Purpose
Potentially inappropriate prescriptions (PIPs) criteria are widely used for evaluating the quality of prescribing in elderly. However, there is limited evidence on their association with ...adverse drug reactions (ADRs) across healthcare settings. The study aimed to determine the prevalence of PIPs, defined by the Screening Tool of Older Persons’ potentially inappropriate Prescriptions (STOPP) criteria, in the Swedish elderly general population and to investigate the association between PIPs and occurrence of ADRs.
Method
Persons ≥65 years old were identified from a random sample of 5025 adults drawn from the Swedish Total Population Register. A retrospective cohort study was conducted among 813 elderly with healthcare encounters in primary and specialised healthcare settings during a 3-month period in 2008. PIPs were identified from the Swedish Prescribed Drug Register, medical records and health administrative data. ADRs were independently identified by expert reviewers in a stepwise manner using the Howard criteria. Multivariable logistic regression examined the association between PIPs and ADRs.
Results
Overall, 374 (46.0 %) persons had ≥1 PIPs and 159 (19.5 %) experienced ≥1 ADRs during the study period. In total, 29.8 % of all ADRs was considered caused by PIPs. Persons prescribed with PIPs had more than twofold increased odds of experiencing ADRs (OR 2.47; 95 % CI 1.65–3.69). PIPs were considered the cause of 60 % of ADRs affecting the vascular system, 50 % of ADRs affecting the nervous system and 62.5 % of ADRs resulting in falls.
Conclusion
PIPs are common among the Swedish elderly and are associated with increased odds of experiencing ADRs. Thus, interventions to decrease PIPs may contribute to preventing ADRs, in particular ADRs associated with nervous and vascular disorders and falls.
Although a majority of patients with hypertension require a multidrug therapy, this is rarely considered when measuring adherence from refill data. Moreover, investigating the association between ...refill non-adherence to antihypertensive therapy (AHT) and elevated blood pressure (BP) has been advocated.
Identify factors associated with non-adherence to AHT, considering the multidrug therapy, and investigate the association between non-adherence to AHT and elevated BP.
A retrospective cohort study including patients with hypertension, identified from a random sample of 5025 Swedish adults. Two measures of adherence were estimated by the proportion of days covered method (PDC≥80%): (1) Adherence to any antihypertensive medication and, (2) adherence to the full AHT regimen. Multiple logistic regressions were performed to investigate the association between sociodemographic factors (age, sex, education, income), clinical factors (user profile, number of antihypertensive medications, healthcare use, cardiovascular comorbidities) and non-adherence. Moreover, the association between non-adherence (long-term and a month prior to BP measurement) and elevated BP was investigated.
Non-adherence to any antihypertensive medication was higher among persons < 65 years (Odds Ratio, OR 2.75 95% CI, 1.18-6.43) and with the lowest income (OR 2.05 95% CI, 1.01-4.16). Non-adherence to the full AHT regimen was higher among new users (OR 2.04 95% CI, 1.32-3.15), persons using specialized healthcare (OR 1.63, 95% CI, 1.14-2.32), and having multiple antihypertensive medications (OR 1.85 95% CI, 1.25-2.75 and OR 5.22 95% CI, 3.48-7.83, for 2 and ≥3 antihypertensive medications, respectively). Non-adherence to any antihypertensive medication a month prior to healthcare visit was associated with elevated BP.
Sociodemographic factors were associated with non-adherence to any antihypertensive medication while clinical factors with non-adherence to the full AHT regimen. These differing findings support considering the use of multiple antihypertensive medications when measuring refill adherence. Monitoring patients' refill adherence prior to healthcare visit may facilitate interpreting elevated BP.
Summary
Aims
To investigate self‐reported beliefs and perceived sensitivity to medicines and their effects in relation to self‐reported use of medicines and herbal remedies.
