Category: Statistics

Pain Physician. 2023 Nov;26(7):575-584.

ABSTRACT

BACKGROUND: Chronic, intractable, neuropathic pain is readily treatable with spinal cord stimulation (SCS). Technological advancements, including device miniaturization, are advancing the field of neuromodulation.

OBJECTIVES: We report here the results of an SCS clinical trial to treat chronic, low back and leg pain, with a micro-implantable pulse generator (micro-IPG).

STUDY DESIGN: This was a single-arm, prospective, multicenter, postmarket, observational study.

SETTING: Patients were recruited from 15 US-based comprehensive pain centers.

METHODS: This open-label clinical trial was designed to evaluate the performance of the Nalu™ Neurostimulation System (Nalu Medical, Inc., Carlsbad, CA) in the treatment of low back and leg pain. Patients, who provided informed consent and were successfully screened for study entry, were implanted with temporary trial leads. Patients went on to receive a permanent implant of the leads and micro-IPG if they demonstrated a >= 50% reduction in pain during the temporary trial period. Patient-reported outcomes (PROs), such as pain scores, functional disability, mood, patient impression of change, comfort, therapy use profile, and device ease of use, were captured.

RESULTS: At baseline, the average pain Visual Analog Scale (VAS) score was 72.1 ± 17.9 in the leg and 78.0 ± 15.4 in the low back. At 90 days following permanent implant (end of study), pain scores improved by 76% (VAS 18.5 ± 18.8) in the leg and 75% (VAS 19.7 ± 20.8) in the low back. Eighty-six percent of both leg pain and low back pain patients demonstrated a >= 50% reduction in pain at 90 days following implant. The comfort of the external wearable (Therapy Disc and Adhesive Clip) was rated 1.16 ± 1.53, on average, at 90 days on an 11-point rating scale (0 = very comfortable, 10 = very uncomfortable). All PROs demonstrated statistically significant symptomatic improvement at 90 days following implant of the micro-IPG.

LIMITATIONS: Limitations of this study include the lack of long-term results (beyond 90 days) and a relatively small sample size of 35 patients who were part of the analysis; additionally, there was no control arm or randomization as this was a single-arm study, without a comparator, designed to document the efficacy and safety of the device. Therefore, no direct comparisons to other SCS systems were possible.

CONCLUSIONS: This clinical study demonstrated profound leg and low back pain relief in terms of overall pain reduction, as well as the proportion of therapy responders. The study patients reported the wearable aspects of the system to be very comfortable.

PMID:37976486

Pain Physician. 2023 Nov;26(7):E761-E773.

ABSTRACT

BACKGROUND: Remimazolam is a novel ultrashort-effect benzodiazepine. In 2020, the US Food and Drug Administration approved it for procedural sedation. Remimazolam is beneficial for consistent sedation and quick recovery in painless gastrointestinal endoscopy. Propofol is one of the most commonly used intravenous anesthetics in clinical practice. Recently, only a few studies have compared propofol with remimazolam for general anesthesia induction.

OBJECTIVES: The purpose of our systematic review and meta-analysis was to compare the hemodynamic effects of remimazolam and propofol during the induction of general anesthesia.

STUDY DESIGN: Systematic review and meta-analysis of randomized, controlled trials.

METHODS: The authors retrieved the PubMed, Embase, Cochrane Library, and Web of Science databases for studies published through September 30, 2022, which reported relevant prospective randomized controlled trials (RCTs) comparing remimazolam with propofol for general anesthesia. The primary outcome was hemodynamic changes, including the absolute value of fluctuation of mean arterial pressure (delta MAP) and heart rate delta HR). The secondary outcomes were the following 2 indicators: the occurrence of total adverse events and the quality of recovery from general anesthesia at 24 hours postsurgery. RevMan 5.4.1 (The Nordic Cochrane Centre for The Cochrane Collaboration) and trial sequential analysis were used to execute the statistical analyses. The different domains of bias were judged by the Cochrane risk of the bias assessment tool.

