Trend of oral antimicrobial use after removal of broad-spectrum antimicrobials from the formulary at a pediatric primary emergency medical center.

INTRODUCTION: While the effects of the Japanese action plan formulated in 2016 have gradually appeared, the appropriate use of antimicrobials in outpatient settings is still important. We conducted a previous study to recommend appropriate antimicrobial use via monthly newsletters at a pediatric primary emergency medical center (PEC). As a result, the rate of inappropriate prescription of oral third-generation cephalosporins (3GCs) decreased by 67.2%. This decrease prompted our institution to change the antimicrobials adopted from 3GCs to first-generation cephalosporins. There have been no reports on the prescribing trend of narrow-spectrum antimicrobials after the discontinuation of 3GCs in pediatric PECs. METHODS: We conducted a single-center, observational study at one pediatric PEC between April 2020 and March 2022. We recorded the total number of patients and oral antimicrobial prescriptions, diagnoses, and descriptions of the electronic health records and evaluated the prescription trends and appropriateness of antimicrobial use after removal of cefditoren-pivoxil and fosfomycin from the formulary. RESULTS: The total number of patients was 22,744 during the study period, and antimicrobials were prescribed to 496 (2.2%) patients. The proportion of amoxicillin prescriptions among total antimicrobials was high (53.4%). For each prescription, 85 of 259 prescriptions (32.8%) for amoxicillin, 161 of 185 prescriptions (87.0%) for cephalexin, and 17 of 43 prescriptions (39.5%) for clarithromycin were judged to be appropriate. CONCLUSION: We suggest that after the removal of broad-spectrum antimicrobials and achieving a reduction in the prescription rate of oral antimicrobials, it is necessary to evaluate whether narrow-spectrum antimicrobials are used properly in pediatric PECs.

Effect of oxaliplatin in elderly colon cancer patients with pathological T4 and/or N2 disease: a multicenter, propensity score-matched analysis.

PURPOSE: Although adjuvant chemotherapy (AC) using fluoro-pyrimidine and oxaliplatin (FU + oxaliplatin) is recommended after curative resection for locally advanced colon cancer patients, several randomized controlled trials have shown no additional effect of oxaliplatin in patients aged ≥ 70 years. Here, we examined the effectiveness of FU + oxaliplatin on the long-term outcome of old patients with a high risk of recurrence. METHODS: This multicenter, retrospective study included 346 colon cancer patients diagnosed with pathological T4 and/or N2 disease from 2016 to 2020. They were divided into an old group (≥ 70 years, n = 197) and a young group (< 70 years, n = 167). Propensity score matching was used to minimize selection bias, and 126 patients per group were matched. RESULTS: Before matching, the rates of poor performance status (p < 0.001) and the presence of comorbidities (76.1% vs. 47.9%, p < 0.001) were higher in the old group. Although all baseline factors were similar between groups, after matching, the AC rate was lower in the old group (45.2% vs. 65.1%, p = 0.002). In the old group, relapse-free (82.2% vs. 55.6% and 69.6%, p < 0.05) and overall survival (83.1% vs. 80.0% and 44.4%, p < 0.05) rates were significantly higher in the AC patients with FU + oxaliplatin than in the AC patients with only FU and the non-AC patients. CONCLUSION: The selected old colon cancer patients with a high risk of recurrence gained an additional benefit with respect to prognosis from FU + oxaliplatin as AC.

Effects of a nudge-based antimicrobial stewardship program in a pediatric primary emergency medical center.

