Antiseizure medications use during pregnancy and congenital malformations: A retrospective study in Saudi Arabia

AimTo evaluate the incidence of congenital malformations in children exposed prenatally to antiseizure medications (ASMs), to assess other perinatal and fetal complications, and to determine the potential predictors for these complications.MethodA retrospective review of pregnancy outcomes of women with epilepsy. Patients were followed up at the King Faisal Specialist Hospital and Research Centre, Riyadh and Jeddah, Saudi Arabia, between Dec 1993 and Oct 2020.ResultsOf 162 pregnancies included, 10 (6.17%) congenital malformations were observed, 6.82% in ASM-exposed babies versus 3.33% in babies of epilepsy-untreated mothers (P = 0.69). The overall incidence of perinatal and fetal complications was 53%; most frequent were low birth weight (24%), preterm birth (19%), transfer to neonatal intensive care unit (18%) and abortion (8%). These complications were higher in the untreated group (66.67%) than in the ASM group (50%). The use of other non-antiseizure medications during pregnancy was the only factor that significantly increased the risk of complications.ConclusionPrenatal exposure to ASMs was associated with increased risk of congenital malformations. However, overall perinatal and fetal complications were higher in the untreated group than in the ASM group, which could be explained by maternal seizures. Therefore, taking ASMs to control epilepsy and prevent perinatal complications may outweigh the risks of teratogenicity.     

Systematic review of drug–drug interactions between rifamycins and anticoagulant and antiplatelet agents and considerations for management

Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the activity of various drug transporting and metabolizing enzymes, which can impact the concentrations and efficacy of substrates. Many anticoagulant and antiplatelet (AC/AP) agents are substrates of these enzymes and have narrow therapeutic indices, leading to risks of thrombosis or bleeding when coadministered with rifamycins. The objective of this systematic review was to evaluate the effects on AC/AP pharmacokinetics, laboratory markers, and clinical safety and efficacy of combined use with rifamycins. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance was performed. The PubMed, Embase, and Web of Science databases were queried for English-language reports on combination use of rifamycins and AC/AP agents from database inception through August 2021. The 29 studies identified examined warfarin (n = 17), direct oral anticoagulants (DOACs) (n = 8), and antiplatelet agents (n = 4) combined with rifampin (n = 28) or rifabutin (n = 1). Eleven studies were case reports or small case series; 14 reported on pharmacokinetic or laboratory markers in healthy volunteers. Rifampin-warfarin combinations led to reductions in warfarin area under the curve (AUC) of 15%–74%, with variability by warfarin isomer and study. Warfarin dose increases of up to 3–5 times prerifampin doses were required to maintain coagulation parameters in the therapeutic range. DOAC AUCs were decreased by 20%–67%, with variability by individual agent and with rifampin versus rifabutin. The active metabolite of clopidogrel increased substantially with rifampin coadministration, whereas prasugrel was largely unaffected and ticagrelor saw decreases. Our review suggests most combinations of AC/AP agents and rifampin are problematic. Further studies are required to determine whether rifabutin or rifapentine could be safe alternatives for coadministration with AC/AP drugs.     

Relationship between drug-related problems and health outcomes: a cross-sectional study among cardiovascular patients

Objective To describe drug-related problems (DRPs) and expense problems (EPs) identified by a standardised community pharmacist-based medication review (MR) program among Swiss cardiovascular outpatients (56–75 years old) and to evaluate the need for collaborative pharmacy practice to achieve economic, clinical and humanistic outcomes. Setting A pilot population of 85 cardiovascular outpatients who were customers of 14 community pharmacies (members of the pharmacieplus virtual chain) and insured with Groupe Mutuel health insurance. Method Cross-sectional study of a structured medication review program, conducted by 11 pharmacists in collaboration with 61 general practitioners (GPs), with patient interviews and access to medical data. Main outcome measure Numbers and types of DRPs and EPs within the study population and odds ratios between them, as well as economic, clinical and humanistic outcomes. Results Of the included patients, 91% had at least one DRP or EP. The odds ratios indicated that not being exposed to DRPs was associated with a higher chance of reaching the clinical target (OR: 3.4; IC95%:1.1–10.5; P = 0.01), of having a better physical quality of life than the median (OR: 2.5; IC95%:0.9–7.3; P = 0.05) and having lower total health care costs (OR: 3.2; IC95%:1.1–9.8; P = 0.02). Conclusions This cross-sectional study shows that the control of cardiovascular risk factors, quality of life and healthcare costs are statistically related to the presence of DRPs detected by a community pharmacist-based MR program.     