RESULTS: The authors identified 189 papers in PubMed, Embase, Cochrane Library, and Web of Science. Eight articles with 964 patients were selected. The included studies had moderate quality. For primary outcomes, the lower delta HR (mean difference [MD] = -4.99; 95% CI, -7.97 to -2.00; I² = 41.6%; P = 0.001] and delta MAP (MD = -5.91; 95% CI. -8.57 to -3.24; I² = 0%; P < 0.0001) represent more stable hemodynamic characteristics in the remimazolam group. Regarding secondary outcomes, a considerably lower incidence of total adverse events was noted in the remimazolam group than that for the propofol group (odds ratio [OR] = 0.40; 95% CI, 0.28 to 0.58; I² = 63%; P < 0.00001). In comparison to the propofol group, remimazolam achieved an advantage score of quality of recovery -15 in 24 hours postsurgery (MD = 5.31, 95% CI, 1.51 to 9.12; I² = 87%; P = 0.006).

LIMITATION: Firstly, there are only a handful of published RCTs on the administration of remimazolam in general anesthesia. In addition, due to patient privacy, we could not extract individual patient data, therefore we could not combine and assess any variations in patient characteristics.

CONCLUSION: Evidence suggests that remimazolam has a lower hemodynamic effect during general anesthesia and fewer perioperative adverse effects after general anesthesia than propofol; however, which agent is superior regarding quality benefit in postoperative recovery based on the studies included here remains inconclusive. Additional RCTs with updated meta-analyses to enlarge the sample size and properly analyze the benefit-to-risk ratio to patients are needed to determine the evidence for such a relatively new medicine.

PMID:37976477

Anesthesiology. 2023 Nov 17. doi: 10.1097/ALN.0000000000004840. Online ahead of print.

ABSTRACT

BACKGROUND: Opioid-free anesthesia (OFA) is increasingly being adopted to reduce opioid consumption, but its impact on early postoperative recovery following major surgery has not been evaluated in comparative trials. We hypothesized that an OFA protocol would enhance the early quality of recovery (QoR) for patients undergoing scheduled major surgery under general anesthesia.

METHODS: The SOFA study was a monocentric, randomized, controlled, assessor- and patient-blinded clinical trial conducted from July 10, 2021, to February 12, 2022. The eligible population included male and female patients undergoing scheduled major surgery, excluding bone procedure, that typically require opioids for postoperative pain management. Patients in the intervention group received a combination of at least two drugs among ketamine, lidocaine, clonidine, and magnesium sulfate, without opioids for anesthesia. The standard group received opioids. The primary outcome was early postoperative QoR, assessed by QoR-15 score at 24 hours (H24) after surgery. Secondary outcomes were QoR-15 at 48 hours (H48) and 72 hours (H72) after surgery, incidence of chronic pain, and quality of life at three months.

RESULTS: Of the 136 randomized patients, 135 were included in the primary analysis (mean age: 45.9±15.7 years; 116 females (87.2%); 85 underwent major plastic surgery (63.9%)), with 67 patients in the OFA group and 68 in the standard group. The mean QoR-15 at H24 was 114.9±15.2 in the OFA group versus 108.7±18.1 in the standard group (difference of 6.2, 95% CI, 0.4-12.0; p=0.026). QoR-15 scores also differed significantly at H48 (difference of 8.7, CI 95% 2.9-14.5); p=0.004) and at H72 (difference of 7.3, CI 95% 1.6-13.0, p=0.013). There was no difference in other secondary outcomes. No major adverse events were noticed.

CONCLUSION: The OFA protocol improved QoR after major elective surgery in a statistically but not clinically significant manner when compared to standard anesthesia.

PMID:37976460 | DOI:10.1097/ALN.0000000000004840

J Clin Oncol. 2023 Nov 17:JCO2301363. doi: 10.1200/JCO.23.01363. Online ahead of print.

ABSTRACT

PURPOSE: The phase III SKYSCRAPER-02 study determined whether the benefits of atezolizumab plus carboplatin and etoposide (CE) could be enhanced by the addition of tiragolumab in untreated extensive-stage small-cell lung cancer (ES-SCLC). We report final progression-free survival (PFS) and overall survival (OS) analyses.