Outpatient medical facilities tend to have high antimicrobial prescription rates and are therefore major targets for antimicrobial stewardship programs (ASPs). Pediatric primary emergency medical centers in Japan have difficulties in implementing conventional ASPs due to the low continuity of stewardship. Accordingly, there is a need to develop effective ASP models for these facilities. We conducted a single-center, quasi-experimental study to evaluate the effects of a nudge-based ASP in reducing unnecessary third-generation cephalosporin (3GC) prescriptions in a pediatric primary emergency care center (PEC). The implemented ASP utilizes monthly newsletters that report current antimicrobial use patterns and prescribing targets. We compared the monthly 3GC prescription numbers and proportions of unnecessary prescriptions before and after the ASP was implemented. The trends in 3GC prescriptions were examined using an interrupted time-series analysis. The numbers of patients before and after ASP implementation were 129,156 and 28,834, respectively. The number of unnecessary 3GC prescriptions decreased by 67.2% in the year after ASP implementation. The interrupted time-series analysis showed that the ASP was significantly associated with a reduction in 3GC prescriptions (regression coefficient - 0.58, P < 0.001).Conclusion: The nudge-based ASP was effective in reducing 3GC use in a Japanese PEC. This simple and inexpensive approach may have applications in other outpatient facilities. What is Known: • Outpatient medical facilities tend to have high antimicrobial prescription rates. Despite the development of several strategies for outpatient antimicrobial stewardship programs, these approaches have not sufficiently reduced antimicrobial use. What is New • Our nudge-based antimicrobial stewardship program using newsletters was shown to be a simple, inexpensive, and feasible method for reducing unnecessary antimicrobial use in a pediatric primary emergency care center. This may represent an effective antimicrobial stewardship strategy in Japanese outpatient facilities.

Prognostic value of the preoperative prognostic nutritional index in oldest-old patients with colorectal cancer.

BACKGROUND: The prognostic nutritional index (PNI), which is calculated using serum albumin and the peripheral lymphocyte count, is a simple and useful score for predicting the prognosis in patients with various cancers. The correlation between the preoperative PNI and long-term outcomes is unclear in oldest-old patients with colorectal cancer. METHODS: A total of 84 consecutive patients ≥ 85 years old who underwent resection for primary colon adenocarcinoma at our institution between April 2008 and March 2017 were retrospectively reviewed. The cut-off value of the PNI for predicting the relapse-free survival (RFS) was 42.4 on a receiver operating characteristic curve analysis. The clinical characteristics and markers of systemic inflammation were then compared between patients with a low PNI (PNI < 42.4, n = 33) and a high PNI (PNI ≥ 42.4, n = 51). RESULTS: A low PNI was associated with systemic inflammation marker levels, including a low neutrophil-to-lymphocyte ratio (p = 0.048), a low platelet-to-lymphocyte ratio (p = 0.006), and a high lymphocyte-to-monocyte ratio (p < 0.001). The median follow-up period of this cohort was 34 months (1-151 months). The 5-year RFS, overall survival (OS), and cancer-specific survival were significantly worse in the low-PNI group than in the high-PNI group (p = 0.032, p = 0.004, p = 0.049, respectively). In the multivariate analysis, a low PNI was an independent predictor for both the RFS (HR 3.188, p = 0.041) and OS (HR 3.953, p = 0.027). CONCLUSIONS: A low-preoperative PNI was significantly associated with a poor prognosis in oldest-old colorectal cancer patients. Perioperative nutritional support may be important for prolonging the survival.

[A case of gastric cancer accompanied by disseminated carcinomatosis of bone marrow wherein long-term chemotherapy was enabled by early supportive palliative care].

Here we report gastric cancer accompanied by bone marrow carcinomatosis in a patient for whom long-term chemotherapy was enabled by early pain-relief therapy. A 45-year-old man was admitted to our hospital because of back pain associated with multiple spinal tumors in June 2011. Blood tests showed a trend toward disseminated intravascular coagulation(DIC) and gastric cancer was suspected as the primary lesion. Because pain was severe, emergency pain relief was provided by flurbiprofen axetil and a continuous subcutaneous infusion of fentanyl citrate. After bone marrow examination gave a diagnosis of poorly differentiated adenocarcinoma, we performed sequential methotrexate(MTX)and 5-fluorouracil(5-FU)therapy. The therapy successfully decreased tumor marker levels, and alkaline phosphatase and lactate dehydrogenase levels normalized. Finally, gastric cancer accompanied by bone marrow carcinomatosis was diagnosed. Because the patient had anxiety and spiritual pain from the time of admission, psychiatric care was also required. In November 2011, the tumor recurred, and we switched therapy to a combination of S-1 and cisplatin. The patient's pain was controlled by combined treatment with a fentanyl patch and etodolac, and he was discharged in December 2011. However, severe pain recurred and pain therapy was continued. DIC developed in February 2012 and transiently resolved after resuming combination therapy with MTX and 5-FU; however, it subsequently recurred, leading to the patient's death in May 2012.

