External validation and updating of the infusion rate individualization of soybean oil-based intravenous lipid emulsion: A descriptive cohort study.

BACKGROUND: Safe and efficient provision of intravenous lipid emulsion (ILE) requires a strategy to individualize infusion rates. Estimating the maximum acceptable infusion rate (MaxInfRate) of soybean oil-based ILE (SO-ILE) in individuals by using a triglyceride (TG) kinetic model was reported to be feasible. In this study, we aimed to externally validate and, if needed, update the MaxInfRate estimation. METHODS: The maximum TG concentration (TGmax) in patients receiving SO-ILE at MaxInfRate was evaluated to determine if it met the definition of being <400 mg/dl for 90th percentile of patients. The TG kinetic model was evaluated through prediction performance checks and was subsequently updated using the data set of both the previous model development and present validation studies. RESULTS: Out of 83 patients, 74 had TGmax <400 mg/dl, corresponding to a probability of 89.2% (95% CI, 81.9%-95.2%), and the 90th percentile of TGmax was 400 mg/dl (95% CI, 328-490 mg/dl), closely aligned with the theoretical values. However, the individual TGmax values were biased by the infusion rate because the covariate effects were overestimated in the TG kinetic model, requiring a minor revision. The updated MaxInfRate with the combined data set showed unbiased and more accurate predictions. CONCLUSION: The MaxInfRate was validated in external inpatients and updated with all available data. MaxInfRate estimation for individuals could be an option for the safe and efficient provision of SO-ILE.

Individualization of the infusion rate of a soybean oil-based intravenous lipid emulsion for inpatients, based on baseline triglyceride concentrations: A population pharmacokinetic approach.

BACKGROUND: A rapid infusion rate for intravenous lipid emulsion (ILE) can cause adverse effects; therefore, safe and efficient infusion rates are desired. This study aimed to develop a triglyceride (TG) kinetic model after soybean oil-based ILE (SO-ILE) administration and individualize the infusion rate via a population pharmacokinetic approach. METHODS: Eighty-three inpatients were enrolled in this prospective observational study. A TG kinetic model was applied to the observations based on population pharmacokinetics using a nonlinear mixed-effect model. The patients' characteristics and laboratory parameters were evaluated to identify predictors of TG kinetics, and the maximum acceptable infusion rate was defined as that for which the maximum TG concentration did not exceed 400 mg/dl in 90% of patients. RESULTS: No adverse events associated with SO-ILE administration were observed. The developed TG kinetic model explained the observed TG concentrations and identified the baseline TG concentration and body weight as predictors of TG kinetics. The estimated maximum acceptable infusion rates greatly varied among individuals, ranging from <0.01 to 0.3 g/kg/h. CONCLUSION: The present study suggested the necessity and demonstrated the feasibility of individualizing the infusion rates of SO-ILE, using a population pharmacokinetic approach.

Clinical Effects of a Pectin-Containing Oligomeric Formula in Tube Feeding Patients: A Multicenter Randomized Clinical Trial.

BACKGROUND: A pectin-containing oligomeric formula (POF) is a unique type of enteral formula that transforms from a liquid to a gel after reacting with gastric acid. Reports on its clinical effects have been limited. The present study was conducted to examine and verify the clinical effects of POF. METHODS: The study subjects were 201 stable patients receiving intragastric tube feeding. They were randomized into 2 groups to receive either POF or a standard polymeric formula (SPF) as a control. The duration of observation was 1 week. Analyses were conducted for the incidence of predefined composite events, including diarrhea, defecation treatments, and other enteral nutrition (EN) management-related events. RESULTS: Composite events occurred in 15 of 98 patients in the POF group and 30 of 100 patients in the SPF group, with a significantly lower incidence in the POF group compared with the SPF group (P = 0.011). In particular, diarrhea occurred in 2 patients in the POF group and 13 patients in the SPF group, with a significantly lower incidence in the POF group compared with the SPF group (P = 0.003). CONCLUSIONS: The results of this study suggest that POF is less likely to cause EN-related events, especially diarrhea, than SPF is.