METHODS: Patients received tiragolumab 600 mg/placebo, plus atezolizumab 1,200 mg and CE (four cycles), then maintenance tiragolumab/placebo plus atezolizumab. Primary end points were investigator-assessed PFS and OS in patients without history/presence of brain metastases (primary analysis set [PAS]). Additional end points included PFS and OS in all patients regardless of brain metastases status (full analysis set [FAS]), response, and safety.

RESULTS: Four hundred ninety patients were randomly assigned (FAS): 243 to tiragolumab arm and 247 to control arm. At the cutoff date (February 6, 2022; median duration of follow-up, 14.3 months [PAS] and 13.9 months [FAS]), final analysis of PFS in the PAS (n = 397) did not reach statistical significance (stratified hazard ratio [HR], 1.11; P = .3504; median, 5.4 months tiragolumab v 5.6 months control). At the cutoff date (September 6, 2022; median duration of follow-up, 21.2 months [FAS]), median OS in the PAS at final OS analysis was 13.1 months in both arms (stratified HR, 1.14; P = .2859). Median PFS and OS in the FAS were consistent with the PAS. The proportion of patients with immune-mediated adverse events (AEs) in the tiragolumab and control arms was 54.4% and 49.2%, respectively (grade 3/4: 7.9% and 7.7%). AEs leading to treatment withdrawal occurred in 8.4% and 9.3% of tiragolumab- and control-treated patients, respectively.

CONCLUSION: Tiragolumab did not provide additional benefit over atezolizumab and CE in untreated ES-SCLC. The combination was well tolerated with no new safety signals.

PMID:37976444 | DOI:10.1200/JCO.23.01363

J Clin Oncol. 2023 Nov 17:JCO2202470. doi: 10.1200/JCO.22.02470. Online ahead of print.

ABSTRACT

PURPOSE: We extended the Breast Cancer Surveillance Consortium (BCSC) version 2 (v2) model of invasive breast cancer risk to include BMI, extended family history of breast cancer, and age at first live birth (version 3 [v3]) to better inform appropriate breast cancer prevention therapies and risk-based screening.

METHODS: We used Cox proportional hazards regression to estimate the age- and race- and ethnicity-specific relative hazards for family history of breast cancer, breast density, history of benign breast biopsy, BMI, and age at first live birth for invasive breast cancer in the BCSC cohort. We evaluated calibration using the ratio of expected-to-observed (E/O) invasive breast cancers in the cohort and discrimination using the area under the receiver operating characteristic curve (AUROC).

RESULTS: We analyzed data from 1,455,493 women age 35-79 years without a history of breast cancer. During a mean follow-up of 7.3 years, 30,266 women were diagnosed with invasive breast cancer. The BCSC v3 model had an E/O of 1.03 (95% CI, 1.01 to 1.04) and an AUROC of 0.646 for 5-year risk. Compared with the v2 model, discrimination of the v3 model improved most in Asian, White, and Black women. Among women with a BMI of 30.0-34.9 kg/m², the true-positive rate in women with an estimated 5-year risk of 3% or higher increased from 10.0% (v2) to 19.8% (v3) and the improvement was greater among women with a BMI of ≥35 kg/m² (7.6%-19.8%).

CONCLUSION: The BCSC v3 model updates an already well-calibrated and validated breast cancer risk assessment tool to include additional important risk factors. The inclusion of BMI was associated with the largest improvement in estimated risk for individual women.

PMID:37976443 | DOI:10.1200/JCO.22.02470

Anesthesiology. 2023 Nov 17. doi: 10.1097/ALN.0000000000004839. Online ahead of print.

ABSTRACT

BACKGROUND: An intraoperative transfer of care from one anesthesia provider to another, or handover, may result in information loss and contribute to adverse patient outcomes. In 2019 we undertook a quality improvement effort to increase the use of a structured intraoperative handover tool incorporated in the electronic medical record. We hypothesized that intraoperative handovers of anesthesia care would be associated with adverse patient outcomes, and that increased use of a structured tool would attenuate this effect.

