Tag: pubmed

Neuro Oncol. 2022 Nov 2;24(Supplement_6):S4-S15. doi: 10.1093/neuonc/noac133.

ABSTRACT

BACKGROUND: Treatment of recurrent glioblastoma (GBM) remains problematic with survival after additional therapy typically less than 12 months. We prospectively evaluated whether outcomes might be improved with resection plus permanent implantation of a novel radiation device utilizing the gamma-emitting isotope Cs-131 embedded within bioresorbable collagen tiles.

METHODS: Recurrent histologic GBM were treated in a single-arm trial. Following radiation, the surgical bed was lined with the tiles. Subsequent treatments were at the treating physician’s discretion.

RESULTS: 28 patients were treated (20 at first recurrence, range 1-3). Median age was 58 years, KPS was 80, female:male ratio was 10:18. Methylguanine methyltransferase (MGMT) was methylated in 11%, unmethylated in 18%, and unknown in 71%. Post implant, 17 patients (61%) received ≥1 course of systemic therapy. For all patients, Kaplan-Meier estimates of median time to local failure were 12.1 months, post-implant survival was 10.7 months for all patients and 15.1 months for patients who received systemic therapy; for all patients, median overall survival from diagnosis was 25.0 months (range 9.1-143.1). Sex, age, and number of prior progressions were not statistically significant. Local control was continuously maintained in 46% of patients. Two deaths within 30 days occurred, one from intracranial hemorrhage and one after persistent coma. Three symptomatic adverse events occurred: one wound infection requiring surgery and two late radiation brain injury, resolved non-surgically.

CONCLUSION: This pre-commercial trial demonstrated acceptable safety and favorable post-treatment local control and survival. The device has received FDA clearance for use in newly diagnosed malignant and all recurrent intracranial neoplasms.

PMID:36322102 | DOI:10.1093/neuonc/noac133

Stat Methods Med Res. 2022 Nov 2:9622802221125913. doi: 10.1177/09622802221125913. Online ahead of print.

ABSTRACT

Risk difference is a frequently-used effect measure for binary outcomes. In a meta-analysis, commonly-used methods to synthesize risk differences include: (1) the two-step methods that estimate study-specific risk differences first, then followed by the univariate common-effect model, fixed-effects model, or random-effects models; and (2) the one-step methods using bivariate random-effects models to estimate the summary risk difference from study-specific risks. These methods are expected to have similar performance when the number of studies is large and the event rate is not rare. However, studies with zero events are common in meta-analyses, and bias may occur with the conventional two-step methods from excluding zero-event studies or using an artificial continuity correction to zero events. In contrast, zero-event studies can be included and modeled by bivariate random-effects models in a single step. This article compares various methods to estimate risk differences in meta-analyses. Specifically, we present two case studies and three simulation studies to compare the performance of conventional two-step methods and bivariate random-effects models in the presence or absence of zero-event studies. In conclusion, we recommend researchers using bivariate random-effects models to estimate risk differences in meta-analyses, particularly in the presence of zero events.

PMID:36322093 | DOI:10.1177/09622802221125913

JAMA Netw Open. 2022 Nov 1;5(11):e2239778. doi: 10.1001/jamanetworkopen.2022.39778.

ABSTRACT

IMPORTANCE: A considerable number of clinical trials of neoadjuvant immunotherapy for patients with resectable esophageal cancer are emerging. However, systematic evaluations of these studies are lacking.

OBJECTIVE: To provide state-of-the-art evidence and normative theoretical support for neoadjuvant immunotherapy for locally advanced resectable esophageal cancer.

DATA SOURCES: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for relevant original articles and conference proceedings that were published in English through April 1, 2022.

STUDY SELECTION: Published phase 2 or 3 clinical trials that included patients with resectable stage I to IV esophageal cancer who received immune checkpoint inhibitors (ICIs) before surgery as monotherapy or in combination with other therapies.

DATA EXTRACTION AND SYNTHESIS: The Preferred Reporting Items for Systematic Reviews and Meta-analyses and the Meta-analysis of Observational Studies in Epidemiology guidelines for meta-analysis were followed to extract data. A random-effects model was adopted if the heterogeneity was significant (I2 statistic >50%); otherwise, the common-effects model was used. Data analyses were conducted from April 2 to 8, 2022.

