Search

Introduction: Telemedicine is increasingly used to deliver healthcare in many clinical specialities. However, the adoption of telemedicine in the delivery of outpatient parenteral antimicrobial therapy (OPAT) has been relatively slow and limited. This study aims to collate current evidence for telemedicine in OPAT regarding clinical efficacy, safety, acceptability and cost-effectiveness., Methods: We systematically searched the Cochrane Library, CINAHL, EMCARE, EMBASE and MEDLINE databases through 24 July 2022, for relevant studies published in English. Research articles and conference abstracts were included if they involved any form of telephone or video consultation in delivering parenteral antibiotics in the home or outpatient setting. Study findings were synthesised into three main themes: patient outcomes and safety, patient and provider satisfaction and cost-effectiveness. The mixed methods appraisal tool was used to review the methodological quality of the studies. PROSPERO CRD42022342874., Results: The literature search yielded 311 articles, of which 12 (five full-length articles and seven conference abstracts) reporting over 1245 telemedicine interventions were reviewed. The reported outcomes were heterogeneous. Telemedicine was cost-effective and associated with high patient satisfaction and comparable complication rates compared to conventional OPAT. Considering six comparative studies, rehospitalisation risk was lower for telemedicine than conventional OPAT (risk ratio, 0.58; 95% confidence interval, 0.38-0.88; I 2   =  31%)., Discussion: The results of this review demonstrate that telemedicine has a role in delivering safe and cost-effective OPAT care, especially for patients residing in remote and geographically isolated locations. Nevertheless, high-quality studies and publication of existing data and experiences are needed to further validate this model of care delivery., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Objectives: Parenteral drug products should be essentially free from visible particulate contamination. To ensure this, every batch produced must be subject to a 100% visual inspection. Monograph 2.9.20 of the European Pharmacopoeia (Ph. Eur.) describes a method for visual inspection of parenteral drug units in front of a black and white panel using a white light source. Nevertheless, several Dutch compounding pharmacies rely on an alternative method for visual inspection by means of polarised light. The objective of this study was to compare the performance of both methods., Methods: Trained technicians in three different hospitals inspected a predetermined set of samples using both methods for visual inspection of parenteral drugs., Results: The results of this study show that the alternative method for visual inspection yields a higher recovery than the Ph. Eur. method, while no significant difference in false positive results was found., Conclusions: Based on these findings, it can be concluded that the alternative method for visual inspection by means of polarised light can very well replace the Ph. Eur. method in pharmacy practice, provided that local validation of the alternative method is performed., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The product information and literature does not provide confirmation of compatibility for co-administration of all commonly used drug pairs in obstetrics. However, there is a need for co-administration of these drugs over one lumen for this group of patients. Therefore, this study focuses on Y-site compatibility. Since different conditions between clinical and laboratory settings can lead to discrepancies in results, a novel approach for drug intravenous compatibility testing was designed to reflect clinical conditions. The aim was to study the compatibility of nine commonly used drug pairs in obstetrics and to evaluate the clinical value of the designed method., Methods: The clinical situation was reflected by using different temperature ranges (20°C and 37°C), actual Y-site flow ratios, clinically relevant drug pairs and an observation time of 120 min. The clinically relevant drugs pairs include atosiban, nicardipine, amoxicillin/clavulanic acid, oxytocin, remifentanil, labetalol and magnesium sulpfate. Drug pairs were visually assessed according to the European Pharmacopoeia (Ph. Eur.) and pH was measured. When incompatibility of a drug pair seemed likely based on literature review or observed abnormalities during visual assessment, subvisual analysis was performed using a particle counter. Y-site compatibility applied for drug pairs when no visual changes occurred or when no additional particles were formed during the observation time., Results: Eight of the nine combinations showed no visual changes or noticeable changes in pH during the observation time. The amoxicillin/clavulanic-acid-oxytocin combination showed a colour change at 37°C at the actual Y-site flow ratio. However, subvisual particle counting showed no formation of additional particles., Conclusions: Y-site compatibility was established for all tested drug pairs. The new clinical approach for analysing Y-site compatibility provides a high certainty of outcomes for clinical practice. In this way, clinical complications and use of several additional intravenous catheters can be avoided., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The increasing amount of hazardous preparations in combination with shortages leads to a call for more efficient compounding methods. This research aims to evaluate the required amount of time, production capacity and direct labour costs of the manual, manual software-supported and robotic compounding of parenteral hazardous drugs., Methods: This multicentre study was conducted at the clinical pharmacy departments of three Dutch hospitals with different compounding methods: St Antonius hospital (manual software-supported compounding), Amsterdam University Medical Centre (Amsterdam UMC) (both robotic compounding and manual compounding without software support) and OLVG (robotic compounding). Time measurements of individual hazardous drugs were performed in all three hospitals. At Amsterdam UMC and St Antonius hospital, the times per compounding phase, the production capacity and the direct labour costs per preparation were also determined. To reflect real-world situations, the combination of robotic and manual compounding was also studied., Results: The total compounding process, including the actions before compounding and the release-time and cleaning time, lasted 6:44 min with robotic compounding and was faster than manual compounding with and without software support (6:48 and 9:48 min, respectively). The production capacity of one full-time equivalent (FTE) on 1 day (P 1FTE1day ) was 15 preparations per FTE per day with manual compounding with and without software support, and 57 preparations per FTE per day with only robotic compounding. If manual and robotic compounding were combined, the production capacity was 30 preparations per FTE per day. In this setting, the direct labour costs per preparation were €5.21, while these costs were €13.18 with only manual compounding., Conclusion: Compared with manual compounding, robotic compounding was faster over the total compounding process. A combination of manual compounding and robotic compounding could lead to 100% more preparations per FTE and 2.5 times lower direct labour costs compared with manual compounding., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival., Objective: To assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks' gestation to mitigate lethal pulmonary hypoplasia., Design, Setting, and Participants: Prospective, nonrandomized clinical trial conducted at 9 US fetal therapy centers between December 2018 and July 2022. Outcomes are reported for 21 maternal-fetal pairs with confirmed anhydramnios due to isolated fetal bilateral renal agenesis without other identified congenital anomalies., Exposure: Enrolled participants initiated ultrasound-guided percutaneous amnioinfusions of isotonic fluid before 26 weeks' gestation, with frequency of infusions individualized to maintain normal amniotic fluid levels for gestational age., Main Outcomes and Measures: The primary end point was postnatal infant survival to 14 days of life or longer with dialysis access placement., Results: The trial was stopped early based on an interim analysis of 18 maternal-fetal pairs given concern about neonatal morbidity and mortality beyond the primary end point despite demonstration of the efficacy of the intervention. There were 17 live births (94%), with a median gestational age at delivery of 32 weeks, 4 days (IQR, 32-34 weeks). All participants delivered prior to 37 weeks' gestation. The primary outcome was achieved in 14 (82%) of 17 live-born infants (95% CI, 44%-99%). Factors associated with survival to the primary outcome included a higher number of amnioinfusions (P = .01), gestational age greater than 32 weeks (P = .005), and higher birth weight (P = .03). Only 6 (35%) of the 17 neonates born alive survived to hospital discharge while receiving peritoneal dialysis at a median age of 24 weeks of life (range, 12-32 weeks)., Conclusions and Relevance: Serial amnioinfusions mitigated lethal pulmonary hypoplasia but were associated with preterm delivery. The lower rate of survival to discharge highlights the additional mortality burden independent of lung function. Additional long-term data are needed to fully characterize the outcomes in surviving neonates and assess the morbidity and mortality burden., Trial Registration: ClinicalTrials.gov Identifier: NCT03101891.

Outpatient parenteral antimicrobial therapy (OPAT) is a cost-effective method of administering intravenous antimicrobial therapy. Although OPAT is well established in the UK and US healthcare systems, few centres in Europe perform it. Here we analysed OPAT for the treatment of patients with spinal infections at our institution. In this retrospective study, patients with spinal infection who required intravenous (i.v.) antimicrobial treatment between 2018 and 2021 were analysed. The duration of short-term antimicrobial treatment for skin and soft tissue infections and complex infections requiring long-term antimicrobial treatment, such as spinal bone or joint infections, were analysed. All patients were discharged with a peripherally inserted central catheter (PICC) line. Prior to discharge, all patients received training in the safe administration of their medications via the PICC line. The duration of OPAT and the rate of readmission after OPAT were analysed. For this study a total of 52 patients who were treated via OPAT due to spinal infections were analyzed. In 35 cases (69.2%) complex spinal infection was reason for i.v. antimicrobial therapy. Surgery was required in 23 of these 35 patients (65.7%). The average hospital stay for these patients was 12 ± 6 days. The remaining 17 patients were treated for an infection of the soft tissue or the skin and hospital stay for these patients was on average 8 ± 4 days. Gram-positive organisms were isolated in 64.4%. Staphylococcus aureus followed by other Staphylococcus species, was the most common detected organism. After discharging i.v. antimicrobial treatment was given for an average of 20 ± 14 days. The duration of antimicrobial treatment for soft tissue was 10.8 ± 8 days, and for complex infections 25.1 ± 18 days. The mean follow-up was 21 ± 14 months. There was one case of readmission due to treatment failure. There were no difficulties encountered in implementing OPAT. OPAT is a feasible and effective option for delivering intravenous antimicrobial therapy to patients with spinal infections who can be managed without hospitalisation. OPAT offers patient-centred treatment at home while avoiding the risks associated with hospitalisation, with high levels of patient satisfaction., (© 2023. The Author(s).)

