Nowadays, malnutrition takes a variety of forms, but both obesity and under nutrition associate major 1 micronutrient deficiencies.  Malnutrition is generally considered of utmost importance at extreme ages – in children and in the elderly. However, a growing body of knowledge shows that the prevalence of malnutrition or undernutrition in the hospitalized general adult population can range from 7% to 50%, and is estimated to be around 31.4% in the USA and European countries.1 Malnutrition has been shown to be associated with increased length of hospital admission,1 and an increased rate of  eadmission in the first 30 days following discharge.2 Furthermore, nutritional interventions, when indicated, can show some improvement in terms of postdischarge outcomes.3 For this reason, the European Society for Clinical Nutrition and Metabolism has recommended the implementation of nutritional screening programs in hospitals, and further nutritional assessment of patients identified to be at risk of malnutrition.4 In patients with infectious diseases, nutrition is a particularly important issue, as the metabolic response to infection generally associates protein hypercatabolism, malabsorption, loss of electrolytes, accelerated gluconeogenesis,5,6 and increased nutrient demand.7 Therefore, infectious diseases leading to hospital admission can be qualified into the “acute disease or injury-related malnutrition” International Consensus category,8 and may require specific nutritional management to ensure compensation of the nutritional impairment associated with inflammation.4 Our study’s objective was to screen for the risk of malnutrition in the first 24 hours following hospital admission in a population of adult patients admitted to a national reference center for infectious diseases in Bucharest, Romania, and to identify the main factors and clinical parameters associated with the malnutrition risk.

We have performed a cross-sectional study in the National Institute for Infectious Diseases“Prof. Dr. Matei Balș” Bucharest, Romania, which consisted of an application of the Malnutrition Universal Screening Tool (MUST) in the first 24 hours of hospitalization to each adult patient admitted to the hospital, and the collection of medical information at discharge, through an internally validated questionnaire filled out by the attending physician, collecting data on: demographics, nutrition and lifestyle, complete medical history, and data on treatment and evolution during the current hospital admission.  The study time span was 16 June 2014 – 16 July 2014, and the study included all consecutive patients who met the inclusion criteria (age over 18 years old, agreement to sign the informed consent form) and none of the exclusion criteria: decompensated liver or heart disease, early hospital discharge (defined as below 24 hours, or any time contrary to medical recommendation). The study protocol, informed consent form and questionnaire were approved by the Institute’s Bioethics Committee (approval no. 2771 dated 06 June 2014). The statistical analysis included the Chi square test and z test for proportions for categorical variables, as well as the MannWhitney U test with effect size calculation and Spearman correlation analysis for continuous non-parametric variables, performed in SPSS Statistics for Windows (v22.0, IBM Corp, USA), with a p value <0.05 considered to be statistically significant.

We have screened 211 patients with a median (interquartile range – IQR) age of 52 (33-68) years, and a male-to-female ratio of 1:1.7. Most patients (74.4%) came from urban areas and had graduated from high school (49.3%), followed by middle school (19.9%) and university (17.1%).

The main reason for admission was reported as: enterocolitis (25.6% of cases), hepatitis (15.6%), pneumonia (13.7%), complicated Gram-negative urinary tract infection (8.1%), skin and soft tissue infection (7.1%), acute tonsillitis (6.2%), complications of HIV infection (4.3%), meningitis (2.8%), viral upper respiratory tract infection (1.9%), and other infectious diseases (14.7%). In the study group, 15.6% of the patients presented concomitant hepatitis C, 6.2% hepatitis B, 8.1% HIV infection, and 10.9% diabetes mellitus.

The median (IQR) duration of hospitalization was 6 (4-10) days, with a range of 2-28 days, and the median (IQR) number of drug classes required during hospitalization was 2 (0, 3). Most patients (92.9%) had favorable evolution, with only 4.3% requiring transfer to a different hospital, 1.4% (3 cases) requiring transfer to intensive care, and one death recorded (0.5%). The number of previous hospitalizations during the past 12 months ranged from 0 (24.2%) to 5 (1.9%), most patients (42.7%) presenting one recent previous hospital admission.

