Barbara M. Holzer

Ten-Year Trends in Intoxications and Requests for Emergency Ambulance Service

Abstract Background. Intoxication, whether from alcohol, drugs, or alcohol and drugs in combination, remains a challenging burden on emergency departments. The increasing alcohol consumption among adolescents and young adults, particularly heavy episodic drinking, and the resulting increase in the use of health care resources for alcohol intoxication has been a widely discussed topic. Objective. The aim of our study was to assess and characterize the use of emergency ambulance services that was required as a result of alcohol and drug intoxication in a major metropolitan area. Methods. We conducted a retrospective, longitudinal study over a 10-year period in the greater metropolitan area of Zurich, Switzerland. The study population included intoxicated patients assessed and initially treated by paramedics of the emergency ambulance service. Data were extracted from the ambulance service reports. The primary outcomes measured were trends over time in the numbers and types of intoxication and trends with respect to gender and age distributions of intoxicated patients. Results. An annual increase of about 5% in the number of intoxicated patients requiring emergency ambulance service was observed over the study period. Alcohol use was present in 73% of the cases. The highest number of cases was among patients 25–44 years of age. The greatest increase in the number of cases over time was among patients under 25 years of age. Women comprised 41% of the patients under 25 years of age but only about 35% of older patients. The number of severe injuries and suicide attempts was small, but the number of suicide attempts increased at a higher rate than the overall number of cases of intoxication. There was a significant increase (17.64% per year on average) in the incidence of aggressive behavior toward paramedics from intoxicated patients, although still small in numbers. Conclusions. Our findings suggest two main vulnerable groups: young persons under 25 years of age, with a particular focus on women, having the greatest increase over time, and middle-aged men, having the greatest proportion among all cases observed. Intervention efforts should include a high-risk approach to reduce alcohol-related problems. Key words: alcohol intoxication; substance-related disorders; aggression; injuries; emergency medical services

Gastrointestinal bleeding and anticoagulant or antiplatelet drugs: systematic search for clinical practice guidelines.

AbstractGastrointestinal (GI) bleeding is a frequently encountered and very serious problem in emergency room patients who are currently being treated with anticoagulant or antiplatelet medications. There is, however, a lack of clinical practice guidelines about how to respond to these situations. The goal of this study was to find published articles that contain specific information about how to safely adjust anticoagulant and antiplatelet therapy when GI bleeding occurs.The investigators initiated a global search on the PubMed and Google websites for published information about GI bleeding in the presence of anticoagulant or antiplatelet therapy. After eliminating duplicate entries, the medical articles that remained were screened to narrow the sets of articles to those that met specific criteria. Articles that most closely matched study criteria were analyzed in detail and compared to determine how many actual guidelines exist and are useful.We could provide only minimal information about appropriate therapeutic strategies because no articles provided sufficient specific advice about how to respond to situations involving acute GI bleeding and concurrent use of anticoagulant or antiplatelet drugs. Only 4 articles provided enough detail to be of any use in an emergency situation.Clinical practice guidelines and also clinical trials for GI hemorrhaging should be expanded to state in which situations the use of anticoagulant or antiplatelet drugs should be suspended and the medications should later be resumed, and they should state the level of risk for any particular action.

Therapeutic Conflicts in Emergency Department Patients with Multimorbidity: A Cross-Sectional Study

Background Patients with multimorbidity are an increasing concern in healthcare. Clinical practice guidelines, however, do not take into account potential therapeutic conflicts caused by co-occurring medical conditions. This makes therapeutic decisions complex, especially in emergency situations. Objective The aim of this study was to identify and quantify therapeutic conflicts in emergency department patients with multimorbidity. Methods We reviewed electronic records of all patients ≥18 years with two or more concurrent active medical conditions, admitted from the emergency department to the hospital ward of the University Hospital Zurich in January 2009. We cross-tabulated all active diagnoses with treatments recommended by guidelines for each diagnosis. Then, we identified potential therapeutic conflicts and classified them as either major or minor conflicts according to their clinical significance. Results 166 emergency inpatients with multimorbidity were included. The mean number of active diagnoses per patient was 6.6 (SD±3.4). We identified a total of 239 therapeutic conflicts in 49% of the of the study population. In 29% of the study population major therapeutic conflicts, in 41% of the patients minor therapeutic conflicts occurred. Conclusions Therapeutic conflicts are common among multimorbid patients, with one out of two experiencing minor, and one out of three experiencing major therapeutic conflicts. Clinical practice guidelines need to address frequent therapeutic conflicts in patients with co-morbid medical conditions.