Background: Many facilities utilize outpatient parenteral intravenous (IV) antimicrobial therapy (OPAT) to reduce cost, length of stay, and risk of nosocomial infections., Objective: The objective of this study was to analyze patient demographics, substance use, mental and physical health diagnoses, and social determinants of health to seek relationships with complications for veterans discharged from the Zablocki Veterans Affairs Medical Center (ZVAMC) on OPAT., Methods: This study was a retrospective chart review of veterans who completed OPAT between the years of 2013 and 2017 at the ZVAMC in Milwaukee, Wisconsin. Prior to discharge, patients were screened by the OPAT team for eligibility; patients were followed after discharge by pharmacy, home care, and providers. OPAT complication was defined as antibiotic change/dose adjustment, IV catheter complication, or an additional hospital visit secondary to current infection or therapy., Results: 294 veterans' charts were reviewed. Of these patients, 106 (36.05%) had a complication. Tobacco use was the only factor significantly associated with OPAT complication., Conclusions: Cohabitation, employment status, mental health diagnosis and alcohol use were not associated with OPAT failure; however, tobacco use merits further review for use in OPAT screening protocols., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To investigate the clinical outcome of patients with infective endocarditis (IE) during and after outpatient parenteral antimicrobial treatment (OPAT), and to further clarify the safety and efficacy of OPAT for IE patients., Methods: Through December 20, 2021, a total of 331 articles were preliminarily searched in Pubmed, Web of Science, Cochrane Library and Embase, and 9 articles were eventually included in this study., Results: A total of 9 articles comprising 1,116 patients were included in this study. The overall mortality rate of patients treated with OPAT was 0.04 (95% CI, 0.02-0.07), that means 4 deaths per 100 patients treated with OPAT. Separately, mortality was low during the follow-up period after OPAT treatment, with an effect size (ES) of 0.03 (95%CI, 0.02-0.07) and the mortality of patients during OPAT treatment was 0.04 (95% CI, 0.01-0.12). In addition, the readmission rate was found to be 0.14 (95% CI, 0.09-0.22) during the follow-up and 0.18 (95% CI, 0.08-0.39) during treatment, and 0.16 (95% CI, 0.10-0.24) for patients treated with OPAT in general. Regarding the relapse of IE in patients, our results showed a low overall relapse rate, with an ES of 0.03 (95% CI, 0.01-0.05). In addition, we found that the incidence of adverse events was low, with an ES of 0.26 (95% CI, 0.19-0.33)., Conclusions: In general, the incidence of adverse events and mortality, readmission, and relapse rates in IE patients treated with OPAT are low both during treatment and follow-up period after discharge, indicating that OPAT is safe and effective for IE patients. However, our study did not compare routine hospitalization as a control group, so conclusions should be drawn with caution. In order to obtain more scientific and rigorous conclusions and reduce clinical risks, it is still necessary to conduct more research in this field and improve the patient selection criteria for OPAT treatment, especially for IE patients. Finally, clinical monitoring and follow-up of OPAT-treated patients should be strengthened., (©The Author 2022. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Background/aim: To evaluate the clinical desire for pressurized intraperitoneal aerosol chemotherapy (PIPAC) in South Korea., Patients and Methods: We performed an online survey on surgical oncologists between November and December 2019 using a questionnaire consisting of 20 questions., Results: A total of 164 respondents answered the questionnaire. Among those specialized in ovarian cancer, pseudomyxoma peritonei, and malignant mesothelioma 41.7-50% preferred PIPAC for the curative treatment of primary diseases, whereas 32.7-33.3% majoring in colorectal and hepatobiliary cancers chose it for the palliative treatment of recurrent diseases. Furthermore, 66.7-95.2% considered PIPAC appropriate for the cancers they specialized in, and 76-78.7% expected a treatment response of more than 50% and considered grade 1 or 2 complications acceptable. Most respondents answered the reasonable costs to purchase and implement PIPAC once at between 1,000,000-5,000,000 South Korean Won (KRW)., Conclusion: Most Korean surgical oncologists expected relatively high tumor response rates with minor toxicities through the repeated implementation of PIPAC., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: To perform a systematic review and meta-analysis of all randomized placebo-controlled trials (RCTs) that inspected the analgesic benefits of intraperitoneal lidocaine instillation among patients undergoing abdominal hysterectomy., Methods: Five electronic databases were inspected from till August 5, 2021. The eligible RCTs were evaluated for risk of bias. The pooled endpoints were summarized as mean difference (MD) or risk ratio (RR) with 95% confidence interval (CI)., Results: Five RCTs met the inclusion criteria comprising 263 patients (119 and 117 patients were allocated to lidocaine and control group, respectively). The included RCTs demonstrated a low risk of bias. The postoperative pain score at rest was significantly lower in favor of the lidocaine group (MD=-1.01, 95% CI [-1.20, -0.81], p<0.001), and subgroup analysis demonstrated the same at 2, 4, 8, 12, 24, and 48 h postoperatively. Moreover, the postoperative pain score at moving was significantly lower in favor of the lidocaine group (MD=-0.67, 95% CI [-1.01, -0.33], p<0.001), and subgroup analysis demonstrated the same at 2 and 48 h postoperatively. The postoperative morphine consumption during 0-24 h was significantly lower in favor of the lidocaine group (n = 5 RCTs, MD=-7.29 mg, 95% CI [-13.22, -1.37], p = 0.02). The rate of postoperative vomiting was significantly lower in favor of the lidocaine group (n = 4 RCTs, RR=0.54, 95% CI [0.31, 0.95], p = 0.03)., Conclusion: Among patients undergoing abdominal hysterectomy, intraperitoneal lidocaine instillation is feasible, cheap, safe, and associates with effective analgesia in terms of reduced postoperative pain score and morphine consumption., Competing Interests: Conflict of interest statement The authors report no conflict of interest., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objective: To evaluate the impact of outpatient parenteral antimicrobial therapy (OPAT) on a public hospital in a middle-income country., Design: A retrospective, observational study analyzing the economic data retrieved on the dehospitalization of patients on antibiotic therapy., Setting: Public university trauma hospital., Patients: Data were collected from June 2017 to May 2020. Antibiotic cost, hospital length of stay, and risk of multidrug-resistant (MDR) infection or colonization were reviewed, along with the break-even point at which a balance occurs between OPAT antimicrobial costs and all in-hospital costs. A cumulative risk curve was constructed showing the incidence of MDR during the review period., Results: In total, 225 patients were studied. The implementation of OPAT resulted in a reduction of $156,681 (49.6%), which is equivalent to an average of $696 per patient, as well as a shortened length of stay, from 33.5 to 15.7 days. OPAT reduces the risk of acquiring infection by MDR bacteria by having the final treatments administered outside of the hospital environment. The breakeven curves, comparing the duration of the OPAT to daily medication costs, allowed for the prediction of the time and dollar costs of antibiotic therapy., Conclusions: OPAT presented a significant cost savings, shortened length of stay, and reduced risk of contamination of patients by MDR.

