The increase of chronic diseases worldwide impact quality of life, cause economic and medical costs, and make it necessary to look for strategies and solutions that allow people with chronic diseases (PwCDs) to lead an active working life. As part of the CHRODIS Plus Joint European Action project, a systematic review was conducted to identify studies of interventions that support the maintenance of work and return to work (RTW) among workers with chronic illnesses. These interventions should target employees with the following conditions: diabetes, cardiovascular diseases, metabolic vascular syndrome, respiratory diseases, musculoskeletal disorders, mental disorders, and neurological disorders. An extensive search was performed in PubMed, EMBASE, and PsycINFO for English language studies. Included in this review were 15 randomized controlled trials (RCT) for adult employees (aged 18+). We found that workplace-oriented and multidisciplinary programs are the most supportive to RTW and reducing the absence due to illness. In addition, cognitive behavioral therapies achieve positive results on RTW and sick leave. Finally, coaching is effective for the self-management of chronic disease and significantly improved perceptions of working capacity and fatigue. More than one third of the European employable population has a chronic illness and two out of three people reaching retirement age have two chronic diseases . About 1Europe pays a heavy price for chronic diseases (CDs): it is estimated that CDs cost EU economies 115 billion EUR or 0.8% of the Gross Domestic Product (GDP) each year. About 70% to 80% of health budgets in the EU are spent on the treatment of CDs  OR chronic diseas* OR chronic condition* OR multiple chronic conditions [MeSH] OR multiple chronic diseases OR multimorbidity [MeSH] OR multimorbid*) AND  AND  AND Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) were included. Studies were selected if they described factors related to RTW of employed adults (aged 18+) with CDs in general or one of the following CDs: diabetes, CVD, MVS, respiratory disease, mental diseases, musculoskeletal disorders, and neurological disorders. The search was carried out without temporal and geographical limitations. Excluded were meta-analysis, reviews, cohort studies, crossover studies, case-control studies, cross-sectional studies, and programs that were not evaluated or tested with a comparison group.All search results were managed with EndNote X7.1 . After the removal of duplicates, title screening and abstract screening were performed independently by two researchers. The screening was done using the predefined inclusion and exclusion criteria. When the title and abstract did not fulfill one or more selection criteria, the record was excluded. In the second round of screening, full text articles were read and selected independently by two reviewers based on the predefined criteria.Within the framework of the CHRODIS Plus project, two systematic reviews were conducted: (1) this review on RTW and chronic diseases in general and (2) a previously published review on RTW and cancer . The revThe CASP methodological quality assessment for RCTs comprised the three sections: “Are the results of the trial valid?” (Section A); “What are the results?” (Section B); and “Will the results help locally?” (Section C) . The CASBased on our clearly defined question, study population, allocation of participants, data analysis, intervention effect, and handling of failure rates, the studies had with a 92.4% agreement among raters a good to very good quality. Six studies were rated with scores of 11 and were found to be of very good quality ,22,23,24Data were extracted by one reviewer and checked by the other reviewers. The extracted study characteristics , patient characteristics , primary and secondary outcomes, and follow-ups are reported in A total of 2560 records were yielded through the search strategy: 1875 from PubMed, 582 from EMBASE, and 103 from PsycINFO. After excluding duplicate records, 2264 records remained. Performing a title and abstract screening excluded 2189 records and identified 75 records for a full-text analysis. Based on the full-text selection, 13 studies met the inclusion criteria and were included in this review. Checking the reference list of the 13 studies yielded two additional records. The research work flow (15 studies) and study selection are presented in The 15 RCTs included in this report were published between 2000 and 2017, mostly in Europe .Among the participants, 46% of the employed persons had musculoskeletal diseases followed by 41% with mental illnesses. Participants with different CDs were described in two studies . CVD andThe participants in the included studies had different working status: 260 (13%) were in paid work, 779 (38%) were absent due to illness, and 172 (8%) of the participants were unemployed. Work status was not reported in two studies ,24.Different interventions for chronically ill workers were identified. These varied both in terms of the objectives and use of the intervention programs, as well as in relation to the comparison strategies and diseases.Christensen et al.  comparedParticipation rates at the start of the studies were noted. The follow-up varied between 6 weeks and 10 years.Our research question defined the maintenance of work and RTW of chronically ill people as the primary outcome. This can be measured as RTW rate, RTW time, RTW percent, duration of sickness absence, sick leave in days, and working ability. Statistical methods for evaluating the results vary and accordingly the effect sizes .We did not have predefined secondary outcomes. However, job satisfaction, quality of life, improvement in functional status, physical activity, and fatigue and pain intensity may have a positive or negative effect on the primary results. Therefore, these were included in our analysis. de Buck et al.  examinedn = 24) of stroke survivors returned to work in the intervention group, compared with 20% (n = 8) in the control group (p < 0.001). The odds ratio for RTW for stroke survivors in the intervention group was 5.2.Four studies ,25,28,30p = 0.000) and 19 versus 8 points (p = 0.032)).Varekamp et al.  found thp = 0.003). The integrated care effectively increased the RTW rate (Hazard ratio (HR) 1.9, 95% CI 1.2 to 2.8). Kim Wong et al. [Lambeek et al.  comparedg et al.  found thTwo studies ,29 examiThe effect of physical therapy (PT), cognitive behavioral therapy (CBT), behavioral medicine rehabilitation (BM), and a “treatment-as-usual” on absenteeism due to chronic neck pain (NP) and/or back pain (LBP) was studied over a 10-year period by Bergström et al. . Three dAn adaptation of the Stanford University’s chronic disease self-management program (CDSMP) was studied by Detaille et al. . The oriDe Buck et al.  evaluateThere have been two studies of coaching intervention programs ,26. McGoIn the study by Nieuwenhuijsen et al. , a new tComparative intervention strategies were evaluated in three studies: Bendix et al., Christensen et al., and Friedrich et al. ,31,32.The effects of a comprehensive program of functional recovery, intensive physical training, ergonomic training, and behavioral support (39 hours a week for 3 weeks) for patients with chronic LBP compared to outpatient intensive physical training (1.5 hours three times a week for 8 weeks) were examined by Bendix et al. . At the p < 0.04).The effects of three different rehabilitation strategies  were observed by Christensen et al. . Video gThe study by Friedrich et al.  comparedTwo studies described interventions intended to prevent or slow chronicity ,24. BakkLinton et al.  comparedAll three comparison groups reported successes. The risk of long-term sick leave was reduced only for the CBT intervention group; the relative risk was nine times lower compared to the information package groups . In addition, the CBT group showed a significant decrease in the use of physicians and physiotherapy compared to the two groups that received information (where such use was increased). All three groups showed improvements for the variables pain, anxiety prevention, and cognition.p-values <0.05). Similarly, a job-preservation program achieved an increase in self-efficacy and significant decrease in fatigue in an intervention group after 24 months, which in the long run could lead to more job-preservation [Fatigue is a commonly referred complaint to chronically ill patients, especially when they have a job . The mulervation .p = 0.01) [An integrated care program that combines patient- and workplace-based interventions for patients with chronic low back pain significantly improved the functional status of patients in the integrated care group at 12 months compared to patients in the usual care group ( = 0.01) . The impSignificant improvements in disability and pain intensity were achieved through combined movement and motivation programs at the disability level of patients with chronic and recurrent LBP .Apart from increasing the chances of RTW, cognitive ability can also increase quality and activities of daily life, as shown by Ntsiea et al. . MoreoveIn four studies ,27,31,32The aim of this study carried out in the framework of the CHRODIS Plus European Joint Action project was to give a summary of the available interventions that aim to enhance or facilitate work reintegration among people with chronic diseases. We included 15 RCTs in this review that were published between 2000 and 2017 in English. Seven studies included workers with musculoskeletal disorders, five included workers with mental health disorders, two included workers with various chronic illnesses, and one included people affected by CVD and stroke. No studies were found for MVS. Most of the studies were published in the Netherlands and in Nordic countries of Europe, namely Denmark and Sweden.The RCTs included in our review reported on interventions aimed both at improving personal skills and improving labor market participation.We found that workplace-based interventions can lead to positive changes in employment status, work ability, RTW, and sick leave rates for people with various chronic conditions ,25,28,30Multidisciplinary interventions are promising strategies that can meet the complexity of the needs of people with chronic conditions . They arIn coping with work-related stress, stress management interventions have proven to be as effective as cognitive-behavioral interventions. These consistently produced greater effects than other types of interventions . In our The return to work for chronically ill patients can be improved by developing their ability to purposefully influence their own behavior. Self-management is an approach increasingly used in chronic disease care to improve self-efficacy and well-being. Detaille et al.  found seCoaching through education, behavioral change, or psychosocial approaches seems to play a significant role in improving the self-management of chronic diseases . The McGNieuwenhuijsen et al.  investigAlthough research on coaching for self-management of chronic illness is limited, existing studies suggest that coaching is effective in the self-management of chronic disease . CombineSome limitations should be mentioned. Although the choice to include only RCTs guaranteed a strong study design, it did not allow us to consider many observational studies that also focused on the effectiveness of interventions, with the consequent loss of some results.Another limitation was that we were looking for literature in English, although some publications of interest may also be published in the languages of the countries where they were performed.Finally, due to the scope of this work, we focused on employment outcomes; other important results that may have had an impact on intervention results, such as health and quality of life, were omitted.Despite these limitations, the study presents the following strengths: (1) we performed a methodological quality assessment of the study and (2) we conducted the search of relevant studies without any time and geographical restrictions, which permitted us to consider a broader range of interventions. The results from our review are very heterogeneous and needs further research. Nevertheless, our results provide a part for the development of a training tool of RTW in the CHRODIS Plus project.Various interventions targeting populations with very different CDs were identified. These interventions focused mainly on changes in work and most of them are effective in improving work participation. This indicates that work-oriented interventions should be considered as a general approach to improve work participation of employees with various CDs.Coaching has great potential for improving self-management in chronic conditions. The literature on this, as well as in our systematic review, is limited. Future research is needed to look at the mechanisms that may make coaching successful in reducing the burden of chronic disease.In dealing with work-related stress, stress management interventions such as cognitive-behavioral interventions have proven effective. Individualized work-oriented CBT with an optional workplace intervention for those with adjustment disorder or reactions to severe stress can significantly improve long-term RTW. In addition, CBT can reduce the risks of long-term sick leave.The best strategy for RTW or for improving functional status, mental health and fatigue are multidisciplinary interventions involving various health and work professionals. Therefore, further multidisciplinary intervention programs should be researched and developed.