Evidence-based design recommendations for prevalence studies on multimorbidity: improving comparability of estimates

BackgroundIn aging populations, multimorbidity causes a disease burden of growing importance and cost. However, estimates of the prevalence of multimorbidity (prevMM) vary widely across studies, impeding valid comparisons and interpretation of differences. With this study we pursued two research objectives: (1) to identify a set of study design and demographic factors related to prevMM, and (2) based on (1), to formulate design recommendations for future studies with improved comparability of prevalence estimates.MethodsStudy data were obtained through systematic review of the literature. Using PubMed/MEDLINE, Embase, CINAHL, Web of Science, BIOSIS, and Google Scholar, we looked for articles with the terms “multimorbidity,” “comorbidity,” “polymorbidity,” and variations of these published in English or German in the years 1990 to 2011. We selected quantitative studies of the prevalence of multimorbidity (two or more chronic medical conditions) with a minimum sample size of 50 and a study population with a majority of Caucasians. Our database consisted of prevalence estimates in 108 age groups taken from 45 studies. To assess the effects of study design variables, we used meta regression models.ResultsIn 58% of the studies, there was only one age group, i.e., no stratification by age. The number of persons per age group ranged from 136 to 5.6 million. Our analyses identified the following variables as highly significant: “mean age,” “number of age groups”, and “data reporting quality” (all p < 0.0001). “Setting,” “disease classification,” and “number of diseases in the classification” were significant (0.01 < p ≤ 0.03), and “data collection period” and “data source” were non-significant. A separate analysis showed that prevMM was significantly higher in women than men (sign test, p = 0.0015).ConclusionsComparable prevalence estimates are urgently needed for realistic description of the magnitude of the problem of multimorbidity. Based on the results of our analyses of variables affecting prevMM, we make some design recommendations. Our suggestions were guided by a pragmatic approach and aimed at facilitating the implementation of a uniform methodology. This should aid progress towards a more uniform operationalization of multimorbidity.

Overcoming cut-off restrictions in multimorbidity prevalence estimates

BackgroundPresently, there is no consensus on how to define multimorbidity. In this paper we investigate the connection between prevalence estimates for two or more and three or more chronic conditions to improve comparability of multimorbidity studies with different cut-offs.MethodsIn a systematic review of the literature published between January, 1990 and December, 2011, we found 52 suitable studies, many providing prevalence estimates for several age groups. A total of 31 studies reported both the prevalence for multimorbidity based on two or more chronic conditions and three or more chronic conditions, which were analysed in this study. Our research question was whether there is a systematic interrelation between these two prevalence estimates, and how this could be used to improve the comparability of studies on the burden of multimorbidity.ResultsActually, we found a tight relationship between the prevalence of two or more and three or more chronic conditions. Moreover, each of these estimates can be predicted from the other. I.e. the cut-offs of two or three for the number of chronic conditions produce essentially the same information on prevalence.ConclusionsOur study shows a way to enhance and improve the comparability of prevalence estimates from different multimorbidity studies.

Assessing adherence to multiple medications and in daily life among patients with multimorbidity

Objective: Chronic conditions often require multiple medication intake. However, past research has focused on assessing overall adherence or adherence to a single index medication only. This study explored adherence measures for multiple medication intake, and in daily life, among patients with multiple chronic conditions (i.e. multimorbidity). Design: Eighty-four patients with multimorbidity and multiple-medication regimens completed three monthly panel questionnaires. A randomly assigned subsample additionally completed a 30-day daily diary. Main outcome measure: The Non-Adherence Report; a brief self-report measure of adherence to each prescribed medication (NAR-M), and in daily life. We further assessed the Medication Adherence Report Scale (MARS), and a subsample of participants were randomised to electronic adherence monitoring. Results: The NAR-M indicated M = 94.7% adherence at Time 1 (SD = 9.3%). The NAR-M was significantly correlated with the MARS (rt1 = .52, rt2 = .57, and rt3 = .65; p < .001), and in tendency with electronically assessed adherence (rt2 = .45, rt3 = .46, p < .10). Variance components analysis indicated that between-person differences accounted for 10.2% of the variance in NAR-M adherence rates, whereas 22.9% were attributable to medication by person interactions. Conclusion: This study highlights the importance and feasibility of studying adherence to multiple medications differentially, and in daily life. Future studies may use these measures to investigate within-person and between-medication differences in adherence.

