Brain-borne IL-1 adjusts glucoregulation and provides fuel support to astrocytes and neurons in an autocrine/paracrine manner.

It is still controversial which mediators regulate energy provision to activated neural cells, as insulin does in peripheral tissues. Interleukin-1β (IL-1β) may mediate this effect as it can affect glucoregulation, it is overexpressed in the 'healthy' brain during increased neuronal activity, and it supports high-energy demanding processes such as long-term potentiation, memory and learning. Furthermore, the absence of sustained neuroendocrine and behavioral counterregulation suggests that brain glucose-sensing neurons do not perceive IL-1β-induced hypoglycemia. Here, we show that IL-1β adjusts glucoregulation by inducing its own production in the brain, and that IL-1β-induced hypoglycemia is myeloid differentiation primary response 88 protein (MyD88)-dependent and only partially counteracted by Kir6.2-mediated sensing signaling. Furthermore, we found that, opposite to insulin, IL-1β stimulates brain metabolism. This effect is absent in MyD88-deficient mice, which have neurobehavioral alterations associated to disorders in glucose homeostasis, as during several psychiatric diseases. IL-1β effects on brain metabolism are most likely maintained by IL-1β auto-induction and may reflect a compensatory increase in fuel supply to neural cells. We explore this possibility by directly blocking IL-1 receptors in neural cells. The results showed that, in an activity-dependent and paracrine/autocrine manner, endogenous IL-1 produced by neurons and astrocytes facilitates glucose uptake by these cells. This effect is exacerbated following glutamatergic stimulation and can be passively transferred between cell types. We conclude that the capacity of IL-1β to provide fuel to neural cells underlies its physiological effects on glucoregulation, synaptic plasticity, learning and memory. However, deregulation of IL-1β production could contribute to the alterations in brain glucose metabolism that are detected in several neurologic and psychiatric diseases.Molecular Psychiatry advance online publication, 8 December 2015; doi:10.1038/mp.2015.174.

Thrombosis during pregnancy: Risks, prevention, and treatment for mother and fetus--harvesting the power of omic technology, biomarkers and in vitro or in vivo models to facilitate the treatment of thrombosis

Maternal thromboembolism and a spectrum of placenta-mediated complications including the pre-eclampsia syndromes, fetal growth restriction, fetal loss, and abruption manifest a shared etiopathogenesis and predisposing risk factors. Furthermore, these maternal and fetal complications are often linked to subsequent maternal health consequences that comprise the metabolic syndrome, namely, thromboembolism, chronic hypertension, and type II diabetes. Traditionally, several lines of evidence have linked vasoconstriction, excessive thrombosis and inflammation, and impaired trophoblast invasion at the uteroplacental interface as hallmark features of the placental complications. "Omic" technologies and biomarker development have been largely based upon advances in vascular biology, improved understanding of the molecular basis and biochemical pathways responsible for the clinically relevant diseases, and increasingly robust large cohort and/or registry based studies. Advances in understanding of innate and adaptive immunity appear to play an important role in several pregnancy complications. Strategies aimed at improving prediction of these pregnancy complications are often incorporating hemodynamic blood flow data using non-invasive imaging technologies of the utero-placental and maternal circulations early in pregnancy. Some evidence suggests that a multiple marker approach will yield the best performing prediction tools, which may then in turn offer the possibility of early intervention to prevent or ameliorate these pregnancy complications. Prediction of maternal cardiovascular and non-cardiovascular consequences following pregnancy represents an important area of future research, which may have significant public health consequences not only for cardiovascular disease, but also for a variety of other disorders, such as autoimmune and neurodegenerative diseases.

Clinical Diagnosis and Staging of Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinomas are the second most common primary liver malignancies with an increasing incidence over the past decades. Due to a lack of early symptoms and their aggressive oncobiological behavior, the diagnostic approach is challenging and the outcome remains unsatisfactory with a poor prognosis. Thus, a consistent staging system for a comparison between different therapeutic approaches is needed, but independent predictors for worse survival are still controversial. Currently, four different staging systems are primarily used, which differ in the way they determine the 'T' category. Furthermore, different nomograms and prognostic models have been recently proposed and may be helpful in providing additional information for predicting the prognosis and therefore be helpful in approaching an adequate treatment strategy. This review will discuss the diagnostic approach to intrahepatic cholangiocarcinoma as well as compare and contrast the most current staging systems and prognostic models.

