Pharmacotherapy for Reducing RBC Transfusion for Patients in the ICU: A Systematic Review and Network Meta-Analysis.

OBJECTIVES: To determine optional therapeutic strategies by comparing monotherapies and combination therapies to reduce RBC transfusion requirement for patients in the ICU. DATA SOURCES: MEDLINE, CENTRAL, and Embase were searched for studies published from database inception until July 2023. DATA EXTRACTION: We included randomized controlled trials comparing erythropoiesis-stimulating agents (Epo), iron, combination therapy with iron and Epo, hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), vitamin D 3 (VD3), and placebo/no treatment. A frequentist network meta-analysis (NMA) was performed using a random effects model, and the confidence in NMA was rated. DATA SYNTHESIS: Of 117 eligible studies, 75 studies (15,091 patients) were included in the quantitative analysis. Compared with placebo/no treatment, the combination therapy reduces the requirement for RBC transfusion (risk ratio [RR]: 0.60; 95% CI, 0.49-0.74; confidence rating: moderate). The Epo or iron monotherapy may reduce the requirement for RBC transfusion (RR: 0.81; 95% CI, 0.63-1.04; confidence rating: low; RR: 0.83; 95% CI, 0.70-0.98; confidence rating: low, respectively). Combination therapy may not increase the prevalence of both venous thromboembolism (VTE) (RR: 0.73; 95% CI, 0.25-2.08; confidence rating: low) and infection. Epo monotherapy may not increase the prevalence of VTE but may increase that of infections (RR: 1.27; 95% CI, 0.94-1.73; confidence rating: low). Iron monotherapy may not increase the prevalence of both VTE and infection. Evidence for VD3 and HIF-PHI remains uncertain. CONCLUSIONS: Combination therapy with iron and Epo likely reduces the requirement for RBC transfusion and may be less harmful than other therapies.

Comparison of clinical characteristics, eating behaviors, and clinical symptoms following fat intake in functional dyspepsia with functional dyspepsia with pancreatic enzyme abnormalities between Singapore and Japan.

BACKGROUND AND AIM: To clarify whether there were any significant differences in clinical symptoms and eating patterns between functional dyspepsia (FD) patients and FD with pancreatic enzyme abnormalities (FD-P) patients as refractory FD, we compared these factors in multicenter studies in Singapore and Japan. METHODS: One hundred ninety-eight consecutive patients presenting with FD (n = 88), FD-P patients (n = 81) based on Rome III classification and controlled group (n = 39) recruited from six institutions in Singapore and Japan. Clinical characteristics, clinical symptoms for dietary fat intake, and eating behaviors were estimated using questionnaires. Anxiety and health-related quality of life were determined by STAI-state/-trait and SF-8, respectively. RESULTS: There were no significant differences in age, sex, BMI, smoking, alcohol intake, past medical history, and history of allergy in FD and FD-P patients between Singapore and Japan. There were no significant differences in FD subtypes, gastrointestinal symptom rating scale score, severity of FD symptoms, and eating pattern in Singapore and Japan. Moreover, there were significant differences in certain eating behaviors between FD and FD-P patients in Singapore and Japan. Interestingly, epigastric pain and early satiety following fat meals in FD-P patients were significantly (P = 0.003 and P = 0.008, respectively) higher compared with those in FD patients in Japan. Physical component score in FD-P patients was significantly (P = 0.019) disturbed compared with those in FD patients in Japan. CONCLUSIONS: Epigastric pain and early satiety following fat meals in FD-P patients may be useful tools to differentiate FD-P patients from FD patients in Japan.

[Seasonal changes in blood pressure and related factors among older patients receiving home medical care].

AIM: We investigated seasonal variations in blood pressure (BP) and factors related to these variations among older patients receiving home medical care. METHOD: A total 57 patients ≥ 65 years old receiving home medical care who participated in the Osaka Home Care REgistry study (OHCARE), a prospective cohort study, were included. We investigated the seasonal patient characteristics and variations in the BP. In addition, to determine the influence of seasonal variations in the systolic blood pressure (SBP) on the occurrence of clinical events (hospitalization, falls and death), we classified patients into larger- and smaller- change groups based on the median seasonal variations in SBP. RESULT: About 60% of subjects were very frail or bedridden. The mean BP was higher in winter than in summer (124.7±11/69.5±7 vs.120.5±12/66.9±8 mmHg) (P< 0.01). On comparing the characteristics of the two groups with larger and smaller changes in the SBP, the group with large BP changes had a significantly lower BP in summer than the group with small BP changes. In addition, the incidence of "hospitalization" was significantly higher in the group with large BP changes than in the group with small BP changes (P = 0.03). CONCLUSION: The present study revealed that there were seasonal changes in the BP in older patients receiving home medical care. It was also suggested that seasonal changes in the BP might be associated with the risk of hospitalization events. Given these BP variations, doctors and visiting nurses should be alert for systemic abnormalities, especially in frail patients receinving home medical care.

Lower risk of postoperative delirium using laparoscopic approach for major abdominal surgery.