Impact of quitting smoking and smoking cessation treatment on substance use outcomes: An updated and narrative review

BackgroundHistorically, smoking cessation was thought to negatively impact substance use outcomes among smokers who use other substances. We sought to synthesize recent reports on this association.MethodsGoogle Scholar, PubMed, and Cinahl were searched for studies published from 2006 to March 29, 2016 that reported impact of smoking cessation treatment or quitting smoking on substance use or substance use disorder treatment outcomes in the general population and among those in substance abuse treatment. Studies were grouped by reported impact as follows: “positive” (i.e. improved), “null” (i.e. no change), or “negative” (i.e. worsened).ResultsTwenty-four studies were included. Eighteen reported the impact of quitting smoking and six reported the impact of smoking cessation treatment intervention, independent of quitting, on substance use outcomes. Eleven studies (46%) reported solely positive impact; four (17%) reported solely null impact; eight (33%) reported mixed positive and null impact by analysis (combined and subgroup, n = 1); substance (n = 4); length of follow-up (n = 2); and comparison group (n = 1). One study (4%) reported mixed negative and null impact by ethnic group. No studies reported increased substance use.ConclusionSmoking cessation does not appear to have a negative effect, and often has a positive effect on substance use outcomes. Smoking cessation advice should be offered, without hesitation, to smokers who report substance use and those in treatment for substance use disorder.     

A narrative systematic review of sexualised drug use and sexual health outcomes among LGBT people

IntroductionChemsex is a specific form of sexualised drug use (SDU) that is an emerging public health issue among men who have sex with men (MSM). Although the recent focus on chemsex is a reflection of the associated harms it is important to understand SDU more broadly and its associations with risk behaviours. Additionally, some of the reasons suggested for MSM engagement in SDU are also likely to apply to women who have sex with women (WSW) and trans people. The aim of this review was to investigate SDU, including chemsex, among lesbian, gay, bisexual and trans (LGBT) people internationally in relation to sexual health outcomes (HIV status, STI diagnosis, condom use).MethodsPapers that were published between January 2010 and June 2020 reporting SDU in MSM, WSW, or trans people were identified through Medline, PsycINFO, CINAHL Plus and Web of Science. Results were synthesised using a narrative approach.ResultsThe search identified 2,710 publications, of which 75 were included in the final synthesis. The majority of studies measured SDU among MSM (n = 71), and four studies measured SDU among trans people. Research into SDU had been conducted in 55 countries and 32 countries had recorded the use of a chemsex drug among MSM, although the drugs used to define chemsex varied. Among studies that researched MSM, SDU was most commonly investigated in relation to condomless anal intercourse (n = 42), followed by HIV prevalence (n = 35), and then STI diagnoses (n = 27). Drug use was generally associated with sexual health outcomes, but particularly in chemsex studies.ConclusionsSDU research is lacking among WSW and trans people, despite trans women having a high HIV prevalence. Among MSM, most drugs were associated with sexual health outcomes, and therefore it is important to include both chemsex drugs and other drugs in SDU research.     