Methods
A survey sent to ...13,931 randomly selected Swedish adults included the Beliefs about Medicines Questionnaire‐General (BMQ‐General) Questionnaire and the Perceived Sensitivity to Medicines Scale (PSM). The survey also asked about individuals' use of prescribed and over‐the‐counter (OTC) medicines and herbal remedies in the past month. We examined all associations between scores on the BMQ‐General subscales and PSM in relation to the use of medicines and herbal remedies, using analysis of covariance adjusted for potential confounders.
Results
Among 7099 respondents, those using herbal remedies exclusively believed strongly that prescription and OTC medicines are harmful and overprescribed. Respondents using prescription and OTC medicines reported more positive beliefs coefficient 0.67 (95% CI 0.47–0.87) and 0.70 (95% CI 0.51–0.90) on the benefits of medicines compared with those using herbal remedies −0.18 (95% CI −0.57–0.20). Perceived sensitivity to medicines was higher among those using herbal remedies only 1.25 (95% CI 0.46–2.03) compared with those using no medicines (reference 0) or prescription −0.44 (95% CI −0.84 to −0.05) or OTC −0.27 (95% CI −0.66–0.12) medicines alone.
Conclusion
Respondents using prescription and/or OTC medicines reported stronger positive beliefs about the benefits of medicines in general, supporting the hypothesis that beliefs influence medicine use. Therefore, addressing beliefs and concerns about medicines during patient counselling may influence medicine use, particularly regarding unintentional non‐adherence.
•Finland had a different drug profile compared to the other countries.•Opioids were the main cause of death among fatal poisoned drug addicts in all countries.•Cocaine and MDMA deaths increased in ...all countries.•Sweden saw a high number of deaths from fentanyl analogues.•New psychoactive substances have emerged in all countries except Iceland.
This study is the seventh report on fatal poisonings among drug addicts in the Nordic countries. In this report, we analyse data from the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. Data on gender, number of deaths, places of deaths, age, main intoxicants and substances detected in blood were recorded to obtain national and comparable Nordic data, and to allow comparison with earlier studies conducted in 1984, 1991, 1997, 2002, 2007 and 2012.
The death rate (number of deaths per 100,000 inhabitants) was highest in Iceland (6.58) followed closely by Sweden (6.46) and then lowest in Denmark (4.29). The death rate increased in Finland (5.84), Iceland and Sweden and decreased in Denmark compared to earlier studies. The death rate in Norway, which has decreased since 2002, has stabilised around 5.7 as of 2017. Women accounted for 7–23% of the fatal poisonings. The percentage was lowest in Iceland and highest in Finland and Norway. The age range was 14–70 years. The median age (41 years) was highest in Denmark and Norway. The other countries had a median age between 33 and 35 years.
Opioids were the main cause of death. Methadone remained the main intoxicant in Denmark, while heroin/morphine was still the main intoxicant in Norway, as was buprenorphine in Finland. However, the picture has changed in Sweden compared to 2012, where heroin/morphine caused most deaths in 2017. Sweden also experienced the highest number of deaths from fentanyl analogues (67 deaths) and buprenorphine (61 deaths). Deaths from fentanyl analogues also occurred in Denmark, Finland and Norway, but to a smaller extent. Over the years, the proportion of opioid deaths has decreased in all countries except Sweden, which has experienced an increase. This decline has been replaced by deaths from CNS stimulants like cocaine, amphetamine and methylenedioxymethamphetamine (MDMA). Cocaine deaths have occurred in all countries but most frequently in Denmark. MDMA deaths have increased in all countries but mostly in Finland.
Poly-drug use was widespread, as seen in the earlier studies. The median number of detected drugs per case varied from 4–6. Heroin/morphine, methadone, buprenorphine, cocaine, amphetamine, methamphetamine, MDMA, tetrahydrocannabinol (THC) and benzodiazepines were frequently detected. Pregabalin and gabapentin were detected in all countries, especially pregabalin, which was detected in 42% of the Finnish cases. New psychoactive substances (NPS) occurred in all countries except Iceland.