MAIN OUTCOMES AND MEASURES: Pathological complete response (pCR) rate and major pathological response (MPR) rate were considered to be the primary outcomes calculated for the clinical outcomes of neoadjuvant immunotherapy. Incidence of treatment-related severe adverse events was set as the major measure for the safety outcome. The rate of R0 surgical resection was summarized. Subgroup analyses were conducted according to histologic subtype and ICI types.

RESULTS: A total of 27 clinical trials with 815 patients were included. Pooled rates were 31.4% (95% CI, 27.6%-35.3%) for pCR and 48.9% (95% CI, 42.0-55.9%) for MCR in patients with esophageal cancer. In terms of safety, the pooled incidence of treatment-related severe adverse events was 26.9% (95% CI, 16.7%-38.3%). Most patients achieved R0 surgical resection (98.6%; 95% CI, 97.1%-99.6%). Regarding histologic subtypes, the pooled pCR rates were 32.4% (95% CI, 28.2%-36.8%) in esophageal squamous cell carcinoma and 25.2% (95% CI, 16.3%-35.1%) in esophageal adenocarcinoma. The pooled MPR rate was 49.4% (95% CI, 42.1%-56.7%) in esophageal squamous cell carcinoma.

CONCLUSIONS AND RELEVANCE: This study found that neoadjuvant immunotherapy with chemotherapy had promising clinical and safety outcomes for patients with resectable esophageal cancer. Randomized clinical trials with long-term follow-up are warranted to validate the findings and benefits of ICIs.

PMID:36322089 | DOI:10.1001/jamanetworkopen.2022.39778

JAMA Netw Open. 2022 Nov 1;5(11):e2239849. doi: 10.1001/jamanetworkopen.2022.39849.

ABSTRACT

IMPORTANCE: There is a large body of epidemiologic evidence that heat is associated with increased risk of mortality. One of the most effective strategies to mitigate the effects of heat is through air conditioning (AC); Texas regulates the internal temperature of jails to stay between 65 and 85 °F degrees, but these same standards do not apply to state and private prisons.

OBJECTIVE: To analyze whether heat during warm months is associated with an increased risk of mortality in Texas prisons without AC.

DESIGN, SETTING, AND PARTICIPANTS: This case-crossover study included individuals who died in Texas prisons between 2001 and 2019. The association of heat in warm months with mortality in Texas prisons with and without AC was estimated. Data analysis was conducted from January to April 2022.

EXPOSURES: Increasing daily heat index above 85 °F and extreme heat days (days above the 90th percentile heat index for the prison location).

MAIN OUTCOMES AND MEASURES: Daily mortality in Texas prisons.

RESULTS: There were 2083 and 1381 deaths in prisons without and with AC, respectively, during warm months from 2001 to 2019. Most of the deceased were male (3339 of 3464 [96%]) and the median (IQR) age at death was 54 (45-62) years. A 1-degree increase above 85 °F heat index and an extreme heat day were associated with a 0.7% (95% CI, 0.1%-1.3%) and a 15.1% (95% CI, 1.3%-30.8%) increase in the risk of mortality in prisons without AC, respectively. Approximately 13% of mortality or 271 deaths may be attributable to extreme heat during warm months between 2001 to 2019 in Texas prison facilities without AC. In prisons with AC, a negative percentage change in mortality risk was observed, although the 95% CI crossed zero (percentage change in mortality risk: -0.6%; 95% CI, -1.6% to 0.5%). The estimates in prisons without AC were statistically different than the estimates in prisons with AC (P = .05).

CONCLUSIONS AND RELEVANCE: This study found an average of 14 deaths per year between 2001 to 2019 were associated with heat in Texas prisons without AC vs no deaths associated with heat in prisons with AC. Adopting an AC policy in Texas prisons may be important for protecting the health of one of our most vulnerable populations.

PMID:36322085 | DOI:10.1001/jamanetworkopen.2022.39849

JAMA Psychiatry. 2022 Nov 2. doi: 10.1001/jamapsychiatry.2022.3541. Online ahead of print.

ABSTRACT

IMPORTANCE: Although dopamine is implicated in the pathophysiology of bipolar disorder (BD), the precise alterations in the dopaminergic system remain unknown.

