel: Results of one-year exposure in an andean tropical atmosphere in Colombia.

In this study was examined the response of carbon steel to atmospheric corrosion after one-year exposure in Valle de Aburrá, a subregion located in northwestern Colombia. The study involved the assessment of material mass loss and corrosion rate, the characterization of atmospheric aggressiveness, and the analysis of the morphology and composition of corrosion products in five different sites. Climatological and meteorological factors were assessed by testing for chloride content, sulfur dioxide levels, and time of wetness (TOW). The analysis of corrosion products was conducted using scanning electron microscopy (SEM), X-ray diffraction (XRD), and Raman spectroscopy. Based on corrosion rates, two sites exhibited a more aggressive environment, with a corrosivity category of C3, while the remaining sites were categorized as C2. The study confirmed the presence of lepidocrocite and goethite phases on the surface of carbon steel at all test sites. Data analysis revealed that both the TOW and the industrial activity significantly influence the corrosion of this metal.

Exploring the Minnesota Multiphasic Personality Inventory (MMPI)-3 in a transgender and gender diverse sample.

Comparisons of transgender and gender diverse (TGD) individuals' mental health functioning with that of cisgender individuals rely almost exclusively on screening measures. The limited research with TGD individuals and omnibus assessment measures has primarily used previous iterations of the Minnesota Multiphasic Personality Inventories (MMPIs). This study sought to examine the psychometric functioning of the MMPI-3 with a TGD community sample (n = 97) and compare mean scores across TGD and cisgender subsamples. We expected MMPI-3 substantive scale reliability to be comparable across all samples and subsamples. Individual MMPI-3 scales were expected to demonstrate appropriate convergent and discriminant validity with relevant criterion measures in the TGD sample. Results generally supported MMPI-3 scale score reliability and validity with TGD individuals. Next, three sets of mean score comparisons were conducted across all MMPI-3 substantive scales: (a) TGD individuals not currently in mental health treatment and the MMPI-3 normative sample, (b) TGD individuals not currently in mental health treatment and TGD individuals currently in mental health treatment, and (c) TGD individuals currently in mental health treatment and an outpatient mental health sample. Fewer differences were found between TGD individuals in our sample who were not currently in mental health treatment and the MMPI-3 normative sample compared to previous work. This initial study indicates that MMPI-3 scales largely have appropriate psychometric properties when administered to a TGD sample and that the test may be helpful in identifying mental health needs of TGD individuals. Needs and directions for further research are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).