Gemtuzumab ozogamicin plus midostaurin in combination with standard '7 + 3' induction therapy in newly diagnosed AML: Results from the SAL-MODULE phase I study.

We conducted a phase I trial in newly diagnosed acute myeloid leukaemia (AML) to investigate the combination of two novel targeted agents, gemtuzumab ozogamicin (GO) and midostaurin, with intensive chemotherapy in FLT3-mutated AML and CBF leukaemia. Three dose levels of midostaurin and one to three sequential doses of 3 mg/m2 GO in combination with '7 + 3' induction were evaluated. Based on safety findings in 12 patients, our results show that 3 mg/m2 GO on Days 1 + 4 and 100 mg midostaurin on Days 8-21 can be safely combined with IC in newly diagnosed AML.

Trifluridine/Tipiracil Plus Bevacizumab for Vulnerable Patients With Pretreated Metastatic Colorectal Cancer: A Retrospective Study (WJOG14520G).

BACKGROUND: Trifluridine/tipiracil (FTD/TPI) plus bevacizumab has shown clinical benefit for metastatic colorectal cancer (mCRC) refractory to standard therapy. However, few data have been available for patients with pretreated mCRC who are intolerant of intensive therapy (vulnerable). METHODS: We performed a multicenter retrospective study (WJOG14520G; TWILIGHT) of FTD/TPI plus bevacizumab for vulnerable patients with pretreated mCRC. Eligibility criteria included previous chemotherapy (although patients treated with all key cytotoxic agents, a fluoropyrimidine, oxaliplatin, and irinotecan, were excluded) and intolerance of full-dose combination therapy with oxaliplatin or irinotecan at the start of FTD/TPI plus bevacizumab. RESULTS: The median age of 93 evaluable patients was 79 years (range, 21-90). Intolerance of intensive therapy was attributable to an older age in 60 (65%) patients, serious concomitant disease in 24 (26%) patients, and a poor performance status in 19 (20%) patients. FTD/TPI plus bevacizumab was administered as second-line treatment in 74 (80%) patients and as third- or fourth-line treatment in 19 (20%) patients. The objective response rate was 4.9% (95% confidence interval [CI], 1.4%-12.2%), and the disease control rate was 67.9% (95% CI, 56.6%-77.8%). With a median follow-up time of 21.6 months, median overall survival and progression-free survival were 18.6 months (95% CI, 12.1-23.2) and 6.3 months (95% CI, 5.0-8.3), respectively. Neutropenia of grade ≥3 developed in 50 (54%) patients, whereas 2 (2%) patients experienced febrile neutropenia, and no treatment-related death was observed. CONCLUSION: Our data show the potential efficacy and acceptable safety profile of FTD/TPI plus bevacizumab for vulnerable patients with pretreated mCRC.

Clinical outcomes of intensive versus less intensive first-line chemotherapy for metastatic colorectal cancer.

Aims: Physicians determine the treatment regimen for metastatic colorectal cancer on a case-by-case bases, according to the individual disease characteristics. We retrospectively compared the baseline characteristics and efficacies of first-line treatment among patients with metastatic colorectal cancer who received intensive therapy involving fluoropyrimidine plus oxaliplatin and/or irinotecan, potentially with molecularly targeted agents as well, versus less intensive fluoropyrimidine and/or bevacizumab therapy. Materials & methods: Data were collected from a medical claims database. The efficacy outcomes were: time to treatment failure, time to first subsequent therapy and overall survival. Results: The less intensive therapy group (n = 633) had higher median age, lower daily activity levels and shorter time to treatment failure, time to first subsequent therapy and overall survival than the intensive therapy group (n = 3829). Combination therapy with molecularly targeted agents and bevacizumab improved treatment efficacy outcomes in the intensive and less intensive groups, respectively. Conclusion: Patient age and daily activity levels were important factors for determining treatment intensity.

In this study we performed a real-world data analysis of treatment for advanced colorectal cancer that had spread to other parts of patients' bodies, by investigating the medical records of 4462 patients. We wanted to see how well different treatments worked and what kinds of patients received them. We found that the most important factors when choosing between different treatments were the patient's age and how well they could perform their everyday tasks. We found that using specialized medicines in the intensive treatment group, and a drug called bevacizumab in the less intensive group, resulted in better patient outcomes.