Joining the dots - understanding the complex interplay between the values we place on wildlife, biodiversity conservation, human and animal health: A review.

The value of wildlife has long been ignored or under-rated. However, growing concerns about biodiversity loss and emerging diseases of wildlife origin have enhanced debates about the importance of wildlife. Wildlife-related diseases are viewed through these debates as a potential threat to wildlife conservation and domestic animal and human health. This article provides an overview of the values we place on wildlife (positive: socio-cultural, nutritional, economic, ecological; and negative: damages, health issues) and of the significance of diseases for biodiversity conservation. It shows that the values of wildlife, the emergence of wildlife diseases and biodiversity conservation are closely linked. The article also illustrates why investigations into wildlife diseases are now recognized as an integral part of global health issues. The modern One Health concept requires multi-disciplinary research groups including veterinarians, human physicians, ecologists and other scientists collaborating towards a common goal: prevention of disease emergence and preservation of ecosystems, both of which are essential to protect human life and well-being.

Coxiella burnetii Infections in Small Ruminants and Humans in Switzerland

The recent Q fever epidemic in the Netherlands raised concerns about the potential risk of outbreaks in other European countries. In Switzerland, the prevalence of Q fever in animals and humans has not been studied in recent years. In this study, we describe the current situation with respect to Coxiella (C.) burnetii infections in small ruminants and humans in Switzerland, as a basis for future epidemiological investigations and public health risk assessments. Specific objectives of this cross-sectional study were to (i) estimate the seroprevalence of C. burnetii in sheep and goats, (ii) quantify the amount of bacteria shed during abortion and (iii) analyse temporal trends in human C. burnetii infections. The seroprevalence of C. burnetii in small ruminants was determined by commercial ELISA from a representative sample of 100 sheep flocks and 72 goat herds. Herd-level seroprevalence was 5.0% (95% CI: 1.6-11.3) for sheep and 11.1% (95% CI: 4.9-20.7) for goats. Animal-level seroprevalence was 1.8% (95% CI: 0.8-3.4) for sheep and 3.4% (95% CI: 1.7-6) for goats. The quantification of C. burnetii in 97 ovine and caprine abortion samples by real-time PCR indicated shedding of >10(4) bacteria/g in 13.4% of all samples tested. To our knowledge, this is the first study reporting C. burnetii quantities in a large number of small ruminant abortion samples. Annual human Q fever serology data were provided by five major Swiss laboratories. Overall, seroprevalence in humans ranged between 1.7% and 3.5% from 2007 to 2011, and no temporal trends were observed. Interestingly, the two laboratories with significantly higher seroprevalences are located in the regions with the largest goat populations as well as, for one laboratory, with the highest livestock density in Switzerland. However, a direct link between animal and human infection data could not be established in this study.

Non-canonical actions of Nogo-A and its receptors

Nogo-A is a myelin associated protein and one of the most potent neurite growth inhibitors in the central nervous system. Interference with Nogo-A signaling has thus been investigated as therapeutic target to promote functional recovery in CNS injuries. Still, the finding that Nogo-A presents a fairly ubiquitous expression in many types of neurons in different brain regions, in the eye and even in the inner ear suggests for further functions besides the neurite growth repression. Indeed, a growing number of studies identified a variety of functions including regulation of neuronal stem cells, modulation of microglial activity, inhibition of angiogenesis and interference with memory formation. Aim of the present commentary is to draw attention on these less well-known and sometimes controversial roles of Nogo-A. Furthermore, we are addressing the role of Nogo-A in neuropathological conditions such as ischemic stroke, schizophrenia and neurodegenerative diseases.

Cell Competition During Growth and Regeneration

Tissue growth and regeneration are autonomous, stem-cell-mediated processes in which stem cells within the organ self-renew and differentiate to create new cells, leading to new tissue. The processes of growth and regeneration require communication and interplay between neighboring cells. In particular, cell competition, which is a process in which viable cells are actively eliminated by more competitive cells, has been increasingly implicated to play an important role. Here, we discuss the existing literature regarding the current landscape of cell competition, including classical pathways and models, fitness fingerprint mechanisms, and immune system mechanisms of cell competition. We further discuss the clinical relevance of cell competition in the physiological processes of tissue growth and regeneration, highlighting studies in clinically important disease models, including oncological, neurological, and cardiovascular diseases.