METHODS: This study included adult patients undergoing non-cardiac surgery of at least 1-hour duration performed during the period 2016-2021. Cases with a handover were identified if either there was a change of attending anesthesiologist or change of nurse anesthetist or resident for > 35 minutes. Our primary outcome was the occurrence of a composite of postoperative mortality and major postoperative morbidity. The effect of the intervention was analyzed by examining the quarterly change in odds ratio for the primary outcome for cases with and without a handover.

RESULTS: A total of 121,077 cases, 40.4% of which had a handover, were included. After weighting, the composite outcome was statistically associated with handovers (3517/48,986 [7.2%] in handover cases, vs. 4470/72,091 [6.2%] in non-handover cases, odds ratio 1.08, 95% CI: 1.04, 1.12). Time series analysis showed a marked increase in usage of the structured tool following the initial intervention. The odds ratio for the composite outcome showed a significant decrease over time following the initial intervention (t = -3.97, p < 0.001), with the slope of the OR vs. time curve decreasing from 0.002 (95% CI: 0.001, 0.004; P=0.018) to -0.011 (-0.01, -0.018; P < 0.001).

CONCLUSION: Intraoperative handovers are significantly associated with adverse outcomes even after controlling for multiple confounding variables. Use of a structured handover tool during anesthesia care may attenuate the adverse effect.

PMID:37976442 | DOI:10.1097/ALN.0000000000004839

JCO Clin Cancer Inform. 2023 Sep;7:e2300070. doi: 10.1200/CCI.23.00070.

ABSTRACT

PURPOSE: This discussion paper outlines challenges and proposes solutions for successfully implementing prediction models that incorporate patient-reported outcomes (PROs) in cancer practice.

METHODS: We organized a full-day multidisciplinary meeting of people with expertise in cancer care delivery, PRO collection, PRO use in prediction modeling, computing, implementation, and decision science. The discussions presented here focused on identifying challenges to the development, implementation and use of prediction models incorporating PROs, and suggesting possible solutions.

RESULTS: Specific challenges and solutions were identified across three broad areas. (1) Understanding decision making and implementation: necessitating multidisciplinary collaboration in the early stages and throughout; early stakeholder engagement to define the decision problem and ensure acceptability of PROs in prediction; understanding patient/clinician interpretation of PRO predictions and uncertainty to optimize prediction impact; striving for model integration into existing electronic health records; and early regulatory alignment. (2) Recognizing the limitations to PRO collection and their impact on prediction: incorporating validated, clinically important PROs to maximize model generalizability and clinical engagement; and minimizing missing PRO data (resulting from both structural digital exclusion and time-varying factors) to avoid exacerbating existing inequalities. (3) Statistical and modeling challenges: incorporating statistical methods to address missing data; ensuring predictive modeling recognizes complex causal relationships; and considering temporal and geographic recalibration so that model predictions reflect the relevant population.

CONCLUSION: Developing and implementing PRO-based prediction models in cancer care requires extensive multidisciplinary working from the earliest stages, recognition of implementation challenges because of PRO collection and model presentation, and robust statistical methods to manage missing data, causality, and calibration. Prediction models incorporating PROs should be viewed as complex interventions, with their development and impact assessment carried out to reflect this.

PMID:37976441 | DOI:10.1200/CCI.23.00070

J Spec Oper Med. 2023 Nov 17:5TNR-B19B. doi: 10.55460/5TNR-B19B. Online ahead of print.

ABSTRACT

This study evaluated the effect of an airway localization device (ALD) on surgical cricothyrotomy (SC) success rates and prehospital provider confidence. SC is indicated in 0.62% to 1.8% of all patients with military trauma, especially those presenting with traumatic airway obstruction. The effect of ALD was evaluated in an airway mannequin model during SC with the Committee on Tactical Combat Casualty Care (CoTCCC)-recommended Control-Cric Cricothyrotomy System. Outcomes included procedural time, Likert measures of operator confidence, and qualitative data/feedback for suggested future improvements in device design and training. The average procedural times of the hospital corpsmen (HM) including 20 men and 8 women were 67 seconds (without ALD) and 87 seconds (with ALD) respectively, which were statistically significant. Provider confidence for all SC procedural steps increased significantly after SC with and without ALD. The average procedural times of the Navy Special Operations Forces (SOF) group comprising 8 males were 56 seconds (without ALD) and 64 seconds (with ALD), which was not statistically significant. Provider confidence for two SC procedural steps (adequate hook retraction and first-attempt SC tube insertion) increased significantly after SC with and without ALD. First-attempt SC success rates were 90% in each group. Both groups provided feedback on the Control-Cric and ALD, with qualitative feedback analyzed for further SC training recommendations. Procedural times were increased with ALD when compared to those without ALD, although the increase may not be clinically significant in this classroom setting.