Background and Aim: Cell-free and concentrated ascites reinfusion therapy (CART) has been performed against cirrhotic ascites, one of the most common complications seen in patients with decompensated cirrhosis. The aim of this study is to investigate its safety and efficacy, and differences in clinical profiles from CART against malignancy-related ascites with different pathological background., Methods: The present investigation involved a sub-analysis of data obtained from a prospective observational study of CART performed at 22 centers. The condition of each procedure, therapeutic options, laboratory data, performance status, dietary intake, and abdominal circumference of participants were analyzed. Clinical parameters were compared between before and after CART, with or without albumin infusion, and also primary diseases including cirrhosis and malignant disease., Results: Between January 2014 and January 2015, a total of 48 and 275 CART procedures were performed in patients with cirrhosis and malignancies. In cirrhotic patients, serum albumin concentration increased significantly in groups both with and without concomitant albumin infusion (P = 0.002 and P = 0.023), and no significant difference in CART interval was seen between these groups (P = 0.393). CART interval was not significantly different between cirrhosis and malignancy groups (P = 0.334). Dietary intake significantly improved after CART in both groups (P = 0.043 and P < 0.001). Adverse events were with no clinical significance as observed in patients with malignancies., Conclusions: Cell-free and concentrated ascites reinfusion therapy was performed safely and effectively in patients with ascites related to decompensated cirrhosis and offers the potential efficacy to maintain plasma colloid osmotic pressure after paracentesis as well as in patients with malignancy., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The intraperitoneal route of administration accounts for less than 1% of insulin treatment regimes in patients with diabetes mellitus type 1 (DM1). Despite being used for decades, a systematic review of various physiological effects of this route of insulin administration is lacking. Thus, the aim of this systematic review was to identify the physiological effects of continuous intraperitoneal insulin infusion (CIPII) compared to those of continuous subcutaneous insulin infusion (CSII) in patients with DM1. Four databases (EMBASE, PubMed, Scopus and CENTRAL) were searched beginning from the inception date of each database to 10th of July 2020, using search terms related to intraperitoneal and subcutaneous insulin administration. Only studies comparing CIPII treatment (≥ 1 month) with CSII treatment were included. Primary outcomes were long-term glycaemic control (after ≥ 3 months of CIPII inferred from glycated haemoglobin (HbA1c) levels) and short-term (≥ 1 day for each intervention) measurements of insulin dynamics in the systematic circulation. Secondary outcomes included all reported parameters other than the primary outcomes. The search identified a total of 2242 records; 39 reports from 32 studies met the eligibility criteria. This meta-analysis focused on the most relevant clinical end points; the mean difference (MD) in HbA1c levels during CIPII was significantly lower than during CSII (MD = -6.7 mmol/mol, [95% CI: -10.3 --3.1]; in percentage: MD = -0.61%, [95% CI: -0.94 -- 0.28], p = 0.0002), whereas fasting blood glucose levels were similar (MD = 0.20 mmol/L, [95% CI: -0.34-0.74], p = 0.47; in mg/dL: MD = 3.6 mg/dL, [95% CI: -6.1-13.3], p = 0.47). The frequencies of severe hypo- and hyper-glycaemia were reduced. The fasting insulin levels were significantly lower during CIPII than during CSII (MD = 16.70 pmol/L, [95% CI: -23.62 --9.77], p < 0.0001). Compared to CSII treatment, CIPII treatment improved overall glucose control and reduced fasting insulin levels in patients with DM1., Competing Interests: The authors have declared that no competing interests exist.

Obesity is a global public health concern associated with increased risk of several comorbidities. Due to the limited effectiveness of current therapies, new treatment strategies are needed. Our aim was to examine the effect of adipose-derived mesenchymal stem cells (AD-MSCs) on obesity and its associated diseases in a diet-induced obese (DIO) animal model. C57BL6 mice were fed with either high fat diet (HFD) or CHOW diet for 15 weeks. Obese and lean mice were then subjected to two doses of AD-MSCs intraperitoneally. Mice body weight and composition; food intake; blood glucose levels; glycated hemoglobin (HbA1c), intraperitoneal glucose tolerance test and atherogenic index of plasma (AIP) were measured. Pro-inflammatory cytokines, tumor necrosis factor-α and interleukin-6, were also determined. AD-MSCs treatment reduced blood glucose levels, HbA1c and AIP as well as improved glucose tolerance in DIO mice. In addition, MSCs caused significant attenuation in the levels of inflammatory mediators in HFD-fed mice. Taken together, AD-MSCs were effective in treating obesity-associated diabetes in an animal model as well as protective against cardiovascular diseases as shown by AIP, which might be partly due to the attenuation of inflammatory mediators. Thus, AD-MSCs may offer a promising therapeutic potential in counteracting obesity-related diseases in patients.

Introduction: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly used to treat peritoneal metastases from appendiceal or colorectal origin. We evaluate our institution's experience and survival outcomes with this procedure, and its efficacy in symptom relief., Methods: This is a single-centre retrospective observational study on patients with peritoneal metastases (PM) from appendiceal neoplasm or colorectal cancer who underwent CRS/HIPEC in Queen Mary Hospital. Our primary endpoints were overall survival (OS) and morbidity and mortality of this procedure; secondary endpoints included disease-free survival (DFS) and symptom-free survival., Results: Between 2006 and 2018, thirty CRS/HIPEC procedures were performed for 28 patients - 17 (60.7%) had appendiceal PM while 11 (39.9%) had colorectal PM. The median peritoneal cancer index was 20; complete cytoreduction was achieved in 83.3% patients. High-grade morbidity occurred in 13.3% cases. There was no 30-day mortality. Two-year OS were 71.6% and 50% for low-grade appendiceal PM and colorectal PM patients (p = 0.20). Complete cytoreduction improved OS (2-year OS 75.4% vs 20%, p = 0.04). Median DFS was 11.8 months. Median symptom-free duration was 36.8 months; patients with complete cytoreduction were more likely to remain asymptomatic (82.9% at 1 year, vs 60% in incomplete cytoreduction group, p < 0.01). 91.7% low-grade appendiceal PM patients and 58.4% colorectal PM patients remained asymptomatic at post-operative one year (p = 0.31)., Conclusion: CRS/HIPEC is beneficial to appendiceal PM and selected colorectal PM patients - improving survival and offering prolonged symptom relief, with reasonable morbidity and mortality. Complete cytoreduction is key to realising this benefit., Competing Interests: Declaration of competing interest We have no conflicts of interest to disclose. We would like to acknowledge Dr JWC Ho and Prof WL Law for starting the cytoreductive surgery/ HIPEC programme in our centre., (Copyright © 2020. Published by Elsevier Taiwan LLC.)

Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) constitutes a recently described surgical technique to administer chemotherapy directly to the peritoneum, under pressure, for patients with peritoneal metastasis (PM). The purpose of an oncological treatment is to improve survival but without altering the patient's quality of life. The aim of this review was to evaluate patient-reported outcomes (PRO) after PIPAC for patients with PM. This systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Between January 1, 2013, and January 1, 2020, studies were selected according to the following criteria: "pressurized intraperitoneal aerosol chemotherapy" OR "PIPAC" AND "patient-reported outcomes" OR "PRO" OR "Quality of life". In this review, 959 PIPAC and five PITAC (Pressurized IntraThoracic Aerosol Chemotherapy) were performed in 425 patients. We highlight the prominent application of generic EORTC QLQ-C30 followed by SF-36 in this review. The PROs according to the EORTC-QLQ-C30 global health score and based on symptom and function scores were stable across most studies. Moreover, PIPAC has improved the PRO of altered patients in two studies. Among 425 patients, the mortality rate was 0.7% and adverse events of Common Terminology Criteria of Adverse Events grade 3 and grade 4 were 9.6% and 1.6%, respectively. We synthesised current research on PROs among patients with PM. This review increases our understanding of the PIPAC strategy from the patient perspective. The implementation of PROs can be complex but will be essential in delivering quality care., (Copyright © 2020. Published by Elsevier Ltd.)

Background & Aims: High output entero-cutaneous fistulas may lead to intestinal failure with parenteral nutrition (PN) as the gold standard treatment to prevent dehydration and malnutrition. However in case of entero-atmospheric fistula (EAF) with the distal limb of the fistula accessible, chyme reinfusion (CR), a technique that restores artificially digestive continuity can be performed until the surgical repair. Our aim was to study the efficacy of CR in EAF regarding nutritional status, intestinal function, PN weaning and liver tests., Methods: Retrospective study of 37 patients admitted for EAF and treated by CR from 1993 to 2017. Delays were expressed in median (25%-75% quartiles) and other data on mean ± SD., Results: Location of EAF: jejunum (29), ileum (8). The length of the upstream intestine was estimated in 21 patients: 19 had a bowel length <150 cm of which 16 had less than 100 cm. During CR, mean digestive losses decreased from 1734 ± 578 to 443 ± 487 ml/24 h (p < 0.000001), nitrogen absorption increased from 45.3 ± 18.6 to 81.8 ± 12.9% of ingesta (p < 0.001). The percentage of patients with plasma citrulline <20 µmol/l decreased from 71 to 10%. PN was stopped in all patients within 3 (0-14) days after CR initiation, 2 patients required an intravenous hydration and 20 had an additional enteral support. The nutritional status improved: albumin (33.1 ± 5.1 g/L vs 28.4 ± 6.5, p < 0.001), NRI (decrease of the number of patients at risk of severe malnutrition from 22 to 10 (p < 0.001)). The number of patients who had one or several liver tests abnormalities (>2 N) decreased from 94 to 41% (p < 0.001)., Conclusion: When the efferent part of the small bowel is accessible, CR is a safe and inexpensive method that restores bowel function. In most cases, it makes it possible to stop PN and helps to improve the nutritional status until surgical reconstruction., Competing Interests: Conflicts of Interest None for any of the authors., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Anemia is common but under-diagnosed and often inadequately treated in KTX recipients. ID is the major cause of early-onset anemia. We introduced routine use of parenteral (IV) iron in patients (2-18 years) who had KTX between January 2011 and December 2015. We explored the clinical benefits of this practice by comparing the iron-treated subjects [TX] with historical controls who had KTX between 2005 and 2010. The prevalence of anemia at 6 months (early-onset) for the cohort (both the study group and controls) was 55% and for anemia at 12 months (late-onset) was 60%. Although cause-effect relationship may not be proven in a retrospective study design, there was a significant greater frequency of ID and anemia at 3 (P < .02) and 6 months (P < .04), and a reduced allograft function (eGFR < 60 mL/min/1.73 m 2 ) at 12 (P = .03) and 24 months (P = .04) of KTX in the control arm. Furthermore, a greater proportion of the control arm required either ESA (P = .03) or blood transfusion (P = .04) as a rescue treatment for moderate-to-severe anemia. In conclusion, routine parenteral iron treatment was associated with a lower prevalence of early- and late-onset anemia, and a lower requirement for either ESA rescue or blood transfusion., (© 2020 Wiley Periodicals LLC.)