Variation of genotype and prevalence of Noro virus in U.S. students in Mexico with Traveler's Diarrhea, summer of 2004 and 2005

Noro virus, a positive single stranded RNA virus has been identified as a major etiologic agent in food borne gastroenteritis and diarrheal diseases. The emergence of this organism as a major non-bacterial cause in such outbreaks is partly due to the improved diagnostic tools like Reverse Transcription Polymerase chain reaction (RTPCR) that enable its detection. Noro virus accounts for nearly 96% of non-bacterial gastroenteritis outbreaks in US (1). Travelers' Diarrhea (TD) has remained a constant public health risk in the developed nations for decades and bacteria like Entero toxigenic Escherichia coli, Entero aggregative Escherichia coli have been described as the main etiologic agents for TD (2-4). A possible viral contribution to TD has been discovered in two studies (5, 6). The current study was designed to determine the prevalence of Noro virus in a population of 107 US students with TD acquired in Mexico in 2005 and to compare the prevalence to the prevalence of Noro virus in a similar study done in 2004. This study involved the testing of clinical stool specimens from 107 subjects in 2005 for the presence of Noro virus using RTPCR. The prevalence of Noro virus in 2004 used for comparison to 2005 data was obtained from published data (5). All subjects were recruited as TD subjects in a randomized, double-blinded clinical trial comparing a standard three day dosing of Rifaximin with and without an anti motility drug Loperamide. The prevalence of Noro virus geno group I was similar in both years, but geno group II prevalence differed across the two years (p = 0.003). This study finding suggests that the prevalence of Noro virus geno groups varies with time even within a specific geographic location. This study emphasizes the need for further systematic epidemiologic studies to determine the molecular epidemiology and the prevalence patterns of different geno groups of this virus. These are essential to planning and implementation of public health measures to lessen the burden of TD due to Noro virus infection among US travelers. ^

Latino perceptions of and barriers to preventive healthcare maintenance in the southwest United States

Between the 1990 and 2000 Censuses, the Latino population accounted for 40% of the increase in the nation’s total population. The growing population of Latinos underscores the importance for understanding factors that influence whether and how Latinos take care of their health. According to the U.S. Department of Human Health Service’s Office of Minority Health (OMH), Latinos are at greater risk for health disparities (2003). Factors such as lack of health insurance and access to preventive care play a major role in limiting Latino use of primary health care (Institute of Medicine, 2005). Other significant barriers to preventive health care maintenance behaviors have been identified in current literature such as primary care physician interaction, self-perceived health status, and socio-cultural beliefs and traditions (Rojas-Guyler, King, Montieth and 2008; Meir, Medina, and Ory, 2007; Black, 1999). Despite these studies, there remains less information regarding interpersonal perceptions, environmental dynamics and individual and cultural attitudes relevant to utilization of healthcare (Rojas-Guyler, King, Montieth and 2008; Aguirre-Molina, Molina and Zambrana, 2001). Understanding the perceptions of Latinos and the barriers to health care could directly affect healthcare delivery. Improved healthcare utilization among Latinos could reduce the long term health consequences of many preventable and manageable diseases. The purpose of this study was to explore Latino perceptions of U.S. health care and desired changes by Latinos in the U.S. healthcare system. The study had several objectives, including to explore perceived barriers to healthcare utilization and the resulting effects on health among Latinos, to describe culturally influenced attitudes about health care and use of health care services among Latinos, and to make recommendations for reducing disparities by improving healthcare and its utilization. The current study utilized data that were collected as part of a larger study to examine multidimensional, cross-cultural issues relevant to interactions between healthcare consumers and providers. Qualitative methods were used to analyze four Spanish-language focus group transcripts to interpret cultural influences on perceptions and beliefs among Latinos. Direct coding of transcript content was carried out by two reviewers, who conducted independent reviews of each transcript. Team members developed and refined thematic categories, positive and negative cases, and example text segments for each theme and sub-theme. Incongruities of interpretations were resolved through extensive discussion. Study participants included 44 self-identified Latino adults (16 male, 28 female) between age 18 and 64 years. Thirty seven (84.1%) of the participants were immigrants. The study population comprised eight ethnic subgroups. While 31% of the participants reported being employed on a full-time basis, only 18.4% had medical insurance that was private or employee sponsored. Five major themes regarding the perceptions and healthcare utilization behaviors of Latinos were consistent across all focus groups and were identified during the analysis. These were: (1) healthcare utilization, experience, and access; (2) organizational and institutional systems; (3) communication and interpersonal interactions between healthcare provider, staff, and patient; (4) Latinos’ perception of their own health status; (5) cultural influences on healthcare utilization, which included an innovation termed culturally-bound locus of control. Healthcare utilization was directly influenced by healthcare experience, access, current health status, and cultural factors and indirectly influenced by organizational systems. There was a strong interdependence among the main themes. The ability to communicate and interact effectively with healthcare providers and navigate healthcare systems (organizational and institutional access) significantly influenced the participant’s health care experience, most often (indirectly) impacting utilization negatively. ^ Research such as this can help to identify those perceptions and attitudes held by Latinos concerning utilization or underutilization of healthcare systems. These data suggest that for healthcare utilization to improve among Latinos, healthcare systems must create more culturally competent environments by providing better language services at the organizational level and more culturally sensitive providers at the interpersonal level. Better understanding of the complex interactions between these impediments can aid intervention developments, and help health providers and researchers in determining appropriate, adequate, and effective measurers of care to better increase overall health of Latinos.^