Knowledge of type of blood sample (serum or plasma) for determination of essential and toxic elements is essential for assessing the health and nutritional status of the animals and the herd. We demonstrate that both plasma and serum samples are suitable and interchangeable for the determination of most of the essential and toxic elements in blood in cattle. Nevertheless, we must take into account that the concentrations of Cu and Se are lower in the serum than in plasma.n = 20) were acid digested, and the concentrations of As, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, Hg, Li, Mg, Mn. Mo, Ni, P, Pb, Sb, Se, Sr and Zn were determined by inductively coupled plasma mass spectrometry (ICP-MS). The study findings indicate that plasma and serum samples appear suitable and interchangeable for the determination of most of the essential and toxic elements in blood in cattle. The only exceptions are Cu and Se, the concentrations of which were significantly lower (40.9 and 29.9% respectively) in serum than in plasma. Some of the Cu in blood samples from bovine ruminants is known to be sequestered during clotting. However, further research on Se in ruminants and other animal species is warranted. Finally, the significantly higher Mn (9.9%) concentrations in serum than in plasma may have been caused by haemolysis of some samples. Special attention should be paid to preventing haemolysis of samples during collection and processing, in order to prevent overestimation of elements present at high concentrations inside erythrocytes .This study was designed to evaluate the influence of type of blood sample (serum or plasma) on essential and toxic element analysis in cattle. Paired plasma and serum samples ( Two centuries after the discovery that I and Fe are essential elements, trace element nutrition in humans and livestock animals remains a challenge. Nowadays, at least 17 trace elements are known to be essential for proper growth, health and reproduction . Trace element disorders have been described in many parts of the world, mainly in relation to their geological origin . They coDetermining trace mineral status and toxic element accumulation in farm animals provides useful information for veterinary practitioners and is a critical part of maintaining herd health . Trace eAn important factor that often is not taken into account is the type of the sample analysed. Whole blood (collected in ethylenediamine tetraacetic acid (EDTA), heparin or other anticoagulants) is scarcely used, but there is little information about the convenience of using serum or plasma samples, or whether the results are comparable. The main difference between serum and plasma is that fibrinogen and clotting factors are consumed in the former, although many other proteins, water, salts and blood cells are caught between the mesh of cross-linked fibrin protein . In relaInformation about the effect of clotting-related sequestration on other essential or toxic elements, as well as the possible influence of the blood sample matrix (serum vs plasma) during ICP-MS analysis of samples is scarce, although it may be very important. This study evaluates the influence of type of blood sample (serum vs plasma) on essential and toxic element analysis in cattle. Cows were managed according to Directive 2010/63/EU on the protection of animals used for scientific purposes and the trial complied with the Spanish legislation on animal care . The procedures applied were supervised by the Bioethics Committee of the University of Santiago de Compostela .n = 20) used in this study were obtained as part of a wider on-going project on mineral nutrition in cattle. Briefly, the study was conducted in June of 2015 in a commercial dairy farm located in the Province of Lugo  . The farm is typical of conventional dairy farms in North Spain, with a loose housed system with slatted floor, beds with sand and a tie-stall system for feeding. It has 236 Holstein Friesian cows in lactation with a 305-d-corrected milk yield of 11.142 kg. The animals were kept indoors and fed total mixed rations (TMR) based mainly on maize silage, hay silage and concentrate with a standard mineral supplementation for lactation, to cover the animal requirements [®, NH Trace Elements, Greiner bio-one, Kremsmünster, Austria), whereas serum samples were fractionated from whole blood samples collected in 9 mL serum tubes . Immediately after collection, the samples were refrigerated, transported to the laboratory and centrifuged at 3000 rpm for 10 min to obtain plasma and serum, within 4 h of collection. Triplicate subsamples were stored at −20° pending analysis.The bovine blood samples . Stock standard solutions of the elements (1000 mg L−1) were ultrapure grade: ICP Multi element standard solution IV certiPUR®, for B, Ba, Ca, Cd, Co, Cr, Cu, Fe, Li, Mg, Mn, Ni, P, Pb, Sr and Zn determination, and ICP standard certiPUR®, for Hg and Se determination, were both purchased from Merck . As, Mo, Sb and U standards were obtained from Panreac . The samples were acid digested in nitric acid  and hydrogen peroxide . The certified reference material  used to validate ICP-MS measurements was obtained from the National Institute for Standards and Technology (NIST) . Polypropylene tubes used for preparation of samples and standards were soaked in 10% Hyperpur® HNO3 for at least 24 h and rinsed with deionised water and dried before use. The sample tubes were tested and found to be free of trace elements.All solutions were prepared using ultrapure water of resistance 18 MΩ cm3 and 0.5 mL H2O2 in propylene tubes and leaving at 60 °C for 2 h. The digest thus obtained was diluted by adding 2.5 mL of ultrapure water and centrifuging at 2000 rpm for 5 min. The working calibration standard solutions were prepared daily by appropriate dilution of the previously described multi-elemental standards in 20% (v/v) nitric acid, and internal standards (20 μg L−1 of Ge and Tb) were added online at a flow rate of 40 μL min−1. Aliquots (1 mL) of plasma and serum samples were digested using an acid digestion procedure, as previously described . Briefly−1) were constructed daily, by analysis of fresh standard solutions, immediately before analysis of the serum samples. In all cases, linear responses were obtained with zero intercept, correlation coefficients higher than 0.999 and a relative standard deviation (RSD) below 5%.ICP-MS-based multi-element determination was performed in an Agilent 7700x ICP-MS system  equipped with collision/reaction cell interference reduction technology. The continuous sample introduction system consisted of an autosampler, a Scott double-pass spray chamber , a glass concentric MicroMist nebuliser , a quartz torch and nickel cones . Elemental concentrations were quantified using MassHunter Work Station Software for ICP-MS . All samples were blank corrected and analysed in triplicate, with Ge and Tb as internal standards. Calibration curves  and inter-assay precision  were determined, for both plasma and serum samples.t-test. Finally, the association between mineral concentrations in plasma and serum was evaluated using the Pearson’s correlation coefficient. AII statistical analyses were conducted with SPSS software for Windows (version 21). The standard relative deviation (SRD) was used to evaluate the precision of the analysis of the plasma and serum samples. Differences between mineral concentrations in plasma and serum were checked by The intra-sample precision (assessed from 10 repetitions of the same sample) and inter-assay precision  of essential and toxic elements determination in plasma and serum samples are shown in n = 20) are presented in The essential and toxic element concentrations in paired plasma and serum samples (−1 (190 mg L−1) lower than the concentrations in plasma [p < 0.05) may suggest that some Se is lost during the clotting process. This finding deserves further investigation.Within the essential trace elements, the concentrations of Cu (40.9%) and Se (29.9%) were statistically significantly higher in the plasma than in the serum, whereas the opposite was true for Mn (9.9%). Significantly lower concentrations of Cu in serum than in plasma have been described for cattle  and othen plasma . Howevern plasma . CP is mn plasma . Althoug−1 0 mg L−1 n plasma , althougn plasma , and altn plasma ,23, we a−1; [p < 0.001) between the serum/plasma ratios of Fe and Mn concentrations, may indicate some leakage from the erythrocytes as one possible reason for the higher Mn and Fe concentrations in the serum in our study. Moreover, to the best of our knowledge the apparently higher Mn concentration in the serum than in plasma samples from cattle has not been previously reported. Higher serum concentrations of Fe and Zn have been described in serum samples in humans  and are −1;  occurred−1, corresponding to a very low level of environmental exposure, [p < 0.05) that would support this hypothesis. Another possible explanation is contamination of the tubes during blood collection; however, this would be expected to affect all serum samples to the same extent, increasing the serum concentrations in all samples above background. If this were the case, plasma and serum concentrations would be correlated , and norrelated ; howeverThe results of the correlation analysis between plasma and serum concentrations are presented in p < 0.001), but was generally high  for most essential elements of main interest from the point of view of health and nutrition. The variation between serum and plasma concentrations can be explained by considering the variability in the analytical precision (intra and inter-assay precision). The only exception was Ca where only a weak association between serum and plasma was found ; our results are in agreement with previous studies that indicate a significant effect of the anticoagulant on the analysis of Ca, that leads to recommend the determination of Ca in serum [p < 0.01), which is in accordance with published data in cattle indicating a weak relationship between Cu in serum and plasma because of the marked variability in the apparent loss of Cu during clotting [The association was very powerful for some elements such as Mo  inside the erythrocytes.


