Tag: statistics

Sci Total Environ. 2023 Mar 17:162865. doi: 10.1016/j.scitotenv.2023.162865. Online ahead of print.

ABSTRACT

Glycol ethers are solvents used in a plethora of occupational and household products exposing the users to potential toxic effects. Several glycol ethers derived from ethylene glycol induce hematological toxicity, such as anemia in workers. The exposure effects on blood cells of glycol ethers derived from propylene glycol are unknown in humans. The aim of our study was to evaluate blood parameters indicative of red blood cell (RBC) hemolysis and oxidative stress in participants exposed to propylene glycol (propylene glycol monobutyl ether (PGBE) and propylene glycol monomethyl ether (PGME), two extensively used propylene glycol derivatives worldwide). Seventeen participants were exposed 2 h in a control inhalation exposure chamber to low PGME (35 ppm) and PGBE (15 ppm) air concentrations. Blood was regularly collected before, during (15, 30, 60, and 120 min), and 60 min after exposure for RBC and oxidative stress analyses. Urine was also collected for clinical effects related to hemolysis. Under the study conditions, our results showed that the blood parameters such as RBCs, hemoglobin concentration, and white blood cells tended to increase in response to PGME and PGBE exposures. These results raise questions about the possible effects in people regularly exposed to higher concentrations, such as workers.

PMID:36933710 | DOI:10.1016/j.scitotenv.2023.162865

J Am Pharm Assoc (2003). 2023 Mar 16:S1544-3191(23)00068-7. doi: 10.1016/j.japh.2023.03.002. Online ahead of print.

ABSTRACT

BACKGROUND: Statin use in people with type 2 diabetes (T2D) reduces cardiovascular events, yet adherence remains suboptimal.

OBJECTIVE(S): This study evaluated the impact of a community pharmacist intervention on statin adherence in new users with T2D.

METHODS: As part of a quasi-experimental study, community pharmacy staff proactively identified adult patients with T2D who were not prescribed a statin. When appropriate, the pharmacist prescribed a statin via a collaborative practice agreement or facilitated acquisition of a prescription from another prescriber. Patients received individualized education and follow up and monitoring for one year. Adherence was defined as the proportion of days covered (PDC) by a statin over 12 months. Linear and logistic regression were used to compare the effect of the intervention on continuous and a binary adherence threshold, defined as PDC > 80%, respectively.

RESULTS: Overall, 185 patients started statin therapy and were matched to 370 control patients for analysis. Adjusted average PDC was 3.1% higher in the intervention group (95% CI: -0.037, 0.098). Patients in the intervention group were 21.2% more likely to have PDC > 80% (95% CI: 0.828, 1.774).

CONCLUSION: The intervention resulted in higher statin adherence compared to usual care; however, the differences were not statistically significant.

PMID:36933697 | DOI:10.1016/j.japh.2023.03.002

Transplant Cell Ther. 2023 Mar 16:S2666-6367(23)01171-5. doi: 10.1016/j.jtct.2023.03.012. Online ahead of print.

ABSTRACT

BACKGROUND: Risks of B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy for patients with multiple myeloma (MM) include cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenias, and infections. The efficacy and safety of BCMA CAR-T therapy in the geriatric setting, including complications such as falls and delirium which may be more prevalent in older patients, have not been fully analyzed.

OBJECTIVES: To analyze the efficacy and safety of BCMA CAR-T therapy among older patients (age ≥70 at infusion) versus younger patients with MM.

STUDY DESIGN: We analyzed all patients with MM who received any autologous BCMA CAR-T therapy over a 5-year period at our institution. Key endpoints included CRS, ICANS incidence, days to absolute neutrophil count (ANC) recovery, incidence of hypogammaglobulinemia (IgG < 400 mg/dL), infections within 6 months, progression-free survival (PFS), and overall survival (OS).