BIOLOGICAL MECHANISMS AND CLINICAL IMPLICATIONS OF BCR-ABL-INDUCED MITOCHONDRIAL OXIDATIVE STRESS AND CELL SURVIVAL IN CHRONIC MYELOID LEUKEMIA

Chronic myeloid leukemia (CML), a myeloproliferative disorder, represents approximately 15-20% of all adult leukemia. The development of CML is clearly linked to the constitutively active protein-tyrosine kinase BCR-ABL, which is encoded by BCR-ABL fusion gene as the result of chromosome 9/22 translocation (Philadelphia chromosome). Previous studies have demonstrated that oxidative stress-associated genetic, metabolic and biological alterations contribute to CML cell survival and drug refractory. Mitochondria and NAD(P)H oxidase (NOX) are the major sources of BCR-ABL-induced cellular reactive oxygen species (ROS) production. However, it is still unknown how CML cells maintain the altered redox status, while escaping from the persistent oxidative stress-induced cell death. Therefore, elucidation of the mechanisms by which CML cells cope with oxidative stress will provide new insights into CML leukemogenesis. The major goal of this study is to identify the survival factors protecting CML cells against oxidative stress and develop novel therapeutic strategies to overcome drug resistance. Several experimental models were used to test CML cell redox status and cellular sensitivity to oxidative stress, including BCR-ABL inducible cell lines, BCR-ABL stably transformed cell lines and BCR-ABL-expressing CML blast crisis cells with differential BCL-XL/BCL-2 expressions. Additionally, an artificial CML cell model with heterogenic BCL-XL/BCL-2 expression was established to assess the correlation between differential survival factor expression patterns and cell sensitivity to Imatinib and oxidative stress. In this study, BCL-XL and GSH have been identified as the major survival factors responsive to BCR-ABL-promoted cellular oxidative stress and play a dominant role in regulating the threshold of oxidative stress-induced apoptosis. Cell survival factors BCL-XL and BCL-2 differentially protect mitochondria under oxidative stress. BCL-XL is an essential survival factor in preventing excessive ROS-induced cell death while BCL-2 seems to play a relatively minor role. Furthermore, the redox modulating reagent β-phenethyl isothiocyanate (PEITC) has been found to efficiently deplete GSH and induce potent cell killing effects in drug-resistant CML cells. Combination of PEITC with BCL-XL/BCL2 inhibitor ABT737 or suppression of BCL-XL by BCR-ABL inhibitor Gleevec dramatically sensitizes CML cells to apoptosis. These results have suggested that elevation of BCL-XL and cellular GSH are important for the development of CML, and that redox-directed therapy is worthy of further clinical investigations in CML.

