design and data source
A retrospective analysis was performed using data extracted from a claim database containing 451 hospitals managed by Medical Data Vision Co., Ltd. (MDV; Tokyo, Japan). This database uses a combined diagnostic procedure/per diem payment system (DPC/PDPS), in which clinic reimbursement is calculated on a flat per diem basis based on diagnostic group. The protocol was approved by the Ethics Committee of Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences (No.2108-041) and Kurume University Graduate School of Medicine (No.21139), and was registered with the university hospital. Information Network Clinical Trial Registry (UMIN000044962). All personal information used in this study was anonymized, so informed consent was not required.
The database includes dates of admission and discharge, age at admission, gender, height, weight, body mass index (BMI), number of hospital beds admitted, year and type of admission, underlying disease (International disease and related health problem statistics). classification, 10th revision [ICD-10]), comorbidities (used to determine the Charlson Comorbidity Index) [CCI]) [9]activities of daily living (ADL) based on the Barthel index (BI) [10]Awareness level based on the Japan Coma Scale (JCS) [11]Malnutrition is defined as inadequate oral intake for at least 10 days and low BMI according to the Global Leadership Initiative on Malnutrition (GLIM) criteria [12], in-hospital treatment (using a Japan-specific medical billing code), and discharge outcome status, and other information not used in our study. Prescribed total daily doses of parenteral energy, amino acids, and ILE were calculated using the names and compositions of parenteral nutrition infusion products and the prescribed doses of these products displayed in the database. When recording these doses, day 1 is considered the start of fasting, day 2 is considered the second day after the start of fasting, and so on.
number of patients
This study included inpatients aged 18 years or older who were fasting for at least 10 consecutive days (not receiving oral or enteral nutrition) and managed with parenteral nutrition between January 2011 and September 2020. Adult patients were included. Patients who were admitted to surgery or intensive care units between the date of admission and the start of fasting were suspected to be terminally ill (prescribed mean energy <10 kcal/kg or mean amino acid <0.5 g/kg). kg). days 4–10), or was considered an overdose (which is based on stipulating her average energy content of 30 kcal/kg or more on days 4–10). The reason for using days 4 through 10 is that parenteral nutrition administration typically involves gradually increasing the dose over the first 3-4 days before reaching the full target dose. [7, 8].
clinical outcome
The primary endpoint was in-hospital mortality. Secondary endpoints included intravenous catheter infection during hospitalization, worsening of her ADL at discharge, length of stay (LOS), readmissions, and total medical costs. His ADL, LOS, and readmission at discharge were recorded only for patients who survived and were discharged, whereas other data were recorded for all patients. Medical costs were calculated based on Japanese Yen and converted to US Dollars (US$) using the 2020 annual exchange rate reported by the Organization for Economic Co-operation and Development (OECD) (1 USD = 107 JPY). [13]Patients were considered to have worse ADL if the total BI score was lower at discharge than at admission. Readmission was defined as readmission to the same hospital within 30 days after discharge.
variable
Variables extracted from the database were categorized as follows: age at admission (18–59, 60–69, 70–79, 80–89, or >90 years), BMI (<16.0, 16.0– 18.5, 18.5–22.5, 22.5–25.0 or ≥ 25.0), number of beds in hospital (< 200, 200–500, or ≥ 500), year of admission (2011–2012, 2013–2014, 2015–2016, 2017–2018, or 2019–2020), type of admission (elective or emergency), underlying disease (by ICD-10 code), comorbidity (CCI 0, 1, 2, or ≥3), ADL (BI 0, 5-20, 25–40), 45–60, 65–95, or 100), level of consciousness (JCS 0 [alert]1–3 [awake]10–30 [arousable]or 100-300 [coma]), and nutritional status (BMI if <70 years < 18.5、または> malnutrition defined as BMI < 20 for age 70 years). Information about medical procedures (e.g., albumin infusions, blood transfusions, ventilator use, dialysis, nutritional support teams, and rehabilitation) ordered between the date of admission and her 10th day was extracted from each patient's database. it was done. Missing values for type of admission, BI, and JCS were placed in the 'unknown' category.
Parenteral Nutrition Prescription Amount
The prescribed mean daily doses of energy, amino acids, and ILE from 4 days to 10 days after the start of fasting were calculated for each patient based on the composition of the parenteral nutrition product and the amount prescribed for that solution.Dosage often takes up to 4 days to reach 100% of target [14]The prescribed daily allowances for energy and amino acids were calculated as kilocalories (kcal) and grams (g), respectively, and reported per kilogram (kg) of body weight, and the prescribed daily allowance for ILE was calculated as It was reported both in grams and as a percentage of calories. (%) of total non-protein energy administered on that day.
statistical analysis
Data management and statistical analysis were performed by an independent third party (A2 Healthcare Co., Ltd., Tokyo, Japan) to eliminate arbitrariness and ensure transparency. Categorical variables were summarized as numbers and percentages, continuous variables were summarized as means and standard deviations (SD). Missing values are not included. First, he divided the eligible patients into two groups. He was prescribed ILE on days 4-10 in the ILE group and the non-ILE group in which he was not prescribed ILE on days 4-10. Then propensity score matching. (PSM) was used to adjust for confounders [15]Propensity scores were estimated by multivariate logistic regression analysis with ILE group as the objective variable and patient characteristics as explanatory variables. PSM was performed using 1:1 nearest neighbor and caliper width. The caliper value was 0.2 and matching was performed within the caliper value. To check the balance of covariates between groups, we calculated standardized differences before and after PSM. A standardized difference of less than 10% was considered to represent a balanced covariate. [16].
To compare the two groups for each outcome, both before and after PSM, students t– test was used for continuous variables and chi-square test was used for categorical variables. Multivariate logistic or multiple regression analyzes were performed as appropriate, even after PSM, to adjust for differences in prescribed mean daily parenteral energy doses between the two groups, and were analyzed on days 4 through 10. was added to the prescribed average daily energy dose. Explanatory variable. For these analyses, odds ratios (OR) or regression coefficients were calculated both before and after adjusting for energy, with 95% confidence intervals (CI) as appropriate.
For in-hospital mortality, the Kaplan-Meier method was used to generate survival curves for the two groups and a log-rank test was performed. In addition, using the Cox proportional hazards model, he calculated the hazard ratio (HR) for in-hospital mortality between the ILE and non-ILE groups with a 95% CI. For these calculations, patients discharged alive were censored on the day of discharge, and inpatients surviving >180 days were censored on his 180th day. All statistical analyzes were performed in SAS version 9.4 (SAS Institute Inc., Cary, NC, USA) with a two-sided significance level of 5%.
Sensitivity analysis
Prior to modeling, patient-specific variance inflation coefficients (VIFs) and prescribed daily mean nonlinearity were compared to ensure no multicollinearity between variables based on multiple regression analysis or multivariate logistic regression analysis. Oral nutrition doses were calculated. [17].
To confirm the robustness of the PSM, we adjusted for confounders by multivariate logistic regression analysis or multiple regression analysis and performed an adjustment analysis consisting of two groups of explanatory variables (model 1, model 2). In model 1, the explanatory variables were the two group and patient characteristics. In model 2, the explanatory variables were those included in model 1 and the average daily parenteral energy prescribed from day 4 to day 10. Either ORs or regression coefficients were calculated for each model, along with 95% CIs.