Safety of unsedated PEG placement using transoral ultrathin endoscopy in patients with amyotrophic lateral sclerosis.

BACKGROUND AND AIMS: In patients with amyotrophic lateral sclerosis (ALS), percutaneous endoscopic gastrostomy (PEG) placement under sedation often causes apnea or hypoventilation. The aim of the present study was to assess whether unsedated PEG placement in ALS patients using ultrathin endoscopy (UTE) via the transoral route can improve safety. METHODS: Between 2003 and 2013, PEG placement was identified and reviewed in 45 patients with ALS. PEG was performed in 14 patients using transoral UTE without sedation (UTE group), 17 patients using conventional normal-diameter esophagogastroduodenoscopy (C-EGD) without sedation (unsedated C-EGD group) and 14 patients using C-EGD with sedation (sedated C-EGD group). We compared the clinical features, cardiopulmonary data before and during PEG placement, and complications related to PEG placement among the three groups. RESULTS: There were no significant differences in age, male/female ratio, forced vital capacity, blood pressure, oxygen saturation before and during PEG, or major complications among the three groups. No minor complications were observed in the UTE group, whereas apnea and/or hypoventilation were observed in the sedated C-EGD group and aspiration pneumonia was observed in the unsedated C-EGD group. CONCLUSIONS: Unsedated PEG placement using transoral UTE in ALS patients is a safe method.

The Effects of Percutaneous Endoscopic Gastrostomy on Quality of Life in Patients With Dementia.

BACKGROUND: To examine the effects of percutaneous endoscopic gastrostomy (PEG) on quality of life (QOL) in patients with dementia. METHODS: We retrospectively included 53 Japanese community and tertiary hospitals to investigate the relationship between the newly developed PEG and consecutive dementia patients with swallowing difficulty between Jan 1st 2006 and Dec 31st 2008. We set improvements in 1) the level of independent living, 2) pneumonia, 3) peroral intake as outcome measures of QOL and explored the factors associated with these improvements. RESULTS: Till October 31st 2010, 1,353 patients with Alzheimer's dementia (33.1%), vascular dementia (61.7%), dementia with Lewy body disease (2.0%), Pick disease (0.6%) and others were followed-up for a median of 847 days (mean 805 ± 542 days). A total of 509 deaths were observed (mortality 59%) in full-followed patients. After multivariate adjustments, improvement in the level of independent living was observed in milder dementia, or those who can live independently with someone, compared with advanced dementia, characterized by those who need care by someone: Odds Ratio (OR), 3.90, 95% confidence interval (95%CI), 1.59 - 9.39, P = 0.003. Similarly, improvement of peroral intake was noticed in milder dementia: OR, 2.69, 95%CI, 1.17 - 6.17, P = 0.02. Such significant associations were not observed in improvement of pneumonia. CONCLUSIONS: These results suggest that improvement of QOL after PEG insertion may be expected more in milder dementia than in advanced dementia.

Survival of geriatric patients after percutaneous endoscopic gastrostomy in Japan.

AIM: To examine the long term survival of geriatric patients treated with percutaneous endoscopic gastrostomy (PEG) in Japan. METHODS: We retrospectively included 46 Japanese community and tertiary hospitals to investigate 931 consecutive geriatric patients (≥ 65 years old) with swallowing difficulty and newly performed PEG between Jan 1st 2005 and Dec 31st 2008. We set death as an outcome and explored the associations among patient's characteristics at PEG using log-rank tests and Cox proportional hazard models. RESULTS: Nine hundred and thirty one patients were followed up for a median of 468 d. A total of 502 deaths were observed (mortality 53%). However, 99%, 95%, 88%, 75% and 66% of 931 patients survived more than 7, 30, 60 d, a half year and one year, respectively. In addition, 50% and 25% of the patients survived 753 and 1647 d, respectively. Eight deaths were considered as PEG-related, and were associated with lower serum albumin levels (P = 0.002). On the other hand, among 28 surviving patients (6.5%), PEG was removed. In a multivariate hazard model, older age [hazard ratio (HR), 1.02; 95% confidence interval (CI), 1.00-1.03; P = 0.009], higher C-reactive protein (HR, 1.04; 95% CI: 1.01-1.07; P = 0.005), and higher blood urea nitrogen (HR, 1.01; 95% CI: 1.00-1.02; P = 0.003) were significant poor prognostic factors, whereas higher albumin (HR, 0.67; 95% CI: 0.52-0.85; P = 0.001), female gender (HR, 0.60; 95% CI: 0.48-0.75; P < 0.001) and no previous history of ischemic heart disease (HR, 0.69; 95% CI: 0.54-0.88, P = 0.003) were markedly better prognostic factors. CONCLUSION: These results suggest that more than half of geriatric patients with PEG may survive longer than 2 years. The analysis elucidated prognostic factors.