Effectiveness of sucralfate in preventing esophageal stricture in children after ingestion of caustic agents.

Ingestion of caustic agents by children is a serious health issue that can affect the patient for the rest of his life. The role of sucralfate in preventing stricture caused by caustic agents is controversial, and limited studies have been conducted in this field. We aimed to investigate the effect of sucralfate on preventing esophageal stricture in children. Sixty children with mean age of 36.69 ± 20.50 months and grade II B esophageal burns due to ingestion of caustic agents were enrolled in the study. In the intervention group, in addition to the usual treatment, sucralfate was administered orally at a dose of 80 mg/kg every 2 h for 3 days. For the control group, only the usual treatment was prescribed. Stricture development was compared between groups based on endoscopic and radiologic findings. Of the 60 patients enrolled in the study, 53 were examined. The incidence of esophageal stricture in the intervention group was significantly lower than in the control group (37% versus 67%, P-value = 0.042). In addition, the odds of esophageal stricture after sucralfate intervention was significantly reduced after adjustment for potential confounders (OR = 0.198, P-value = 0.031).  Conclusions: The results of this study showed that sucralfate may reduce the development of esophageal stricture in children when used to manage IIB esophageal burns due to ingestion of caustic agents. What is Known: • Ingestion of caustic agents by children is a serious health issue that can affect the patient for the rest of his life. • The role of sucralfate in preventing stricture caused by caustic agents is controversial and limited studies have been conducted in this field. What is New: • It seems that sucralfate significantly reduces the incidence of esophageal stricture following the ingestion of caustic agents in children compared to the control group. • We believe that the prognosis may be improved and the risk of stricture formation may be reduced with high doses of sucralfate therapy in grade IIB esophageal injury.

Effect of upfront intensive therapy on oncological outcomes in older patients with high tumor burden metastatic castration-sensitive prostate cancer: A multicenter retrospective study.

BACKGROUND: The effect of upfront intensive therapy on the prognosis of older patients with metastatic castration-sensitive prostate cancer (mCSPC) remains unclear. Thus, we assessed the impact of older age (≥75 years) on oncological outcomes in mCSPC patients with a high tumor burden. METHODS: This multicenter retrospective study included 252 patients aged ≥75 years treated with either upfront or conventional therapy between 2014 and 2021. We compared castration-resistant prostate cancer (CRPC)-free survival (FS) and overall survival (OS) between patients with androgen deprivation therapy (ADT) plus upfront intensive therapy (docetaxel [DTX] or abiraterone acetate [ABI] plus prednisolone) and conventional therapy (ADT monotherapy or ADT combined with bicalutamide). We evaluated the effect of upfront intensive therapy on prognosis by multivariable Cox regression analysis. RESULTS: The 231 patients enrolled in our study were classified in the conventional group (n = 148) or the upfront group (n = 104; DTX = 27 and ABI = 77). The upfront group had significantly prolonged CRPC-FS and OS compared with the conventional group, and this was also the case in the background-adjusted multivariable Cox regression analysis. CONCLUSION: Patients aged ≥75 years who received upfront intensive therapy had significantly longer CRPC-FS and OS compared with similar age patients treated with conventional therapy in real-world practice. The oncological benefit may not diminish in this older population.