OBJECTIVE: To assess dopamine transporter (DAT) density in the striatum in patients with BD with current and recently remitted mania in comparison to healthy control individuals and its correlation with severity of manic symptoms.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study conducted in a tertiary care referral center for mood disorders in Vancouver, British Columbia, Canada, recruited 26 patients with BD (9 with current mania; 17 with recently remitted mania) and 21 matched healthy control individuals. DAT density was measured using positron emission tomography with [11C]d-threo-methylphenidate (MP). The differences between the groups in nondisplaceable binding potential (BPND) for DAT was assessed using statistical parametric mapping. The study was conducted from November 2001 to February 2007 and the data were analyzed from November 2020 to December 2021.

MAIN OUTCOMES AND MEASURES: DAT density as indexed by BPND for MP across groups; manic symptom severity as measured with the Young Mania Rating Scale (YMRS) and correlated with BPND values in patients with BD.

RESULTS: Of 47 total participants (mean [SD] age, 37.8 [14.4] years), 27 (57.4%) were female; 26 individuals had BD (9 with current mania and 17 with recently remitted mania) and there were 21 healthy control individuals. MP BPND was significantly lower in patients with BD in the right putamen and nucleus accumbens (mean reduction [MR] = 22%; cluster level familywise error [FWE]-corrected P < .001) as well as left putamen and caudate (MR = 24%; cluster level FWE-corrected P < .001). The reduction in BPND was more extensive and pronounced in patients with current mania, while patients with recently remitted mania had lower BPND in the left striatum but not the right. There was a significant negative correlation between YMRS scores and MP BPND in the right striatum in patients with current mania (ρ = -0.93; 95% CI, -0.99 to -0.69; P < .001) and those with recently remitted mania (ρ = 0.64; 95% CI, -0.86 to -0.23; P = .005) but not in the left striatum in either group.

CONCLUSIONS AND RELEVANCE: These findings indicate that mania was associated with reduced DAT density and remitted mania was associated with DAT levels that approximated those present in individuals without BD. These results have potential implications for drug development for mania.

PMID:36322065 | DOI:10.1001/jamapsychiatry.2022.3541

JAMA Cardiol. 2022 Nov 2. doi: 10.1001/jamacardio.2022.3844. Online ahead of print.

ABSTRACT

IMPORTANCE: Patient-reported health data can facilitate clinical event capture in pragmatic clinical trials. However, few data are available on the fitness for use of patient-reported data in large-scale health research.

OBJECTIVE: To evaluate the concordance of a set of variables reported by patients and available in the electronic health record as part of a pragmatic clinical trial.

DESIGN, SETTING, AND PARTICIPANTS: Data from ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness), a pragmatic clinical trial, were used in a concordance substudy of a comparative effectiveness research trial. The trial randomized 15 076 patients with existing atherosclerotic cardiovascular disease in a 1:1 ratio to low- or high-dose aspirin from April 2016 through June 30, 2019.

MAIN OUTCOMES AND MEASURES: Concordance of data was evaluated from 4 domains (demographic characteristics, encounters, diagnoses, and procedures) present in 2 data sources: patient-reported data captured through an online portal and data from electronic sources (electronic health record data). Overall agreement, sensitivity, specificity, positive predictive value, negative predictive value, and κ statistics with 95% CIs were calculated using patient report as the criterion standard for demographic characteristics and the electronic health record as the criterion standard for clinical outcomes.

RESULTS: Of 15 076 patients with complete information, the median age was 67.6 years (range, 21-99 years), and 68.7% were male. With the use of patient-reported data as the criterion standard, agreement (κ) was high for Black and White race and ethnicity but only moderate for current smoking status. Electronic health record data were highly specific (99.6%) but less sensitive (82.5%) for Hispanic ethnicity. Compared with electronic health record data, patient report of clinical end points had low sensitivity for myocardial infarction (33.0%), stroke (34.2%), and major bleeding (36.6%). Positive predictive value was similarly low for myocardial infarction (40.7%), stroke (38.8%), and major bleeding (21.9%). Coronary revascularization was the most concordant event by data source, with only moderate agreement (κ = 0.54) and positive predictive value. Agreement metrics varied by site for all demographic characteristics and several clinical events.

CONCLUSIONS AND RELEVANCE: In a concordance substudy of a large, pragmatic comparative effectiveness research trial, sensitivity and chance-corrected agreement of patient-reported data captured through an online portal for cardiovascular events were low to moderate. Findings suggest that additional work is needed to optimize integration of patient-reported health data into pragmatic research studies.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02697916.