A large proportion of injuries were documented for the lower extremities , followed by the upper extremities  and the spine . Death was mainly caused by drowning. Overall mortality was 1.9% (n = 9), and the absolute risk was 0.02 deaths per 1000 hrs of canyoning. Many uninjured persons required evacuation , which resulted in a substantial expense and workload for emergency medical services. Increased safety precautions are required to reduce accidents while jumping and rappelling and fatalities caused by drowning.Canyoning has become a popular recreational sport. Nevertheless, little is known about injuries or diseases associated with canyoning. The aim of this study was to examine accident causes, injury patterns, out-of-hospital and in-hospital treatment and outcomes. For this purpose, national out-of-hospital data from the Austrian Alpine Safety Board and regional in-hospital data from Innsbruck Medical University Hospital were analysed for the period from November 1, 2005 to October 31, 2018. Nationally, 471 persons were involved in such accidents; 162 (34.4%) were severely injured, nine of whom died. Jumping ( Canyoning is a wilderness recreational sport that has grown in popularity, especially in Europe, the USA and Australia ,2. CanyoIn 2017, the International Commission for Mountain Emergency Medicine (ICAR MEDCOM) defined consensus guidelines for the on-site management and transport of patients in canyoning accidents, as well as summarising, commenting on and grading the literature available . AlthougThis retrospective study was approved by the Ethics Committee of the Medical University of Innsbruck (AN4757 315/4.4) and was registered with Clinical Trials (NCT03405467). In Austria, Alpine Police officers collect and store anonymised data on accidents and rescue operations. These officers are members of the Federal Ministry of the Interior, are qualified alpinists and have basic paramedical training. Whenever an emergency call triggers a professional rescue, an entry into the national registry for mountain accidents in Austria is made. By October 31, 2018, this registry contained more than 109,710 mountain emergencies, thus being one of the largest registries for mountain accidents. For the purpose of this study, accidents related to canyoning during the timeframe from initiation of the registry on November 1, 2005 to October 31, 2018, were extracted and analysed. For in-hospital data and patient outcome, the hospital information system of Innsbruck Medical University Hospital, a level-one trauma centre, was analysed. In a first step, registry data containing the sex, age, and nationality of involved persons; circumstances and accident cause; body region; type and severity of injury; type of extrication and rescue; weather; location; elevation; and several other data were collected . The epiIn a second step, the local hospital information system at Innsbruck Medical University Hospital, a level-one trauma centre for Western Austria, was analysed with a full text query for „canyon“, „canyoning” and „canyoning accidents” for the same period . Records of patients involved in canyoning accidents, irrespective of their age, were included in this study. Medical information was obtained by searching in-hospital medical reports, emergency physician protocols and investigations like X-rays or CT scans. Persons only swimming in a gorge or not doing canyoning were not included. Hospital information systems at other Austrian hospitals were not analysed due to restrictions imposed by the Austrian Data Protection Authority. Steps involved for data acquisition from the national registry of the Austrian Alpine Safety Board and from the hospital information system at Innsbruck Medical University Hospital are depicted in a CONSORT Flowchart . Data arn = 69, 14.6%; July n = 131, 27.8%; August n = 161, 34.2%; September n = 57, 12.1%) and most frequently on Saturdays  or Sundays . The median time of day of the emergency was 13:43 ± 2:35 h. Of the study patients, 303 (64.3%) were on a guided canyoning tour. The registry of the Austrian Alpine Safety Board shows 297 canyoning accidents as accidents, environmental or medical emergencies. Males (73.9%) more often suffered a canyoning accident than females (25.7%). Of the 471 persons involved, 392 (83.2%) were located in Austria’s western states . Of them, 314 (66.7%) were in the state of Tyrol. Most incidents occurred during the summer , strains or sprains  and dislocations . The region affected most by injury was the lower extremity , followed by the shoulder  and the spine  From the 302 injured, data on the injured body region were missing in 22 cases. These were excluded, resulting in a total of 280 injured individuals  persons, while 169 (35.9%) persons were involved, but not injured. ividuals .n = 96, 20.4%). Overall, 116 (24.6%) canyoneers, although uninjured, needed to be rescued. Seventy-one persons practicing canyoning were involved in, but not in need of, a rescue mission. Helicopters were frequently dispatched in sunny  and cloudy  weather conditions, whereas ground-based rescue missions were more common in bad weather conditions . The type of rescue in relation to the injured body region is illustrated in Injuries to the lower extremity, shoulder and spine were common and frequently prompted rescues by a helicopter. Some persons were uninjured, but needed to be rescued after their companions had been involved in an accident  were more frequently involved than females (43.1%). Details of the canyoning activity performed when the accident occurred and the required rescue are shown in n = 25, 45.5%), followed by the upper extremity  and the vertebral column . Seven surgeries and one percutaneous transluminal coronary angioplasty (PTCA) were necessary  sought out the emergency department on their own.Only nine (15.5%) patients required a rescue mission of any kind. The other patients  were uninjured but needed rescuing, which caused a substantial expense and workload for emergency medical services.By analysing the national registry of the Austrian Alpine Safety Board on alpine accidents, we were able to discern the epidemiology, injury severity and pattern, mortality and mode of rescue of persons involved in canyoning accidents in Austria. Jumping, rappelling, sliding and stumbling were the most common causes of canyoning accidents. Injuries most commonly involved the lower extremity, followed by the shoulder and the spine. Death was mainly caused by drowning. Nearly half of the rescue operations required a helicopter to be dispatched. A quarter of all canyoneers  reported a ratio of 2.7:1 and a Spanish study from Aragon reported a ratio of 1.4:1 . The mean = 302). Therefore, a total of 1933 individuals can be estimated as injured during canyoning in Austria. We assume that the Austrian Alpine Safety Board underestimates the number of patients with minor or no injuries as they can mostly rescue themselves, without alerting the dispatch centre and triggering a professional rescue.Of the 58 patients treated at Innsbruck Medical University Hospital, only nine required a professional rescue (1:6.4). This means that of the 58 persons injured while canyoning, only nine were registered nationally. By extrapolating this ratio to our data from the national registry, the actual total number injured during canyoning can be hypothesised to be 6.4 times higher than those injured and registered nationally (as in requiring a rescue mission). By subtracting the uninjured from the total persons involved in a canyoning emergency nationally, one can calculate those injured and registered , lower leg or foot (25%) in a nine-month period. They were mostly minor and limited to soft tissues . AnotherWith regard to the injury pattern and severity, as noted in the national registry, we observed a large number of severe injuries, a smaller proportion of mild injuries and a minor number of deaths. Cause of death was mainly drowning. The most affected body region was the lower extremity, followed by the shoulder and spine, with the main type of injury being fractures, followed by sprains or strains and dislocations. Similar to the Swiss prospective survey, a retrospective analysis from Aragon, Spain, described 90% of injuries as minor to moderate  reported a large percentage of uninjured or non-ill 79%) persons , while t9% personThe data from Innsbruck Medical University Hospital show that injury primarily occurred to the lower extremity, the upper extremity and the vertebral column. Although other studies have also shown that lower extremity and spinal injuries are common in canyoning, our in-hospital data show a larger proportion of spinal injuries, as well as higher rates of fracture and dislocation in comparison to data from other studies ,8.Medical emergencies were few. Gastrointestinal infections were documented in our in-hospital data, but did not permit direct linkage to canyoning. As no microbiological samples were collected in our patients with gastrointestinal infections, it is unknown whether a specific pathogen was causative. Canyoning-related waterborne, infectious diseases, e.g., tularaemia and leptospirosis, have been described in warmer countries ,6,16,17 n = 1933) by this incidence results in over 460,000 hrs of canyoning in our observed timeframe . In the Swiss online survey conducted by Ernstbrunner et al., 109 