Maternal pregnancy outcomes in women with cardiomyopathy: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to systematically assess the impact of cardiomyopathy on maternal pregnancy outcomes. DATA SOURCES: PubMed, Ovid Embase, Ovid MEDLINE, Cochrane Library, and ClinicalTrials.gov were systematically searched from inception to April 24, 2022. STUDY ELIGIBILITY CRITERIA: Observational cohort, case-control, and case-cohort studies in human populations were included if they reported predefined maternal outcomes for pregnant women with cardiomyopathy (any subtype) and for an appropriate control population (pregnant women with no known heart disease or pregnant women with noncardiomyopathy heart disease). METHODS: Two reviewers independently assessed the articles for eligibility and risk of bias, and conflicts were resolved by a third reviewer. Data were extracted and synthesized according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analyses of Observational Studies in Epidemiology guidelines. RESULTS: A total of 14 studies (n=57,539,306 pregnancies) were eligible for inclusion. Women with cardiomyopathy were more likely to deliver by cesarean delivery than women with no heart disease (odds ratio, 2.96; 95% confidence interval, 2.47-3.55; I2=95%; P≤.00001) or women with noncardiomyopathy heart disease (odds ratio, 1.90; 95% confidence interval, 1.62-2.22; I2=91%; P<.00001). Having cardiomyopathy conferred a greater risk for experiencing severe maternal adverse cardiovascular events during pregnancy when compared with not having any heart disease (odds ratio, 206.64; 95% confidence interval, 192.09-222.28; I2=73%; P<.0001) or having noncardiomyopathy heart disease (odds ratio, 7.09; 95% confidence interval; 6.08-8.27; I2=88%; P<.00001). In-hospital mortality was significantly higher among women with cardiomyopathy than among women with no heart disease (odds ratio, 126.67; 95% confidence interval, 43.01-373.07; I2=87%; P<.00001) or among women with noncardiomyopathy heart disease (odds ratio, 4.30; 95% confidence interval, 3.42-5.40; I2=0%; P<.00001). CONCLUSION: Pregnant women with cardiomyopathy have increased risks for adverse maternal outcomes, including maternal death, when compared with both women with no heart disease and women with noncardiomyopathy heart disease. Our results highlight the importance of preconception risk assessments to allow for informed decision-making before pregnancy. Pregnancies affected by cardiomyopathy are high risk and should be managed by expert, multidisciplinary obstetrical and cardiology teams.

Intensive Stuttering Therapy with Telepractice Follow-Up: Longitudinal Outcomes.

PURPOSE: This study estimated the treatment outcomes of a behavioral stuttering therapy program that blended a combination of intensive face-to-face therapy with telepractice-based follow-up therapy. METHOD: A total of 17 participants (mean age = 22 years) who stutter participated in the program, preceded by an extended baseline period. The participants completed a series of assessments conducted over multiple time points, spanning a total of 42 weeks. Growth curve modeling was used to analyze the changes participants experienced in the frequency of stuttering, stuttering severity, communication attitudes, and quality of life. RESULTS: The participants demonstrated stability throughout the extended baseline period, and experienced positive outcomes from the intensive program and the gains in communication attitudes and quality of life were largely maintained with weekly follow-up telepractice sessions. However, stuttering frequency and severity increased when the telepractice follow-up session frequency transitioned to a biweekly basis. Neither gender nor age group predicted the treatment outcomes for frequency or severity of stuttering. Gender-based differences were found for the treatment outcomes of specific self-report measures, with male participants having demonstrated a greater proportional decline on their standard scores, relative to female participants. Outcomes were similar for both adolescents and adults. CONCLUSIONS: Participants attending the intensive stuttering therapy program experienced positive and significant changes in their speech, attitudes toward communication, and overall quality of life, which were maintained over time with structured, weekly telepractice follow-up sessions.

5-HT3 SEROTONIN RECEPTOR BLOCKERS FOR INTENSIVE THERAPY OF TRAUMATIC DISEASE IN PATIENTS WITH MULTIPLE TRAUMA.

OBJECTIVE: The aim: To find the most rational choice of drugs that have anti-emetic effect in patients with polytrauma in acute and early periods. PATIENTS AND METHODS: Materials and methods: We examined 82 patients with polytrauma, 62 men and 20 women. The age of patients ranged from 19 to 50 years. Patients were divided into the main and control group with 36 and 46 people respectively, who did not differ significantly by sex, age, anthropometric data, the nature and severity of injuries, and the time from injury to admission to hospital. RESULTS: Results: Full antiemetic effect was achieved in 72.4% of patients, where metoclopramide was used. Сomplete antiemetic effect was achieved in 96.3% of patients, where sturgeon was used. Decrease of peristaltic activity does not increase postoperative intestinal paresis, and also prevents irritable bowel syndrome and diarrhea caused by dysbacteriosis on the background of antibiotic therapy. Anxiolytic effect without sedative effect and impairment of motor coordination, decrease of the somatic and psychopathological symptoms intensity in alcohol-toxic withdrawal syndrome contributes to the correct interpretation of the traumatic disease. CONCLUSION: Conclusions: Use of drugs with antiemetic effect is an important part of the complex of traumatic disease treatment in patients with polytrauma. The use of osetron is rational in patients with polytrauma with cranio-abdominal injuries.

