Bacterial-Host Interactions: Physiology and Pathophysiology of Respiratory Infection.

It has long been thought that respiratory infections are the direct result of acquisition of pathogenic viruses or bacteria, followed by their overgrowth, dissemination, and in some instances tissue invasion. In the last decades, it has become apparent that in contrast to this classical view, the majority of microorganisms associated with respiratory infections and inflammation are actually common members of the respiratory ecosystem and only in rare circumstances do they cause disease. This suggests that a complex interplay between host, environment, and properties of colonizing microorganisms together determines disease development and its severity. To understand the pathophysiological processes that underlie respiratory infectious diseases, it is therefore necessary to understand the host-bacterial interactions occurring at mucosal surfaces, along with the microbes inhabiting them, during symbiosis. Current knowledge regarding host-bacterial interactions during asymptomatic colonization will be discussed, including a plausible role for the human microbiome in maintaining a healthy state. With this as a starting point, we will discuss possible disruptive factors contributing to dysbiosis, which is likely to be a key trigger for pathobionts in the development and pathophysiology of respiratory diseases. Finally, from this renewed perspective, we will reflect on current and potential new approaches for treatment in the future.

Transcriptomic and clinical heterogeneity of metastatic disease timing within metastatic castration-sensitive prostate cancer.

BACKGROUND: Metastatic castration-sensitive prostate cancer (mCSPC) is commonly classified into high- and low-volume subgroups which have demonstrated differential biology, prognosis, and response to therapy. Timing of metastasis has similarly demonstrated differences in clinical outcomes; however, less is known about any underlying biologic differences between these disease states. Herein, we aim to compare transcriptomic differences between synchronous and metachronous mCSPC and identify any differential responses to therapy. PATIENTS AND METHODS: We performed an international multi-institutional retrospective review of men with mCSPC who completed RNA expression profiling evaluation of their primary tumor. Patients were stratified according to disease timing (synchronous versus metachronous). The primary endpoint was to identify differences in transcriptomic profiles between disease timing. The median transcriptomic scores between groups were compared with the Mann-Whitney U test. Secondary analyses included determining clinical and transcriptomic variables associated with overall survival (OS) from the time of metastasis. Survival analysis was carried out with the Kaplan-Meier method and multivariable Cox regression. RESULTS: A total of 252 patients were included with a median follow-up of 39.6 months. Patients with synchronous disease experienced worse 5-year OS (39% versus 79%; P < 0.01) and demonstrated lower median androgen receptor (AR) activity (11.78 versus 12.64; P < 0.01) and hallmark androgen response (HAR; 3.15 versus 3.32; P < 0.01). Multivariable Cox regression identified only high-volume disease [hazard ratio (HR) = 4.97, 95% confidence interval (CI) 2.71-9.10; P < 0.01] and HAR score (HR = 0.51, 95% CI 0.28-0.88; P = 0.02) significantly associated with OS. Finally, patients with synchronous (HR = 0.47, 95% CI 0.30-0.72; P < 0.01) but not metachronous (HR = 1.37, 95% CI 0.50-3.92; P = 0.56) disease were found to have better OS with AR and non-AR combination therapy as compared with monotherapy (P value for interaction = 0.05). CONCLUSIONS: We have demonstrated a potential biologic difference between metastatic timing of mCSPC. Specifically, for patients with low-volume disease, those with metachronous low-volume disease have a more hormone-dependent transcriptional profile and exhibit a better prognosis than synchronous low-volume disease.

Self-exclusion and breaching of self-exclusion from gambling: a repeated survey study on the development of a nationwide self-exclusion service.