Objective: The objectives were to define the maximum tolerated dose (MTD), safety profile and pharmacokinetics (PKs) of intraperitoneal oxaliplatin delivered by pressurised intraperitoneal aerosol chemotherapy (PIPAC) in patients with advanced peritoneal carcinomatosis from gastrointestinal tract cancers., Methods: PIPAC was applied every 4-6 weeks, for 5 cycles, in a phase I dose-escalation study using a 3 + 3 design. The first dose level was 90 mg/m 2 with planned increases of 50 mg/m 2 per level. Platinum concentration was measured in plasma, tissues and intraperitoneal fluid samples. The trial was registered at ClinicalTrials.gov (NCT03294252)., Results: Ten patients with 33 PIPAC sessions were included. No dose limiting toxicity (DLT) occurred at 90 mg/m 2 and two at 140 mg/m 2 . The MTD was therefore set at 90 mg/m 2 . Overall treatment included a median number of three PIPAC sessions (range: 1-5) and secondary complete cytoreductive surgery for two patients. Overall safety showed 67 grade I-II and 11 grade III-IV toxicities, usually haematologic, digestive (nausea/vomiting, abdominal pain), and fatigue. Oxaliplatin concentrations were three- to four-fold higher in tissue in contact with aerosol than in muscle without contact. At 140 mg/m 2 , the plasma oxaliplatin concentration was high with Cmax and area under the curve (AUC) 0-48h of 1035 μg/l and 9028 μg h/L, respectively., Conclusions: The MTD of oxaliplatin during PIPAC is 90 mg/m 2 . PK data demonstrate a high tumour concentration and a significant systemic absorption., Competing Interests: Conflict of interest statement O.G. received honoraria from Gamida. The others authors have no interest conflict to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Intestinal dysbiosis may contribute to the pathogenesis of necrotising enterocolitis (NEC) in very preterm or very low birth weight infants. Dietary supplementation with probiotics to modulate the intestinal microbiome has been proposed as a strategy to reduce the risk of NEC and associated mortality and morbidity.  OBJECTIVES: To determine the effect of supplemental probiotics on the risk of NEC and mortality and morbidity in very preterm or very low birth weight infants., Search Methods: We searched Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 2) in the Cochrane Library; MEDLINE Ovid (1946 to 17 Feb 2020), Embase Ovid (1974 to 17 Feb 2020), Maternity & Infant Care Database Ovid (1971 to 17 Feb 2020), the Cumulative Index to Nursing and Allied Health Literature (1982 to 18 Feb 2020). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs., Selection Criteria: We included RCTs and quasi-RCTs comparing probiotic supplementation with placebo or no probiotics in very preterm or very low birth weight infants., Data Collection and Analysis: We used the standard methods of Cochrane Neonatal. Two review authors separately evaluated trial quality, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference. We used the GRADE approach to assess the certainty of evidence for effects on NEC, all-cause mortality, late-onset infection, and severe neurodevelopmental impairment., Main Results: We included 56 trials in which 10,812 infants participated. Most trials were small (median sample size 149). Lack of clarity on methods to conceal allocation and mask caregivers or investigators were the main potential sources of bias in about half of the trials. Trials varied by the formulation of the probiotics. The most commonly used preparations contained Bifidobacterium spp., Lactobacillus spp., Saccharomyces spp., and Streptococcus spp. alone or in combinations. Meta-analysis showed that probiotics may reduce the risk of NEC: RR 0.54, 95% CI 0.45 to 0.65 (54 trials, 10,604 infants; I² = 17%); RD -0.03, 95% CI -0.04 to -0.02; number needed to treat for an additional beneficial outcome (NNTB) 33, 95% CI 25 to 50. Evidence was assessed as low certainty because of the limitations in trials design, and the presence of funnel plot asymmetry consistent with publication bias. Sensitivity meta-analysis of trials at low risk of bias showed a reduced risk of NEC: RR 0.70, 95% CI 0.55 to 0.89 (16 trials, 4597 infants; I² = 25%); RD -0.02, 95% CI -0.03 to -0.01; NNTB 50, 95% CI 33 to 100. Meta-analyses showed that probiotics probably reduce mortality (RR 0.76, 95% CI 0.65 to 0.89; (51 trials, 10,170 infants; I² = 0%); RD -0.02, 95% CI -0.02 to -0.01; NNTB 50, 95% CI 50 to 100), and late-onset invasive infection (RR 0.89, 95% CI 0.82 to 0.97; (47 trials, 9762 infants; I² = 19%); RD -0.02, 95% CI -0.03 to -0.01; NNTB 50, 95% CI 33 to 100). Evidence was assessed as moderate certainty for both these outcomes because of the limitations in trials design. Sensitivity meta-analyses of 16 trials (4597 infants) at low risk of bias did not show an effect on mortality or infection. Meta-analysis showed that probiotics may have little or no effect on severe neurodevelopmental impairment (RR 1.03, 95% CI 0.84 to 1.26 (five trials, 1518 infants; I² = 0%). The certainty on this evidence is low because of limitations in trials design and serious imprecision of effect estimate. Few data (from seven of the trials) were available for extremely preterm or extremely low birth weight infants. Meta-analyses did not show effects on NEC, death, or infection (low-certainty evidence)., Authors' Conclusions: Given the low to moderate level of certainty about the effects of probiotic supplements on the risk of NEC and associated morbidity and mortality for very preterm or very low birth weight infants, and particularly for extremely preterm or extremely low birth weight infants, further, large, high-quality trials are needed to provide evidence of sufficient quality and applicability to inform policy and practice., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Efficacy for alleviating signs/symptoms of malignant ascites of a renovated CART (cell-free and concentrated ascites reinfusion therapy) system, called KM-CART, was evaluated. A total of 4781 KM-CART procedures were performed in 2109 patients. All patients were accepted unless hemodynamically unstable or consciousness impaired. The ascites were processed and drip-infused into the patient. There were no major complications or deaths. The mean drainage volume was 6.2 L (maximum: 27.7 L), patient symptoms (numerical scale system) were significantly alleviated (45.1 ± 19.0 reduced to 21.2 ± 14.2, P < .001), and patient leg circumference significantly decreased (33.3 ± 4.4 cm reduced to 30.5 ± 4.4 cm, P < .001) without exacerbation of renal function. Collected cancer cells could be utilized for immune therapy. KM-CART is capable of improving the "quality of best supportive care" and can be beneficial in conjunction with medication for alleviating malignant pain., (© 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Objective: To investigate the efficacy and safety of prophylactic infusion of norepinephrine (NE) versus normal saline in patients undergoing cesarean section., Methods: Patients (n = 97) were randomized to receive a bolus of NE (6 μg) immediately following spinal anesthesia with maintenance NE (0.05 μg/kg/min IV) or normal saline (n = 98). The primary endpoint was the incidence of postspinal anesthesia hypotension [systolic blood pressure (SBP) < 80% of baseline] at 1-20 min following spinal anesthesia. Secondary outcomes were the overall stability of SBP control versus baseline, inferior vena cava collapsibility index (IVC-CI), other adverse events (bradycardia, nausea, vomiting, and hypertension), and neonatal outcomes (blood gas values and Apgar scores)., Results: The rates of postspinal anesthesia hypotension and severe postspinal anesthesia hypotension (SBP < 60% of the baseline) were significantly lower in the NE group (17.5% vs. 62.2%, p < 0.001; 7.2% vs. 17.4%, p = 0.031). In the NE group, SBP remained more stable and closer to baseline (p < 0.001), and IVC-CI values were lower 5 min after spinal anesthesia and 5 min after fetal delivery (p = 0.045; p < 0.001, respectively). Other adverse effects and neonatal outcomes were not different between the two groups., Conclusion: Prophylactic NE infusion effectively lowers the incidence of postspinal anesthesia hypotension and does not increase other adverse events in patients or neonates.