RESULTS: Of 83 analyzed patients (age range 33-77), 22 (27%) were aged ≥70 at infusion. The older cohort had lower creatinine clearances (median 67.3 vs 91.9 mL/min, p<0.001) and a higher proportion of patients with performance status ≥1 (59% vs 30%, p=0.02) but were otherwise similar. Rates of any-grade CRS, any-grade ICANS, and days to ANC recovery were similar between groups. Rates of baseline hypogammaglobulinemia were 36% in older patients and 30% in younger patients (p=0.60), while post-infusion hypogammaglobulinemia occurred in 82% vs 72% respectively (p=0.57). Infections occurred in 36% (n=8) of the older cohort versus 52% (n=32) of the younger cohort (p=0.22). There were no statistically significant differences between the older and younger cohorts in terms of documented falls (9% vs 15%, p=0.72) or non-ICANS delirium (5% vs 7%, p=1.0). Median PFS was 13.1 months in older patients (95% CI 9.2-not reached [NR]) vs 12.5 months in younger patients (95% CI 11.3-22.5, p=0.42. Median OS was not reached in the older cohort (95% CI: NR-NR) vs 31.4 months in the younger cohort (95% CI 24.8-NR) with p=0.04. However, age ≥70 was not a significant predictor of OS after adjusting for high-risk cytogenetics, triple-class refractoriness, extramedullary disease, and bone marrow plasma cell burden.

CONCLUSIONS: While limited by small sample size and unmeasured confounders, our retrospective analysis did not demonstrate significant increases in CAR-T toxicity among older patients. This included toxicities associated with geriatric populations such as falls and delirium. Our paradoxical finding of borderline better OS among patients aged ≥70, which was not significant in regression modeling, may have been due to selection bias in favor of disproportionately healthy CAR-T candidates in the geriatric population. Overall, BCMA CAR-T remains a safe and effective option for older patients with MM.

PMID:36933659 | DOI:10.1016/j.jtct.2023.03.012

J Shoulder Elbow Surg. 2023 Mar 16:S1058-2746(23)00243-4. doi: 10.1016/j.jse.2023.02.116. Online ahead of print.

ABSTRACT

BACKGROUND: Recent evidence indicates that combined upper extremity blood flow restriction (BFR, applied distally to the shoulder) and low-load resistance exercise (LIX) augments clinically meaningful responses in shoulder region tissues proximal to the occlusion site. The purpose of this investigation was to determine the efficacy of BFR-LIX for the shoulder when added to standard offseason training in Division IA collegiate baseball pitchers. We hypothesized that BFR-LIX would augment training-induced increases in shoulder-region lean mass, rotator cuff strength, and endurance. As secondary outcomes, we sought to explore the impact of BFR-LIX rotator cuff training on pitching mechanics.

METHODS: Twenty-eight collegiate baseball pitchers were randomized into 2 groups (BFR^N=15, NOBFR^N=13) that, in conjunction with offseason training, performed 8wks of shoulder LIX [Throwing arm only; 2/wk, 4 sets (30/15/15/fatigue), 20%isometric max] using 4 exercises [cable external and internal rotation (ER/IR), dumbbell scaption, and side-lying dumbbell ER]. The BFR group also trained with an automated tourniquet on the proximal arm (50%-occlusion). Regional lean mass (dual-energy x-ray absorptiometry), rotator cuff strength (dynamometry: IR0&90, ° ER0&90, ° Scaption, Flexion), and fastball biomechanics were assessed pre- and post-training. Achievable workload (sets × reps × resistance) was also recorded. An ANCOVA (covaried on baseline measures) repeated on training timepoint was used to detect within-group and between-group differences in outcome measures (α=0.05). For significant pairwise comparisons, effect size (ES) was calculated using a Cohen’s d statistic and interpreted as: 0-0.1, negligible(N); 0.1-0.3, small(S); 0.3-0.5, moderate(M); 0.5-0.7, large(L); >0.7, very large(VL).