BACKGROUND: Voluntary self-exclusion from gambling is a common harm reduction tool in individuals with a gambling disorder. Previous data have demonstrated that many gamblers breach their own self-exclusion, typically through other online services outside the jurisdiction in which they are self-excluded. The present study aimed to carry out a new follow-up measure-similar to previous studies in the same setting-of self-exclusion and its breaching in Sweden, in order to allow for the follow-up assessment of a nationwide, multi-operator self-exclusion system introduced in Sweden in 2019. METHODS: A web survey to the web panel of a market survey company addressed 1505 past-year gamblers, who responded to a number of questions about gambling habits, including screening for gambling problems using the Problem Gambling Severity Index and self-exclusion-related items corresponding to previous studies. RESULTS: Nine percent of past-year gamblers had self-excluded using the Spelpaus service. In logistic regression, self-exclusion was significantly associated with gambling problems, past-year online casino gambling, and absence of online poker gambling. Among self-excluders, 49 percent had ever gambled despite being self-excluded. Among those breaching their self-exclusion, the most common gambling types during self-exclusion were online casino (82 percent), sports betting (47 percent) and lotteries (43 percent). DISCUSSION: Self-exclusion remains a popular harm reduction tool against problem gambling, more common than in previous studies, mostly in individuals with recent gambling problems and in online casino gamblers. However, breaching self-exclusion is somewhat more common than in previous research. Online casino represents the most common means of self-exclusion breaching. Policy-making in the area needs to further address the risk of breaching one's self-exclusion and may further address the risk of overseas gambling.

A nationwide case-control study on cardiovascular and respiratory-related disorders in patients with gambling disorder in Sweden.

OBJECTIVES: We aimed to examine potential relationships and gender differences between cardiovascular disease (CVD), diabetes, obesity, respiratory-related disorders, and gambling disorder (GD). We hypothesized that (1) GD patients would be more likely than controls to have CVD, diabetes, obesity, and respiratory-related diseases; and (2) females with GD would be more likely than men with GD to have CVD, diabetes, obesity, and respiratory-related diseases. STUDY DESIGN: National retrospective case-control study. METHODS: We used data from the Swedish National Board of Health and Welfare between 2005 and 2019. A total of 10,766 patients were included, and 3592 of them had GD. Every GD patient was matched with two age- and gender-matched controls. Patient data, including the history of medical diagnoses, were extracted. Descriptive statistics, Chi-squared and Fisher's exact tests were used to compare GD patients and controls. RESULTS: GD patients had a higher prevalence of CVD and respiratory-related disorders than controls. Diabetes rates were 5% for GD patients and 2% for controls; CVD (18% vs 12%); respiratory-related disease (7% vs 4%); and obesity (7% vs 3%). Women with a diagnosis of GD have a higher prevalence of obesity and somatic comorbidities other than diabetes compared to men. CONCLUSIONS: This is the largest case-control study conducted to date showing GD patients have a higher prevalence of CVD, diabetes, obesity, and respiratory-related disorders than controls. Women with GD appear to be more susceptible than men to CVD, obesity, and respiratory-related disorders; however, this may be partially explained by differences in help-seeking behavior. Thus, our findings highlight the importance of early identification of GD patients who may also have somatic conditions requiring treatment. This can be accomplished by implementing a screening program for GD, CVD, diabetes, obesity, and respiratory-related disorders, and by including healthy lifestyle management strategies.

An interrupted time series analysis of gambling behavior based on gambling operator revenue-based taxation during the COVID-19 pandemic in Sweden.

OBJECTIVES: The impact of COVID-19 on gambling behavior and the gambling industry itself has been widely speculated. Prior studies have shown how boredom, social isolation, poor mental health, and financial hardships, all of which have been associated with COVID-19, can aggravate problem gambling behaviors in patients with gambling disorders while also luring newcomers. Few studies have used methods other than self-report to assess longitudinal behavioral changes in gambling behavior before versus during the pandemic. STUDY DESIGN: The present study addresses this gap by using an interrupted time series approach on data obtained from the Swedish Gambling Authority measuring taxation on gambling vendors' revenue between January 2019 and November 2021. METHODS: March, June, and October 2020 were chosen as interruption points as they correspond to the pandemic's commencement, the return of elite sports, and the second wave of cases in Sweden, respectively. We hypothesized that the pandemic would be associated with both temporary changes for select gambling types and long-term increases in online gambling. RESULTS: Results revealed the pandemic's onset was associated with transient effects at each point of interruption, as well as long-term upward trends in total gambling and commercial online gambling, excluding horse betting and the state-owned operator for online casinos and betting. CONCLUSIONS: The present study's findings, although consistent with the theory that gambling activity could increase during the pandemic, contradict previous studies that found no changes or a decrease from pre-COVID-19 levels. Findings indicate that the pandemic and Sweden's reaction to it were associated with increased use of some gambling products.

The societal costs of problem gambling in Sweden.