Purpose: To identify the cost and reasons of returned parenteral chemotherapy regimens at a tertiary hospital in Kuala Lumpur, Malaysia., Methods: Data were retrospectively extracted from all the Chemotherapy Return Forms in 2016, which is a compulsory documentation accompanying each return of parenteral chemotherapy regimen. The following data were extracted: patient's diagnosis, gender, location of treatment (i.e. ward/daycare clinic), start date of chemotherapy regimen, type of cytotoxic drug returned, dose of cytotoxic drug returned, number of cytotoxic drug preparations returned and reason for return as well as whether the returned cytotoxic drug preparations could be re-dispensed. The cost of wastage was calculated based on the cost per mg (or per unit) of the particular returned cytotoxic drug., Results: One hundred and fifty-nine cases of returned chemotherapy regimen comprising of 231 parenteral cytotoxic drug preparations were analysed. The total cost of returned chemotherapy regimen for 2016 was €3632, with €756 (20.8%) worth of chemotherapy regimens returned due to preventable reasons and €2876 (79.2%) worth of chemotherapy regimens returned due to non-preventable reasons. Approximately 50% of cases returned chemotherapy regimen were due to deterioration of patient's clinical condition and another 24.5% of cases of returned chemotherapy regimen were attributed to adverse drug reactions., Conclusion: Wastage associated to non-preventable reasons such as adverse drug reactions and preventable causes like refusal of patients can be further reduced by using newer healthcare innovations and establishment of written institutional protocols or standard operating procedures as references for in-charge healthcare personnel when cytotoxic drug-related issues occur. Adoption of cost-saving strategies that have been proven by studies could further improve current cost containment strategies.

Study Aim: To assess whether Outpatient Parenteral Antimicrobial Therapy (OPAT) is provided equitably across gender and social groups in a tertiary care setting., Background: OPAT is a widely used and growing approach in high income countries to early discharge or admission avoidance for patients requiring intravenous antimicrobials. There is however a risk that equitable access to healthcare could be eroded unintentionally by expansion of outpatient or ambulatory approaches such as this. Anecdotal evidence in our service, and from published studies, have identified a gender and social group equity gap in outpatient services., Methods: Service data on inpatient cellulitis episodes over a seven-year period were matched to OPAT referral data to create a retrospective cross-sectional linked dataset. All individuals admitted from 2012 to 2017 inclusive for a primary diagnosis of cellulitis were included: 6295 admissions of 4944 individuals. Demographics, number of co-morbidities, length of hospital stay, number of admissions, distance from OPAT unit and Scottish Index of Multiple Deprivation (SIMD; as a metric of deprivation) were recorded. Adjusted odds of a referral to OPAT across SIMD quintiles and for females compared to males were calculated using multiple logistic regression., Results: Inequitable access to OPAT was identified. Deprivation was negatively associated with likelihood of OPAT referral. Inpatients from the most affluent SIMD quintile were more than twice as likely to have received an OPAT referral compared to those resident in the most deprived quintile (adjusted OR 2.08, 95% CI: 1.60-2.71, p <  0.0001). Women were almost a third less likely to receive an OPAT referral than men (adjusted OR 0.69, 95% CI: 0.58 to 0.82, p <  0.001). Results were adjusted for age, number of co-morbidities, admissions, length of stay, distance from nearest OPAT unit, time since first admission, deprivation and gender., Conclusions: OPAT services and other ambulatory care programmes should routinely evaluate the equity of their service provision and consider how they can reduce any identified imbalance. It is a critical responsibility of service planning to ensure an inequitable system does not develop, with those least able to access ambulatory care dispossessed of the associated benefits.

In the formulation of parenteral dosage forms, pH is a critical factor and can be a complicated factor in compounding intravenous admixtures since the additives and the vehicle may have different pH values. This is especially important, as a significant number of parenteral medications require compounding involving dissolution of lyophilized powders; dilution of drug doses for infusion; mixing of dextrose, amino acids, vitamins, and electrolytes for parenteral nutrition; etc. Compounding intravenous admixtures is common practice, but each admixture may present a different set of problems to consider, especially as it relates to pH., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

Background: To evaluate the feasibility and effectiveness of artificial ascites to assist thermal ablation of liver cancer adjacent to the gastrointestinal tract in patients with previous abdominal surgery., Methods: Thirty-nine patients with a total of 40 liver malignant tumors were enrolled between January 2016 and June 2019. All had histories of hepatectomy, splenectomy, cholecystectomy, and intestinal surgery. The distance between the tumor and the gastrointestinal tract was < 5 mm. Normal saline was used as artificial ascites to protect the gastrointestinal tract during thermal ablation. The success rate of the procedure, incidence of major complications, and the technical efficacy of ablation were recorded. Patients were followed for local tumor progression (LTP), and overall survival (OS)., Results: The use of artificial ascites was successful in 38 of the 40 procedures (95%). Major complications occurred in two of the 39 patients (5.1%) following the procedure. One was an intestinal fistula that occurred in a failed case and was associated with an infection. The other was a liver abscess that occurred in a successful case. The technical efficacy of ablation was 100% (40/40 procedures). The median follow-up was 16 months. The 1-, 2-, and 3-year LTP rates were 2.9, 5.7 and 5.7%. The 1-, 2-, and 3-year OS rates were 97.1, 86.8 and 69.5%., Conclusion: In patients with previous abdominal surgery, artificial ascites is feasible and effective for assisting thermal ablation of liver cancer adjacent to the gastrointestinal tract.

Objectives: Heated intraperitoneal chemotherapy (HIPEC) has not been universally adopted at the time of interval cytoreductive surgery for primary epithelial ovarian cancer (EOC) despite evidence of a 12-month overall survival (OS) benefit in a recent landmark randomized trial. We performed a systematic review and meta-analysis to assess oncologic outcomes and perioperative morbidity following HIPEC among primary EOC patients., Methods: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, from inception to August 2019, for observational and randomized studies of primary EOC patients undergoing HIPEC. We assessed risk of bias using the Institute of Health Economics Quality Appraisal Checklist for single-arm cohort studies, Newcastle-Ottawa Scale for comparative cohort studies, and Cochrane Collaboration's Tool for randomized trials. We qualitatively summarized survival outcomes and calculated the pooled proportion of 30-day grade III-IV morbidity and postoperative death., Results: We identified 35 articles including 2252 primary EOC patients; one study was a randomized trial, and only six studies included a comparator group of surgery alone. The timing, temperature, and chemotherapeutic agents used for HIPEC differed across studies. Reported OS was highly variable (3-year OS range: 46-77%); three comparative cohort studies and the sole randomized trial reported statistically significant survival benefits for HIPEC over surgery alone, while two comparative cohort studies did not. The pooled proportions for grade III-IV morbidity and postoperative death at 30 days were 34% (95% CI 20-52) and 0% (95% CI 0-5) respectively., Conclusion: One randomized trial suggests that HIPEC at time of interval cytoreductive surgery should be considered in patients with primary EOC. However, there is significant heterogeneity in literature with respect to an appropriate HIPEC regimen, short- and long-term outcomes. High-quality prospective randomized trials are urgently needed to clarify the role of HIPEC in the first-line treatment of primary EOC., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: This prospective, randomized, controlled study aimed to explore the efficacy of dexmedetomidine combined with epidural blockade on postoperative recovery of elderly patients after radical resection for colorectal cancer., Methods: Ninety-six elderly patients who underwent radical resection for colorectal cancer were randomly divided into the following four groups: dexmedetomidine, epidural blockade (ropivacaine), combined (dexmedetomidine + epidural blockade), and control (0.9% saline). The Mini-Mental State Examination (MMSE), Visual Analog Scale (VAS), and Ramsay scores at 48 hours, and time to first activity, length of hospital stay, and postoperative complication rates at 3 months were assessed., Results: Twelve hours after surgery, Ramsay scores were higher in the combined compared with the control and epidural blockade groups. Twenty-four hours after surgery, MMSE scores were higher in the combined compared with the other groups. The combined group showed the lowest VAS scores except at 48 hours. Time to first activity and length of hospital stay were significantly shorter in the combined compared with the other groups. There was no difference in total postoperative complication rates among the groups., Conclusions: A combination of intraoperative dexmedetomidine infusion and epidural blockade could mitigate pain after surgery, improve cognitive dysfunction in early surgery, and facilitate recovery.