PMID:36322059 | DOI:10.1001/jamacardio.2022.3844

Acta Chir Orthop Traumatol Cech. 2022;89(5):353-359.

ABSTRACT

PURPOSE OF THE STUDY The authors focused on the topic of tibiotalocalcaneal arthrodesis. It is a surgical procedure used to manage severe comprehensive ankle and hindfoot pathology. The scope of surgery and the negative impact on the walking stereotype are offset by preserving a weight-bearing and pain-free limb. The purpose of the study was to evaluate the group of patients who had undergone surgery at the First Department of Orthopaedic Surgery, St. Anne s University Hospital Brno and to identify the most suitable fixation for arthrodesis. It also aimed to compare the outcomes achieved by the authors with those reported by other departments. MATERIAL AND METHODS The group included patients operated on at the authors department between 2011 and 2021. The surgery was indicated in patients with severe concomitant arthritis of the upper and lower ankle, complex hindfoot instability, Charcot arthropathy. Contraindications included acute infection, decompensated diabetes and heavy smoking. The study compares fixation using a lateral plate, a retrograde nail and a retrograde nail with fibula acting as biological plate. The patients were scored preoperatively and postoperatively using the AOFAS Ankle-Hindfoot Score. Statistical analysis of the results was also carried out. RESULTS The group included 23 patients, of whom a lateral plate was opted for in 7 patients, a retrograde nail in 8 patients and a retrograde nail with fibula used as a biological plate in 8 patients. The patients of the group were followed up for the period ranging from 0.5 to 9 years after surgery. Serious complications were observed by the authors in 6 patients of the group. The failure of osteosynthesis material was reported in 2 cases with lateral plating fixation. A stress fracture above the apex of the nail developed in 2 cases. A serious infection was observed by the authors in 1 patient. The method associated with the lowest incidence of complications was the fixation with a retrograde nail and fibula used as a biological plate. DISCUSSION The forms of fixation for tibiotalocalcaneal arthrodesis have recently advanced considerably, the methods of fixation for arthrodesis in particular. The modern implants enable to compress the individual structures, to provide stable fixation and potentially to avoid long-term plaster cast fixation. Nonetheless, these surgical procedures are associated with a high complication rate. Currently, there is no consensus in international studies on the optimal fixation for arthrodesis. Numerous papers describe complications including postoperative infections, failure of osteosynthesis material and fractures close to osteosynthesis material. The number and the type of complications observed by the authors in their group of patients were similar to those reported by other authors. CONCLUSIONS Tibiotalocalcaneal arthrodesis is a surgical procedure reserved exclusively for patients indicated based on strict criteria and should be performed by an experienced team able to cope with potential complications. In the followed-up group of patients, the optimal method of fixation for arthrodesis appeared to be the fixation with a retrograde nail and fibula used as a biological plate. Key words: tibiotalocalcaneal arthrodesis, retrograde nail, lateral ankle plate, ankle instability, ankle arthrosis, biological plate.

PMID:36322036

Acta Chir Orthop Traumatol Cech. 2022;89(5):349-352.

ABSTRACT

PURPOSE OF THE STUDY Minimal and limited access techniques are gaining increasing interest for the treatment of displaced intra-articular calcaneal fractures. The ideal treatment method is however still debated and largely based on individual case factors and surgeon experience. Aim of this study was thus to compare the treatment characteristics and radiographic correction potential of a locking nail system with a sinus tarsi approach to plate fixation via an extended lateral approach. MATERIAL AND METHODS We retrospectively reviewed 39 cases of patients with calcaneal fractures that received primary fracture treatment for displaced intra-articular calcaneal fractures between July 2017 and March 2020. Patient characteristics, time to surgery, time to discharge, OR time and the correction achieved were analyzed and comparative statistics performed. RESULTS In total 19 patients treated with the locking nail and 20 patients treated with plate fixation were analyzed. Patient age and fracture severity according to the Sanders classification were comparable between the groups. Overall surgical time, as well as the achieved reduction was equal between both groups. Time to surgery, as well as time from surgery to discharge was significantly shorter in the locking nail group. 2 additional soft tissue procedures were necessary in the extended lateral approach group. DISCUSSION AND CONCLUSIONS The results with the locking calcaneus nail and sinus tarsi approach suggest, that similar treatment results can be achieved as with plate osteosynthesis and an extended lateral approach. Soft tissue management, as well as pre- and postoperative timing and discharge management can be improved with the nail. Further controlled trials comparing the longterm outcome between the treatment options are needed. Key words: calcaneus fracture, sinus tarsi approach, calcaneal nail, C-Nail.