BACKGROUND: Problem gambling is a public health issue affecting both the gamblers, their families, their employers, and society as a whole. Recent law changes in Sweden oblige local and regional health authorities to invest more in prevention and treatment of problem gambling. The economic consequences of gambling, and thereby the potential economic consequences of policy changes in the area, are unknown, as the cost of problem gambling to society has remained largely unexplored in Sweden and similar settings. METHODS: A prevalence-based cost-of-illness study for Sweden for the year 2018 was conducted. A societal approach was chosen in order to include direct costs (such as health care and legal costs), indirect costs (such as lost productivity due to unemployment), and intangible costs (such as reduced quality of life due to emotional distress). Costs were estimated by combining epidemiological and unit cost data. RESULTS: The societal costs of problem gambling amounted to 1.42 billion euros in 2018, corresponding to 0.30% of the gross domestic product. Direct costs accounted only for 13% of the total costs. Indirect costs accounted for more than half (59%) of the total costs, while intangible costs accounted for 28%. The societal costs were more than twice as high as the tax revenue from gambling in 2018. Direct and indirect costs of problem gambling combined amounted to one third of the equivalent costs of smoking and one sixth of the costs of alcohol consumption in Sweden. CONCLUSIONS: Problem gambling is increasingly recognized as a public health issue. The societal costs of it are not negligible, also in relation to major public health issues of an addictive nature such as smoking and alcohol consumption. Direct costs for prevention and treatment are very low. A stronger focus on prevention and treatment might help to reduce many of the very high indirect and intangible costs in the future.

Who chooses to enroll in a new national gambling self-exclusion system? A general population survey in Sweden.

BACKGROUND: Self-exclusion from gambling is a common method for prevention and harm reduction in hazardous gambling. However, few national self-exclusion programs, involving a large number of gambling operators and activities in a country, have been assessed scientifically. This study aimed to examine characteristics of individuals who chose to enroll in a recently introduced (January, 2019) national self-exclusion system in Sweden. METHODS: Adults and adolescents (from age 16 and above) were addressed with an online survey sent to members of the web panel of a market survey company (1940 respondents). Psychological distress, previous history of addictive disorders, sociodemographic data, and recent history of gambling patterns and over-indebtedness were recorded. Logistic regression tested associations with self-exclusion, with unadjusted analyses conducted for the sub-group of moderate-risk or problem gamblers. RESULTS: Four percent reported having self-excluded using the new national self-exclusion system. In logistic regression, self-exclusion was significantly associated with younger age (OR 0.65 [0.54-0.79] for increasing age groups) and with the highest level of problem gambling (OR 2.84 [1.10-7.37]). In moderate-risk or problem gamblers, in unadjusted analyses, younger age (p < 0.05) and psychological distress (p = 0.02) were associated with self-exclusion. In none- or low-risk gamblers, 3% had self-excluded, which was significantly associated with younger age (p < 0.001) and self-reported over-indebtedness (p < 0.001). CONCLUSIONS: In a national, multi-venue online and land-based self-exclusion system, aiming to reduce the harm of problem gambling, self-exclusion is expectedly more common in problem gamblers, but also occurs among people without recent gambling problems. Further efforts may be needed in order to increase gambling self-exclusion in problem gamblers, and research in reasons for self-excluding, even in non-problem gamblers, is needed.

Antibiotic treatment of pregnant non-obese diabetic mice leads to altered gut microbiota and intestinal immunological changes in the offspring.

The intestinal microbiota is important for tolerance induction through mucosal immunological responses. The composition of the gut microbiota of an infant is affected by environmental factors such as diet, disease and antibiotic treatment. However, already in utero, these environmental factors can affect the immunological development of the foetus and influence the future gut microbiota of the infant. To investigate the effects of antibiotic treatment of pregnant mothers on the offspring's gut microbiome and diabetes development, we treated non-obese diabetic (NOD) mice with a cocktail of antibiotics during gestation and the composition of the gut microbiota, diabetes incidence and major gut-related T lymphocyte populations were investigated in the offspring. We observed a persistent reduction in the general diversity of the gut microbiota in the offspring from NOD mothers treated with antibiotics during gestation compared with offspring from control mothers. In addition, by clustering the present bacterial taxa with principal component analysis, we found a differential clustering of gut microbiota in the offspring from NOD mothers treated with antibiotics during gestation compared with offspring from control mothers. Offspring from NOD mothers treated with antibiotics during gestation also showed some immunological alterations in the gut immune system, which could be related to the diversity of the gut microbiome and influence modulation of diabetes development at 20 weeks. Our data point out maternal derangement of the intestinal microbiota as a potential environmental risk factor for T1D development.

