Anticholinergic medicine burden and older patients

Anticholinergic medicines are commonly used to treat e.g. incontinence. These medicines have side effects, which may cause and also exacerbate e.g. dryness of the mouth, increased heart rate, and even cognitive impairment. Older people may be more at risk for these side effects as they may be experiencing similar symptoms as a natural effect of aging, and because they may be using several medicines causing these effects. Older people often have a high medicine burden and also a high disease burden. Measuring anticholinergic effects to change medicine regimens and to reduce the symptoms is difficult as there is no golden standard method. This thesis investigated the published methods available for estimating anticholinergic burden in the literature review part, and used one anticholinergic scoring system, the Anticholinergic Risk Scale, in a cross-sectional study to test the effects of anticholinergics on mortality in 1004 older institutionalised patients from Helsinki area public hospitals. Cross-tabulations and Kruskal-Wallis or Chi square methods were used to detect differences between variables such as nutritional status or certain diagnoses when the patients were stratified according to their anticholinergic use. Cox Proportional Hazard regression, the logrank test and Kaplan-Meier curve were used to investigate the effects of anticholinergics on 5-year all-cause mortality. An in vitro serum assay and seven anticholinergic scoring systems were identified in the literature search. Also, 17 anticholinergic lists were identified, which covered 278 medicines, of which 21 appeared on at least eight of the lists. In the empirical study, the women's (n = 745) mean (± SD) age was 83.35 (± 9.99) years, and they were older than the men (n = 241, mean age ± SD 75.11 ± 11.48, p < 0.001). The 1004 patients (response rate 70 %) were using a mean (± SD) number of 7.1 ± 3.4 regular medicines (range 0-20). 455 patients used no anticholinergics, 363 had some anticholinergic burden (score 1 or 2), and 186 had a high burden, with anticholinergic scores of 3 or more. The mean ARS score (± SD) was 1.2 ± 1.5 (range 0-10). When three anticholinergic lists were compared, all three lists identified only 280/791 of patients who were anticholinergic users according to at least one list. No association was found between anticholinergic medicine use and mortality. There are several methods available for measuring anticholinergic burden, but there is a need for a consensus method. This was highlighted by the lack of agreement on medicines on different lists and when three anticholinergic lists tested identified different patients when compared to each other. Anticholinergic use was common in this frail, older patient sample, but no effect on mortality was shown in this study setting. The cross-sectional nature of the data limits the reliability of the study, and any conclusions beyond older patients in Helsinki area must be done very cautiously. Future research should define anticholinergics better and investigate their possible effect on mortality in a prospective, randomised, and controlled setting.Antikolinergisiä lääkkeitä käytetään yleisesti mm. inkontinenssin hoitoon. Näillä lääkkeillä on sivuvaikutuksia, jotka voivat aiheuttaa tai pahentaa esim. suun kuivumista, sydämentykytystä tai jopa kognitiivisia kykyjä. Vanhukset saattavat kärsiä näistä oireista osana luonnollista vanhenemista, ja heillä saattaa olla käytössään useita antikolinergisia lääkkeitä. Tästä johtuen heillä saattaa olla suurempi riski kärsiä näistä sivuvaikutuksista. Vanhuksilla on usein suuri lääke- ja sairaustaakka. Antikolinergisten vaikutusten mittaaminen lääkehoitojen muuttamiseksi ja oireiden vähentämiseksi on vaikeaa, koska saatavilla ei ole referenssimenetelmää. Tässä tutkimuksessa tutkittiin kirjallisuusosiossa antikolinergisten lääkkeiden taakan mittaamiseen käytettäviä menetelmiä. Erästä tällaista menetelmää, Anticholinergic Risk Scalea (ARS) käytettiin läpileikkaustutkimuksessa arvioitaessa antikolinergien käytön vaikutusta kuolleisuuteen potilasaineistolla, jossa mukana oli 1004 laitoshoidossa olevaa vanhusta Helsingin alueen julkisista sairaaloista. Ristiintaulukoinnin ja Kruskal-Wallisin sekä Khin neliö -testien avulla tutkittiin eri antikolinergisen taakan omaavien ihmisten eroja mm.ravitsemustilassa ja tietyissä diagnooseissa. Coxin suhteellisen riskin regressio-menetelmällä, logrank-testillä ja Kaplan-Meier-kuvaajalla tutkittiin antikolinergien vaikutusta kuolleisuuteen viiden vuoden tarkasteluvälillä. Kirjallisuushaussa löytyi in vitro seerumimääritys sekä 7 antikolinergien pisteytysmenetelmää. Lisäksi löydettiin 17 antikolinergilistaa, joilla oli yhteensä 278 lääkeainetta, joista 21 löytyi vähintään kahdeksalta listalta.Kokeellisessa tutkimuksessa naisten (n = 745) keski-ikä oli 83.35 (± 9.99, SD) vuotta, he olivat vanhempia kuin miehet (n = 241, keski-ikä 75.11 ± 11.48 vuotta, p < 0.001). Tutkimuksen 1004 osallistujaa (vastaus-% 70) käytti 7.1 ± 3.4 lääkettä säännöllisesti (vaihteluväli 0-20). 455 potilasta ei käyttänyt lainkaan antikolinergeja, 363 käytti jonkin verran (pisteysaldo 1 tai 2), ja 186 käytti paljon (pistesaldo 3 tai yli). Keskimääräinen ARS-pistemäärä oli 1.2 ± 1.5 (vaihteluväli 0-10). Verrattaessa kolmea antikolinergilistaa toisiinsa, vain 280/791 potilasta tunnistettiin antikolinergien käyttäjäksi yhtä aikaa kolmen listan avulla. Antikollinergien käytöllä ei ollut tässä tutkimuksessa yhteyttä kuolleisuuteen. Useasta antikolinergikuormitusta mittaavasta menetelmästä huolimatta tarvitaan konsensus-menetelmä. Tätä korosti tutkimuksessa havaittu vaihtelu siinä, mitkä lääkkeet olivat antikolinergisilla listoilla, ja miten eri listat tunnistivat eri potilaita antikolinergien käyttäjiksi. Tämä heikkokuntoinen vanhusväestö käytti yleisesti antikolinergeja, mutta yhteyttä kuolleisuuteen ei löydetty tässä koeasetelmassa. Tutkimuksen läpileikkausrakenne rajoittaa sen luotettavuutta, eikä tuloksia voida varauksetta yleistää muihin potilasryhmiin. Tulevissa tutkimuksissa tulisi keskittyä määrittelemään antikolinergit paremmin, ja tutkia niiden mahdollista vaikutusta kuolleisuuteen prospektiivisissa, satunnaistetuissa ja kontrolloiduissa tutkimuksissa