Unity in diversity: A systematic review on the GHB using population

BackgroundOver the past decades gamma-hydroxybutyrate (GHB) has emerged as a popular drug with high potential of (ab)use due to its euphoric and relaxing effects. An overview of different populations using GHB is urgently needed, since this would enable development of adequate prevention and treatment policies to diminish the risks associated with GHB use. We systematically reviewed literature on different GHB using populations, comparing demographic characteristics, GHB use patterns, psychosocial aspects and psychiatric comorbidity.MethodsWe conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using Rayyan software. Original studies published from January 1997 up to October 2019 on GHB use were included. Out of 80 full-text articles, 60 articles of 51 unique studies were included. Most studies included people using GHB 1) presenting at emergency departments (n = 22), 2) recruited from the general population (n = 11), or 3) presenting at addiction care (n = 8).ResultsThree main sub-populations of people using GHB are described in the literature: people using GHB recreationally without adverse effects; people using GHB recreationally with adverse effects, and people with dependence on GHB. These groups show considerable overlap in gender, age range, and comorbid substance use, as well as amount of GHB use per occasion. Differences are related to frequency and function of GHB use, the number of comas experienced, as well as work status, and psychiatric comorbidity.ConclusionPolicy interventions should aim at preventing the transition from recreational substance use to GHB use, as most users are experienced recreational substance users prior to starting GHB use. When people use GHB regularly, interventions should aim at reducing the level of GHB use and preventing GHB use-related harm. Longitudinal studies and population-based probability sampling are required for more insight in the dynamics of GHB use in different sub-populations, and the transition from one group to the other, ultimately leading to dependence on GHB.     

Systematic review of social media interventions for smoking cessation

BackgroundPopular social media could extend the reach of smoking cessation efforts. In this systematic review, our objectives were: 1) to determine whether social media interventions for smoking cessation are feasible, acceptable, and potentially effective; 2) to identify approaches for recruiting subjects; and 3) to examine the specific intervention design components and strategies employed to promote user engagement and retention.MethodsWe searched Scopus, Medline, EMBASE, Cochrane Central, PsychINFO, CINAHL, and Web of Science through July 2016 and reference lists of relevant articles. Included studies described social media interventions for smoking cessation and must have reported outcomes related to feasibility, acceptability, usability, or smoking-related outcomes.ResultsWe identified 7 studies (all were published since 2014) that enrolled 9755 participants (median = 136 [range 40 to 9042]). Studies mainly used Facebook (n = 4) or Twitter (n = 2), and emerged as feasible and acceptable. Five studies reported smoking-related outcomes such as greater abstinence, reduction in relapse, and an increase in quit attempts. Most studies (n = 6) recruited participants using online or Facebook advertisements. Tailored content, targeted reminders, and moderated discussions were used to promote participant engagement. Three studies found that active participation through posting comments or liking content may be associated with improved outcomes. Retention ranged from 35% to 84% (median = 70%) across the included studies.ConclusionsOur review highlights the feasibility, acceptability and preliminary effectiveness of social media interventions for smoking cessation. Future research should continue to explore approaches for promoting user engagement and retention, and whether sustained engagement translates to clinically meaningful smoking cessation outcomes.     

An in vivo assessment of the genotoxic potential of bisphenol A and 4-tert-octylphenol in rats

Bisphenol A (BPA) and octylphenol (OP) are industrial chemicals used in the manufacture of polycarbonate plastics, epoxy resins, and non-ionic surfactants. In the present study, we investigated the possible in vivo genotoxic effects of these compounds in rats using single-cell gel electrophoresis, the so-called comet assay. Adult male Wistar albino rats were divided randomly into six groups as follows: BPA125 (received 125 mg/kg bw BPA; n = 6), OP125 (received 125 mg/kg bw OP; n = 6), BPA250 (received 250 mg/kg BPA; n = 6), OP250 (received 250 mg/kg bw OP; n = 6), control (n = 5), and MMS (positive control group that received methyl methanesulfonate; n = 3). Both BPA and OP were orally administrated for 4 weeks. Controls were orally inoculated with corn oil for 4 weeks as well. Comet parameters including tail length and tail moment were evaluated for possible genotoxic effects. There were no significant differences in the OP125 and in the BPA125 compared with the control group, regarding tail length and tail moment (P > 0.05). However, there were significant differences in the OP250 and in the BPA250 compared with the control group, regarding tail length and tail moment (P < 0.05 and P < 0.01, respectively). The genotoxic potential of BPA and OP was investigated in vivo; there is a need for further studies exploring further mechanisms of the genotoxic potential of these chemicals in vivo.     