Feasibility and efficacy of newly developed eco-friendly, automatic washer for endoscope using electrolyzed alkaline and acidic water.

INTRODUCTION: As well as preventing nosocomial and healthcare-associated infections, a reliable and eco-friendly washer for medical equipment would also be safe for the global environment. The aim of this study was to evaluate the efficacy of a newly developed automatic washing system (Nano-washer) that uses electrolyzed water and ultrasonication without detergent for washing endoscopes. METHODS: Patients who underwent laparoscopic lobectomy or laparoscopic colectomy at Nagasaki University between 2018 and 2022 were included. A total of 60 cases of endoscope use were collected and classified according to endoscope washing method into the Nano-washer group (using no detergent) (n = 40) and the manual washing group (n = 20). Protein and bacterial residues were measured before and after washing, using absorbance spectrometry and 16S rRNA polymerase chain reaction. The effectiveness of protein and bacterial removal and endoscope surface damage after washing were compared under specular vision between the groups. RESULTS: Nano-washer did not use detergent unlike manual washing. There was no difference in demographic or clinical characteristics between the groups except for the presence of comorbidities in the lobectomy group (Nano-washer, 85%; manual washing, 40%, P = .031). Compared with the manual washing group, residual protein levels in the Nano-washer group were significantly reduced after washing (lobectomy, 0.956 mg/mL vs 0.016 mg/mL, P < .001; colectomy, 0.144 mg/mL vs 0.002 mg/mL, P = .008). Nano-washer group showed a significant reduction in bacteria between before and after lobectomy (9437 copies/cm2 vs 4612 copies/cm2 , P = .024). CONCLUSION: Nano-washer is a promising, effective, and eco-friendly automatic washing device that is safer and more efficient than manual washing.

Risk factors for infection of totally implantable central venous access ports among patients requiring port removal.

BACKGROUND: Totally implantable central venous access ports, are required for various purposes, ranging from chemotherapy to nutrition. Port infection is a common complication. In many patients with port infection, the ports are removed because antibiotics are ineffective. We evaluated the risk factors associated with port removal due to port infection. METHODS: By retrospective chart review, we collected data of 223 patients who underwent port removal for any reason. Port infection was defined as infection symptoms, such as fever; elevated white blood cell counts or C-reactive protein levels; or redness at the port site, in the absence of other infections, which improved with port removal. The characteristics of patients with or without port infection were compared using univariate (chi-squared test, t-test) and multivariate logistic regression analyses. RESULTS: We compared 172 patients without port infection to 51 patients with port infection. Univariate analysis identified sex (p = 0.01), body mass index (BMI) ⩽20 kg/m2 (p = 0.00004), diabetes mellitus (p = 0.04), and purpose of use (p = 0.0000003) as significant variables. However, male sex (p = 0.03, 95% confidence interval [CI]: 0.01-0.23), BMI ⩽20 kg m2 (p = 0.002, 95% CI: 0.06-0.29), and purpose of use (total parenteral nutrition (TPN); p = 0.000005, 95% CI: 0.31-0.76) remained significant using multivariate analysis. Moreover, the patients with short bowel syndrome and difficulty in oral intake tended to be infected easily. Additionally, Staphylococcus species were the most common microbes involved in port infection. CONCLUSIONS: Male sex, BMI ⩽20 kg/m2, and purpose of use as a TPN were risk factors for port infection. Ports should not be used for long duration of TPN or used only in exceptional cases.

[The role of cooperating hospitals in homecare].