Data Collected about Intentional Self-poisoning in New Zealand Emergency Departments and the Implications of Data Limitations for Prevention Planning

Background Intentional self-poisoning (ISP; taking a purposeful overdose) results in significant morbidity and is a burden on population health. In order to reduce ISP by, for example, restricting inappropriate access to substances, information is required about which specific substances are commonly used. Aims I. What information about ISP can be obtained from Ministry of Health (MOH) datasets to plan poisoning prevention initiatives? What are the gaps in these data, and how could these be addressed? II. How do emergency medicine professionals identify poisonings and investigate intent behind them, and how does that information become national hospital presentation data? III. Which specific substances do people use in episodes of intentional self-poisoning, and where do they obtain these substances? Methods The MOH Mortality data and National Minimum Dataset (NMDS) public hospital presentation cases of intentional and undetermined intent self-poisoning were analysed to investigate demographic characteristics of people who present with ISP, and to investigate limitations of the current data. Poisonings of undetermined intent were included as they may be poorly identified cases of ISP. Specific poisoning data collected at one Emergency Department (ED; Wellington) were analysed to provide more information about specific substances used in ISP, and to investigate feasibility of clinicians recording these data. The process of identifying poisoning and intentionality in patients presenting to an ED, which is then recorded in NMDS data, was investigated through interviews with clinicians and clinical coders. Cross-sectional data were collected prospectively from three EDs. This included data on specific substances and sources to these substances. Results Females were at higher risk of hospital presentations for ISP, and males were at higher risk of death. Young people, Māori, New Zealand Europeans and people from deprived areas were most at risk. There are few details about specific substances in existing MOH data. The data recorded by clinicians in Wellington ED provided more detail about substances but coding was less systematic. A range of information along the care pathway is used to determine whether a poisoning has occurred and whether it is intentional. Intent can be complex to determine as it may change over time from the substance exposure to the time of treatment at the ED, particularly in cases of alcohol/recreational drug co-intoxication. We found that clinical coders do send data on specific substances to the MOH although these do not appear in the MOH datasets. The five most frequent substances used by people in the prospective study were paracetamol, ethanol, ibuprofen, quetiapine, and venlafaxine. Most people used their own prescription drugs. Conclusions Current national MOH datasets describing ISP are not detailed enough to identify specific substances of concern. The study shows that it is feasible to collect this data, but attention needs to be paid to standardisation. This data could inform measures to prevent ISP

A descriptive study of intentional self‐poisoning from New Zealand national registry data