STRATEGIES FOR THE TRANSFER OF APPROPRIATE TECHNOLOGY TO DEVELOPING COUNTRIES: THE IMPLEMENTATION AND DEVELOPMENT OF ENVIRONMENTAL HEALTH PROGRAMS IN TUNISIA

This dissertation focuses on Project HOPE, an American medical aid agency, and its work in Tunisia. More specifically this is a study of the implementation strategies of those HOPE sponsored projects and programs designed to solve the problems of high morbidity and infant mortality rates due to environmentally related diarrheal and enteric diseases. Several environmental health programs and projects developed in cooperation with Tunisian counterparts are described and analyzed. These include (1) a paramedical manpower training program; (2) a national hospital sanitation and infection control program; (3) a community sewage disposal project; (4) a well reconstruction project; and (5) a solid-waste disposal project for a hospital.^ After independence, Tunisia, like many developing countries, encountered several difficulties which hindered progress toward solving basic environmental health problems and prompted a request for aid. This study discusses the need for all who work in development programs to recognize and assess those difficulties or constraints which affect the program planning process, including those latent cultural and political constraints which not only exist within the host country but within the aid agency as well. For example, failure to recognize cultural differences may adversely affect the attitudes of the host staff towards their work and towards the aid agency and its task. These factors, therefore, play a significant role in influencing program development decisions and must be taken into account in order to maximize the probability of successful outcomes.^ In 1969 Project HOPE was asked by the Tunisian government to assist the Ministry of Health in solving its health manpower problems. HOPE responded with several programs, one of which concerned the training of public health nurses, sanitary technicians, and aids at Tunisia's school of public health in Nabeul. The outcome of that program as well as the strategies used in its development are analyzed. Also, certain questions are addressed such as, what should the indicators of success be, and when is the time right to phase out?^ Another HOPE program analyzed involved hospital sanitation and infection control. Certain generic aspects of basic hospital sanitation procedures were documented and presented in the form of a process model which was later used as a "microplan" in setting up similar programs in other Tunisian hospitals. In this study the details of the "microplan" are discussed. The development of a nation-wide program without any further need of external assistance illustrated the success of HOPE's implementation strategies.^ Finally, although it is known that the high incidence of enteric disease in developing countries is due to poor environmental sanitation and poor hygiene practices, efforts by aid agencies to correct these conditions have often resulted in failure. Project HOPE's strategy was to maximize limited resources by using a systems approach to program development and by becoming actively involved in the design and implementation of environmental health projects utilizing "appropriate" technology. Three innovative projects and their implementation strategies (including technical specifications) are described.^ It is advocated that if aid agencies are to make any progress in helping developing countries basic sanitation problems, they must take an interdisciplinary approach to progrm development and play an active role in helping counterparts seek and identify appropriate technologies which are socially and economically acceptable. ^

The relationship between obesity, autoimmune disease, and C-reactive protein: A secondary data analysis of the National Health and Nutrition Examination Survey (NHANES) 2009--2010

Autoimmune diseases are a group of inflammatory conditions in which the body's immune system attacks its own cells. There are over 80 diseases classified as autoimmune disorders, affecting up to 23.5 million Americans. Obesity affects 32.3% of the US adult population, and could also be considered an inflammatory condition, as indicated by the presence of chronic low-grade inflammation. C-reactive protein (CRP) is a marker of inflammation, and is associated with both adiposity and autoimmune inflammation. This study sought to determine the cross-sectional association between obesity and autoimmune diseases in a large, nationally representative population derived from NHANES 2009–10 data, and the role CRP might play in this relationship. Overall, the results determined that individuals with autoimmune disease were 2.11 times more likely to report being overweight than individuals without autoimmune disease and that CRP had a mediating affect on the obesity-autoimmune relationship. ^

Population-based cross -sectional survey on intestinal helminth infections with a focus on taeniasis among residents of El Paso, Texas and Ciudad Juarez, Mexico