participants undertook 13,690 hrs of canyoning in one season. Projecting this to our results would equal an average of 282 fulltime active canyoneers per year in the Austrian mountains. Given the nine deaths observed in our 13-year timeframe, we can also compute an absolute risk of mortality of 0.02/1000 hrs of canyoning, or 1/407 active canyoneers per year. This extrapolation is vague as the data leading to the initial 6.4 ratio were taken from only one hospital. However, given the fact that Innsbruck Medical University Hospital is a level-one trauma centre serving western Austria, some injured individuals probably also seek help from a doctor in a private practice. Therefore, the ratio of rescue to no rescue is most likely underestimated, thus overestimating the mortality rate.The prospective Swiss online survey concluded that the incidence of canyoning-related injuries was 4.2/1000 hrs of canyoning . DividinA very recent study conducted by Gatterer et al. compared the mortality in different mountain sports . Some ofNearly half the canyoning-related rescues nationwide were performed by the helicopter emergency medical service (HEMS), while 27.6% were strictly ground-based. The majority of patients with trauma to the spine, pelvis, upper and lower leg, as well as shoulder and ankle, were rescued by helicopter (>70%), alone or in combination with a ground-based rescue service. Consistent with the injury severity, we found that 88.9% of patients with hand-injuries needed only ground-based rescue or no rescue at all. We suspect that patients with isolated injuries of the upper extremity were more easily able to leave the canyon on their own. Only nine patients treated at Innsbruck Medical University Hospital were transported with an organised rescue service.The alpine regions of Austria are equipped with numerous HEMS that are easily accessible. In 2018, there were 30 HEMS bases covering the Austrian Alps, with 19 operating all year round, flying a total of more than 18,000 rescue missions ,22. RemoInterestingly, the majority of patients treated at Innsbruck Medical University Hospital did not require a professional rescue mission and sought out the emergency department on their own. Merely nine patients were brought to Innsbruck Medical University Hospital by some form of emergency medical service. The national registry data showed that 314 people were involved in canyoning accidents in the state of Tyrol and 190 of those were injured. Obviously, the majority of rescued, injured patients must have been treated elsewhere. This is easily possible as there are another six smaller public and three private hospitals in Tyrol. The small number of injured patients brought to Innsbruck Medical University Hospital does, however, give a hint as to the total injury severity, as there was apparently no need for treatment at the only level-one trauma centre in western Austria.In Austria, 24.6% of all canyoneers were uninjured but involved in rescue operations. The majority of them were either lost or trapped in a canyon or accompanying someone who was injured. With a view to the required workload for emergency medical services and the consumption of their resources, this is an interesting finding. However, the helicopter evacuation of uninjured persons can reduce the rescue time in difficult and remote terrain, thereby potentially minimising the risk of further injuries and vital risks .Our study has several limitations. Firstly, the data provided by the Austrian Alpine Safety Board are anonymised, so it was only possible to directly link four cases from the national registry data with in-hospital data. The accuracy of police data is unknown, though these data are often used for prosecution and insurance purposes. Additionally, it seems that, regarding our in-hospital data, many patients are treated elsewhere and a majority also come to the hospital on their own and are therefore not registered by officials in the national registry. Minor incidents which could be solved by the persons on site did not result in a call to the dispatch centre and thus were not in the national registry. The retrospective analysis of emergency medical registries is naturally biased as very minor injuries often do not require rescue operations or emergency medical services. Therefore, comparisons with prospective surveys must be conducted with caution. Additionally, comparing different retrospective analyses with differences in reasons for a rescue operation (search and rescue vs. merely rescue operations) and of course different geographic regions observed, as well as different injury definitions, limits the interpretation possibilities with regard to the entire background of observed variations in the injury severity and rate of uninjured persons.Restrictions imposed by the Austrian Data Protection Authority prevented us from analysing hospitals other than Innsbruck Medical University Hospital. We thus do not know the incidence and severity of canyoning-related injuries or the rescue-to-no-rescue ratio elsewhere in Austria or Tyrol. Furthermore, the modality of our in-hospital analysis, namely searching for keywords, is dependent on the documentation strength. Missing cases caused by absent keywords in the documentation could result in a smaller number of hits. Moreover, the exact number of persons practicing canyoning in Austria is unknown. An exact assessment of accident incidence and mortality is therefore not possible. Finally, the rescue mode may depend on the location of the accident. Unfortunately, our databases do not provide these data.Jumping, rappelling, sliding and stumbling were the most common causes of canyoning accidents. Most injuries involved the lower extremities, spine and upper extremity. Death was mainly caused by drowning, although mortality was low. A quarter of all involved persons, although uninjured, required evacuation by a professional rescue service. Increased safety precautions are required to reduce accidents while jumping and rappelling and fatalities caused by drowning.


The pooled prevalence for suicide ideation (24 studies) and suicide attempts (18 studies) were 23.2% (95% CI: 0.176–0.301) and 7.4% (95% CI: 0.031–0.169) respectively. The pooled rate of death due to suicide (10 studies) was 0.5% (95% CI: 0.002–0.016). Meta-regression showed that mean age and proportion of male gender were significant moderators for prevalence of suicide attempts and death due to suicide in PWE. Young PWE could be triggered by relationship problems and male PWE might use more lethal methods to attempt suicide. This meta-analysis provides the most up-to-date information on the prevalence of suicide among people with epilepsy and guidance on strategies to improve current psychiatric services provided for this population. This meta-analysis aimed to evaluate the association between epilepsy and suicide. We systematically searched PubMed, PsycINFO, Embase and Web of Science for studies that reported the prevalence of suicidality in the form of suicide ideation, attempts and deaths among people with epilepsy (PWE). Studies were included if they reported the numbers of patients who died by suicide and concurrently suffered from epilepsy, assessed suicide ideation, or studied suicide attempts in PWE by validated instruments or diagnostic interviews. We used the random effects model to calculate the pooled odds ratios (OR) and standard mean differences (SMDs). We performed subgroup analyses. Seven case-control studies were included in the comparison of rates of suicide attempts between PWE and controls, with a total of 821,594 participants. Our analyses demonstrated a positive association between epilepsy and suicide attempts : 2.69–3.92,  Epilepsy is a significant disease burden among the worldwide population. A recent meta-analysis found the median incidence of epilepsy per 100,000 people per year to be 45.0 in high income economies and 81.7 per 100,000 people in the rest of the world , psychosWe conducted a systematic search of PubMed, PsycINFO, Embase and Web of Science from inception to 22 April 2018. The key terms used in the search were referenced epilepsy , seizures , and suicidality . We did not include the term “deliberate self-harm” (DSH) as a search term, as when only DSH is reported without reference to suicidality, it is not possible to differentiate suicidal from non-suicidal self-harm . Using tWe included the studies that examined the association between epilepsy and suicide in all patients. We only included studies that had assessed suicidality based on diagnostic interviews ) or other questionnaires and diagnostic tools , Hamilton Depression Rating Scale (HDRS), and Beck Depression Inventory (BDI)). For the diagnosis of epilepsy, we also only included studies that had quantified the number of PWE based on a diagnosis established by clinicians or a diagnosis that had been reflected in the patient’s medical records.We used the meta-analysis software Comprehensive Meta-analysis  to calculate the effect sizes and calculate the pooled mean effect size with the random effects model. The random effects model was used, as it assumes varying effect sizes between studies, because of differing study design and study population . We convp < 0.05. For the studies that reported outcomes, including number of patients with suicidal ideation, suicide attempts, and