Abstract Objective: Understanding which population groups intentionally poison themselves by overdose and which substances are used are key to developing prevention efforts for such injuries. This paper uses Ministry of Health (MOH) data to explore the demographic characteristics of those who intentionally self‐poison and the substances used, identifies limitations of existing data collections and makes recommendations for the future. Methods: MOH mortality data from 2000 to 2012, and public hospital presentation data from 2000–2014 of cases of intentional self‐poisoning (ISP), and poisoning of undetermined intent (UDP), were examined. Results: Men were more at risk of fatal intentional poisonings, while young women and people from deprived areas were predominant in hospital presentations for ISP and UDP. While ICD‐10 categories were available, there was limited information in the majority of MOH data about specific substances used in the poisonings. Conclusions: The current format of MOH data indicates that developing interventions to help young people and those living in deprived areas may be useful. Finding specific solutions is challenging when only limited nationwide substance‐specific poisoning information is available. Implications for public health: Including specific substances in national data collections is important for addressing the public health challenge of intentional overdose morbidity and mortality

Suicide prevention for men

The ways in which suicide prevention initiatives can target different stages of the suicidal process have been described by Mann et al. (2005). These authors argue that suicidal ideation may stem from stressful life events and/or psychiatric disorders. These factors can be influenced through education and awareness programs, screening of individuals at risk, and various treatments. However, it must be noted that while the impacts of environmental factors, such as stressful life events, can sometimes be reduced, the events themselves may be unavoidable. Aspects of suicide prevention can focus on building resilience as a way to combat the impacts of these inevitable events. Once suicidal ideation is present, it can be detected by screening individuals at risk. Before ideation leads to a suicidal act, it can be targeted through treating issues such as underlying disorders and impulsivity, hopelessness and/or pessimism. Other suicide prevention initiatives may also limit access to suicide means and exposure to negative or harmful examples in the media. Australia was the one of the first countries to reflect upon the national and global evidence which recognised the devastating consequences of suicidal behaviours (Jenkins and Kovess, 2002; Department of Health and Ageing, 2008). Since the early 1990s, the Department of Health and Ageing has led the national approach for suicide prevention. The National Youth Suicide Prevention Strategy 1995-1999 was further expanded into the National Suicide Prevention Strategy (NSPS); a strategic plan to prevent suicide across the whole lifespan. In 2000, the Living Is For Everyone: A Framework for Prevention of Suicide and Self-harm in Australia (LIFE Framework) was launched. This was later evaluated and further development led to the release of the Living is For Everyone (LIFE) Framework (2007)

Optical Genome Mapping as an Alternative to FISH-Based Cytogenetic Assessment in Chronic Lymphocytic Leukemia

The fluorescence in situ hybridization (FISH) technique plays an important role in the risk stratification and clinical management of patients with chronic lymphocytic leukemia (CLL). For genome-wide analysis, FISH needs to be complemented with other cytogenetic methods, including karyotyping and/or chromosomal microarrays. However, this is often not feasible in a diagnostic setup. Optical genome mapping (OGM) is a novel technique for high-resolution genome-wide detection of structural variants (SVs), and previous studies have indicated that OGM could serve as a generic cytogenetic tool for hematological malignancies. Herein, we report the results from our study evaluating the concordance of OGM and standard-of-care FISH in 18 CLL samples. The results were fully concordant between these two techniques in the blinded comparison. Using in silico dilution series, the lowest limit of detection with OGM was determined to range between 3 and 9% variant allele fractions. Genome-wide analysis by OGM revealed additional (>1 Mb) aberrations in 78% of the samples, including both unbalanced and balanced SVs. Importantly, OGM also enabled the detection of clinically relevant complex karyotypes, undetectable by FISH, in three samples. Overall, this study demonstrates the potential of OGM as a first-tier cytogenetic test for CLL and as a powerful tool for genome-wide SV analysis

Optical genome mapping as an alternative to FISH-based cytogenetic assessment in chronic lymphocytic leukemia

Abstract The fluorescence in situ hybridization (FISH) technique plays an important role in the risk stratification and clinical management of patients with chronic lymphocytic leukemia (CLL). For genome-wide analysis, FISH needs to be complemented with other cytogenetic methods, including karyotyping and/or chromosomal microarrays. However, this is often not feasible in a diagnostic setup. Optical genome mapping (OGM) is a novel technique for high-resolution genome-wide detection of structural variants (SVs), and previous studies have indicated that OGM could serve as a generic cytogenetic tool for hematological malignancies. Herein, we report the results from our study evaluating the concordance of OGM and standard-of-care FISH in 18 CLL samples. The results were fully concordant between these two techniques in the blinded comparison. Using in silico dilution series, the lowest limit of detection with OGM was determined to range between 3 and 9% variant allele fractions. Genome-wide analysis by OGM revealed additional (&gt;1 Mb) aberrations in 78% of the samples, including both unbalanced and balanced SVs. Importantly, OGM also enabled the detection of clinically relevant complex karyotypes, undetectable by FISH, in three samples. Overall, this study demonstrates the potential of OGM as a first-tier cytogenetic test for CLL and as a powerful tool for genome-wide SV analysis