Realising the long-term promise of insulin therapy: the DCCT/EDIC study.

The introduction of insulin in the treatment of juvenile-onset, now type 1, diabetes mellitus transformed a rapidly fatal disease into a chronic degenerative one. During the insulin-treatment era, long-term microvascular and cardiovascular complications proved to be the bane of existence for people with type 1 diabetes, leading to blindness, kidney failure, amputations, cardiovascular disease (CVD) and premature mortality. The nascent understanding of the link between non-physiologically regulated glucose levels and these complications led to the development of new treatment tools in the 1970s and 1980s that facilitated the delivery of insulin to achieve glucose levels closer to non-diabetic levels. These therapeutic advances set the stage for definitive testing of the glucose hypothesis. The Diabetes Control and Complications Trial (DCCT), supported by the National Institute of Diabetes Digestive and Kidney Diseases, National Institutes of Health (NIH), definitively established the benefits and risks of intensive therapy that substantially lowered mean blood glucose levels, measured by HbA1c, over a mean 6.5 years of therapy. Intensive therapy in the DCCT, resulting in a mean HbA1c of ~7% (53 mmol/mol), reduced the development and progression of early microvascular and neurological complications associated with diabetes by 34-76% compared with the conventional-treatment group, which maintained an HbA1c of ~9% (75 mmol/mol). Intensive therapy was also associated with weight gain and a threefold increased risk for hypoglycaemia. At the end of the DCCT, a long-term observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC) study, commenced. Despite the convergence of HbA1c levels between the two groups during EDIC, owing to the adoption of intensive therapy by the original DCCT conventional-treatment group and the return of all participants to their own healthcare providers for diabetes care, the development and progression of complications continued to be substantially less in the original intensive-treatment group vs the conventional-treatment group; this phenomenon was termed 'metabolic memory'. The DCCT demonstrated a major reduction in early-stage complications with intensive therapy and the metabolic memory phenomenon during EDIC contributed to a substantially lower burden of advanced complications over time. These included a 57% lower risk of CVD events and 33% lower rate of mortality in the original intensive-treatment group compared with the conventional-treatment group. DCCT/EDIC has ushered in the intensive-treatment era, which has been universally adopted and includes the goal of achieving HbA1c levels less than 7% (53 mmol/mol) for most patients. Although the challenge of making intensive therapy (with the aim of achieving normoglycaemia) as widely accessible and safe as possible remains, continuing improvements in insulin therapy 100 years after its introduction promise a brighter future for people with type 1 diabetes.

Long-Term Efficacy of Intensive Zoledronate Therapy and Predictors of Retreatment in Paget's Disease of Bone.

Despite the current debate on the best therapeutic approach, i.e. symptomatic vs intensive strategy, one zoledronate (Zol) infusion is effective in most patients with Paget's disease of bone (PDB), whereas few need retreatment, whose predictors are not well established. We aimed to evaluate long-term efficacy of intensive Zol therapy and predictors of retreatment in PDB. Pagetic complications, clinical and biochemical response to Zol together with frequency of retreatment were retrospectively assessed in forty-seven PDB patients (age, mean ± SD: 72.5 ± 8.9 years, M/F: 24/23; symptomatic/asymptomatic: 16/31). Statistical analysis for retreatment prediction were based on Mann-Whitney U test, Pearson's Χ2 and ROC curve analysis. During seven-year follow-up, all patients achieved pain relief and only one underwent arthroplasty. Bone alkaline phosphatase (BAP) detected three non-responder (6%) and six relapsing (13%) patients needing retreatment. Retreated patients had less old age (66.1 ± 11.2 vs 74.0 ± 7.7 years), higher frequency of polyostotic disease (78% vs 40%) and higher baseline (96.5 ± 24.8 vs 44.9 ± 27.7 mcg/l) and post-Zol nadir BAP levels (24.7 ± 24.1 vs 8.1 ± 4.1 mcg/l) than patients treated once (p < 0.05 for all comparisons). In multivariate analysis both serum baseline and post-Zol nadir BAP significantly predicted retreatment (OR 1.09, 95%CI 1.01-1.17 and 1.29, 1.03-1.62, respectively), with ROC curve analysis showing the greatest accuracies for threshold values of 75.6 and 9.9 mcg/l (sensitivity 88 and 90%, specificity 94 and 86%, AUC 0.92 and 0.93, respectively). Our data in mostly asymptomatic, metabolically active PDB patients treated with intensive Zol therapy show a negligible incidence of pagetic complications and long-term optimal disease control, with BAP being the best predictor of retreatment.

