Distribution of intranasal naloxone to potential opioid overdose bystanders in Sweden: effects on overdose mortality in a full region-wide study.

OBJECTIVES: Distribution of take-home naloxone is suggested to reduce opioid-related fatalities, but few studies have examined the effects on overdose deaths in the general population of an entire community. This study aimed to assess the effects on overdose deaths of a large-scale take-home naloxone programme starting in June 2018, using an observational design with a historic control period. DESIGN: From the national causes of death register, deaths diagnosed as X42 or Y12 (International Classification of Diseases, 10th revision, ICD-10) were registered as overdoses. Numbers of overdoses were calculated per 100 000 inhabitants in the general population, and controlled for data including only individuals with a prior substance use disorder in national patient registers, to focus on effects within the primary target population of the programme. The full intervention period (2019-2021) was compared with a historic control period (2013-2017). SETTING: Skåne county, Sweden. PARTICIPANTS: General population. INTERVENTIONS: Large-scale take-home naloxone distribution to individuals at risk of overdose. PRIMARY AND SECONDARY OUTCOME MEASURES: Decrease in overdose deaths per 100 000 inhabitants, in total and within the population with substance use disorder diagnosis. RESULTS: Annual average number of overdose deaths decreased significantly from 3.9 to 2.8 per 100 000 inhabitants from the control period to the intervention period (a significant decrease in men, from 6.7 to 4.3, but not in women, from 1.2 to 1.3). Significant changes remained when examining only prior substance use disorder patients, and decreases in overdose deaths could not be attributed to a change in treatment needs for opioid use disorders in healthcare and social services. CONCLUSIONS: The present study, involving 3 years of take-home naloxone distribution, demonstrated a decreased overdose mortality in the population, however, only in men. The findings call for further implementation of naloxone programmes, and for further studies of potential effects and barriers in women. TRIAL REGISTRATION NUMBER: NCT03570099.

Alloplasmic effects on mitochondrial transcriptional activity and RNA turnover result in accumulated transcripts of Arabidopsis orfs in cytoplasmic male-sterile Brassica napus.

Mitochondrial transcription was investigated in a cytoplasmic male-sterile (CMS) Brassica napus line with rearranged mitochondrial (mt) DNA mostly inherited from Arabidopsis thaliana. The transcript patterns were compared with the corresponding male-fertile progenitors, B. napus and A. thaliana, and a fertility-restored line. Transcriptional activities, gene stoichiometry and transcript steady-state levels were analysed for all protein and rRNA coding genes and for several orfs present in the A. thaliana mitochondrial genome. The transcriptional activities were highly variable when comparing the parental species, while the CMS and restored lines displayed similar activities. For several ribosomal protein genes transcriptional activity was reduced while it was increased for orf139 in comparison with the parental species. The differences in transcriptional activity observed could be related to differences in relative promoter strength, as gene stoichiometry between lines was very limited. Transcript steady-state levels were more homogenous than the transcriptional activities demonstrating RNA turnover as a compensating mechanism. In the CMS line higher transcript abundance and novel transcript patterns in comparison with the parental lines were found for several genes. Of those, the transcripts for orf139, orf240a and orf294 were less abundant in the fertility-restored line. These putative CMS-associated transcripts were mapped by cRT-PCR. In conclusion we show that (mt) DNA from A. thaliana was non-correctly transcribed and processed/degraded in the B. napus nuclear background. Furthermore, the introgressed nuclear A. thaliana DNA in the fertility-restored line contributes to a more rapid degradation of transcripts accumulated from A. thaliana derived orfs in the CMS line.

Usage of antifungal drugs for therapy of genital Candida infections, purchased as over-the-counter products or by prescription: I. Analyses of a unique database.

OBJECTIVES: To present sales figures of antifungal drugs for treatment of genital Candida infections in females, which had been purchased in the Swedish county of Skåne (with approximately 1.2 million inhabitants) during the 1990s. To study the relative proportions of the drugs sold by prescription and as over-the-counter (OTC) products. METHODS: Sales figures of antifungal drugs for therapy of vulvovaginal candidiasis (VVC) and such recurrent infections (RVVC), for the years 1990--99, were collected from the 'ACS' database of the National Corporation of Swedish Pharmacies. RESULTS: The study showed an increase in sales of the type of drugs studied from 45,000 packages in 1990 until mid-93/94, when approximately 70,000 packages were sold (mainly azoles for topical use and fluconazole for oral intake). Thereafter there was a decrease until the end of November 1999, when 54,000 packages were purchased. Of the total sales, 93% were OTC products. Sales of clotrimazole and econazole (for vaginal installation) in 1993--1994 were equal to 85-90 packages/1000 women in the age group 15-45 years. Extremely high sales volumes of fluconazole and itraconazole, for one single year each, could be explained by marketing-related activities directed to the medical community. CONCLUSIONS: As many women with RVVC are not cured by iatrogenic initiatives and women consider themselves able to diagnose episodes of genital Candida infection, affected women generally turn to self-medication with antifungal OTC products. This stresses the role of pharmacy counseling. Short-term marked alterations in sales volumes may be due to marketing factors rather than changes in the epidemiology of genital Candida infections.

Usage of antifungal drugs for therapy of genital Candida infections, purchased as over-the-counter products or by prescription: 2. Factors that may have influenced the marked changes in sales volumes during the 1990s.

BACKGROUND: The epidemiology of vulvovaginal candidiasis (VVC) and such recurrent infections (RVVC) has been difficult to study as the majority of episodes of these conditions are self-treated by the women affected. In Sweden, all pharmacies are owned by the state and all prescriptions and over-the-counter (OTC) products, such as antifungals, are registered in a database, which offers unique possibilities to study the epidemiology of VVC/RVVC. OBJECTIVES: To analyze all prescriptions and OTC products purchased for therapy of VVC/RVVC and to establish reasons for any observed variation in the sales figures. METHODS: Sales figures in the Swedish county of Skåne of antifungal drugs for therapy of VVC/RVVC were analyzed by the aid of the 'ACS' database of the National Corporation of Swedish Pharmacies for the years 1990--1999. The size of the female population in the county is approximately half a million. RESULTS: The study showed that 93% of all antifungal drugs for VVC/RVVC were sold as OTC products. An increase in sales of the drugs occurred until mid- 1993/94, followed by a decrease until end of the study period in 1999. Demographic factors (e.g. the number of female inhabitants in the county, pharmacies and health-care units), the pregnancy rate and pharmacy-dependent factors (such as the introduction of shelves for self-selection of antifungal products) did not explain the observed variations in sales. Distinct short-term variations in the number of prescriptions of fluconazole and itraconazole could be explained by drugs company sales campaigns and logistics factors in drug distribution. The sales volumes in the 33 municipalities in the county correlated with the density of the population, which was not the case for the total number of prescriptions made in the county during the 1990s. The variation in antifungal drug sales was similar to that of hormonal intrauterine devices, but this was not the case for oral contraceptives. The total Swedish usage of antibiotics showed a similar variation to that of the antifungal drugs analyzed. CONCLUSION: The study stresses the limited impact on the treatment of VVC/RVVC by the medical community. Behavior-related factors in the female population are the most likely explanation for the marked variations found in the usage of drugs for the two conditions.