The Japan Baptist Medical Foundation forms a so-called hospice triangle, with a general ward, a hospice ward, and home hospice, and it is possible to provide palliative care in the desired place. The ratio of homecare is 65.0%, and there were 2 cases in which a physician was present at the time of death. The average number of home-visit medical treatments during the week prior to death was 3.7. The median value of the period of home-visit medical treatment is 36 days. The group of homecare patients who were temporarily hospitalized during the period of home-visit medical treatment was 17.1%, and the most common reason was exacerbation of symptoms related to the primary disease. The group of patients who were hospitalized in a hospice ward was 17.0%, and many were for the purpose of respite care or trial hospitalization. Because some patients are reluctant to be hospitalized in a hospice ward, it was thought that adding an option of hospitalizing in a cooperating hospital to the homecare support system would give patients peace of mind. In order to increase the use of homecare from now on, it was thought that even further education about homecare is necessary in addition to a support system of cooperating hospitals.

Impacts of trans-anal tube placement in patients with sigmoid colon cancer: Risk verification analysis using inverse probability weighting analysis.

Purpose: Anastomotic leakage (AL) is a serious postoperative complication that affects short- and long-term outcomes. The use of a trans-anal drainage tube (TDT) is reported to prevent AL in rectal cancer patients, but its value in sigmoid colon cancer patients is unknown. Methods: Admitted to the study were 379 patients who underwent surgery for sigmoid colon cancer between 2016 and 2020. Patients were divided into two groups according to the placement (n = 197) or nonplacement of a TDT (n = 182). To determine the factors affecting the association between TDT placement and AL, we estimated average treatment effects by stratifying each factor using the inverse probability of treatment weighting method. The association between prognosis and AL was evaluated in each identified factor. Results: Factors associated with postsurgical insertion of a TDT were advanced age, male sex, high body mass index (BMI), poor performance status, and presence of comorbidities. TDT placement was associated with a significantly lower AL in male patients (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.07-0.73; P = .013) and for BMI ≥ 25 kg/m2 (OR, 0.13; 95% CI, 0.02-0.65; P = .013). In addition, there was a significant association of AL with poor prognosis in patients with BMI ≥ 25 kg/m2 (P = .043), age > 75 y (P = .021), and pathological node-positive disease (P = .015). Conclusion: Sigmoid colon cancer patients with BMI ≥ 25 kg/m2 are the most appropriate candidates for postoperative TDT insertion, in terms of reduced incidence of AL and improved prognosis.

Safety and Effectiveness Analyses of Dolutegravir/Lamivudine in Patients with HIV: 2-Year Report of Post-Marketing Surveillance in Japan.

INTRODUCTION: Since 2019, for the first time, a two-drug regimen with dolutegravir/lamivudine (DTG/3TC) has been recommended for HIV treatment as initial and subsequent therapy in the international guidelines. However, safety and efficacy data of DTG/3TC in Japanese people living with HIV (PLHIV) in clinical trials are limited and have not been evaluated in clinical practice. In this report, we evaluated safety and effectiveness of DTG/3TC in Japanese PLHIV through post-marketing surveillance. METHODS: Post-marketing surveillance was conducted to evaluate the real-world safety and effectiveness of DTG/3TC in Japanese PLHIV. One hundred ninety-seven patients who received oral DTG 50 mg/3TC 300 mg as a single-tablet fixed-dose combination regimen (STR) were registered in clinical practice. The safety was evaluated by incidence of adverse drug reactions (ADRs). The effectiveness was evaluated by plasma HIV RNA and peripheral CD4+ cell counts. RESULTS: This is a 2-year (from 2020 to 2022) report of approximately 6 years of survey, and 187 patients were registered from 21 Japanese sites. The number of antiretroviral therapy (ART)-experienced patients was 178, and > 60% of their previous antiretrovirals (ARVs) were DTG/abacavir (ABC)/3TC. There were only nine ART-naïve patients. Four of 178 ART-experienced patients (2.25%) reported ADRs, and 1 serious ADR of syphilis was reported. There was no clear causal relationship between DTG/3TC and the ADRs. Plasma HIV RNA and peripheral CD4+ cell counts maintained the pre-DTG/3TC level in ART-experienced patients. CONCLUSION: No new clinical concerns of safety and effectiveness were identified in Japanese ART-experienced PLHIV treated with DTG/3TC. We could not discuss the safety and effectiveness in ART-naïve patients because of the small sample size.