Mortality, morbidity, and predictors of death among amphetamine-type stimulant users - a longitudinal, nationwide register study.

Introduction: Use of amphetamine-type stimulants (ATS) contributes substantially to the global burden of disease. Large-scale follow-up studies of morbidity and mortality in ATS users are few. This study analysed morbidity, mortality, and potential predictors of all-cause mortality in a nationwide cohort of patients with ATS use disorder. Methods: Data was acquired from national Swedish registers. All Swedish residents 18 years or older, with a registered ATS use diagnosis in 2013-2014 were included (N = 5,018) and followed until December 31, 2017. Comorbid diagnoses and causes of death were assessed and potential predictors of all-cause mortality were examined through Cox regression. Results: Median age at inclusion was 36.6 years (interquartile range 27.4---48.1) and 70.5 % were men. The crude mortality rate was 24.6 per 1,000 person-years. The adjusted all-cause standardized mortality ratio was 12.4 (95 % CI [11.34-13.55]). The most common cause of death was overdose (28.9 %). Multiple drug use (hazard ratio 1.39, 95 % CI [1.14-1.70], p = 0.004), anxiety (hazard ratio 1.39, 95 % CI [1.11-1.72], p = 0.014), viral hepatitis (hazard ratio 1.85, 95 % CI [1.50-2.29], p = 0.004), and liver disease (hazard ratio 2.41, 95 % CI [1.55-3.74], p = 0.004) were predictors of all-cause mortality. Conclusions: Multiple drug use, anxiety disorders, viral hepatitis and liver diseases were identified as risk factors for death. Our findings call for better screening, prevention, and treatment of somatic and psychiatric comorbidity among ATS users to reduce mortality.

Nationwide, Multioperator Self-Exclusion and Psychiatric Comorbidity in Patients with Gambling Disorder: A Retrospective Chart Review Study from a Regional Treatment Unit.

Gambling disorder is an addictive disorder that has been shown to have a detrimental effect on an individual's health, social, and financial situations. Voluntary self-exclusion is one way for patients to reduce harm in gambling disorder, but breaching one's self-exclusion appears to be common. In January 2019, Sweden launched a nationwide, multioperator self-exclusion instrument called Spelpaus (literally "game break"). Spelpaus is unique to Sweden, and there is limited research on the use of this type of nationwide, multioperator self-exclusion services, also in relation to gambling disorder and mental health. There is a reason to follow the clinical picture of treatment seeking for gambling disorder over time, and this study aims to explore clinical characteristics of patients seeking clinical gambling disorder treatment, including sex distribution and mental health comorbidity, as well as the use of Spelpaus amongst patients with gambling disorder and how frequently users gambled despite ongoing self-exclusion, in relation to sex and psychiatric comorbidities. A retrospective chart study was carried out on patients presenting to a regional gambling disorder treatment unit. Information regarding self-exclusions using Spelpaus, gambling despite self-exclusion, and the method of gambling despite self-exclusion as well as psychiatric comorbidities were extracted from medical records. Females were markedly more likely to report overall psychiatric comorbidities (48% vs. 25% among males, p < 0.001), affective, neurotic/anxiety-related (p < 0.001), and behavioral/emotional (p = 0.028) diagnoses and more likely to have two or more diagnoses excluding gambling disorder (p = 0.001). From 120 patients from whom information regarding self-exclusion was present, 114 (95%) had chosen to self-exclude. From the 114 self-excluders, 67 reported to have gambled despite self-exclusion, with unregistered websites being the most common method. Self-exclusion was not significantly related to sex (p = 0.146) or to psychiatric comorbidities (p = 0.178). In conclusion, psychiatric comorbidity was particularly common in female gambling disorder patients and gambling despite self-exclusion was common. Gambling regulations should be improved to help self-excluders avoid being able to gamble on unlicensed gambling operators. Further research should focus on sex differences and the association with psychiatric comorbidities.

Increased sensitivity through maximizing the extinction ratio of SOI delay-interferometer receiver for 10G DPSK.