The use of ampicillin in the outpatient setting has traditionally been avoided because of the short half-life and instability in solution of this drug. However, recent in vitro data and two case series support the safe and effective administration of ampicillin by continuous infusion in the community. Therapeutic drug monitoring (TDM) of beta-lactam antibiotics can be used to optimise antibiotic exposure and ensure adequate clinical responses. A case series is presented of patients receiving ampicillin via prolonged infusion in the outpatient setting, with TDM to ensure adequate plasma antibiotic levels were achieved. Three patients who received ampicillin by continuous infusion under the Outpatient Parenteral Antimicrobial Therapy (OPAT) program are described, including details of antibiotic dose and steady-state plasma drug concentration as measured by high-performance liquid chromatography. All three patients had an infection with ampicillin-susceptible Enterococcus faecalis; one patient had post-partum endometritis, one had urosepsis and one had a complex polymicrobial bone and joint infection. Adequate plasma drug levels were achieved in all patients. Management of the antibiotic temperature and infusion times, and appropriate timing of drug levels in the community were required. Two patients achieved clinical cure, while the third required further surgical debridement and antibiotic therapy. TDM in this setting enabled the contemporaneous management and dose alteration of ampicillin. Ampicillin may be a safe and effective drug when administered by continuous infusion with appropriate TDM in the community setting., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Febrile neutropaenia (FN) is a very common complication in patients with haematological malignancies and is associated with considerable morbidity and mortality. Broad-spectrum antipseudomonal β-lactam antibiotics (BLA) are routinely used for the treatment of cancer patients with FN. However, the clinical efficacy of BLA may be diminished in these patients because they present with pathophysiological variations that compromise the pharmacokinetic (PK) parameters of these antibiotics. Optimised administration of BLA in prolonged infusions has demonstrated better clinical outcomes in critically ill patients. However, there is a paucity of data on the usefulness of this strategy in patients with FN. The aim of this study is to test the hypothesis that the administration of BLA would be clinically more effective by extended infusion (EI) than by intermittent infusion (II) in haematological patients with FN., Methods: A randomised, multicentre, open-label, superiority clinical trial will be performed. Patients with haematological malignancies undergoing chemotherapy or haematopoietic stem-cell transplant and who have FN and receive empirical antibiotic therapy with cefepime, piperacillin-tazobactam or meropenem will be randomised (1:1) to receive the antibiotic by EI (during half the time of the dosing interval) in the study group, or by II (30 min) in the control group. The primary endpoint will be clinical efficacy, defined as defervescence without modifying the antibiotic treatment administered within the first 5 days of therapy. The primary endpoint will be analysed in the intention-to-treat population. The secondary endpoints will be pharmacokinetic/pharmacodynamic (PK/PD) target achievement, bacteraemia clearance, decrease in C-reactive protein, overall (30-day) case-fatality rate, adverse events and development of a population PK model of the BLA studied., Discussion: Data on the usefulness of BLA administration in patients with FN are scant. Only three clinical studies addressing this issue have been published thus far, with contradictory results. Moreover, these studies had some methodological flaws that limit the interpretation of their findings. If this randomised, multicentre, phase IV, open-label, superiority clinical trial validates the hypothesis that the administration of BLA is clinically more effective by EI than by II in haematological patients with FN, then the daily routine management of these high-risk patients could be changed to improve their outcomes., Trial Registration: European Clinical Trials Database: EudraCT 2018-001476-37. ClinicalTrials.gov, ID: NCT04233996.

Parenteral treatments (either subcutaneous or intravenous) are frequently used in rheumatology practice. In this study, drug side effects in patients who were followed up with a rheumatic disease and treated with parenteral administration methods were evaluated. The drug side effects in children who were followed up with a rheumatic disease and treated with parenteral treatments between 2010 and 2019 were recorded, retrospectively. All parenteral treatments are applied by a clinical nurse specialist (CNS) who is experienced in pediatric rheumatology for 10 years. Four hundred and thirteen patients were evaluated in this study. The mean age was 12.09 ± 5.05 years. Most of them were diagnosed with juvenile idiopathic arthritis (n = 317) and colchicine-resistant familial Mediterranean fever (n = 57). Among the patients, 287 was treated with methotrexate, 130 with etanercept, 90 with adalimumab, 71 with anakinra, 64 with canakinumab, 55 with tocilizumab, seven with rituximab, six with infliximab, and four with abatacept. Two of the patients had a history of drug allergy (ceftriaxone = 1, ranitidine = 1). The most common adverse reactions were as follows: nausea-vomiting in 52, rash in 11, itching in three, chest tightening in two, bruising in two, headache in two, and abdominal pain in one of the patients. Drug side effects were observed after an average of three (1-4) administrations. Antihistaminic and steroids (tocilizumab = 3, infliximab = 1, methotrexate = 1) were administered to five patients due to hypersensitivity reactions. Considering the possible side effects and preparation protocols of parenteral treatments, experienced physicians and nurses are required in the field.

Background and Aim: Post endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis is not an uncommon adverse event but may not be avoidable. Various pharmacological and endoscopic techniques have been used to prevent post-ERCP pancreatitis (PEP), but most have been ineffective. The aim of this study was to evaluate the preventative effect of an intrapancreatic duct injection of nafamostat mesilate (NM) on PEP. Methods: This experimental study was conducted on 8 mini pigs. Animals were randomly allocated to a control group ( n  = 4) and or a NM group ( n  = 4). Pancreatitis was induced by infusing contrast medium into the main pancreatic duct by ERCP in all animals. After contrast medium injection, NM (50 mg/5 cc) was infused in the NM group and the same amount of 5% dextrose solution was infused in the control group. Twenty-four hours after endoscopic procedures, pancreatic inflammation, edema, vacuolization, necrosis and hemorrhage were evaluated histologically. Results: All animals survived until the end of the experiment. No peri-procedural technical difficulty or adverse event was encountered. Histologic examinations confirmed acute pancreatitis in all animals. In histologic acute pancreatitis scoring, no significant intergroup differences were observed between edema ( P  = 0.134), leukocyte infiltration ( P  = 0.356), vacuolization ( P  = 1.000), or hemorrhage ( P  = 0.071) scores. However, mean necrosis score was significantly lower in the NM group (1.0) than in controls (1.75, P  = 0.024). Conclusion: NM injection into the intrapancreatic duct produced promising results with respect to the prevention of PEP development, especially regarding the prevention of necrosis.

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is used in the palliative treatment of peritoneal metastasis. The combination of intraperitoneal and systemic chemotherapy seems rational, and the aim of this systematic review was to compare PIPAC directed monotherapy with a bidirectional treatment approach (PIPAC in combination with systemic chemotherapy). Main outcomes were survival and quality of life., Methods: A systematic literature search in Medline, Embase, Cochrane and the "Pleura and Peritoneum" was conducted and analyzed according to PRISMA guidelines. Studies in English reporting on bidirectional treatment with PIPAC and systemic chemotherapy and published before April 2019 were included., Results: Twelve studies with a total of 386 patients were included. None were specifically designed to compare mono- versus bidirectional treatment, but 44% of the patients received bidirectional treatment. This was more frequent in women (non-gynecological cancers) and one-third of the bidirectional treated patients had received no prior chemotherapy. Data from the included studies provided no conclusions regarding survival or quality of life., Conclusion: Bidirectional treatment with PIPAC and systemic chemotherapy is practised and feasible, and some patients are enrolled having received no prior systemic chemotherapy for their PM. The difficulty in drawing any conclusions based on this systematic review has highlighted the urgent need to improve and standardize reports on PIPAC directed therapy. We have, therefore, constructed a list of items to be considered when reporting on clinical PIPAC research., Trial Registration: International Prospective Register of Systematic Reviews, PROSPERO. Registration number: 90352, March 5, 2018.