PMID:36322035

Acta Chir Orthop Traumatol Cech. 2022;89(5):339-343.

ABSTRACT

PURPOSE OF THE STUDY Many physicians believe that loco-regional anaesthesia and analgesia improve the postoperative course of patients indicated for total hip arthroplasty compared to general anaesthesia. However, there are many patients who refuse subarachnoid or epidural anaesthesia, or have contraindications or conditions making the use of such techniques impossible. An alternative option is the combination of general anaesthesia and a peripheral nerve blockade. The aim of this prospective randomized open-label clinical trial was to compare the efficacy and quality of postoperative analgesia between fascia iliaca block combined with general anaesthesia (GA) and subarachnoid anaesthesia with morphine and bupivacaine (SAB). MATERIAL AND METHODS After having obtained the ethics committee approval and the patients consent, a prospective, open-label, randomized trial was conducted in patients referred for total hip arthroplasty (THR). The GA group was administered ultrasound-guided fascia iliaca block with 40 ml of 0.25% bupivacaine solution after the induction of general anaesthesia. In the SAB group, subarachnoid blockade was performed with a mixture of 3 ml of 0.5% bupivacaine with 0.150 mg morphine prepared in the hospital pharmacy. Right after surgery the patients were taken to the ICU for 24 hours, after which they were transferred to a general ward. In addition to vital signs monitoring, pain intensity using a 0-10 numeric rating scale (NRS), first morphine administration at NRS >4, total morphine consumption and potential adverse effects were observed over the period of 72 hours. RESULTS There was no statistical difference between the GA (14 persons) and the SAB (14 persons) group in demographic parameters, time to first morphine administration (10 hrs vs. 19 hrs, p=0.10), number of persons with no need for morphine after surgery (5 vs. 7), tingling sensation (1 vs. 0) or numbness of the limb (0 vs. 1). There was no difference in cardiorespiratory parameters or side effects of therapy. In neither case was there respiratory depression or delayed rehabilitation. No patient developed delirium after surgery, and no patient reported dissatisfaction with pain management. DISCUSSION The fascia iliaca block and subarachnoid anaesthesia using local anaesthetic with opioid addition have been repeatedly published for patients after total hip arthroplasty, but this study is unique by comparing the two methods. The study added a new piece of knowledge to the findings of several recent meta-analyses on the comparable outcomes of general and subarachnoid anaesthesia for hip replacement in the perioperative period. CONCLUSIONS If subarachnoid anaesthesia cannot be used in hip arthroplasty, general anaesthesia with fascia iliaca block provides comparable analgesia and quality of postoperative course. Key words: total hip arthroplasty, general anaesthesia, fascia iliaca block, subarachnoid anaesthesia, postoperative analgesia, postoperative course.

PMID:36322033

Lab Med. 2022 Nov 2:lmac120. doi: 10.1093/labmed/lmac120. Online ahead of print.

ABSTRACT

OBJECTIVE: Presence of autoantibodies against troponin I (cTnI) or T (cTnT) has been reported to interfere with troponin assays. However, the extent of the interference with the measurement has not been explored sufficiently. The aims of this study were to examine the frequencies of autoantibodies against troponin I and troponin T and how much these antibodies would affect the measurement.

METHODS: The study comprised 52 subjects who visited Hokkaido University Hospital with suspected ischemic heart diseases. To evaluate the presence of autoantibodies, we calculated the recoveries of cTnI or cTnT after immunoglobulin G depletion, and the distributions of peaks reactive with cTnI or cTnT by high-performance liquid chromatography were examined.

RESULTS: Autoantibodies against cTnI and cTnT were identified in 8 subjects (15.4%) and 1 subject (1.9%), respectively. Although the greatest difference between cTnI and cTnT was 32-fold, the distributions of cTnI-to-cTnT ratios in groups with and without anti-cTnI were not statistically different.

CONCLUSION: Autoantibodies against cTnI were more frequent by several fold than those against cTnT. Their presence did not significantly expand the discrepancy between cTnI and cTnT assays.

PMID:36322014 | DOI:10.1093/labmed/lmac120