We present an optimized design for a 10G- differential-phase-shift-keyed (DPSK) receiver based on a silicon-on-insulator (SOI) unbalanced tunable Mach-Zehnder interferometer (MZI) switch in sequence with a Mach-Zehnder delay interferometer (MZDI). The proposed design eliminates the limitation in sensitivity of the device produced by the waveguide propagation losses in the delay line. A 2.3 dB increase in receiver sensitivity at a bit-error-rate (BER) of 10(-9) is experimentally measured over a standard implementation. The enhanced sensitivity is achieved with zero power consumption by tuning the operating wavelength or with less than 5 mW for a fixed wavelength using microheaters. Also the foot-print of the device is minimized to 0.11 mm(2) by the use of compact spirals.

Fear of COVID-19, compliance with recommendations against virus transmission, and attitudes towards vaccination in Sweden.

Following the immense impact of the COVID-19 pandemic on health and everyday lives world-wide, people's fear of COVID-19 has been studied in a number of settings using the Fear of COVID scale. In Sweden, virus-preventing strategies have differed from comparable countries, with low use of formal lock-down procedures. It is crucial to study correlates of non-compliance with COVID-19 recommendations, and unwillingness to become vaccinated. This study aims to study whether fear of COVID is associated with mental distress and attitudes towards the pandemic, and to study correlates of non-compliance with key anti-COVID recommendations and with reluctancy to vaccination. This anonymous online survey study in web panel participants (N = 1,501) aimed to study a range of behavioral changes during COVID-19. Recommendations and vaccinations reluctancy were analyzed in logistic regressions against socio-demographic data, COVID-19 status, and mental health history. Internal consistency of the Fear of COVID scale was calculated. The Fear of COVID scale had a satisfactory internal consistency (Cronbach-alpha 0.84), and was significantly associated with compliance with all COVID-19 recommendations and with mental health. Non-compliance with recommendations was associated with low fear of disease and younger age, among other variables. Being against vaccination was associated, among other variables, with low fear of disease and with low education. In conclusion, the Fear of COVID scale appears to be associated with key attitudes towards the COVID-19 disease. Anti-virus strategies may need to promote compliance with recommendations in subgroups who feel low fear of disease or who believe not to be in a risk group for severe disease.

The live bacterial load and microbiota composition of prepacked "ready-to-eat" leafy greens during household conditions, with special reference to E. coli.

Ready-to-eat (RTE) leafy greens are popular products that unfortunately have been associated with numerous foodborne illness outbreaks. Since the influence of consumer practices is essential for their quality and safety, the objective of this study was to analyze the microbiota of RTE products throughout shelf life during simulated household conditions. Products from different companies were analyzed in terms of plate counts, and resealed and unopened packages were compared. High bacterial loads were found, up to a total plate count of 9.6 log10 CFU/g, and Enterobacteriaceae plate counts up to 6.0 CFU/g on the expiration date. The effect of consumer practice varied, thus no conclusions regarding resealed or unopened bags could be drawn. The tested products contained opportunistic pathogens, such as Enterobacter homaechei, Hafnia paralvei and Pantoea agglomerans. Amplicon sequencing revealed that the relative abundance of major taxonomic groups changed during shelf life; Pseudomonadaceae and Xanthomonadaceae decreased, while Flavobacteriaceae and Marinomonadaceae inceased. Inoculation with E. coli CCUG 29300T showed that the relative abundance of Escherichia-Shigella was lower on rocket than on other tested leafy greens. Inoculation with E. coli strain 921 indicate growth at the beginning of shelf-life time, while E. coli 731 increases at the end, seemingly able to adapt to cold storage conditions. The high levels of live microorganisms, the detection of opportunistic pathogens, and the ability of E. coli strains to grow at refrigeration temperature raise concerns and indicate that the shelf life may be shortened to achieve a safer product. Due to variations between products, further studies are needed to define how long the shelf-life of these products should be, to ensure a safe product even at the end of the shelf-life period.

Efficacy of mobile telephone contact for follow-up in injecting heroin users.