BACKGROUND: A laparoscopic approach is increasingly being used for major abdominal surgeries and is reportedly associated with a lower incidence of postoperative complications. However, the association of laparoscopic approach and postoperative delirium remains unclear. We aimed to retrospectively investigate risk factors for postoperative delirium after abdominal surgery particularly assessing the association between a laparoscopic approach and postoperative delirium. METHODS: We retrospectively studied 801 patients who underwent major abdominal surgery between April 2012 and December 2013. Among these, 181 (22.6%) patients underwent a laparoscopic and 620 (77.4%) patients underwent an open procedure. A Cox proportional hazard model analysis was used to identify risk factors for the development of postoperative delirium or overall survival within 180 days after surgery. Cumulative incidence of postoperative delirium was assessed using a propensity score-matching analysis. RESULTS: Postoperative delirium occurred in 56 patients (7.0%). A Multivariate Cox proportional hazard model analysis revealed that a laparoscopic approach reduced the risk of postoperative delirium [hazard ratio (HR) 0.30, 95% confidence interval (CI) 0.07-0.84, p = 0.019]. Postoperative delirium was associated with worse overall survival within 180 days (HR 4.91, 95% CI 1.96-12.22, p = 0.001) after adjusting for other confounders using the Cox proportional hazard model analysis. Patients who developed postoperative delirium showed worse outcomes including higher rate of morbidity except delirium (p < 0.001), longer hospitalization (p < 0.001), and post-discharge institutionalization (p < 0.001). After propensity score-matching, cumulative incidence rates of postoperative delirium were significantly lower in the laparoscopic group compared to the open group (30-day cumulative incidence rate, 1.7% vs. 7.8%, p = 0.006). CONCLUSIONS: The risk of postoperative delirium after major abdominal surgery is reduced using laparoscopic approach. Postoperative delirium should be prevented as it precipitates adverse postoperative events.

Development and validation of a nomogram predicting postoperative pneumonia after major abdominal surgery.

PURPOSE: Postoperative pneumonia (POP) is a common complication that can adversely affect the outcomes after surgery. This study aimed to devise and validate a model for stratifying the probability of POP in patients undergoing abdominal surgery. METHODS: We included 1050 patients who underwent major abdominal surgery between 2012 and 2013. A nomogram was devised by evaluating the predictive factors for POP. RESULTS: Of the 1050 patients, 56 (5.3%) developed POP. Multivariable logistic regression analysis revealed that the independent predictive factors for POP were age, male sex, history of cerebrovascular disease, Brinkman Index (BI) ≥ 900, and upper midline incision. A nomogram was devised by employing these five significant predictive factors. The prediction model showed a relatively good discrimination performance, with a concordance index of 0.77. CONCLUSIONS: A nomogram based on age, male sex, history of cerebrovascular disease, BI ≥ 900, and upper midline incision may be useful for identifying patients with a high probability of developing POP after major abdominal surgery.

[Factors associated with behavioral and psychological symptoms in patients with dementia who received home medical treatment: A cross-sectional study (OHCARE study)].

AIM: The present study investigated the behavioral and psychological symptoms of dementia (BPSD) and pharmacological therapy among elderly people with dementia who received home medical treatment. METHODS: This study was part of the Osaka Home Care Registry study (OHCARE-study). Participants were >65 years old with dementia. Demographic and medical data, BPSD, and the LTCI [long-term care insurance] care-need level were collected. A multiple logistic regression analysis was performed in order to clarify the factors associated with BPSD. RESULTS: Among 110 subjects (82.0±11.3 years old), 64.6% had a diagnosis of dementia, most commonly Alzheimer's dementia. Aside from home medical treatment, 58.1% had a nurse visit, 48.1% received home care, and 40.0% used a day service. The prevalence of BPSD was 53.0%. Those with BPSD most frequently had an LTCI care-need level of 3, and the prevalence of BPSD declined as the level increased after 3. Psychotropic drugs were prescribed in 61.5% of those with BPSD. Antipsychotic drugs were used significantly more frequently in those with nursing care resistance, assault and delusions than in others (all, p <0.005). A multivariate analysis showed that the positive predictor of BPSD was antipsychotic drug use, while negative predictors were an LTCI care-need level and the use of visiting rehabilitation. CONCLUSION: The BPSD in elderly dementia patients receiving home medical treatment were clarified. The LTCI care-need level is an independent predictor of BPSD after adjusting for the activities of daily life. Further longitudinal investigations including the BPSD severity and frequency are needed.

Comparisons of financial and short-term outcomes between laparoscopic and open hepatectomy: benefits for patients and hospitals.