Detectability of fifteen aquatic micro/mesocosms

Zooplankton abundance and species richness in 15 untreated 12,000 L outdoor microcosms (n = 15) were monitored over the course of 1 year to document the inherent variability and statistical detectability between replicates. Statistical power analysis were applied to derive the statistically minimal detectable difference (MDD) between replicates with default values set at; α = 0.1 and β = 0.2. Copepod abundance and species richness generally demonstrated the best detectability at 0.31 and 0.16, respectively, (n = 15); 0.59 and 0.33 (n = 3). Total zooplankton abundance and species richness had the lowest detectabilities at 0.19 and 0.14, respectively, (n = 15); 0.35 and 0.3 (n = 3). Rotifers, due to their opportunistic and rapid life traits, had the lowest single-species abundance detectabilities at 0.54 (n = 15); 0.8 (n = 3), whereas macroinvertebrate species richness had the lowest detectability at 0.43 (n = 15); 0.7 (n = 3) over 1 year. We recommend a priori calibration of the study design relative to relevant MDDs. Moreover, it is suggested to consider alternatives to statistical null hypothesis testing.     

Phase I trial of weekly docetaxel,weekly doxorubicin,daily oral cyclophosphamide,and G-CSF (ConTAC Regimen)in advanced malignancies

Purpose: This was a phase I study evaluating the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of weekly docetaxel, doxorubicin and daily oral cyclophosphamide with G-CSF support (ConTAC regimen). Patients and Methods: Cohorts of 3–6 patients with advanced breast or other solid malignancies were entered at subsequently higher dose levels until dose-limiting toxicities (DLT) were noted in 2 or more patients per dose level during the first 6 weeks of therapy. This study escalated dosages of docetaxel and doxorubicin simultaneously, while the dose of oral cyclophosphamide was fixed at 60 mg/m² daily. Results: Sixteen patients were enrolled. Grade 3–4 adverse events during the first 6 weeks of treatment were neutropenia (n = 1 at dose level #1 and n = 3 at dose level #4), anemia (n = 2 at dose levels 1 and 4), and nausea/vomiting (n = 1 at dose level #4). After 6 weeks of therapy, grade 3–4 toxicities included anemia (n = 3), neutropenia (n = 7), Hand-Foot syndrome (n = 2) and grade 3 cystitis and pneumonia (n = 1 at dose level #4). Five patients with advanced breast cancer and 1 patient with metastatic lung cancer responded to the chemotherapy. Conclusions: Grade 4 neutropenia was the DLT. The MTD, was established at dose level #3 (doxorubicin at 25 mg/m² and docetaxel at 25 mg/m² weekly with oral cyclophosphamide dose of 60 mg/m² daily). Myelosuppression at that dose level was moderate with G-CSF given concurrently.     

Is spinal manipulation effective for paediatric conditions? An overview of systematic reviews

The aim of this overview was to critically evaluate the evidence of effectiveness for spinal manipulation in any paediatric condition. Four electronic databases were searched from their inception to July 2011 to identify all relevant systematic reviews of spinal manipulation for any paediatric condition. Reviews were defined as systematic if they included explicit and repeatable inclusion and exclusion criteria. Five systematic reviews were included, which covered the following conditions: infant colic (n=2), kinetic imbalance due to suboccipital strain (n=1), nocturnal enuresis (n=1) and otitis media (n=1). None of the systematic reviews generated conclusive evidence to suggest that spinal manipulation is an effective treatment for any paediatric condition. Collectively these data failed to demonstrate that spinal manipulation is a useful therapy for paediatric complaints. The safety of spinal manipulation in paediatrics is also less than clear.     