Intensive induction regimens after deferring initial therapy for mantle cell lymphoma are not associated with improved survival.

INTRODUCTION: While most patients with mantle cell lymphoma (MCL) receive therapy shortly after diagnosis, a subset of patients with indolent-behaving disease can safely defer treatment. In this subgroup, we evaluated the importance of treatment intensity in patients with MCL who defer initial therapy. METHODS: Out of 1134 patients with MCL from 12 academic centers, we analyzed 219 patients who initiated therapy at least 90 days after diagnosis. Patients who received induction with high-dose cytarabine and/or autologous stem cell transplantation (ASCT) in first remission were considered to have received intensive therapy (n = 88) while all other approaches were non-intensive (n = 131). RESULTS: There was no difference in progression-free (PFS; P = .224) or overall survival (OS; P = .167) in deferred patients who received non-intensive vs. intensive therapy. Additionally, univariate and multivariate Cox proportional hazards models were performed for PFS and OS. Treatment at an academic center (HR 0.43, P = .015) was associated with improved OS in both univariate and multivariate models, while intensity of treatment was not associated with improved OS in either model. CONCLUSIONS: These results indicate that intensified initial treatment is not associated with improved survival after deferring initial therapy, although prospective studies are needed to determine which of these patients with MCL may benefit from intensive therapy.

Efficacy and Safety of Regional Anticoagulation with 4% Trisodium Citrate Versus Heparin in Extended Hemodialysis among Critical Patients with Cancer and Acute Kidney Injury.

INTRODUCTION: Patients with cancer admitted to critical care units are at increased risk of being affected with acute kidney injury (AKI) and mortality. Sustained low-efficiency dialysis (SLED) combines the cardiovascular stability of continuous therapy with the operational facility of conventional hemodialysis (HD). Citrate has become an alternative to heparin in anticoagulation because it favors the maintenance of filter patency and reduces bleeding. We analyzed the efficacy and safety of citrate versus heparin use in extended HD for patients with cancer and AKI. METHODS: This retrospective cohort study evaluated patients with cancer and dialytic AKI who received SLED with anticoagulation using citrate versus heparin from January 2014 to June 2017. After stratifying patients by the type of anticoagulation received, we evaluated demographic and clinical data, plus SLED session characteristics. We also analyzed dialysis outcomes, including insufficient session time, hypotension, poor catheter flow, line inversion, and dialysis system coagulation. RESULTS: We identified 423 SLED sessions among 124 patients (41 patients in the heparin group and 83 patients in the citrate group). More sessions with citrate (26.6 vs. 40.9%, p < 0.001) had serum platelet concentrations <50,000/mm3 or <100,000/m3 and ionic calcium (Ca++) values <1.16 mmol/L (33.2 vs. 18.5%, p < 0.001). Dialysis intercurrence occurred in 27% of sessions. The highest odds were associated with heparin sessions (OR 2.88). Compared with the citrate group, the heparin group was subject to more dialysis system coagulation (12.3%), the need for line reversal (9.8%), and insufficient session time (23.9%). CONCLUSION: Citrate represents a safe and effective anticoagulant for SLED for cancer patients with AKI undergoing treatment in the intensive care unit.

The efficacy of virtual distance training of intensive therapy and anaesthesiology among fifth-year medical students during the COVID-19 pandemic: a cross-sectional study.