Overall, 22.7% of the patients included in the study presented a risk of malnutrition, with MUST scores of 1 (5.7%), 2 (7.1%), 3 (5.2%), 4 (2.8%) or 5 (1.9%). We identified a positive correlation between MUST scores and patient age (p=0.030, r_s=0.2, N=211), number of previous hospitalizations during the past 12 months (p=0.002, r_s=0.2, N=207), number of drug classes required during the current admission (p=0.034, r_s=0.2, N=211), and duration of the current hospital admission (p=0.029, r_s=0.2, N=208), which was increased by 1.4 days in patients at high malnutrition risk (p=0.041, t(206)=-1.8, d=0.4). Importantly, we found a statistically significant association between a positive (i.e., ≥1) malnutrition risk score and the outcome of the current hospitalization, with all three patients who needed transfer to intensive care (MUST scores of 4, 4, and 5) and one patient who subsequently died (MUST score of 5), presenting positive scores, compared to only 21.9% in patients with favorable evolution (p=0.004, χ(3)=13.1, Cramer’s V=0.3).

We identified a risk of malnutrition more frequently in patients from urban (28%) rather than rural (7.4%) areas (OR: 0.2, IC95%: 0.07-0.60, p=0.001, Phi=-0.2, χ(1)=9.7), and in those requiring anticoagulant treatment (OR: 2.7, IC95%: 1.2-6.3, p=0.026, Phi=0.2, χ(1)=5.6). Patients who had been admitted for viral upper respiratory tract infections had the highest prevalence of nutritional risk (50%), followed by HIV infection and meningitis (33.3% each) – Figure 1.

We did not identify a significantly different risk of malnutrition between genders (p=0.397), different levels of education (p=0.479), dietary intolerance (p=0.181), alcohol consumption (p=0.721), drug use (p=0.681), smoking (p=0.688), bacterial or viral infections (p=0.348), concomitant HIV infection (p=0.228), concomitant viral hepatitis (p=0.109).

In a sub-analysis of patients with positive MUST scores we identified the following characteristics significantly associated with a higher malnutrition risk: male gender (p=0.031, χ(4)=10.6, Cramer’s V = 0.5) and history of urinary tract disease (0=0.044, χ(1)=9.8, Cramer’s V=0.5).