Aim: Given the scarcity of relevant reports, this study aimed to elucidate whether pregnancy can be prolonged by maintaining the amniotic fluid volume with continuous transabdominal amnioinfusion (TA) for patients with mid-trimester preterm premature rupture of membranes (PPROM) and oligoamnios., Methods: We retrospectively examined patients who were managed during hospitalization at our department after developing PPROM between week 22 day 0 and week 25 day 6 of gestation and subsequent oligoamnios (amniotic fluid index [AFI] <5 cm) within 7 days after PPROM onset. Cases between 2006 and 2011 comprised the conventional management group (n = 14); cases administered continuous TA between 2012 and 2017 comprised the continuous TA group (n = 14). The primary outcome was the number of days between PPROM and delivery. The secondary outcomes were the proportion of normal amniotic fluid volume (AFI ≥ 5 cm) maintained between PPROM and delivery and the perinatal prognosis for the mother and infant., Results: The continuous TA group had significantly more days between PPROM and delivery and a significantly higher proportion of days that a normal amniotic fluid volume was maintained during that period, regardless of antimicrobial agents administered. Although no significant differences in the perinatal prognosis of disease were found between groups, there was a decreasing trend of composite perinatal mortality and morbidity, and the incidence rates were reduced by half., Conclusion: Continuous TA for PPROM with oligoamnios may allow significant prolongation of the gestation period while maintaining the amniotic fluid volume and may lead to improved perinatal prognosis., (© 2019 Japan Society of Obstetrics and Gynecology.)

Cell therapy products represent an exciting new class of medicinal products, which must be parenterally administered. Thus, compliance with parenteral preparation guidelines is required. One requirement for parenteral products is the characterization of particle contaminations. As cell-based products are turbid suspensions, containing particles, the cells, characterization and control of foreign particle impurities remain a challenge. Within this study, we evaluated a flow imaging microscopy method for the detection and characterization of subvisible particle contaminations in cell-based products. We found that flow imaging microscopy is a potential method where subvisible particle contaminations can be differentiated from the cells in cell therapy products., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: The hepatobiliary tract may be a valuable administration site for gene delivery. We demonstrated the role of temporary biliary obstruction for gene transfection by retrograde intrabiliary infusion., Methods: Male Sprague-Dawley rats received intrabiliary infusion of luciferase plasmid via an artificial common bile duct, with temporary biliary obstruction for 0 minutes (NO group), 30 minutes (30 min group) and 24 hours (24 h group), respectively (n = 4 for each group). Gene expression levels were evaluated by luciferase bioluminescence on postoperative days (POD) 1, 2 and 7. Serum and livers were collected on POD 1 and 14 for liver biochemistry, hematoxylin and eosin staining, and immunohistochemistry., Results: On POD 1, luciferase chemoluminescence was significantly higher in the 24 h group than in the NO group (p = 0.002) and the 30 min group (p = 0.002). However, it decreased rapidly after reversal of the obstruction in the 24 h group (POD 1 versus POD 2, p = 0.002; POD 1 versus POD 7, p = 0.002). Liver biochemistry was changed on POD 1, but no significant differences were detected after 14 days of recovery (p > 0.05). Similar histological changes were found in the three groups, with no unwanted proliferation of biliary epithelial cells. The obstruction did not cause serious liver damage., Conclusions: Temporary biliary obstruction for 24 hours facilitated the safe, feasible and effective transfection of plasmid DNA into the liver via the hepatobiliary tract. In the future, endoscopic retrograde cholangiopancreatography and its dilation balloon could be used to create biliary obstruction and allow the direct gene delivery into the liver. More research is necessary for achieving stable gene expression, as well as in terms of weighing its benefits against potential complications., (© 2019 John Wiley & Sons, Ltd.)

Background: Continuous intra-duodenal infusion of levodopa-carbidopa intestinal gel (LCIG) is a well-established therapy for patients with advanced Parkinson's disease (PD) suffering from motor complications despite optimized treatment with oral dopaminomimetics. However, time to discontinuation of treatment with LCIG varies considerably between patients, ranging from a few months to more than ten years. To improve the selection of candidates for LCIG, knowledge of prognostic factors is of paramount importance., Objective: To explore baseline predictors of time to discontinuation of LCIG., Methods: In this two-center retrospective cohort study, we reviewed the medical files of 98 PD patients treated with LCIG between April 2006 and December 2015 (53% male; mean age: 66.2 years; mean disease duration: 12.3 years). Baseline patient characteristics were used as covariates in Cox regression models., Results: During follow-up (mean observation time: 2.6 years; range: 0.1-9.3) eighteen patients discontinued treatment (18.4%), while seven patients died (7.1%). Median duration of treatment with LCIG, estimated with Kaplan-Meier analysis, was 7.8 years (95% CI: 6.7-9.0). Disease duration (in years) at baseline was a statistically significant predictor of time to discontinuation of LCIG (HR: 0.85; 95% CI: 0.75-0.96, p = 0.006). All other characteristics studied, e.g. age >70 years, did not show statistically significant associations with the total duration of treatment with LCIG., Conclusion: Our findings show a low overall rate of discontinuation of LCIG infusion, with a median duration of treatment of 7.8 years. Shorter disease duration at baseline appeared to be a predictor of earlier discontinuation of LCIG.

Objective: To identify factors associated with non-completion of intraperitoneal with intravenous chemotherapy [IP/IV] in women with epithelial ovarian cancer (EOC)., Methods: This was an Institutional Review Board approved, retrospective cohort study in women with stage III EOC following optimal cytoreductive surgery (CRS) (<1 cm) followed by IP/IV chemotherapy from 2000-2016. Demographic, surgical, and oncologic variables were collected. Pearson χ² test and 2 sample t-test evaluated for variables associated with IP/IV chemotherapy completion. Kaplan-Meier survival analysis was performed for progression-free survival (PFS) and overall survival (OS)., Results: Of 96 women, 71.9% (n=69) completed 6 cycles of IP/IV chemotherapy. The majority had high grade serous histology (n=82; 85.4%) and stage IIIC disease (n=83; 86.5%). Common reasons for IP/IV chemotherapy discontinuation were grade 3-4 gastrointestinal (n=10; 37.0%), neurologic (n=6; 22.2%), hematologic (n=3; 11.1%), renal toxicities (n=3; 11.1%) and port infections (n=3; 11.1%). Incidence of IP port complications was 20.8% (n=20). Port complications (48.0% vs. 11.6%; p<0.001) and hospitalization during chemotherapy (29.6% vs. 2.9%; p<0.001) were more frequent in patients who discontinued IP/IV chemotherapy. Patients who completed IP/IV chemotherapy had higher rates of home discharge following CRS (92.2% vs. 72.0%; p<0.01) and lower Eastern Cooperative Oncology Group (ECOG) score (0 vs. 1.0; p=0.04). There was no significant difference in PFS (p=0.51) nor OS (p=0.38) between the cohorts., Conclusion: In this series, the rate of IP/IV chemotherapy completion is high. Non-home discharge and higher ECOG status following CRS are associated with IP/IV chemotherapy non-completion and should be considered in treatment planning., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Outpatient parenteral antimicrobial therapy (OPAT) offers safe, effective and patient-centred care for adults and children. The OPAT UK good practice recommendations for adults and children have recently been updated through a process of literature review, expert consensus and extensive stakeholder consultation. Here we discuss the key changes in the updated recommendations in the context of recent developments, including novel antimicrobial agents and delivery devices, the place of oral antimicrobials as an alternative to intravenous therapy, new OPAT service models and the broader antimicrobial stewardship agenda., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Study Objective: Iron deficiency anemia is the most common form of anemia, and parenteral iron therapy is necessary in select patients. The objective of this analysis was to assess the impact of initial complete parenteral iron repletion on serum hemoglobin (Hgb) level normalization and on health care resource utilization in real-world practice., Design: Retrospective observational study., Data Source: Decision Resources Group Real-World Data Repository (United States databases)., Patients: A total of 2966 patients who had a baseline Hgb level below normal (< 12 g/dl for females and < 13.5 g/dl for males) and were treated with parenteral iron between March 2015 and February 2017., Measurements and Main Results: The effect of receiving the required parenteral iron dose to replete the deficit, calculated by a modified Ganzoni formula, within 3 weeks of the first parenteral iron therapy claim (index date) on the likelihood of Hgb level normalization, was estimated by using logistic regression. All analyses were adjusted for sex, age, comorbidities, and use of prescription oral iron therapy. The adjusted mean numbers of all-cause inpatient admissions, outpatient visits, and emergency department (ED) visits within 6 months and 1 year after the index date were compared between patients with and without normalized Hgb levels by using negative binomial regression. Of the 2966 included patients, 33.9% received the required iron dose within 3 weeks of the index date, and 19.6%, 48.2%, and 53.9% had a normalized Hgb level within 8 weeks of the index date, within 1 year of the index date, and until the end of data availability, respectively. Patients who received the required iron dose within 3 weeks of the index date were significantly more likely to have a normalized Hgb level within 8 weeks of the index date and at any time during the study period than those who did not: adjusted odds ratio (OR) (95% confidence interval [CI]) 2.67 (2.20, 3.24) and 2.33 (1.96, 2.77), respectively. Hgb level normalization within 1 year of the index date was associated with fewer inpatient admissions and outpatient visits and a similar number of ED visits compared with no Hgb level normalization 1 year after the index date., Conclusion: The results of these analyses underscore the importance of initial complete parenteral iron repletion for rapidly improving clinical outcomes. Prompt achievement of a normalized Hgb level may also provide an opportunity to reduce health care resource utilization in patients with iron deficiency anemia receiving parenteral iron therapy., (© 2019 Pharmacotherapy Publications, Inc.)