BACKGROUND: The coronavirus disease (COVID-19) brought several challenges in medical education. The aim of our study was to investigate whether virtual distance trainings (VDT) organized during the COVID-19 pandemic at our university were effective in replacing in-person bed-side education in intensive therapy and anaesthesiology among fifth-year medical students, both from students' and instructors' perspectives. METHODS: This was a cross-sectional study consisting of three parts: a 20-item students' questionnaire filled out by students participating in VDT, a 22-item instructors' questionnaire filled out by instructors taking part in virtual distance education and a 20-item knowledge test completed by students participating in VDT, as well as by students visiting bed-side trainings (BT) during the same semester, before COVID-19 pandemic. The questionnaires focused on effectiveness, content, self-preparedness, technical background and interactivity of VDT. Instructors' and students' responses given to the common questions, as well as the knowledge test results were compared. Mann-Whitney U test was used for group comparisons and binary logistic regression was performed to analyze the influence of previous health-care experience on students' feeling of self-preparedness. RESULTS: One hundred thirthen students (response rate {RR}: 68%) and 29 instructors (RR: 97%) filled out the questionnaires. The majority of students found our VDT useful and effective; however, a considerable number of participants felt disadvantaged by taking VDT instead of BT sessions and would recommend keeping virtual distance education methods combined with BT. Instructors found VDT overall effective and deemed the transfer of their knowledge satisfactory; however, they described worse interactivity and contact with students during virtual sessions compared to in-person teaching. Instructors showed a clearer consensus that VDT should not replace BT in the future, while students' answers were more divided in this regard. Previous health-care experience did not influence students' feeling of self-preparedness. One hundred and twenty-seven students (56 after VDT {RR: 34%}; 71 after BT {RR: 67%}) completed the end-of-semester knowledge test. Students attending VDT performed better than students visiting BT (median score VDT:83.5 vs BT:77.3; p = 0.015). CONCLUSIONS: Virtual distance learning incorporating virtual practice sessions was effective in maintaining continuous education of intensive therapy and anaesthesiology among fifth-year medical students during the COVID-19 outbreak.

[Cross-sectional study of COVID-19 patients on working conditions and quality of care]. / Querschnittsstudie zu Arbeitsbedingungen und Versorgungsqualität in der Versorgung von COVID-19-Patienten.

BACKGROUND: The COVID-19 pandemic challenges hospital clinicians by additional burdens. Key questions are whether hospital clinicians have experienced more stress in the care of COVID-19 patients and whether patient safety and quality of care have changed. METHODS: Cross-sectional study using an online survey with clinicians in German hospitals on working conditions and quality of care during the COVID-19 pandemic, comparing clinicians with (MmK) vs. without direct contact (MoK) to COVID-19 patients. RESULTS: In total, 2122 clinicians participated. Most clinicians were physicians (15.4%, n = 301) or nurses (77.0%, n = 1505) working in major acute care hospitals (46.0%, n = 899). Every second respondent stated that they worked more than usual (46.4%, n = 907) and took on additional activities (47.7%, n = 932). A quarter of the participants did not receive any training or get instructions in devices (21.5%, n = 421). Only 51.5% (n = 1006) of the respondents were provided with sufficient personal protective equipment. More than 30% (32.7%, n = 639) were more satisfied than usual. The comparing clinicans with vs. without direkt contact to Covid-19 patients worked more shifts than usual (> 2 shifts: 24.1%, n = 306 vs. 13.7%, n = 63, p < 0.001) and without instruction (27.9%, n = 364 vs. 17.1%), n = 57, p < 0.001). In terms of patient safety, there were more deficiencies in the care, mechanical ventilation and nursing (all p < 0.001). CONCLUSION: The cross-sectional study indicates an increased burden on clinicians and a restricted quality of care for patients with COVID-19. A risk to patients or clinicians cannot be excluded.

[Risk factors of nosocomial meningitis in neurological intensive care unit. Results of a five-year prospective study]. / Faktory riska razvitiya nozokomial'nykh meningitov u patsientov neirokhirurgicheskogo profilya v otdelenii reanimatsii i intensivnoi terapii. Rezul'taty pyatiletnego prospektivnogo issledovaniya.