Naltrexone for the treatment of alcohol dependence among African Americans: Results from the COMBINE Study

These analyses of the COMBINE Study were designed to examine the effects of naltrexone among African Americans during the course of the 16-week treatment. Participants (total n = 100; 70% male) who received naltrexone during the 16-week treatment trial (n = 51) were compared to those who received placebo (n = 49), controlling for acamprosate and behavioral intervention. Results did not support the efficacy of naltrexone on percent days abstinent, time to first heavy drinking day, and global clinical outcome in this subsample of African Americans. These results suggest that further work is needed to test naltrexone, as well as other medications, in this population and to identify treatment responders via genetics or other psychosocial predictor variables. Implications for pharmacogenetic studies of naltrexone are discussed.     

Body condition and mercury concentration in apparently healthy goosander (<Emphasis Type="Italic">Mergus merganser</Emphasis>) wintering in the Odra estuary,Poland

Goosanders (Mergus merganser, ad, adult n = 42: M, males 33 and F, females 9; im, immature n = 17: M 8, F 9) were collected in 2005 at wintering site in the River Odra estuary (Poland). The body size (BM, body mass; BL, body length; KL, keel length), weights of organs (LM, liver; KM, kidneys; EM, encephalon), and two condition-related indices (BM/BL and BM/KL) were determined. Based on BM/BL and BM/KL indices, the birds were divided into 3 condition groups: A (very good), B (good), and C (moderate). Total mercury (Hg) concentrations (mg kg⁻¹ dry weight) were determined in liver, kidney, brain, breast muscle, and bone of 17 birds (ad, n = 8: 8 M, 1 F; im, n = 9: 6 M, 3 F). The highest Hg concentrations (in n = 17) were recorded in liver and kidney (14.7 and 9.9 mg kg⁻¹, respectively); the concentrations found in muscle and brain were lower (2.3 and 1.3 mg kg⁻¹, respectively), the lowest concentrations being typical of bone (0.08 mg kg⁻¹). Mercury concentrations in the same organs of immature and adult goosanders, as well as males and females, did not differ significantly. On the other hand, distinct differences in Hg concentrations in the organs studied (except for the liver) were observed between individuals assigned to Group A (n = 11) and C (n = 6). Mercury levels were higher in the birds characterised by very good condition, which was most probably related to those birds being more efficient hunters, consuming higher amounts of Hg-containing fish. Significant and negative correlations between the muscle Hg concentration and the two condition-related indices (r > –0.70) were recorded in Group A only: the higher the concentration, the lower the BM/LM and BM/KL values.     

In silico screening of chemicals for bacterial mutagenicity using electrotopological E-state indices and MDL QSAR software

Quantitative structure–activity relationship (QSAR) software offers a rapid, cost effective means of prioritizing the mutagenic potential of chemicals. MDL QSAR models were developed using atom-type E-state indices and non-parametric discriminant analysis. Models were developed for Salmonella typhimurium gene mutation, combining results from strains TA97, TA98, TA100, TA1535, TA1536, TA1537, and TA1538 (n = 3228), and Escherichia coli gene mutation tests WP2, WP100, and polA (n = 472). Composite microbial mutation models (n = 3338) were developed combining all Salmonella, E. coli, and the Bacillus subtilis rec spot test study results. The datasets contained 74% non-pharmaceuticals and 26% pharmaceuticals. Salmonella and microbial mutagenesis external validation studies included a total of 1444 and 1485 compounds, respectively. The average specificity, sensitivity, positive predictivity, concordance, and coverage of Salmonella models was 76, 81, 73, 78, and 98%, respectively, with similar performance for the microbial mutagenesis models. MDL QSAR and discriminant analysis provides rapid and highly automated mutagenicity screening software with good specificity, sensitivity, and coverage that is simpler and requires less user intervention than other similar software. MDL QSAR modules for microbial mutagenicity can provide efficient and cost effective large scale screening of compounds for mutagenic potential for the chemical and pharmaceutical industry.     