Patients who require hospital admission for infectious diseases make up a particular type of patient population, at risk for malnutrition either due to the catabolic processes, generalized inflammation and higher nutrient demand associated with infection, or due to an underlying comorbidity predisposing them to acquire an infectious disease (for example in our study a history of urinary tract disease was associated with a high malnutrition risk). Furthermore, malnutrition may, in turn, associate a certain degree of immune  impairment, and a potentially higher susceptibility to infections, or a more severe evolution of infection.7,9 In this study, we have identified an overall malnutrition risk of 22.7% in patients hospitalized for infectious diseases (5.7% medium risk and 17% high risk), and we have also determined the main types of infections which are associated with a risk of malnutrition in Romania and, interestingly, viral upper respiratory tract infections ranked first in our study (with 50% risk of malnutrition), followed by HIV infection and bacterial infections with different localizations. This finding is in line with a study performed in Singapore, where respiratory medicine ranked third following oncology and endocrinology, in terms of prevalence of malnutrition (47%).10 Importantly, patients with vURTIs generally tend to be managed as outpatients, in our Institute and elsewhere, and only those with severe disease, influenza, or complicating underlying comorbidities are admitted to the hospital to be managed as inpatients.11 This is in line with our overall results pointing to an association between higher MUST scores and
longer duration of hospitalization, higher medication requirement, and, implicitly, the severity of the infectious disease. Therefore, our result of 50% is probably an overestimation of the rate of malnutrition in patients with vURTIs and a targeted study is necessary to determine the exact prevalence of malnutrition in this category of patients, by screening three different types of patients with vURTIs:  inpatients, outpatients, and the general population, who might not even present to the doctor for a mildly symptomatic vURTI. The rate of malnutrition of 33.3% identified in our study in patients admitted for complications of HIV infections is 2.3-fold lower compared to that reported in China (77.2%) in patients living with HIV.12 This might be a reflection of the highly proficient national HIV programme, which offers nationwide screening and reimbursed treatment to all patients with HIV infection.13,14 A very interesting recent study has highlighted the important differences in terms of both prevalence of malnutrition and national differences in policies for screening and nutritional support. Compared to this international study, our data calculated for one National Institute for Infectious Diseases places Romania on the lower end of the malnutrition prevalence scale, with 22.7%, higher than  Lithuania with 14.2% and Poland with 21.9%, but twice as low compared to Turkey at 39.5% or Estonia at 57.4%.15 Canada also reports a higher overall rate of malnutrition risk, as high as 45%, with 14% of patients at medium risk and 31% at high risk according to MUST results.16 Our results are comparable with those from Greece, which reported 22.9% malnutrition on MUST screening.17 One of the few other studies addressing patients admitted to the hospital for infectious diseases, performed in 2015, has shown that higher malnutrition scores associated a 2.7-fold higher risk of SIRS, a 2.9-fold higher risk of sepsis (defined according to the older 2008 SIRS-based consensus criteria),18 and a 2.8-fold higher risk of death during hospitalization.19 However, these numbers might be slightly higher than those expected for Romania, as this study was performed in Turkey,19 a country which has been previously reported to have twice the prevalence of malnutrition compared to the rate identified in our study,15 and the same is true for Colombia, reporting a rate of malnutrition of 61% and a 3.2 days increase in the length of stay in malnourished patients.20 The rate, degree and duration of malnutrition are also extremely important, but given the cross-sectional nature of our study, we are unable to perform an in-depth analysis, as we only applied MUST screening at one time point, close to patient admission. Patients who tested positive on malnutrition screening in our study were more frequently residents from urban areas (p=0.001), or had an indication for anticoagulant treatment (p=0.026). The MUST score was directly dependent on patient age (p=0.030), number of previous hospitalizations during the past 12 months (p=0.002), number of drug classes required for treatment (p=0.034), and the duration of the current hospital admission (p=0.029), a high risk of malnutrition associating 1.4 days increase in the meanlength of hospital stay (p=0.041) in our patient group. This data is in accordance with a study performed in Singapore, where the average increase in hospitalization duration in patients with malnutrition was 2.3 days, and the overall prevalence of malnutrition was 27%.10 In our study, a positive malnutrition risk score was associated with the outcome of the current hospitalization, indicating that malnutrition screening may indeed play a prognostic role in patients with infectious diseases in Romania (p=0.004), as previously reported in field literature for other countries, where strong correlations between malnutrition and unfavorable outcomes such as sepsis or death have been described.19 Given the profound interrelation between malnutrition and infectious diseases, screening for malnutrition remains an important predictor of clinical prognosis, and patients identified to be at risk should undergo a complete nutritional assessment, and should receive a personalized nutritional intervention. In our study, MUST appeared to be a useful, inexpensive tool, which can quickly orient the clinician if further malnutrition assessment is warranted, such as quantifying serum prealbumin, for the short term onset of the restricted food intake, or albumin for longer duration of malnutrition and malabsorption. In patients screening positive on MUST evaluation, a malabsorption assessment may also give supplemental information on actions to be taken. One of the strengths of this study resides in the fact that MUST is a validated instrument, and its use in different geographical and clinical settings can ensure a high degree of comparability of results. This study also has a set of limitations. First, the cross-sectional nature of the study did not allow the assessment of associations between the presence of malnutrition risk and long-term outcomes such as death following hospital discharge or the rate of hospital readmissions. Second, the study was performed during a short time frame (one month), in a relatively small sample (211 patients) from a single institution from Romania. Third, the prevalence of malnutrition in different studies has been studied through various instruments and tools, and therefore the exact numbers cannot be  directly compared. And fourth, the lack of similar studies in infectious diseases does not allow an interpretation of our results in an European context, but the data is informative nonetheless. This study has focused on identification of the clinical evolution of patients with recent malnutrition. As it has been able to provide prognostic orientation, a more detailed analysis of its significance in specific medical conditions correlated with clinical or laboratory results is needed, for complementing the current picture.  

In conclusion, we have identified an overall malnutrition risk of 22.7% in Romanian patients hospitalized for infectious diseases, and we have ascertained the main categories of patients and types of infections associated with a higher risk of malnutrition, findings which can serve to orient and substantiate future national screening policies.
Authors’ contributions statement: All authors had equal contributions. All authors have read and approved the final version of the manuscript.

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