Nosocomial meningitis (NM) is a serious complication in neurosurgery. Understanding the risk factors of nosocomial meningitis is important for their prevention. OBJECTIVE: To determine the main risk factors of NM in neurological intensive care unit. MATERIAL AND METHODS: A prospective study included all patients (n=2140) treated at the neurological intensive care unit for more than 48 hours between October 1, 2010 and October 31, 2015. Cases of nosocomial meningitis were registered. We analyzed risk factors in 2 groups of patients (with and without NM). RESULTS AND DISCUSSION: The incidence of NM in neurological intensive care unit was 8.4% (95% CI 6.8-10.0) (n=180). Relative risk of NM under external ventricular drainage was 3.98 (99 cases of NM, p<0.05). Relative risk of NM in patients with CSF leakage (including nasal CSF leakage after transsphenoidal surgery) was 5.2 (49 cases of NM, p<0.05). The incidence of nosocomial meningitis was significantly higher among patients with surgery time ≥8 hours (17.68%, p<0.01). Nosocomial meningitis was also significantly more common after redo surgery (13.07%, p<0.05). Insertion of intracranial pressure sensor was not a significant risk factor of NM. The risk of meningitis was 2.67% if the above-mentioned factors were absent. Extracranial factors are not specific for NM. No significant relationship between certain neurosurgical disease and NM was found. CONCLUSION: We found higher risk of NM in ICU patients with the following factors: external ventricular drainage, CSF leakage, redo surgery and surgery time.

Trifluridine/tipiracil plus bevacizumab in patients with untreated metastatic colorectal cancer ineligible for intensive therapy: the randomized TASCO1 study.

BACKGROUND: We designed an open-label, noncomparative phase II study to assess the safety and efficacy of first-line treatment with trifluridine/tipiracil plus bevacizumab (TT-B) and capecitabine plus bevacizumab (C-B) in untreated patients with unresectable metastatic colorectal cancer (mCRC) who were not candidates for combination with cytotoxic chemotherapies. PATIENTS AND METHODS: From 29 April 2016 to 29 March 2017, 153 patients were randomly assigned (1:1) to either TT-B (N = 77) or C-B (N = 76). The primary end point was progression-free survival (PFS). The primary PFS analysis was performed after 100 events (radiological progression or death) were observed. Secondary end points included overall survival (OS), quality of life (QoL; QLQ-C30 and QLQ-CR29 questionnaires), and safety. RESULTS: Median (range) duration of treatment was 7.8 (6.0-9.7) months and 6.2 (4.1-9.1) months in the TT-B and C-B groups, respectively. Median (range) PFS was 9.2 (7.6-11.6) and 7.8 (5.5-10.1) months, respectively. Median (range) OS was 18 (15.2 to NA) and 16.2 (12.5 to NA) months, respectively. QoL questionnaires showed no relevant changes over time for either treatment. Therapies were well tolerated. Patients receiving TT-B had more grade ≥3 neutropenia (47% versus 5% with C-B). Patients receiving C-B had more grade ≥3 hand-foot syndrome (12% versus 0% with TT-B) and grade ≥3 diarrhea (8% versus 1% with TT-B), consistent with the known safety profiles of these agents. CONCLUSION: TT-B treatment showed promising clinical activity in untreated patients with unresectable mCRC ineligible for intensive therapy, with an acceptable safety profile and no clinically relevant changes in QoL. CLINICAL TRIAL INFORMATION: NCT02743221 (ClinicalTrials.gov).

Effectiveness of Hand-Arm Bimanual Intensive Therapy on Hand Function among Children with Unilateral Spastic Cerebral Palsy: A Meta-Analysis.