deaths attributed to suicide without a control group, pooled prevalence rates were calculated. To assess for publication bias, we conducted Egger’s test [The studies were classified and analysed based on the number of PWE who had one of the following three outcomes: suicidal ideation, suicide attempts, and death from suicide. For case-control studies, the ORs for the number of PWE who attempted suicide were calculated with reference to the number of controls without epilepsy who attempted suicide. A Forest plot was then constructed for comparison, for which we reported the pooled OR, 95% confidence interval (CI) and p-value based on the method used by a previous meta-analysis . The star’s test  and failr’s test . The I2 ogeneity , which dstantial .The process of study selection is shown in p < 0.001) using the random effects model. This finding suggests that PWE were 3.07 times more likely to have made a suicide attempt than individuals who did not suffer from epilepsy. The p = 0.001). The mean age of PWE  was identified as a significant moderator that contributed to heterogeneity between the studies. The percentage of male patients  was a non-significant moderator. There was no evidence of publication bias .p < 0.001) using the random effects model. This suggests that 7.4% of PWE had a history of suicide attempts. The p < 0.001). The percentage of males  and mean age  were significant moderators that contributed to heterogeneity between the studies. There was no evidence of publication bias .We also analysed the number of PWE who had attempted suicide among PWE in studies that did not include a control group. A total of 18 studies, with a total sample size of 109,938 PWE, were analysed. p < 0.001) using the random effects model. After removing an outlier study by Fukuchi et al. [p < 0.001) using the random effects model. The p < 0.001). The percentage of males  and mean age  were significant moderators that contributed to heterogeneity between the studies. There was no evidence of publication bias .A total of 10 studies, with a total sample size of 595,605, were analysed for a pooled prevalence rate of death due to suicide among PWE. i et al.  the poolp < 0.001) using the random effects model. The p < 0.001). The percentage of males  and mean age  were significant moderators that contributed to heterogeneity between the studies. There was evidence of publication bias . We also analysed studies to quantify the rate of suicide ideation among PWE. A total of 24 studies, with a total sample size of 71,328 were analysed. p < 0.001). Our results corroborate previous studies, which concluded that a clear relationship between epilepsy and suicidality exists [This meta-analysis was conducted to quantify the associations between epilepsy and suicidality, globally, in the forms of suicide ideation, suicide attempts, and death due to suicide. In the meta-analysis of seven studies with 821,954 participants in total, we found a significant association between suicide attempts and epilepsy  approximated that about 800,000 people die from suicide per year . In thisAmong the 23 studies that measured the association between suicidal ideation and epilepsy, we analysed that the pooled event rate was 23.2%. In contrast, the prevalence of suicidal ideation in the general population was reported to be 3.1% in a cross-national study including 17 countries . The preOverall, we found that there were few studies that compared the prevalence rate of suicidal ideation or death due to suicide between PWE and healthy controls. Having a control group would allow better comparison and better understanding of the increased risk of suicidality among PWE. Further research is required to determine the rate of PWE seeking psychiatric or pharmacological intervention for suicidality and other psychiatric co-morbidities, as well as the factors which influence this. This research will identify the treatment gap that prevents this potentially vulnerable group from seeking psychiatric help and guide the improvement of psychiatric services provided for people with epilepsy. Furthermore, the prevalence rate of suicidal ideation or death by suicide should be compared with a control group that has other challenging conditions including patients with psychiatric conditions.This study has several inherent limitations, which are commonly found in meta-analyses of prevalence studies. Firstly, the included studies showed a high level of heterogeneity. Heterogeneity appears to be the norm rather than the exception in meta-analyses of large numbers of cross-sectional studies globally . SecondlOur meta-analysis has indicated that suicidality in people with epilepsy (PWE) is more common than among the general population in the context of suicide attempts. Additional analysis has also shown that other indicators of suicide risk, including suicidal ideation and death by suicide, are also increased among PWE. This highlights a need for improved suicide risk screening, as well as the identification and implementation of preventive and precautionary strategies, for people with epilepsy.


The increasing prevalence of high myopia has been noted. We investigated the epidemiological characteristics and the related factors of high myopia in a Japanese adult population. Japan Public Health Center-Based Prospective Study for the Next Generation (JPHC-NEXT) Eye Study was performed in Chikusei-city, a rural area in mid-east Japan, between 2013 and 2015. A cross-sectional observational analysis was conducted to investigate prevalence and related factors of high myopia. A total of 6101 participants aged ≥40 years without a history of ocular surgeries was included. High myopia was defined as a spherical equivalent refraction of ≤−6.00 diopters according to the American Academy of Ophthalmology. Potential high myopia-related factors included intraocular pressure (IOP), corneal structure, corneal endothelial cell density, age, height, body mass index, heart rate, blood pressure, biochemical profile, and current history of systemic and ocular disorders. The odds ratios of high myopia were estimated using the logistic regression models adjusted for the associated factors. The prevalence of high myopia was 3.8% in males and 5.9% in females with a significant difference. Age was inversely associated, IOP was positively associated, and none of other factors were associated with high myopia in both sexes. In conclusion, only age and IOP were associated with high myopia in this community-based sample. Myopia is one of the most prevalent conditions of the eye. It causes visual impairment in both children and adults that is usually correctable by optical aids such as glasses and contact lenses. High myopia is generally determined as −6.00 diopters (D) or less in refraction and axial lengths of 26.5 mm and more by the American Academy of Ophthalmology . High myOver the past few decades, some studies have provided information on the prevalence and risk factors for myopia, including genetic predisposition and environmental factors such as extended near work, less exercise, and luck of outdoor activities ,6,7. HowHuman lifestyles are rapidly changing. The factors that may affect the progression of myopia are essential to understanding and to finding countermeasures for myopia. Community-based population-based research is a reliable way to elucidate the associated factors. In order to elicit the high-myopia-associated factors, it was thought to be important to eliminate biases and prejudices as much as possible. We established this study to screen all the possible factors which were available in the collected data and personal information without manipulation. In addition, this study targeted adult population as subjects. Pathological myopia, which is usually preceded by high myopia and seen mostly in adults, is theoretically thought to be originated from myopia in children. To know possible associated factors for high myopia in adults is considered to be a crucial key to render solutions to diminish the number of future high or pathological myopia in children.We conducted the Japan Public Health Center-Based Prospective Study for the Next Generation (JPHC-NEXT) Eye Study, an ancillary study of the JPHC-NEXT, to examine the prevalence of refractive status of the participants and factors associated with high myopia in Chikusei, a rural city in mid-east Japan. To our knowledge, this is the first large, community-based study to determine the factors associated with high myopia.This study followed the tenets of the World Medical Association’s Declaration of Helsinki. The study protocol was approved by the Institutional Review Boards of Keio University, Osaka University, the University of Tsukuba, and the National Cancer Center. Written informed consent was obtained from all the participants.JPHC-NEXT Eye Study was performed in two regions: Saku-city and Chikusei-city. The subjects of this study are participants of annual checkups who are aged 40 years or more in Chikusei-city, and a total of 7098 subject who had taken ocular examination between 2013 and 2015 were included in this study. Out of them, 997 participants who had undergone ocular surgeries were excluded because their refraction may have changed after the procedures. In the end, 6101 participants aged from 40 to 93 years (86.0%) were included in this analysis .