The sky blue method as a screening test to detect misplacement of percutaneous endoscopic gastrostomy tube at exchange.

BACKGROUND: During tube exchange for percutaneous endoscopic gastrostomy (PEG), a misplaced tube can cause peritonitis and death. Thus, endoscopic or radiologic observation is required at tube exchange to make sure the tube is placed correctly. However, these procedures cost extensive time and money to perform in all patients at the time of tube exchange. Therefore, we developed the "sky blue method" as a screening test to detect misplacement of the PEG tube during tube exchange. METHODS: First, sky blue solution consisting of indigocarmine diluted with saline was injected into the gastric space via the old PEG tube just before the tube exchange. Next, the tube was exchanged using a standard method. Then, we checked whether the sky blue solution could be collected through the new tube or not. Finally, we confirmed correct placement of the tube by endoscopic or radiologic observation for all patients. RESULTS: A total of 961 patients were enrolled. Each tube exchange took 1 to 3 minutes, and there were no adverse effects. Four patients experienced a misplaced tube, all of which were detectable with the sky blue method. Diagnostic parameters of the sky blue method were as follows: sensitivity, 94% (95%CI: 92-95%); specificity, 100% (95%CI: 40-100%); positive predictive value, 100% (95%CI: 100-100%); negative predictive value, 6% (95%CI: 2-16%). CONCLUSION: These results suggest that the number of endoscopic or radiologic observations to confirm correct replacement of the PEG tube may be reduced to one fifteenth using the sky blue method.

Emergence of clarithromycin-resistant Helicobacter pylori (CRHP) with a high prevalence in children compared with their parents.

BACKGROUND: Clarithromycin-resistant Helicobacter pylori (CRHP) is increasing worldwide. Clarithromycin resistance in H. pylori from familial members has not been investigated. MATERIALS AND METHODS: Biopsy specimens were taken from 13 families living in Tokyo, Yokohama, and Niigata between 1998 and 2001. Drug resistance was tested with the replica plating method. The minimum inhibitory concentrations of antimicrobial agents for H. pylori strains were determined by the agar dilution method. Molecular analyses of H. pylori strains were performed by ribosomal RNA gene restriction pattern analysis. The DNA region, associated with clarithromycin resistance, was analyzed by PCR and sequencing. RESULTS: Helicobacter pylori strains isolated from a 5-year-old-son displayed clarithromycin resistance with a mutation (A --> G at position 2143) in the 23S ribosomal RNA, whereas H. pylori strains from his parents did not. DNA analyses revealed that the boy was infected with his father's strain. The boy had repeatedly developed otitis media and received clarithromycin since the age of 2 years. Studies on an additional 12 families demonstrated that clarithromycin resistance in the children's strains reached 42.9% and was significantly higher than those of H. pylori strains from their parents (0%) or from adult patients (11.1%) (p <.05). CONCLUSIONS: The rate of clarithromycin resistance in H. pylori strains from Japanese children was extremely high, in contrast to those from their parents or adult patients. Prior history of clarithromycin usage in a child suggested development of clarithromycin resistance in resident H. pylori, which was originated from a parent.