The multimorbidity interaction severity index (MISI): A proof of concept study

Abstract Therapeutic decision-making for patients with multimorbidity (MM) is challenging. Clinical practice guidelines inadequately address harmful interactions and resulting therapeutic conflicts within and among diseases. A patient-specific measure of MM severity that takes account of this conflict is needed. As a proof of concept, we evaluated whether the new Multimorbidity Interaction Severity Index (MISI) could be used to reliably differentiate patients in terms of lower versus higher potential for harmful interactions. Two hypothetical patient cases were generated, each with 6 concurrent morbidities. One case had a low (i.e., low conflict case) and the other a high (i.e., high conflict case) potential for harmful interactions. All possible interactions between conditions and treatments were extracted from each cases record into a multimorbidity interaction matrix. Experienced general internists (N = 18) judged each interaction in the matrix in terms of likely resource utilization needed to manage the interaction. Based on these judgements, a composite index of MM interaction severity, that is, the MISI, was generated for each physician and case. The difference between each physicians MISI score for the 2 cases (MISIdiff) was computed. Based on MISIdiff, the high conflict case was judged to be of significantly greater MM severity than was the low conflict case. The positive values of the inter-quartile range, a measure of variation (or disagreement) between the 2 cases, indicated general consistency of individual physicians in judging MM severity. The data indicate that the MISI can be used to reliably differentiate hypothetical multimorbid patients in terms of lesser versus greater severity of potentially harmful interactive effects. On this basis, the MISI will be further developed for use in patient-specific assessment and management of MM. The clinical relevance of the MISI as an alternative approach to defining MM severity is discussed.

Chronic Pain: How Challenging Are DDIs in the Analgesic Treatment of Inpatients with Multiple Chronic Conditions?

Background Chronic pain is common in multimorbid patients. However, little is known about the implications of chronic pain and analgesic treatment on multimorbid patients. This study aimed to assess chronic pain therapy with regard to the interaction potential in a sample of inpatients with multiple chronic conditions. Methods and Findings We conducted a retrospective study with all multimorbid inpatients aged ≥18 years admitted to the Department of Internal Medicine of University Hospital Zurich in 2011 (n = 1,039 patients). Data were extracted from the electronic health records and reviewed. We identified 433 hospitalizations of patients with chronic pain and analyzed their combinations of chronic conditions (multimorbidity). We then classified all analgesic prescriptions according to the World Health Organization (WHO) analgesic ladder. Furthermore, we used a Swiss drug-drug interactions knowledge base to identify potential interactions between opioids and other drug classes, in particular coanalgesics and other concomitant drugs. Chronic pain was present in 38% of patients with multimorbidity. On average, patients with chronic pain were aged 65.7 years and had a mean number of 6.6 diagnoses. Hypertension was the most common chronic condition. Chronic back pain was the most common painful condition. Almost 90% of patients were exposed to polypharmacotherapy. Of the chronic pain patients, 71.1% received opioids for moderate to severe pain, 43.4% received coanalgesics. We identified 3,186 potential drug-drug interactions, with 17% classified between analgesics (without coanalgesics). Conclusions Analgesic drugs-related DDIs, in particular opioids, in multimorbid patients are often complex and difficult to assess by using DDI knowledge bases alone. Drug-multimorbidity interactions are not sufficiently investigated and understood. Today, the scientific literature is scarce for chronic pain in combination with multiple coexisting medical conditions and medication regimens. Our work may provide useful information to enable further investigations in multimorbidity research within the scope of potential interactions and chronic pain.

Multimorbidität, Komorbidität und phytotherapeutische Vielstoffgemische als Arzneimittel