In this work process water from a thermomechanical pulp mill was divided into five fractions by filtration and membrane filtration. Suspended matter was mainly isolated in the retentate from the drum ...filter, extractives in the microfiltration retentate, hemicelluloses in the ultrafiltration retentate and lignin in the nanofiltration retentate. The final water fraction was of fresh water quality. For each tonne of pulp produced, about 10
kg of suspended matter, more than 0.3
kg of extractives, 11
kg of hemicelluloses and 8
kg of aromatic compounds (lignin) could be recovered from the drum filtration retentate, the microfiltration retentate, the ultrafiltration retentate and the nanofiltration retentate, respectively. About 40% of the treated process water could be recovered as fresh water.
We report four previously undescribed families with germline BRCA1‐associated protein‐1 gene (BAP1) mutations and expand the clinical phenotype of this tumor syndrome. The tumor spectrum in these ...families is predominantly uveal malignant melanoma (UMM), cutaneous malignant melanoma (CMM) and mesothelioma, as previously reported for germline BAP1 mutations. However, mutation carriers from three new families, and one previously reported family, developed basal cell carcinoma (BCC), thus suggesting inclusion of BCC in the phenotypic spectrum of the BAP1 tumor syndrome. This notion is supported by the finding of loss of BAP1 protein expression by immunochemistry in two BCCs from individuals with germline BAP1 mutations and no loss of BAP1 staining in 53 of sporadic BCCs consistent with somatic mutations and loss of heterozygosity of the gene in the BCCs occurring in mutation carriers. Lastly, we identify the first reported recurrent mutation in BAP1 (p.R60X), which occurred in three families from two different continents. In two of the families, the mutation was inherited from a common founder but it arose independently in the third family.
•Postmortem reference concentrations are presented for 13 substances.•The study includes both intoxication subgroups and controls.•The impact of sample size on the reliability of the reference ...concentrations is investigated.
Evaluating postmortem toxicological results is a challenging task due to multiple factors affecting blood concentrations after death. In order to improve the diagnostic accuracy in cases of suspected fatal intoxication different compilations of postmortem reference drug concentrations are often used. However, it is not clear what constitutes a reliable postmortem reference value.
The current study presents reference concentrations for 13 substances from seven substance groups according to a standardized protocol. The reference concentrations were gathered from 3767 autopsy cases and subdivided into intoxications by one substance only (Group A, n=611), multi-substance intoxications (Group B, n=1355) and postmortem controls, in which incapacitation by drugs were excluded (Group C, n=1801). In particular, this study presents statistical information about the precision and conformity change with various sample sizes.
Based on the present data >10 detections are usually needed, for the substances examined, to differentiate between intoxication cases and controls. Repeated samplings show that the median of small samples (N=≤5) has a high variation (normalized interquartile range 138–75%) and that a high number of detections (N=>20) in each group are needed to reduce the variation.
Innate immune activation by macrophages is an essential part of host defence against infection. Cytosolic recognition of microbial DNA in macrophages leads to induction of interferons and cytokines ...through activation of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). Other host factors, including interferon-gamma inducible factor 16 (IFI16), have been proposed to contribute to immune activation by DNA. However, their relation to the cGAS-STING pathway is not clear. Here, we show that IFI16 functions in the cGAS-STING pathway on two distinct levels. Depletion of IFI16 in macrophages impairs cGAMP production on DNA stimulation, whereas overexpression of IFI16 amplifies the function of cGAS. Furthermore, IFI16 is vital for the downstream signalling stimulated by cGAMP, facilitating recruitment and activation of TANK-binding kinase 1 in STING complex. Collectively, our results suggest that IFI16 is essential for efficient sensing and signalling upon DNA challenge in macrophages to promote interferons and antiviral responses.