® G1200  and AIA2000  were used; and for blood glucose tests, BM9130  was used. Refractive status and intraocular pressure (IOP) were measured using an auto refractometer . Central corneal thickness and corneal endothelium density were measured by using a specular-type pachymeter .The screening included ophthalmic examinations ; measurement of height (HT); weight (WT); blood pressure; and serum laboratory data including glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), gamma-glutamyl transpeptidase (GGTP), total cholesterol (T cholesterol), fasting triglyceride (triglycerides), high density lipoprotein (HDL cholesterol), low density lipoprotein (LDL cholesterol), fasting blood glucose (glucose), hemoglobin A1c (HbA1c), and creatinine; and a history of systemic and ocular disorders. Serum T cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, HbA1c, GGTP, and creatinine were measured by visible absorption spectrometry. Serum glucose, GOT, and GPT were measured using ultraviolet absorption spectrometry. Blood pressure was measured two times, and the second reading was adopted. Height and body weight were measured with AD-6350 . For blood pressure, TN2657P, TM 2657P, TM 2655P, and UM-102  were used; for biochemical examinations, BM8060G , LUMIPULSEInformation on histories of hypertension, diabetes, and dyslipidemia was collected through face-to-face interviews at the baseline survey. Likewise, inquiry about smoking history and alcohol history as well as histories of ocular disease and its surgery were also performed.p = 0.10). Thus, we used the SEq of the right eyes to evaluate the refractive status in this study. A high myopia was defined as SEq of −6.00 D or less based on the American Academy of Ophthalmology criteria [The spherical equivalent refraction (SEq) was calculated from the refraction using the following formula: the full spherical power plus half of the cylindrical power. Initially, the mean values of the SEq of the right eyes and the left eyes were compared in the entire population of the current study. There was no significant difference in the median SEq between the right eyes and the left eyes (−0.13 vs −0.00 (D), p < 0.05) are different from each other by comparison between non-high myopia and high myopia groups in both sexes. Units are different among variables, and therefore, they are categorized by quartiles. A p value of less than 0.05 was considered statistically significant. Statistical analyses were performed with the SPSS version 23.0 for Windows .The prevalence of high myopia was calculated in total participants, in men and women, and in the groups classified by age. Chi-square test for the prevalence of high/non-high myopia in each sex was performed. When it demonstrated significant difference, comparison of variables between high myopia and non-high myopia groups in each sex was performed; continuous variables showing parametric distribution were analyzed with Student’s t-test, and variables showing nonparametric distribution were analyzed with Mann–Whitney U test. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age and for likely possible risk factors associated with high myopia. Multivariate logistic analyses were performed using variables showing significant difference in each sex as adjustment factors, since variables showing significance (p < 0.001). According to the age distribution, the prevalence of high myopia in the 40s, 50s, 60s, 70s, 80s, and 90s was 10.6%, 8.8%, 3.5%, 2.0%, 1.2%, and 0.0%, respectively (p = 0.52).Among a total of 5987 subjects, the numbers of men and women were 2427 and 3557, respectively. The prevalence of high myopia in the current study was 5.0%, 3.8% in men and 5.9% in women. High myopia was more prevalent among women than men (ectively . The medp < 0.001). The peak of the high myopia prevalence by age was from 40 to 49 years (6.2% among the men and 13.0% among the women). The mean height for the high myopia group was significantly higher than others . A similar difference was also found in the age and heights of men and women, respectively . Similar differences were found in the median IOPs of the men or women, respectively. A significant difference was also observed in the median corneal radius between the high myopia group and the others . However, no significant difference was found in the median corneal radii of the men and women, respectively. There was no significant difference in central corneal thickness and corneal endothelial cell number between the two groups.Associations between ocular features and high myopia were also evaluated . The medp for trend 0.049). The ORs adjusted with other factors for high myopia in the groups of IOP were ≤11.2 mmHg (OR 1), 11.3–13.2 mmHg , 13.3–15.2 mmHg , and ≥15.3 mmHg , respectively (p for trend <0.001).A multivariable logistic regression analysis was performed to identify the factors associated with high myopia . The ORsp for trend <0.001). The ORs adjusted with other factors in each IOP group were ≤11.6 mmHg (OR 1), 11.7–13.6 mmHg , 13.7–15.6 mmHg , and ≥15.7 mmHg , respectively (p for trend 0.023). In summary, as the age increases, the OR decreases and, as the IOP increases, the OR increases in both men and women.In women, the values were as follows: the ORs adjusted with other factors for high myopia in each age group were 40–54 years (OR 1), 55–62 years , 63–68 years , and no younger than 69 years  (This community-based study showed the prevalence of high myopia and associated factors including physical, ocular, and demographic factors among adult Japanese for the first time. The factors associated with myopia were widely investigated as we analyzed biochemistry tests, blood pressure, height, body weight, habit of smoking, alcohol intake, past medical history, and present diseases. In this current study, we found that high myopia is more prevalent in women and younger age and that it has higher IOP.High myopia affects approximately 1–4% of adults aged ≥40 years, and its prevalence was higher in some studies of East Asian adults and adolescents ,23,24,25Some previous studies reported the relationship of height ,27,28 anAs for the other laboratory factors, there was no significant difference. A few studies suggested that hyperglycemia and hyperlipidemia led to myopic shift, whereas other studies revealed that the refractive shift was more likely hyperopic with hypoglycemia ,33,34,35In terms of alcohol intake and smoking history, both factors did not show any associations with high myopia according to our results. Also, liver functions, represented by GOT, GPT, and GGTP, did not show any relationship to high myopia. Previous reports also found that there were no significant trends observed between smoking and refractive errors .The percentages of high myopia in men and women were 3.8% and 5.9%, respectively, indicating significant gender difference. It has been reported that female sex had a predisposition of high myopia . LikewisThe mean IOP linearly increased parallel to the myopic progression. It has been reported that IOP was associated with central corneal thickness, age, and blood pressure ,41. EvenAlthough this cross-sectional study is to investigate the risk factors for high myopia through a large-scale cross-sectional study, a few studies with relatively small number of subjects were undertaken. Mo et al.  concludeThere are some limitations in this study. First of all, the study design is not completely reasonable because the data used for the analysis are practically limited. Although the JPHC-NEXT study is large scale in terms of the participant number, it is basically a universal data collection based on regular checkups performed in a rural area. Therefore, this is not conducted specifically for ophthalmological analysis. The study would have been more informative if it contained questionnaires or interviews concerning the time for near-work and indoor/outdoor activities as well as academic levels and heredity of myopia. In addition, another limitation of this study is the lack of ophthalmological analysis including the measurement of axial length and lens corrections, which are crucial to determine the participants’ classification of non-/high myopia. This study should be completed with these detailed data to make the conclusions more reliable; however, it could be done only beyond the limitation of this cross-sectional study. Owing to the large-scale study, instead, we were able to effectively assess a large number of basically healthy participants altogether and to draw these critical results. The factors associated with high myopia were undetermined. This study did not suggest that height, BMI, blood glucose, hypocholesteremia, liver dysfunction, kidney dysfunction, smoking, and alcohol intake were associated with high myopia, whereas women, young age, and high IOP were found to be related to high myopia. Meanwhile, high IOP and young age were found to be risk factors for high myopia, which may indicate the path for future studies concerning myopia control.In conclusion, this epidemiological study performed in a Japanese rural area revealed significant results: being a women, being young, and having high IOP were factors associated with high myopia, while height, BMI, cholesterol level, glucose level, and other considered possible risk factors for high myopia in previous studies were not associated with prevalence of myopia.