BACKGROUND: Hand-arm bimanual intensive therapy (HABIT) has been shown to be an effective method for improving upper-extremity function. However, owing to ambiguity within the evidence of HABIT's effects on hand function among children with unilateral spastic cerebral palsy (CP), this meta-analysis sought to elucidate whether the same was true in this patient population. SUMMARY: A computerized database search yielded 468 studies. After meticulous scrutiny and screening of these studies according to the selection criteria, 4 full-text articles were included in the meta-analysis. All 4 studies underwent a methodological quality assessment according to the Physiotherapy Evidence Database Scale (PEDro), with a score of greater than 8. Five comparisons were then made involving the 4 selected randomized controlled trials (RCTs). The effect size was measured using the correlation coefficient (r value). The effect sizes of the individual studies were 0.006, 0.03, 0.04, 0.22, and 0.15. The total effect size was 0.06. Key Message: This meta-analysis determined that there is a trivial benefit using HABIT when compared to constraint-induced movement therapy or structured and unstructured bimanual therapy in pediatric patients with unilateral spastic CP. More RCTs are needed to substantiate our evidence.

An interdisciplinary approach to the management of critically ill patients during covid-19 pandemic; an experience of a university hospital in England.

COVID-19 pandemic presents significant challenges in delivering safe and efficient patient care, especially during the surges. In all health care systems, provision of available critical care facilities is a scarce resource, even in normal times. Problematic is not just the limitation of physical spaces in intensive care units, but also the availability of trained personnel. The critical care model, developed in Queen Elizabeth Hospital Birmingham to cope with the surge of COVID-19 patients, is based on early implementation of an interdisciplinary approach and extensive cooperation between the branches of practice, allowing to address both challenges. The main pillars are early upskilling of non-critical care staff, creation of safe, streamlined clinical pathways, adjustment of the physical layout of critical care units and comprehensive cross-town cooperation allowing to accommodate an increased number of patients, requiring intensive care. The model was well tested in clinical practice, enabling the hospital to increase the critical care footprint by more than 200% during the pandemic's surge between March and May 2020.

Evaluation of a Magic Camp for Children with Hemiparesis: A Pilot Study.

This single-group open trial was designed to evaluate the effectiveness of a two-week magic camp as a means of hand-arm motor skills training to improve upper limb motor function (unilateral and bilateral) in children with hemiparesis. Seven children with hemiparesis participated in a magic camp program which met 3 days a week, 4 hours each day, for two consecutive weeks for a total of 24 hours. Participants completed three assessments at the beginning of the camp, post-camp, and at a three-month follow-up: the Jebsen Hand Function Test (JHFT), Children's Hand Experience Questionnaire (CHEQ), and a box opening task that required coordination of both upper limbs. A Wilcoxon signed-rank test revealed significant improvement in JHFT composite scores of the affected limb at post-camp (p = .04) and three-month follow-up (p = .04). In addition, a significant improvement in the number of activities performed using two hands from baseline to three-month follow-up was observed (p = .03). This pattern of improvement was also observed in the speed of completion for the box opening task. The improvement in motor function seems related to the participants' continuing performing daily activities with the affected hand and two hands after the magic camp.

Upper Limb Function of Children with Unilateral Cerebral Palsy After a Magic-Themed HABIT: A Pre-Post-Study with 3- and 6-Month Follow-Up.

Aims: To examine changes in upper limb function, and performance in everyday tasks, for children with unilateral cerebral palsy who participated in a magic-themed hand-arm bimanual intensive therapy (HABIT). Methods: Twenty-eight children participated; mean age 10 y 6 mo (SD 2 y 2 mo), n = 15 male and n = 13 female. Using a single group, pre-and post-test design, the magic-themed HABIT was delivered for 60 hours over 10 days. Bimanual and unimanual hand function were measured using the Assisting Hand Assessment (AHA) and Box and Blocks Test (BBT). Occupational performance was rated using the Canadian Occupational Performance Measure (COPM). Two parent questionnaires explored change in bimanual hand use in everyday activities; ABILHAND-Kids and Children's Hand-use Experience Questionnaire (CHEQ). Assessments were completed pre-, immediately post, 3 months and 6 months after the intervention. Results: Friedman's ANOVA revealed a significant improvement for COPM and CHEQ grasp subscale. Repeated measures ANOVA revealed a significant improvement in BBT, and ABILHAND-Kids, and no significant change for AHA. Conclusions: Children who participated in the magic-themed HABIT experienced improved occupational performance, unimanual skills, and parent ratings of performance in challenging everyday tasks.