BACKGROUND: Prospective follow-up of heroin users is known to be difficult due to their unstable lifestyle, and high follow-up rates have usually demanded major tracking efforts. In Sweden, mobile telephones are commonly used by heavy drug users for drug trading. OBJECTIVES: This methodology study aims to examine the efficacy of mobile telephone contact for prospective follow-up interviews with injecting heroin users recruited at the syringe exchange program of Malmö, Sweden. METHODS: Seventy-eight heroin users with mobile telephone numbers were included. Subjects reported using heroin for 28 days of the previous 30 days, and only 8% reported they had recently been engaged in work or studies. Clients were contacted between 15 and 21 times over 2 years, with each contact attempt generally involving two telephone calls on consecutive days. RESULTS: During follow-up, 68% of subjects had been successfully contacted for at least one follow-up interview (on average 6.9 interviews), and 25% of follow-up attempts were successful. In 23% of the sample (n=18), at least 50% of follow-up attempts were successful, and these subjects tended to be older (p=.05) and more likely to be female (p=.07), whereas follow-up rates were unrelated to baseline heroin use. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Despite limited effort, and despite the severe situation of intravenous heroin users, mobile telephone contact can be used with heavy drug users in the present setting.

Patient specific biomodel of the whole aorta - the importance of calcified plaque removal.

BACKGROUND: The use of anatomical models produced by 3D printing technique (rapid prototyping, RP) is gaining increased acceptance as a complementary tool for planning complex surgical interventions. This paper describes a method for creating a patient specific replica of the whole aorta. METHODS: Computed tomography angiography (CTA) DICOM-data was converted to a three-dimensional computer aided design-model (CAD) of the inner wall of the aorta representing the lumen where the calcified plaque contribution was removed in a multi-step editing-manoeuvre. The edited CAD-model was used for creating a physical plaster model of the true lumen in a 3D-printer. Elastic and transparent silicon was applied onto the plaster model, which was then removed leaving a silicon replica of the aorta. RESULTS: The median (interquartile range) difference between diameters obtained from CTA- and RP plaster-model at 19 predefined locations was 0.5 mm (1 mm) which corresponds to a relative median difference of 4.6% (7.0%). The average wall thickness of the silicone model was 3.5 mm. The elasticity property and performance during intervention was good with an acceptable transparency. CONCLUSIONS: The integration of RP-techniques with CAD based reconstruction of 3D-medical imaging data provides the needed tools for making a truly patient specific replica of the whole aorta with high accuracy. Plaque removal postprocessing is necessary to obtain a true inner wall configuration.

Match-Fixing Causing Harm to Athletes on a COVID-19-Influenced Gambling Market: A Call for Research During the Pandemic and Beyond.

Match-fixing, although not a new problem, has received growing attention during the COVID-19 pandemic, which has been reported in the media to have increased the risk of match-fixing events. Gambling is a well-documented addictive behavior, and gambling-related fraud, match-fixing, is a challenge to the world of sports. Most research on match-fixing has a judicial or institutional perspective, and few studies focus on its individual consequences. Nevertheless, athletes may be at particular risk of mental health consequences from the exposure to or involvement in match-fixing. The COVID-19 crisis puts a spotlight on match-fixing, as the world of competitive sports shut down or changed substantially due to pandemic-related restrictions. We call for research addressing individual mental health and psycho-social correlates of match-fixing, and their integration into research addressing problem gambling, related to the pandemic and beyond.

Role of Gambling in Payback Failure in Consumer Credit-Data from a Large Body of Material Regarding Consumer Loan Recipients in Sweden.

Indebtedness is associated with poor health outcomes, and problem gambling may contribute to indebtedness through consumer credits related to gambling expenses. The assessment of consumers' applications for loans may be an opportunity to detect and prevent further problem gambling. The present study analyzed a number of variables including gambling-related transactions and their association with payback failure in 48,197 loans to 20,750 individuals in Sweden. Sums and frequency of gambling deposits or withdrawals generally did not predict failure to pay back loans. Instead, having a loan defaulted at some time was associated with a baseline pattern describing a theoretical loss-of-control gambling pattern (short-term intense gambling), with a higher ratio of gambling deposits or withdrawals per occasion, and with several instances of gambling in close association with a loan. While several group differences were modest, signs of rapid, short-term and intense gambling, rather than gambling itself, may identify risk of payback failure and risk of indebtedness. Implications for early problem-gambling detection and prevention, such as by gambling operators and financial institutes, are discussed and may promote better public health in relation to gambling indebtedness.

Clinical characteristics distinguishing tramadol-using adolescents from other substance-using adolescents in an out-patient treatment setting.