The purpose of this study was to ascertain multimorbidity patterns using a non-hierarchical cluster analysis in adult primary patients with multimorbidity attended in primary care centers in Catalonia.Cross-sectional study using electronic health records from 523,656 patients, aged 45–64 years in 274 primary health care teams in 2010 in Catalonia, Spain. Data were provided by the Information System for the Development of Research in Primary Care (SIDIAP), a population database. Diagnoses were extracted using 241 blocks of diseases . Multimorbidity patterns were identified using two steps: 1) multiple correspondence analysis and 2) k-means clustering. Analysis was stratified by sex.The 408,994 patients who met multimorbidity criteria were included in the analysis . Six multimorbidity patterns were obtained for each sex; the three most prevalent included 68% of the women and 66% of the men, respectively. The top cluster included coincident diseases in both men and women: Metabolic disorders, Hypertensive diseases, Mental and behavioural disorders due to psychoactive substance use, Other dorsopathies, and Other soft tissue disorders.Non-hierarchical cluster analysis identified multimorbidity patterns consistent with clinical practice, identifying phenotypic subgroups of patients.The online version of this article (10.1186/s12875-018-0790-x) contains supplementary material, which is available to authorized users. In the first decade of the twenty-first century, tremendous effort was concentrated on surfacing data about multimorbidity patterns in order to increase the knowledge of how the diseases were clustered –3. In evNo consensus has been established about a standard model to determine multimorbidity patterns. Differences between studies have been observed, such as the unit of analysis selected (patients versus diseases), the statistical method for grouping diseases , diseases included , and number of diseases included in the models , 5.To identify the multimorbidity patterns, methods that identify and separate certain population groups from others and study non-random associations between diseases in those sub-groups are needed , 6. TherAmong cluster analysis methods, there are two main types of techniques: hierarchical (HCA) and non-hierarchical cluster analysis (NHCA) . The firAmong the NHCA methods, K-means is the most frequently used. In contrast to HCA, this approach does not involve the construction of groups via iterative division or clustering; instead, patients are assigned to clusters once the number of clusters is specified. The results are less susceptible to outliers in the data, to the influence of choosing a distance measure, or to the inclusion of inappropriate or irrelevant variables. Algorithms that do not require a distance matrix, such as k-means, can analyse extremely large data sets –11.The study of biological heterogeneity requires the identification of subgroups of populations with specific combinations of coexisting diseases. This “multimorbidity patient” approach identifies phenotypes of the subgroups, describes the patterns of diseases within each one, and facilitates the development of more targeted patient management .The purpose of this study was to obtain the multimorbidity patterns in adult patients with multimorbidity attended in primary care in Catalonia (Spain), stratified by sex, using a k-means cluster analysis.A cross-sectional study was conducted in Catalonia (Spain), a Mediterranean region with 7,434,632 inhabitants, 81% of which live in urban municipalities (2010 census). The Spanish National Health Service (NHS) provides universal coverage, financed mainly by tax revenue. The Catalan Health Institute (CHI) manages primary health care teams (PHCTs) that serve 5,501,784 patients (274 PHCT), or 74% of the population; the remaining PHCTs are managed by other providers.The CHI’s Information System for the Development of Primary Care Research (SIDIAP) contains the coded clinical information recorded in electronic health records (EHR) by its 274 PHCTs since 2006. A subset of SIDIAP records meeting the highest quality criteria for clinical data, the SIDIAP-Q, includes 1,833,125 patients attended by the 1365 general practitioners (GPs). SIDIAP Q represents 40% of the SIDIAP population whose data recording scores contain information on the majority of the population of Catalonia, and is highly representative of the whole region in terms of geography, age, sex, and diseases. This study was limited to SIDIAP-Q, as the sample was representative of the population : 5.8), 53.3% were women, and the mean number of diagnoses per patient was 5.7 (SD: 3.3). The analysis included 217,823 women and 191,171 men with 79 and 73 different diagnoses, respectively  met the multimorbidity criteria. Women had a higher multimorbidity prevalence than men  in women and 35.3% for Metabolic disorders in men.The clusters were sorted in descending order by number of individuals included. The first cluster included about 40% of the population (40.7% of women and 38.7% of men) and no O/E ratio higher than 2 was observed in these first clusters. In these first clusters, the highest exclusivity value was 46.1% for Metabolic disorders, Hypertensive diseases, Mental and behavioural disorders due to psychoactive substance use, Other dorsopathies and Other soft tissue disorders   Cluster 4 (women) and cluster 3 (men), composed mostly of diseases of the digestive and musculoskeletal system; 2) Cluster 2 (women) and Cluster 4 (men), connective tissue diseases; 3) Cluster 5 was composed of a cardiometabolic pattern  in both groups; and 4) Cluster 6, infectious and injurious diseases . It is the most common in the population with multimorbidity aged 45–65 years. This pattern seems to be consistent with other studies which obtained similar associations of diseases with other methods of analysis , 3.Other data of interest are the higher exclusivity values obtained in some clusters. For example, 77% of women who suffered diabetes mellitus have other associated diseases, such as forms of heart disease, obesity, and hypertension. These results are similar to the report from Hughes et al. that 71% of people with diabetes had multimorbidity . Other cThese results can be translated into clinical practice. When a disease is first diagnosed, we can suspect other associated diseases. Clinical practice guidelines could orient their recommendations toward these sub-groups . On the other hand, some results could be difficult to interpret in the context of current knowledge. Some patterns obtained included many diseases with no apparent connection between them.In general, it is difficult to compare our results with the findings of other studies because of variations in methods, data sources and structures, populations, and diseases studied. However, there are some similarities between the current study and others. The first pattern is similar to the cardio-metabolic pattern reported by Prados et al. in adults aged 45 to 64 years  with an exploratory factor analysis .The major strength of this study is the large, high-quality population database of primary care records that have been shown to be representative of a much larger population . The anaA number of limitations need to be taken into account as well. The use of MCA can produce low percentages of variation on principal axes and make it difficult to choose the number of dimensions to retain. We assumed a 5-dimension solution using the elbow rule in the scree plot to achieve the most accurate solution possible without including too many dimensions in the analysis . In someFew studies have focused on the MM patterns in patients rather than on diseases –27. ThisMultimorbidity can present a problem for health services delivery, affecting patients, health professionals, and managers who are attempting to improve service delivery . Our stuThis study illustrates the need to pay careful attention to the methods used to support policies and decision-making. The study results have implications for three fundamental areas of action: a) the need to change the orientation of clinical guidelines that focus on a single disease; b) the need to change health policy that is based on a disease rather than on the whole person; and c) the need to change current incentive policies that focus the health professional’s attention on a disease rather than on multimorbidity, which includes not only diseases but also drug interactions, polypharmacy and the process of patient-health professional interactions.Future studies on the current topic are therefore recommended, with a special focus on three major issues. First, the genetic typing of these multimorbidity patterns will identify genetic confluence in these patterns. Second, the delimitation of environment factors  associated with these patterns. Third, longitudinal studies should be done to establish the order of disease onset. Finally, the influence of polypharmacy, or the use of multiple drugs, could decrease treatment efficacy and cause unexpected adverse events or even the development of other diseases , 30.These findings suggest that multimorbidity patterns obtained using non-hierarchical cluster analysis identified clusters more consistent with clinical practice, identifying phenotypes of certain sub-groups of patients.Non-hierarchical cluster analysis identified multimorbidity patterns consistent with clinical practice, identifying phenotypic subgroups of patients.Additional file 1:Study Flow Chart, Catalonia, 2010. (DOCX 35 kb)Additional file 2:n = 217,823) and men  aged 45–64 years. (DOCX 1468 kb)Patients factor map for women  included in the Multimorbidity patterns in women and men aged 45–65 years, Catalonia, 2010. (DOCX 26 kb)Additional file 4:Multimorbidity patterns considering only blocks of diagnoses with Observed/Expected ratio ≥ 2, ordered by exclusivity in women and men aged 45–65 years, Catalonia, 2010. (DOCX 25 kb)


Objectives: To determine the association between home enteral nutrition (HEN) administration modality and its complications in patients. Methods: This is a prospective multicenter longitudinal study including 15 Spanish hospitals, from April 2015 to March 2017. A 4-month follow-up period was conducted for each patient by home visit. The study subjects were adult patients who began their nutrient intake by tube feeding, known as HEN, during the recruitment period. The variables studied included the type and modality of HEN administration and its related complications, such as vomiting, regurgitation, constipation, diarrhea, and abdominal distention. Mechanical complications and bronchoaspiration were also evaluated. Descriptive variables were used for fitting. Results: The study consisted of 306 patients; 4 were lost due to death. Specific HEN modalities protected against constipation (odds ratio (OR) = 0.4) and regurgitation (OR = 0.4). The use of a nasogastric tube (NGT) resulted in a lower risk of diarrhea compared to percutaneous endoscopic gastrostomy (PEG) (OR = 0.4) but resulted in a higher risk of tube obstruction (OR = 7.4). The use of intermittent gravity versus bolus feeding was a protection factor against vomiting (OR = 0.4), regurgitation (OR = 0.3), constipation (OR = 0.3), diarrhea (OR = 0.4) and abdominal distension (OR = 0.4). The increase in the number of doses was a risk factor for the incidence of regurgitation (OR = 1.3). Conclusions: Gastrointestinal complications were the most frequent problems, but an adequate choice of the formula, route, feeding modality, number of doses, administration time, and dose volume can reduce the risk of these complications. Keeping a patient hospitalized for the sole purpose of administering nutritional support has become an inappropriate decision from a bio-psycho-social perspective, and wasteful for health institutions and for society from an economic perspective. The introduction of home enteral nutrition (HEN) involves the concerns of correctly selecting candidates, applying a good training programme to the patient and the caregiver, ensuring the supply of formula and necessary materials, providing