Distal pancreatectomy with en bloc celiac resection for locally advanced pancreas carcinoma.

In locally advanced pancreatic body cancers, cancer infiltrates major vessels such as the celiac axis, common hepatic artery and superior mesenteric artery or vein, which is the borderline of resectability. Patients also suffer severe abdominal pain. Kondo and Hirano et al. developed a radical operation called "distal pancreatectomy with en bloc celiac resection (DP-CAR)" for such cases. We applied this procedure three times in two patients with pancreatic body carcinomas, in which combined vascular resection was necessary. Radical operation was eventually achieved.

A modified Foker's technique for long gap esophageal atresia.

External traction using the Foker's technique enables elongation in the esophageal segments within days, and allows the primary repair of the long gap. This article presents our modified Foker's technique which was easily applicable for long-gap esophageal atresia.

[Aging problem in the home hospice care].

Home hospice care is not merely an extension of hospital-based medical care administered at the hospital, but refers to hospice care for patients with life-threatening diseases that can only be given at their homes. The rapid growth of the elderly population in Japan has led to not only the need for home hospice care, but also social problems such as living alone, living with only one elderly family member, and problems that are particularly acute in cancer patients with dementia. We analyzed data for 262 patients for whom home hospice care was provided by our clinic. Overall, elderly persons with dementia tended to request admission before death, but most elderly persons living alone preferred home hospice care. We found that 58% of the patients living with only one elderly family member requested admission before death, which was lower than the rate of the study group as a whole. We further performed an in-depth analysis of the current situation in order to improve home hospice care of terminally ill patients in Japan, focusing on problems related to the aging population.

[Development of a cooperative system for palliative care among a hospice ward, general ward, geriatric health services facility, and home in Japan Baptist Hospital-provision of home-based care by hospice physicians].

In November 2009, a home hospice palliative care clinic(clinic)was opened in addition to a hospice ward, general ward, and geriatric health services facility at our hospital. This marked the initiation of a health care system able to provide the palliative care desired by patients and families. We studied the characteristics and hospitalization status of 514 patients with cancer who died at the hospice ward, general ward, or their homes from November 2009 through December 2011. Overall, 373 patients died at the hospice ward, 11 at the general ward, and 130 at home. Hospice physicians participated in the home care of 20 patients. Hospice physicians provide home-based care in cooperation with clinic physicians, facilitating the palliative care of patients who initially do not have a place to receive terminal care and the prompt discharge of patients who want to live at home.

Usefulness of structured-cadaveric training for trans-anal pelvic exenteration.

PURPOSE: Structured training using cadaveric simulation is useful for trans-anal surgery; however, no studies have examined the effectiveness of cadaveric training for advanced trans-anal surgery including pelvic exenteration (PE). METHODS: Twelve colorectal surgeons attended a total of 10 cadaveric simulation training courses between 2016 and 2021 and completed a questionnaire at the end of the program. We divided 14 consecutive patients who underwent trans-anal PE between 2015 and 2021 into two groups: pre-training group and post-training group, and compared the clinico-pathological features between the groups. RESULTS: The median length of clinical experience of the surgeons was 12 years. There was high score agreement among the surgeons that the course was useful for recognition of anatomical and layer structure, training for trans-anal total mesorectal excision and trans-anal PE, and reducing complications specific to the trans-anal approach. Compared with the pre-training group, patients in the post-training group had a higher rate of two-team surgery (77.8% vs 0%, P = .021), and shorter time to specimen removal (273 vs 423 min, P = .045). CONCLUSIONS: Structured-cadaveric training has potential use as a technical step-up in advanced trans-anal surgery that might contribute to better short-term outcomes in the clinical setting.