Angesichts der demografischen Entwicklung und der damit einhergehenden deutlichen Zunahme von chronischen Beschwerden gewinnen die Konzepte von Komorbiditat und Multimorbiditat an Bedeutung. Unter Multimorbiditat fasst man im Allgemeinen das gleichzeitige Auftreten von zwei oder mehr Erkrankungen oder Krankheitszustanden in ein und derselben Person zusammen [1, 2]. Dies kann sich auf das Zusammentreffen von nur chronischen Erkrankungen oder auch von akuten und chronischen Erkrankungen bei Patienten beziehen. Allerdings gibt es in der Literatur keine standardisierte (und damit allgemein akzeptierte) Definition. Multimorbiditat ist ein komplexes Phanomen mit einer potenziell unuberschaubaren Zahl an Kombinationsmoglichkeiten von Krankheiten mit teils unklaren Auswirkungen. Dementsprechend konnte eine grose Anzahl von therapeutischen Targets vorliegen. Insgesamt kann Multimorbiditat als ein eigenes Krankheitsbild mit moglichen eigenstandigen Pathophysiologien charakterisiert werden. Demgegenuber setzt Komorbiditat per definitionem das Vorhandensein einer Index-Erkrankung und die Entwicklung von Folgeerkrankungen voraus [3, 4]. Die Abgrenzung der Multimorbiditat zur Komorbiditat ist nicht ganz scharf; ein wichtiger Unterschied ist, dass bei der Komorbiditat eine Hierarchisierung der Erkrankungen vorgenommen wird. Operationalisiert bedeutet dies, dass es sich bei beiden Konstrukten, speziell aber bei der Multimorbiditat um sehr komplexe Behandlungssituationen handelt, die eine MultiTarget-Orientierung nahelegen. Trotzdem werden in den herkommlichen Ansatzen meist einzelne oder kombinierte Mono-Target-Therapien mit uberwiegend selektiven Arzneimitteln eingesetzt. Dies kann zu einer erheblichen Polypharmazie fuhren. Pflanzliche Arzneimittel (Phytotherapeutika) unterscheiden sich in wesentlichen Gesichtspunkten erheblich von anderen modernen Arzneimitteln, z.B. chemisch-synthetischen. Sie sind genuine phytogene Vielstoffgemische, und nicht Einzelsubstanzen oder einfache Kombinationen von Monosubstanzen. Dies hat erhebliche wissenschaftliche und praktischtherapeutische Konsequenzen. Der Wirkstoff (Vielstoffgemisch) z.B. muss in seiner dynamischen Natur betrachtet werden; das reine Erfassen der Einzelkomponenten ergibt kein hinreichendes Funktionsbild. Die Wirkstoffkomponenten gehen untereinander vielfaltige strukturelle und funktionelle, zumeist schwache Bindungen ein. Die Gesamtheit der zahlreichen funktionell-plastischen Interaktionsmoglichkeiten der Einzelkomponenten untereinander kann im Sinne eines flexiblen Netzwerkes auf die zahlreichen Targets des Organismus einwirken (netzwerkartige phytotherapeutische Wirkmechanismen). Zu den Haupt-Targets gehoren Proteine, DNA, RNA sowie dazugehorige Enzyme und Transskriptionsfaktoren sowie Biomembranen [5, 6]. Der gesamte Wirkungsmechanismus eines solchen Wirkstoffes weist auf eine genuine Pleiotropie hin, d.h. er setzt sich unter anderem aus einer Reihe mehrerer, gegebenenfalls zahlreicher, voneinander unabhangiger Mechanismen zusammen. Die Einzelkomponenten des Wirkstoffes liegen zumeist in sehr geringen Konzentrationen vor, sodass in der Regel nicht das gesamte konzentrationsabhangige quantitative Wirkungspotenzial dieser Komponenten zum Tragen kommt (z.B. keine vollstandige Stimulation oder Hemmung physiologischer bzw. pathophysiologischer Ablaufe). Die haufig relativ geringe Inzidenz unerwunschter Wirkungen phytotherapeutischer Arzneimittel konnte unter anderem auf dem Vielstoffcharakter, der Pleiotropie, dem Multi-Target-Ansatz und den niedrig konzentrierten Bestandteilen der jeweiligen Wirkstoffe beruhen. Eine Reihe der Komponenten pflanzlicher Wirkstoffe kommt nahezu ubiquitar im Pflanzenreich bzw. in zahlreichen

Prospective and retrospective memory are differentially related to self-rated omission and commission errors in medication adherence in multimorbidity

ABSTRACT We investigated the relations of self-rated omission errors (i.e., forgetting to take one’s medication) and commission errors (i.e., unnecessary repetitions of medication intake because of forgetting that it has already been taken) in medication adherence in multimorbidity to prospective and retrospective memory performance. Moreover, we examined whether these relations were moderated by the number of medications that had to be taken. Eighty-four patients with multimorbidity (aged 28–84 years, M = 62.4) reported medication adherence regarding the last seven days and the number of medications they had to take. In addition, we administered psychometric tests on prospective memory (PM) and retrospective memory performance. We found that reported omission errors in medication adherence were related significantly to lower PM performance. This relationship was increased in individuals with a lower number of medications. In comparison, reported commission errors in medication adherence were related significantly to lower retrospective memory performance. This relationship was increased in individuals with a larger number of medications. Present data suggest that omission errors in medication adherence in multimorbidity may reflect primarily PM errors, particularly if few medications have to be taken, while commission errors may reflect mainly retrospective memory failures, especially with a large number of medications that need to be taken as prescribed. From an applied neuropsychological perspective, these results underline the importance of trying to enhance PM and retrospective memory performance in patients with multimorbidity.