Validation of the Lebanese Medication Adherence Scale among Lebanese diabetic patients

Background Adherence to oral antidiabetics plays a pivotal role in controlling diabetes. Healthcare workers evaluate this adherence when visited by patients. Objectives The primary objective of this study was to validate the existing LMAS-14 (Lebanese Medication Adherence Scale) in Lebanese diabetic adults. The secondary objective was to evaluate factors affecting adherence among this population. Setting The main five Lebanese governorates. Methods This study was conducted between May and September 2019, and community dwelling adult participants were enrolled using a proportionate random sample. The scale was validated using factor analysis and reliability testing, while bivariate and multivariable analyses assessed correlates of adherence. Main outcomes measures Validity of LMAS-14. Results A total of 308 participants were included, and the response rate was 91.25%. All LMAS-14 items converged over a solution of four factors, explaining a total of 64.39% of the variance (α = 0.859). The cutoff point between controlled and uncontrolled patients was set at 11. The sensitivity and specificity were good at this cutoff (71.1% and 94.74%, respectively). Results showed that 167 (57.2%) patients had good medication adherence. Advanced age (Beta = 0.046; p = 0.001) and having medical coverage (Beta = 1.452; p = 0.005) were significantly associated with higher adherence. Furthermore, adherence to oral antidiabetic drugs (Beta = 1.197; p = 0.018), female gender (Beta = 2.695; p = 0.011), and taking dyslipidemia medication (Beta = 3.527; p = 0.005) predicted higher diabetes control. Conclusion This study validated the LMAS among Lebanese adult diabetic patients taking oral antidiabetic drug. Advanced age and having medical coverage were associated with higher medication adherence. Further national studies are warranted to corroborate our findings.

     

Views, attitudes and self-assessed training needs of Scottish community pharmacists to public health practice and competence

Objective To assess the education and training needs of community pharmacists to support the delivery of an expanded public health role. Setting Community pharmacy in Scotland. Method Two focus groups of community pharmacists (n = 4 in each) in geographically distinct regions of Scotland explored issues of public health function, competencies and education and training. Findings from thematic analysis were used to develop a draft postal questionnaire. Following piloting, pharmacist managers from a random sample of 500 community pharmacies in Scotland were contacted by telephone to ascertain the number of pharmacists working in each pharmacy in the following 14-day period. A survey pack containing questionnaires for each identified pharmacist working in the study period was sent by post to the pharmacist manager in each pharmacy. The questionnaire contained items on: demographics; views and attitudes towards: public health; competencies for public health practitioners; and education and training needs. One postal reminder was sent 2 weeks later. Main Outcome Measures Main themes identified from focus group discussions; questionnaire response rate; views and attitudes towards public health competencies and education and training. Results Four hundred and fifteen managers agreed to participate, providing 904 potential participants. The response rate was 25% (223/904). Most (n = 179, 80%) were aware of the term ‘pharmaceutical public health’. While a majority saw the importance of public health to their practice (n = 177, 79%) agreeing/strongly agreeing, they were less comfortable with the term ‘specialist’. Respondents viewed competencies relating to health promotion (n = 192, 86%) more relevant than surveillance (n = 70, 31%), risk management (n = 29, 13%) and strategic developments (n = 12, 5%). Responses indicated a desire for education and training with more than half (n = 121, 54%) agreeing/strongly agreeing that they had a need now, with 69% (n = 153) expressing a future need. Conclusion Results should be interpreted with caution due to the response rate. However, this research highlights the self assessed gap in competence related to pharmaceutical public health for community pharmacists in Scotland.