BACKGROUND: Non-medical Prescription Opioid Use (NMPOU) has increased worldwide during the last decades, and specifically, tramadol misuse may represent a novel pattern of substance use among adolescents. The present study aims to analyze characteristics distinguishing tramadol-using adolescents from other substance-using adolescents seeking out-patient treatment. METHODS: This is a cross-sectional study of treatment-seeking patients between 13 and 24 years of age in an out-patient facility for substance use problems in Malmö, Sweden. A total of 526 treatment-seeking adolescents at an out-patient treatment center were included. Data on substance use, treatment history and socio-demographic variables were extracted through a semi-structured interview method aimed specifically for adolescents with alcohol or drug problems (Ung-DOK). Lifetime tramadol users were compared to non-users, and also, primary tramadol users were compared to remaining subjects. RESULTS: Thirty-one percent (n = 162) were tramadol users (lifetime prevalence). In logistic regression, the tramadol group showed a significantly increased risk of tobacco use, problematic lifetime cocaine, benzodiazepine and amphetamine use, and were more likely to report contacts with the judicial system, and less likely to report contacts with child or adult psychiatry, and more likely to have parents born outside the Scandinavian countries. In logistic regression, primary tramadol use was negatively associated with frequent cannabis use. CONCLUSIONS: Tramadol use appears to be a novel pattern among treatment-seeking adolescents. They showed a significantly increased risk of initiation of other illicit drugs and criminal behaviour, despite less contact with psychiatric care. More attention may be needed to this relatively novel pattern of opioid use.

Panel 7 - Pathogenesis of otitis media - a review of the literature between 2015 and 2019.

OBJECTIVE: To perform a comprehensive review of the literature from July 2015 to June 2019 on the pathogenesis of otitis media. Bacteria, viruses and the role of the microbiome as well as the host response are discussed. Directions for future research are also suggested. DATA SOURCES: PubMed database of the National Library of Medicine. REVIEW METHODS: PubMed was searched for any papers pertaining to OM pathogenesis between July 2015 and June 2019. If in English, abstracts were assessed individually for their relevance and included in the report. Members of the panel drafted the report based on these searches and on new data presented at the 20th International Symposium on Recent Advances in Otitis Media. CONCLUSIONS: The main themes that arose in OM pathogenesis were around the need for symptomatic viral infections to develop disease. Different populations potentially having different mechanisms of pathogenesis. Novel bacterial otopathogens are emerging and need to be monitored. Animal models need to continue to be developed and used to understand disease pathogenesis. IMPLICATIONS FOR PRACTICE: The findings in the pathogenesis panel have several implications for both research and clinical practice. The most urgent areas appear to be to continue monitoring the emergence of novel otopathogens, and the need to develop prevention and preventative therapies that do not rely on antibiotics and protect against the development of the initial OM episode.

Cytochrome P450 2E1 gene polymorphisms/haplotypes and Parkinson's disease in a Swedish population.

Cytochrome P450 2E1 (CYP2E1), which inter alia is located in dopamine containing neurons in the substantia nigra, has been hypothesized to be of importance for the pathophysiology of Parkinson's disease (PD), either by its production of reactive oxygen species (ROS) or by its capability to detoxify putative neurotoxins. Numerous polymorphisms in the coding and non-coding regions of the gene for this enzyme have been reported. Different variants may account for inter-individual differences in the activity of the enzyme or production of ROS. In this study, the CYP2E1 gene was examined in a control population (n = 272) and a population with PD (n = 347), using a tag-single nucleotide polymorphism (tSNP) approach founded on HapMap Data. Six tSNPs were used in the analysis and haplotype block data were obtained. In case of significance, the SNP was further examined regarding early/late age of disease onset and presence of relatives with PD. We found an association between allele and genotype frequencies of the C/G polymorphism at intron 7 (rs2070676) of this gene and PD (P value of 0.026 and 0.027, respectively). Furthermore, analysis of the rs2070676 polymorphism in subgroups of patients with age of disease onset higher than 50 years and those not having a relative with PD also demonstrated a significant difference with controls. This was seen in both genotype (corresponding to P value = 0.039 and 0.032) and allele (P = 0.027 and 0.017 respectively) frequency. As a representative of many polymorphisms or in possible linkage disequilibrium with other functional variants, it is possible that rs2070676 could influence the regulation of the enzyme. In conclusion, our results display an association between the rs2070676 polymorphism and PD. Additional investigations are needed to elucidate the importance of this polymorphism for the activity of CYP2E1 and PD susceptibility.