Anemia is common in patients with mechanical circulatory support and is associated with increased morbidity. Repletion using parenteral iron infusions has been proven to be beneficial in patients with heart failure. In this report, we describe a case of increased power and flows of continuous-flow left ventricular assist device (LVAD) during an iron dextran infusion. We subsequently studied the effects of iron dextran infusion in an in vitro LVAD mock circulatory loop. The observed increase in flow and power was most likely due to drug-patient interaction rather than drug-LVAD interaction. Mock loops and in vivo animal models may be necessary for proactive evaluation of the safety of intravenous (IV) preparations in this patient population.

Background: The analgesic benefits of programmed intermittent bolus infusion for thoracic paravertebral block remain unknown., Objective: The aim of this study was to compare the analgesia from intermittent bolus infusion with that of a continuous infusion after thoracic paravertebral block., Design: A randomised controlled study., Setting: A single centre between December 2016 and November 2017. Seventy patients scheduled for video-assisted thoracoscopic surgery were included in the study., Intervention(s): Patients were randomly assigned to receive 0.2% levobupivacaine via continuous infusion (5 ml h, continuous group) or programmed intermittent bolus infusion (15 ml every 3 h, bolus group) after an initial 15-ml bolus injection of 0.2% levobupivacaine., Main Outcome Measures: The main outcome was the amount of rescue fentanyl (per kg of body weight) consumed within 24 h after surgery. Secondary outcomes were postoperative pain scores, plasma levobupivacaine concentrations and the number of dermatomes anaesthetised., Results: There was no significant difference between the continuous and bolus groups in the postoperative consumption of fentanyl (median [interquartile range] 5.5 [4 to 9.5] μg kg versus 6 [3.5 to 9] μg kg respectively, P = 0.45) and postoperative pain scores within 24 h. At 20 h after initiating the infusions, there was no statistically significant difference between the two groups in terms of the plasma levobupivacaine concentration. The number of dermatomes anaesthetised to pinprick and cold testing was significantly greater in the bolus group., Conclusion: Our findings suggest that postoperative pain and opioid usage are similar with either programmed intermittent bolus infusion or continuous infusion after thoracic paravertebral block. Programmed intermittent bolus infusion provides a wider sensory blockade and could benefit patients requiring a wider extent of anaesthesia., Trial Registration: UMIN Clinical Trials Registry (UMIN-CTR; URL: http://umin.ac.jp/ctr/, ID: UMIN000023378).

These first German S2k guidelines for bacterial skin and soft tissue infections were developed as one chapter of the recommendations for "calculated initial parenteral treatment of bacterial infections" issued under the auspices of the Paul-Ehrlich Society, of which the main part is presented here. Well-calculated antibiotic therapies require precise diagnostic criteria. Erysipelas is defined as non-purulent infection considered to be caused by beta-hemolytic strepto-cocci. It is diagnosed clinically by its bright-red erythema and early fever or chills at disease onset. Penicillin is the treatment of choice. Limited soft tissue infection (cellulitis) is usually caused by Staphylococcus (S.) aureus, frequently originates from chronic wounds and presents with a more violaceous-red hue and only rarely with initial fever or chills. Treatment consists of first- or second--generation cephalosporins or flucloxacillin (IV). Severe cellulitis is a purulent, partially necrotic infection which extends through tissue boundaries to fascias and requires surgical management in addition to antibiotics. Moreover, it frequently fulfills the criteria for "complicated soft tissue infections", as previously defined by the Food and Drug Administration for use in clinical trials (they include comorbidities such as uncontrolled diabetes, peripheral artery disease, neutropenia). It requires antibiotics which besides S. aureus target anaerobic and/or gramnegative bacteria. The rare so-called necrotizing skin and soft tissue infections represent a distinct entity. They are characterized by rapid, life-threatening progression due to special bacterial toxins that cause ischemic necrosis and shock and need rapid and thorough debridement in addition to appropriate antibiotics. For cutaneous abscesses the first-line treatment is adequate drainage. Additional antibiotic therapy is required only under certain circumstances (e.g., involvement of the face, hands, or anogenital region, or if drainage is somehow complicated). The present guidelines also contain consensus-based recommendations for higher doses of antibiotics than those approved or usually given in clinical trials. The goal is to deliver rational antibiotic treatment that is both effective and well-tolerated and that exerts no unnecessary selection pressure in terms of multidrug resistance., (© 2019 The Authors | Journal compilation © Blackwell Verlag GmbH, Berlin.)

Background: Drug-related adverse events (AEs) are reported to be common amongst patients receiving outpatient parenteral antimicrobial therapy (OPAT). However, comparative data regarding intravenous (iv) catheter-related AEs are lacking., Objectives: To compare drug- and iv catheter-related AEs from a large UK OPAT centre., Patients and Methods: We reviewed 544 OPAT episodes [median (IQR) age: 57 (39-71) years, 60% male, 13% with diabetes] with a median (IQR) duration of 7 (2-18) days. Clinically significant drug- and iv catheter-related AEs were calculated as a percentage of OPAT episodes with an AE and also as AEs per 1000 iv drug/catheter days., Results: Drug-related AEs complicated 13 (2.4%) OPAT episodes at 1.7 (95% CI 0.9-2.9) per 1000 drug days. Catheter-related AEs occurred more frequently, complicating 32 (5.9%) episodes at 5.7 (95% CI 4.2-7.9) per 1000 iv catheter days (χ2 test for difference in AE rate: P < 0.001). Non-radiologically guided midline catheters were associated with the most frequent AEs (n = 23) at 15.6 (95% CI 10.3-23.4) per 1000 iv catheter days compared with other types of iv catheters (HR 8.4, 95% CI 2.4-51.9, P < 0.004), and self-administration was associated with a higher rate of catheter-related AEs at 12.0 (95% CI 6.0-23.9) per 1000 iv catheter days (HR 4.15, 95% CI 1.7-9.1, P = 0.007)., Conclusions: Clinically significant iv catheter-related AEs occurred more frequently than drug-related AEs, especially when using non-radiologically guided midline catheters. Regular review of the need for iv therapy and switching to oral antimicrobials when appropriate is likely to minimize OPAT-related AEs., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

The programmed intermittent epidural bolus (PIEB) technique offers multiple benefits over continuous epidural infusion (CEI), but controversy still exists when it is used in conjunction with a parturient-controlled epidural analgesia (PCEA) regimen. A systematic review and meta-analysis was thus conducted using the Medline, EMBASE, CENTRAL and Web of Science databases with the aim of identifying those randomized controlled trials (RCTs) that performed a comparison between PIEB and CEI in healthy parturients using a PCEA regimen with regard to the duration of labor, labor pain, anesthesia interventions, maternal satisfaction and main side effects. The data were analyzed using a random-effects model. Eleven eligible trials were included, in which 717 participants were allocated to the PIEB + PCEA group and 650 patients were allocated to the CEI + PCEA group. The rate of instrumental delivery, incidence of breakthrough pain, PCEA usage rates and local anesthetic usage were significantly reduced, the labor duration was statistically shorter, and the maternal satisfaction score was significantly improved in the PIEB + PCEA group compared with that in the CEI + PCEA group. There were no differences in the side effects between the two groups. The results of the present study suggest that the PIEB technique in conjunction with the PCEA regimen was more advantageous than CEI + PCEA, but additional studies should be conducted to consistently demonstrate an improvement in the maternal and fetal obstetric outcomes.

For women with newly diagnosed ovarian cancer, the goal of surgery is to achieve a maximal, if not complete, cytoreduction. In cases when this is not possible, whether because of the extent of disease or patient-specific reasons, neoadjuvant chemotherapy using a platinum-based combination (on a typical every-2-week schedule) is often recommended. After neoadjuvant therapy and surgery, women proceed with additional adjuvant chemotherapy, which is typically given in a similar fashion to what was done in the preoperative setting. The question remains as to whether this is the optimal strategy, particularly in light of other data suggesting the use of an alternative regimen in the adjuvant context might yield a survival advantage. In this article, we review the outcomes of randomized trials that compared primary debulking to neoadjuvant chemotherapy and contemporary neoadjuvant chemotherapy trials that incorporated a novel schedule or regimen for testing in the adjuvant setting, including both intraperitoneal and heated intraperitoneal chemotherapy. We describe our center's approach to these data, and we conclude that both options should be considered for women with ovarian cancer undergoing neoadjuvant therapy.