PMID:37976434 | DOI:10.55460/5TNR-B19B

J Aging Health. 2023 Nov 17:8982643231215475. doi: 10.1177/08982643231215475. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine if the association between posttraumatic stress disorder (PTSD) and substance use (alcohol misuse or smoking tobacco) is mediated/moderated by exercise or volunteering among aging (≥40 years) men who have sex with men (MSM), and if this mediation/moderation differs by HIV serostatus.

METHODS: Multicenter AIDS Cohort Study data were used. Three datasets with PTSD measured during different time periods (10/1/2017-3/31/2018, 898 men; 4/1/2018-9/30/2018, 890 men; 10/1/2018-3/31/2019, 895 men) were analyzed. Longitudinal mediation analyses estimated the mediation effect of exercise and volunteering on the outcomes.

RESULTS: Nine percent of MSM had evidence of PTSD. There was no statistically significant mediation effect of exercise or volunteering regardless of substance use outcome. The odds of smoking at a future visit among MSM with PTSD were approximately double those of MSM without PTSD. Results did not differ by HIV serostatus.

DISCUSSION: There is a particular need for effective smoking cessation interventions for aging MSM with PTSD.

PMID:37976419 | DOI:10.1177/08982643231215475

Hepatology. 2023 Nov 17. doi: 10.1097/HEP.0000000000000694. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: A simple non-invasive score, the Agile3+ score, combining liver stiffness measurement (LSM), aspartate aminotransferase/alanine aminotransferase ratio, platelet count, diabetes status, sex, and age, has been proposed for identification of advanced fibrosis in patients with suspected non-alcoholic fatty liver disease (NAFLD). We performed a systematic review and meta-analysis of observational studies to evaluate the diagnostic accuracy of the Agile 3+ score in identifying patients with NAFLD and advanced fibrosis. Recently, an International consensus changed the nomenclature of NAFLD into metabolic-associated steatotic liver disease (MASLD), so currently, the two terms are interchangeable.

METHODS: We systematically searched MEDLINE, Ovid Embase, Scopus, and Cochrane Library electronic databases for full-text published articles in any language from the inception to the 24th of April 2023. We included original articles reporting data on the sensitivity and specificity of the Agile 3+ score, according to previously described rule-out (≤0.451) and rule-in (≥0.679) cut-offs.

RESULTS: We included 6 observational studies (total 6955 participants) with biopsy-proven NAFLD (mean age 53 [SE 4] years, mean BMI 30.9 [SE 2.3] Kg/m2, 54.0% men, prevalence of diabetes 59.6%). The pooled prevalence of advanced fibrosis (≥F3) was 42.1%. By the rule-out cut-off, the overall sensitivity and specificity were 88% (95%CI 81-93%; I2=89.2%) and 65% (95%CI 54-75%; I2=97.6%), respectively. By the rule-in cut-off, the overall sensitivity and specificity were 68% (95%CI 57-78%; I2=91.1%) and 87% (95%CI 80-92%; I2=96.7%), respectively. Meta-regression analyses reported that the diagnostic accuracy was partly mediated by age (p<0.01), BMI (p<0.01), and, although not statistically significant, sex (p=0.06).

CONCLUSION: Our systematic review and meta-analysis suggest that Agile3+ accurately diagnoses NAFLD with advanced fibrosis and can identify patients eligible for biopsy and emerging pharmacotherapies.

PMID:37976417 | DOI:10.1097/HEP.0000000000000694