Pathological complete response to pembrolizumab in patients with metastatic ascending colon cancer with microsatellite instability.

Pembrolizumab is a novel immune-checkpoint inhibitor used for treatment of microsatellite instability-high (MSI-H) colorectal cancer. Several studies have reported clinical complete response (CR) after treatment with pembrolizumab, but none has confirmed pathological CR. Here we provide the first description of pathological CR with R0 resection after immune-checkpoint therapy. A 45-year-old man presented at our hospital with abdominal distention and highly elevated tumor markers. Contrast-enhanced abdominal CT showed a 110 × 75 mm bulky mass with markedly swollen lymph nodes and an isolated peritoneal metastasis in the pelvic space. Biopsy revealed poorly differentiated adenocarcinoma. We diagnosed ascending colon cancer cT4aN2bM1c Stage IVc. A biopsy specimen obtained during systemic chemotherapy (FOLFOXIRI) was confirmed pathologically as MSI-H, after which the treatment was changed to pembrolizumab. The tumor markers rapidly decreased to within normal ranges after three courses of treatment. After twenty courses, CT revealed shrinkage of the main tumor, lymph node metastases, and the peritoneal metastasis, and we performed extended right hemi-colectomy with dissection of the peritoneal metastasis. No residual tumor cells were found histologically. The patient achieved pathological CR and the postoperative course was uneventful. An accurate diagnosis and appropriate follow up are crucial for obtaining sufficient therapeutic effect of pembrolizumab.

Anti-spastic effect of low-frequency rTMS applied with occupational therapy in post-stroke patients with upper limb hemiparesis.

OBJECTIVE: To determine the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) combined with occupational therapy (OT) on the spasticity of the hemiparetic upper limb after stroke. SUBJECTS AND METHODS: The study subjects were 39 post-stroke patients with spastic upper limb hemiparesis (age: 56.5 ± 16.0 years, time after onset: 50.3 ± 37.8 months). At admission, the severity of hemiparesis was categorized as Brunnstrom stage 3-5 for hand-fingers. During 15-day hospitalization, each patient received 22 sessions of low-frequency rTMS applied to the non-lesional hemisphere and OT (one-to-one training and self-training). The spasticity of finger and wrist flexors of the affected upper limb was evaluated using the modified Ashworth scale (MAS) on the day of admission and discharge and 4 weeks after discharge. Each subject underwent Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT). RESULTS: The low-frequency rTMS/OT protocol significantly decreased the MAS scores for both finger and wrist flexors at discharge and at 4 weeks after discharge. In addition, the low-frequency rTMS/OT protocol significantly increased the FMA score and shortened the WMFT performance time. CONCLUSIONS: The 15-day in-patient protocol of low-frequency rTMS/OT is potentially suitable for reducing spasticity as well as improving motor function on the affected upper limb after stroke.

Combination treatment of low-frequency rTMS and occupational therapy with levodopa administration: an intensive neurorehabilitative approach for upper limb hemiparesis after stroke.

The combination treatment of low-frequency repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy was applied with concomitant oral administration of levodopa in five post-stroke patients with upper limb hemiparesis (age at treatment: 56-66 years; interval between onset of stroke and treatment: 18-143 months) as a 15-day inpatient protocol. Daily levodopa administration of 100 mg was initiated 1 week before admission and continued until 4 weeks after discharge. Low-frequency rTMS of 1 Hz was applied to the contralesional hemisphere for 40 min daily (two 20-min sessions) combined with intensive occupational therapy consisting of 60-min one-on-one training and 60-min self-exercise. Motor function of the affected upper limb was serially evaluated with the Fugl-Meyer Assessment and the Wolf Motor Function Test. At the end of the treatment, all patients showed improved motor function in the affected upper limbs. In some patients, the improvement was maintained until 4 weeks after discharge. No patient showed any adverse effect from the intervention. Our proposed protocol featuring levodopa administration, low-frequency rTMS, and intensive occupational therapy could provide a safe and feasible intervention for upper limb hemiparesis after stroke.