adequate follow-up and monitoring the quality of patient care .Interestingly, Parsons et al.  concludeIn Spain, HEN is included and regulated in the portfolio of services of the National Health System . This leHEN is a safe procedure  whose coKnowing the HEN-related complications is crucial to achieving the objectives of this therapy and to determining its safety level outside the hospital setting, which justifies this study. For the nutritional treatment to be carried out effectively and safely, it is essential that the patient and/or the main caregiver acquires a degree of responsibility in managing the administration of nutrition and, above all, can detect the first signs or symptoms of possible complications. Caregivers must provide the first point of care and demand proper healthcare services for the patient.The different types of complications and possible medical interventions associated with HEN are already known ,8,9,10. This is a prospective and multicenter longitudinal study.The study involved 15 Spanish hospitals from 7 different autonomous communities: Valencia, Madrid, Cantabria, Canarias, Andalucía, Aragón, and Baleares. Recruitment was carried out from April 2015 to March 2017. The data collection and follow-up period for the patients included in the study was 4 months and was conducted through home visits.Inclusion criteria: Adult patients (≥18 years) who were admitted to the participating home hospitalization units or were dependent on nutrition units, who began their nutrient intake by tube feeding, known as home enteral nutrition (HEN), during the recruitment period.During the four month follow-up a monthly visit was carried out by the head of each of the participating hospitals, moment in which the patient or their caregiver reported on the adverse effects incurred.All patients had to provide informed consent to be included in the study. In cases where the patient’s situation did not allow for this, consent was obtained from the primary caregiver.The protocol used in this work was approved by the Clinical Research Ethics Committee of the General University Hospital of Alicante , dated January 8, 2014 (registration number CE20PI2013/40).http://www.cafane.net/), which provided an ad hoc questionnaire developed for this study. The questionnaire complied with all data protection regulations; therefore, it did not record any patient personal data. The participating researchers were granted personalized access (username and password). The questionnaire variables are listed below.The data logging was performed through a platform available on the Internet ; HEN with fiber: yes or no; Route of administration: percutaneous endoscopic gastrostomy (PEG), nasogastric tube (NGT) and other ostomies (including jejunostomy); Feeding modality: bolus feeding, intermittent gravity, other modalities (including continuous gravity or pump feeding); Administration time of each intake in minutes; Number of intake periods per day; Dose volume (mL); Total daily volume (mL); Washing of the probe: yes or no; Position during intake (≥45° or <45°) and after intake (at least 1 h) .Digestive complications: vomiting, regurgitation, constipation, diarrhea and abdominal distention; Mechanical complications: tube obstruction; Other complications: aspiration pneumonia (bronchoaspiration).Gender: man or woman; Age: in years; Weight: in kilograms (kg) ; HeightFor the qualitative variables, the absolute and relative frequencies (percentages) were calculated. For the quantitative variables, the mean and its standard deviation, the median (Me), the interquartile range (IQR) and the standard deviation were calculated.The association between the qualitative variables was analyzeanalyzed by the chi-squared test, while Student’s t-test was used for the quantitative variables to verify the significance of the difference in means for the independent samples. To compare the means between more than 2 groups for a quantitative variable, analysis of variance (ANOVA) was performed using the Tukey method.The incidence rate (IR) was calculated to find the number of complications involved in the study period (4 months).A logistic regression model was applied using each of the different complications as a dependent variable . The independent variables were route of administration ; feeding modality ; fiber ; administration time; number of intake periods; volume of intake; and total volume. All models included the following variables: gender, age, BMI, place of residence, caregiver, and diagnostic group. The probability was measured by the odds ratio (OR).p ≤ 0.05.The level of significance used in all hypotheses was Quality control of the data was carried out through double tables, and the potential errors were corrected by consulting the originals. The statistical software IBM SPSS Statistics for Windows, version 23.0  was used to analyze the data.The data from 306 patients were included; 4 patients were lost due to death. The descriptive data of the population is presented in The base pathology did not influence the relationship of the complications associated with the HEN modality.p = 0.054), regurgitation (p = 0.415), constipation (p = 0.401), diarrhea (p = 0.113) and probe obstruction (0.204). However, there were significant differences in abdominal distension between the normal weight and obese groups (p = 0.040) and for aspiration pneumonia among the overweight and obese groups (p = 0.031).No intergroup associations were found between the BMI and the mean of the majority of the complications: vomiting  patients being exclusively tube-fed, while 52 (17.0%) took in some food orally. The HEN-related descriptive results and the HEN administration modalities are presented in p-value 0.001) and constipation . The number of episodes (n) and the IRs of HEN-related complications are shown in The most frequent complications recorded in the 4 months of follow-up were digestive, predominantly abdominal distension, with an IR of 2.4, while regurgitation had an IR of 2.2. Aspiration pneumonia presented the lowest IR of 0.1. Some significant differences were found, with higher values in men for abdominal distension . Likewise, in the post-fitting results, NGT showed a lower risk of vomiting (OR = 0.4), regurgitation (OR = 0.4) and abdominal distension (OR = 0.5). However, a greater risk of probe obstruction was observed (OR = 7.4).Regarding the feeding modality, the use of intermittent gravity was a protective factor against vomiting , regurgitation , constipation , diarrhea  and abdominal distension  when compared to bolus feeding. However, in the case of abdominal distension, other feeding modalities were also more favourable than bolus feeding .The use of HEN with fiber presented a lower risk of constipation .The increase in the number of doses represented a risk for the appearance of regurgitation (OR = 1.3 in pre-fitting and post-fitting) and for the obstruction of the catheter . Likewise, the intake position was associated with probe obstruction (OR = 0.1 in pre-fitting and post-fitting).The post-fitting results showed association with an increased risk of diarrhea when the administration time (OR = 4.5) and the dose volume (OR = 1.4) increased.The results of the complications related to the type and modality of HEN administration are shown in This study enabled us to determine the complications associated with enteral nutrition administration in a considerable number of patients over a period of several months, which is a strength of this study.In terms of their pathology, the studied patients presented similar characteristics as those of previous studies—they were older adults with neurological or oncological disease, with a dependence on and a need for a caregiver ,14.There was no clear significant association between the BMI and the complications resulting from HEN, although a greater number of complication episodes in relation to obesity was observed, a situation already highlighted by Wiggins et al. .Given the median age of the studied population, it is normal in the Spanish socio-cultural context that the place of residence was primarily the family home, a nucleus with sufficient roots and a caretaker tradition. Likewise, the fact that the main caregiver is typically a woman has been widely noted in the scientific literature ,17 and mThe greater use of PEG compared to NGT, common in the participating health centers, contrasts with previous research that observed a greater tendency to use NGT in older adults ,14,19. IBolus feeding continued to be used with a greater frequency, though it could be inferred that the infusion speed is not easy to regulate, and there could be alterations in the administration that would lead to some complications. On the other hand, the formula type, the volume administered and the number of doses were all within normal ranges, and it was not surprising that a formula with fiber was administered to patients with long-term HEN, a recommended practice in the absence of contraindicateons .The IR of HEN-related complications demonstrated the intimate relationship with the route and administration modality. The correct management of HEN reduces these complications and minimizes laryngopharyngeal reflux .The differences in the observed complications between men and women show an important gender background. Women typically take better responsibility for their own healthcare, especially regarding communication between the patient and the doctor, the understanding of the disease, and their attitudes at the end of life ,24.It is important to know that specific formulas are associated with fewer episodes of regurgitation and constipation. However, in many patients, these complications are already present before the initiation of HEN therapy. Therefore, the addition of prokinetic drugs would be useful to prevent regurgitation. In addition, constipation is more frequent than diarrhea in patients fed exclusively by HEN .The current evidence does not allow us to determine the causes of the increased risk of aspiration pneumonia in nonspecific HEN; the evidence could possibly indicate a recommendation for using a post-pyloric probe, but it is not certain .Regarding the administration modality, PEG has become the method of choice for enteral feeding in the medium and long term. Most of the complications related to PEG are minor; however, rare major complications can be more serious. The increased risk of diarrhea, vomiting and regurgitation that was observed in this study in relation to PEG was mainly associated with abdominal distension and could show a stronger relation with the administration modality and the volume of the shot. Some complications occur shortly after tube placement; others develop later when the gastrostomy tract has matured. Senior patients with comorbidities and infections appear to be at greater risk of developing complications . Gomes eBolus feeding has been associated with virtually all gastrointestinal complications, and this feeding modality may explain the increased infusion rate, with an abrupt change in the gastrointestinal walls or rapid temperature change. Contrary to these findings, a previous study by Kadamani et al.  did not Likewise, the present study has shown that an enteral diet containing fiber is a protective factor against intestinal motility disorders ,30.It has also become clear that an increase in the number of doses and the volume of the intake cause greater gastrointestinal problems and that the patient’s position upon intake is related to the possibility of probe obstruction.It can be concluded that there was a higher incidence of gastrointestinal complications. However, an adequate choice of the formula type, the route and feeding modality, the number of doses, administration time and volume of intake can greatly reduce the IR. Therefore, to reduce these complications, the existence of multidisciplinary teams focused on the follow-up of patients is essential to optimize the results. However, all health care providers should have knowledge regarding the most frequent HEN-related complications and the skills to manage these problems.