What is already known about this subject
• Although drugs generally are safe and effective therapies for numerous diseases, adverse drug reactions do occur and may even be fatal.
• The incidence of ...fatal adverse drug reactions in hospitalized patients has been estimated to be approximately 5%.
• In previous studies the incidence of fatal adverse drug reactions in hospitalized patients has been reported, but the incidence of fatal adverse drug reactions in the general population is largely unknown.
What this study adds
• Fatal adverse drug reactions account for approximately 3% of all deaths in the general population.
• Haemorrhages amount to almost two‐thirds of the fatal adverse drug reactions and antithrombotic agents are implicated in more than half of the suspected fatal adverse drug reactions.
• Fatal adverse drug reactions are estimated to be the seventh most common cause of death in Sweden.
Aims
To determine the incidence of fatal adverse drug reactions (FADRs) in a Swedish population.
Methods
Every seventh randomly selected deceased in three counties in South‐east Sweden during 1 January 2001–31 December 2001 was identified in the Cause of Death Register. Relevant case records (hospitals and/or primary care centres and medicolegal files) were reviewed to identify suspected drug‐related fatalities.
Results
Of 1574 deceased study subjects, 49 (3.1%; 95% CI 2.2%, 4.0%) were suspected to have died from FADRs. The most common suspected FADRs were gastrointestinal haemorrhages (n = 18; 37%), central nervous system haemorrhages (n = 14; 29%), cardiovascular disorders (n = 5; 10%), other haemorrhages (n = 4; 8%) and renal dysfunction (n = 3; 6%). The drugs most commonly implicated in FADRs were antithrombotic drugs (n = 31; 63%), followed by nonsteroidal anti‐inflammatory drugs (NSAIDs) (n = 9; 18%), antidepressants (n = 7; 14%) and cardiovascular drugs (n = 4; 8%). Of all the 639 fatalities in hospital 41 (6.4%; 95% CI 4.5%, 8.3%) were suspected to be due to FADRs.
Conclusions
The medical burden of FADRs is significant. Haemorrhages were seen in a majority of the FADRs; antithrombotic agents or NSAIDs were implicated in most of these events. These results suggest that preventive measures should be taken to reduce the number of deaths caused by drugs.
Various gastroscopic features may be interpreted as signs of gastritis, but the significance of such features in relation to histomorphology is uncertain. The aim of this study was to determine how ...macroscopic findings were related to histomorphological changes and the presence of Helicobacter pylori in the gastric mucosa, in a sample of the general population.
488 adult individuals, randomly selected from a general population, were screened with gastroscopy and biopsy. The macroscopic features recorded were erythema (diffuse, spotty, linear), erosions, absence of rugae in the gastric corpus, and presence of visible vessels. Gastritis was classified microscopically according to the Sydney system. The presence of H. pylori was determined histologically and using the urease test on fresh biopsy specimens.
The sensitivity and specificity of absence of rugae for moderate to severe atrophic gastritis in the gastric corpus were 67 % and 85 %, respectively. Corresponding values for severe atrophy were 90 % and 84 %. The sensitivity and specificity of the presence of visible vessels for moderate to severe atrophy in the corpus were 48 % and 87 %, and for severe atrophy the values were 80 % and 87 %, respectively. Considering the antrum, the sensitivity and specificity of the presence of visible vessels for moderate to severe atrophy was 14 % and 91 %, respectively. With regard to chronic inflammation (moderate to severe in the corpus or antrum), none of the features, alone or in combination, showed a sensitivity of more than 56 %. No endoscopic features (alone or in combination) showed a sensitivity of more than 57 % for H. pylori infection.
Except for the absence of rugae and visible vessels in the gastric corpus, macroscopic features as observed during gastroscopy are of very limited value in the evaluation of whether or not gastritis or H. pylori infection are present. This is in accordance with most previous studies in patient populations, and it must be emphasized that the diagnosis of gastritis should be based on histological examination of the gastric mucosa.
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