PURPOSES: This retrospective analysis compared the cost outcomes for both patients and hospitals, as well as the short-term outcomes, for laparoscopic hepatectomy (LH) and open hepatectomy (OH). METHODS: The subjects comprised 70 patients who underwent LH or OH. The total hospital charge was calculated using the Japanese lump-sum payment system according to the diagnosis procedure combination. RESULTS: Of the 70 patients, 10 in the LH group and 16 in the OH group underwent primary single limited/anatomic resection or left lateral sectoriectomy. The operation time, blood loss, and postoperative complications did not differ significantly between the two groups. The median [range] time of inflow occlusion was significantly longer [120 (50-194) vs. 57 (17-151) min, P = 0.03] and the postoperative hospital stay was significantly shorter [5 (4-6) vs. 9 (5-12) days, P < 0.01] in the LH group than in the OH group, respectively. The mean ± standard deviation surgical costs (1307 ± 596 vs. 1054 ± 365 US$, P = 0.43) and total hospital charges (12046 ± 1174 vs. 11858 ± 2096 US$, P > 0.99) were similar in the LH and OH groups, respectively, although the charges per day were significantly higher in the LH group than in the OH group (1388 ± 217 vs. 1016 ± 134 US$, P < 0.01). CONCLUSIONS: The costs to patients for LH are similar to those for OH. However, LH provides a financial advantage to hospitals due to a reduced hospital stay and comparable surgical costs.

Intrathecal AAV serotype 9-mediated delivery of shRNA against TRPV1 attenuates thermal hyperalgesia in a mouse model of peripheral nerve injury.

Gene therapy for neuropathic pain requires efficient gene delivery to both central and peripheral nervous systems. We previously showed that an adenoassociated virus serotype 9 (AAV9) vector expressing short-hairpin RNA (shRNA) could suppress target molecule expression in the dorsal root ganglia (DRG) and spinal cord upon intrathecal injection. To evaluate the therapeutic potential of this approach, we constructed an AAV9 vector encoding shRNA against vanilloid receptor 1 (TRPV1), which is an important target gene for acute pain, but its role in chronic neuropathic pain remains unclear. We intrathecally injected it into the subarachnoid space at the upper lumbar spine of mice 3 weeks after spared nerve injury (SNI). Delivered shTRPV1 effectively suppressed mRNA and protein expression of TRPV1 in the DRG and spinal cord, and it attenuated nerve injury-induced thermal allodynia 10-28 days after treatment. Our study provides important evidence for the contribution of TRPV1 to thermal hypersensitivity in neuropathic pain and thus establishes intrathecal AAV9-mediated gene delivery as an investigative and potentially therapeutic platform for the nervous system.

[Scintigraphic imaging in the diagnosis of failed intrathecal baclofen therapy: a case report of a 7-year-old boy with ventriculoperitoneal shunt].

Intrathecal baclofen (ITB) therapy is popular for the management of intractable spasticity. In 2007, the indications of ITB therapy expanded to include spasticity of children in Japan. In this report, we assessed the utility of radioisotopic scintigraphy in the diagnosis of failed ITB therapy. A 7-year-old boy with schizencephaly, hydrocephalus, and spastic quadriplegia had an ITB pump implanted. In his infancy, he had undergone ventriculoperitoneal shunt implantation. One month after the ITB operation, the ITB therapeutic effect diminished. Several examinations confirmed that the pump function was normal and catheter failure had not occurred. However, radioisotopic scintigraphy revealed that the baclofen had been washed out to blood circulation more rapidly than is typically observed. We considered two possible causes for this; obstruction of the cerebrospinal space due to kyphosis and excessive washout of celebrospinal fluid through the ventriculoperitoneal shunt. The catheter was moved to a more caudal site surgically, and his spasticity improved. The use of radioisotopic scintigraphy to identify the distribution of baclofen is an effective technique for investigation of baclofen pump system malfunction.

Central Nervous System Adverse Reactions to Amantadine Intoxication: A Case Report and Analysis of JADER.

BACKGROUND/AIM: A few case reports of central nervous system (CNS) symptoms caused by amantadine intoxication have been published, detailing various types of symptoms and differing times to onset. We encountered a patient who developed CNS symptoms with amantadine. This prompted us to investigate the types, time to onset, and outcome of CNS adverse reactions to amantadine by analyzing data from a pharmacovigilance database. PATIENTS AND METHODS: The patient was evaluated at Chutoen General Hospital, Shizuoka, Japan. Analysis was performed using the Japanese Adverse Drug Event Report (JADER) database. RESULTS: In our case, the amantadine blood concentration was 4,042 ng/ml, i.e., in the toxic range. The time to onset was 26 days for dyskinesia and 90 days for depressed level of consciousness. Symptoms resolved when amantadine was discontinued. The JADER database contained 974 cases of adverse reactions to amantadine. The most frequently reported CNS adverse reaction was hallucination, with a reporting odds ratio of 64.28 (95% confidence interval=52.67-78.46). Positive signals were detected for all CNS adverse reactions. For all CNS reactions, clinical outcomes were poor in a comparatively low percentage of cases. Most CNS reactions occurred soon after administration of amantadine, usually within approximately one month. CONCLUSION: Because most CNS adverse reactions to amantadine usually occur within approximately one month of initiating treatment, healthcare providers should exercise heightened vigilance in monitoring patients for such reactions during this period.