Few studies have been conducted on the epidemiology of enteric infectious diseases of public health importance in communities along the United States-Mexico border, and these studies typically focus on bacterial and viral diseases. The epidemiology of intestinal helminth infections along the border has not recently been explored, and there are no published reports for El Paso and Ciudad Juarez, both of which are high traffic urban areas along the Texas-Mexico border. The purpose of this research project was to conduct a cross-sectional epidemiologic survey for enteric helminths of medical importance along the Texas-Mexico border region of El Paso and Ciudad Juarez and to evaluate risk factors for exposure to these parasites. In addition, an emphasis was placed on the zoonotic tapeworm, Taenia solium. This tapeworm is especially important in this region because of the increasing incidence of neurocysticercosis, a severe disease spread by carriers of intestinal T. solium. Fecal samples were collected from individuals of all ages in a population-based cross-sectional household survey and evaluated for the presence of helminth parasites using fecal flotations. In addition, a Taenia coproantigen enzyme linked immunosorbent assay (ELISA) was performed on each stool sample to identify tapeworm carriers. A standardized questionnaire was administered to identify risk factors and routes of exposure for enteric helminth infections with additional questions to assess risk factors specific for taeniasis. The actual prevalence of taeniasis along the Texas-Mexico border was unknown, and this is the first population-based study performed in this region. Flotations were performed on 395 samples and four (1%) were positive for helminths including Ascaris, hookworms and Taenia species. Immunodiagnostic testing demonstrated a prevalence of 2.9% (11/378) for taeniasis. Based on the case definition, a 3% (12/395) prevalence of taeniasis was detected in this area. In addition, statistical analyses indicate that residents of El Paso are 8.5 times more likely to be a tapeworm carrier compared to residents of Juarez (PR=8.5, 95% CI=2.35, 30.81). This finding has important implications in terms of planning effective health education campaigns to decrease the prevalence of enteric helminths in populations along the Texas-Mexico border. ^

PM2.5, PM10, and PM10-associated elements in the air in Bamako, Mali (2012-2013)

Saharan dust incursions and particulates emitted from human activities degrade air quality throughout West Africa, especially in the rapidly expanding urban centers in the region. Particulate matter (PM) that can be inhaled is strongly associated with increased incidence of and mortality from cardiovascular and respiratory diseases and cancer. Air samples collected in the capital of a Saharan-Sahelian country (Bamako, Mali) between September 2012 - July 2013 were found to contain inhalable PM concentrations that exceeded World Health Organization (WHO) and US Environmental Protection Agency (USEPA) PM2.5 and PM10 24-h limits 58 - 98% of days and European Union (EU) PM10 24-h limit 98% of days. Mean concentrations were 1.2-to-4.5 fold greater than existing limits. Inhalable PM was enriched in transition metals, known to produce reactive oxygen species and initiate the inflammatory reaction, and other potentially bioactive and biotoxic metals/metalloids. Eroded mineral dust composed the bulk of inhalable PM, whereas most enriched metals/metalloids were likely emitted from oil combustion, biomass burning, refuse incineration, vehicle traffic, and mining activities. Human exposure to inhalable PM and associated metals/metalloids over 24-h was estimated. The findings indicate that inhalable PM in the Sahara-Sahel region may present a threat to human health, especially in urban areas with greater inhalable PM and transition metal exposure.

Polypharmacy and specific comorbidities in university primary care settings.

AIMS Polypharmacy is associated with adverse events and multimorbidity, but data are limited on its association with specific comorbidities in primary care settings. We measured the prevalence of polypharmacy and inappropriate prescribing, and assessed the association of polypharmacy with specific comorbidities. METHODS We did a cross-sectional analysis of 1002 patients aged 50-80years followed in Swiss university primary care settings. We defined polypharmacy as ≥5 long-term prescribed drugs and multimorbidity as ≥2 comorbidities. We used logistic mixed-effects regression to assess the association of polypharmacy with the number of comorbidities, multimorbidity, specific sets of comorbidities, potentially inappropriate prescribing (PIP) and potential prescribing omission (PPO). We used multilevel mixed-effects Poisson regression to assess the association of the number of drugs with the same parameters. RESULTS Patients (mean age 63.5years, 67.5% ≥2 comorbidities, 37.0% ≥5 drugs) had a mean of 3.9 (range 0-17) drugs. Age, BMI, multimorbidity, hypertension, diabetes mellitus, chronic kidney disease, and cardiovascular diseases were independently associated with polypharmacy. The association was particularly strong for hypertension (OR 8.49, 95%CI 5.25-13.73), multimorbidity (OR 6.14, 95%CI 4.16-9.08), and oldest age (75-80years: OR 4.73, 95%CI 2.46-9.10 vs.50-54years). The prevalence of PPO was 32.2% and PIP was more frequent among participants with polypharmacy (9.3% vs. 3.2%, p<0.006). CONCLUSIONS Polypharmacy is common in university primary care settings, is strongly associated with hypertension, diabetes mellitus, chronic kidney disease and cardiovascular diseases, and increases potentially inappropriate prescribing. Multimorbid patients should be included in further trials for developing adapted guidelines and avoiding inappropriate prescribing.