RESULTS: Following training, the BFR group experienced greater increases in shoulder-region lean mass [BFR: ↑227±60g, NOBFR: ↑75±37g, P=0.018, ES=1.0(VL)] and isometric strength for IR90° (↑2.4±2.3kg, P=0.041, ES=0.9VL). The NOBFR group experienced decreased shoulder flexion (↓1.6±0.8kg, P=0.007, ES=1.4VL) and IR at 0°(↓2.9±1.5kg, P=0.004, ES=1.1VL). The BFR group had a greater increase in achievable workload for the scaption exercise (BFR: ↑190±3.2kg, NOBFR: ↑90±3.3kg, P=0.005, ES=0.8VL). Only the NOBFR group was observed to experience changes in pitching mechanics following training with increased shoulder external rotation at lead foot contact (↑9.0°±7.9, P=0.028, ES=0.8VL) as well as reduced forward (↓3.6°±2.1, P=0.001, ES=1.2VL) and lateral (↓4.6°±3.4, P=0.007, ES=1.0VL) trunk tilt at ball release.

CONCLUSION: BFR-LIX rotator cuff training performed in conjunction with a collegiate offseason program augments increases in shoulder lean mass as well as muscular endurance while maintaining rotator cuff strength and possibly pitching mechanics in a manner that may contribute to favorable outcomes and injury prevention in baseball pitching athletes.

PMID:36933646 | DOI:10.1016/j.jse.2023.02.116

Environ Res. 2023 Mar 16:115683. doi: 10.1016/j.envres.2023.115683. Online ahead of print.

ABSTRACT

Management of cancer metastasis has been associated with remarkable reduction in progression of cancer cells and improving survival rate of patients. Since 90% of mortality are due to cancer metastasis, its suppression can improve ability in cancer fighting. The EMT has been an underlying cause in increasing cancer migration and it is followed by mesenchymal transformation of epithelial cells. HCC is the predominant kind of liver tumor threatening life of many people around the world with poor prognosis. Increasing patient prognosis can be obtained via inhibiting tumor metastasis. HCC metastasis modulation by EMT and HCC therapy by nanoparticles are discussed here. First of all, EMT happens during progression and advanced stages of HCC and therefore, its inhibition can reduce tumor malignancy. Moreover, anti-cancer compounds including all-trans retinoic acid and plumbaging, among others, have been considered as inhibitors of EMT. The EMT association with chemoresistance has been evaluated. Moreover, ZEB1/2, TGF-β, Snail and Twist are EMT modulators in HCC and enhancing cancer invasion. Therefore, EMT mechanism and related molecular mechanisms in HCC are evaluated. The treatment of HCC has not been only emphasized on targeting molecular pathways with pharmacological compounds and since drugs have low bioavailability, their targeted delivery by nanoparticles promotes HCC elimination. Moreover, nanoparticle-mediated phototherapy impairs tumorigenesis in HCC by triggering cell death. Metastasis of HCC and even EMT mechanism can be suppressed by cargo-loaded nanoparticles.

PMID:36933639 | DOI:10.1016/j.envres.2023.115683

Pharmacol Biochem Behav. 2023 Mar 16:173543. doi: 10.1016/j.pbb.2023.173543. Online ahead of print.

ABSTRACT

ProSAAS is one of the most abundant proteins in the brain and is processed into several smaller peptides. One of which, BigLEN, is an endogenous ligand for the G protein-coupled receptor, GPR171. Recent work in rodent models has shown that a small-molecule ligand for GPR171, MS15203, increases morphine antinociception and is effective in lessening chronic pain. While these studies provide evidence for GPR171 as a possible pain target, its abuse liability has not yet been assessed and was evaluated in the current study. We first mapped the distribution of GPR171 and ProSAAS throughout the reward circuit of the brain using immunohistochemistry and showed that GPR171 and ProSAAS are localized in the hippocampus, basolateral amygdala, nucleus accumbens, prefrontal cortex. In the major dopaminergic structure, the ventral tegmental area (VTA), GPR171 appeared to be primarily localized in dopamine neurons while ProSAAS is outside of dopamine neurons. Next, MS15203 was administered to mice with or without morphine, and VTA slices were stained for the immediate early gene c-Fos as a marker of neuronal activation. Quantification of c-Fos-positive cells revealed no statistical difference between MS15203 and saline, suggesting that MS15203 does not increase VTA activation and dopamine release. The results of a conditioned place preference experiment showed that treatment with MS15203 produced no place preference indicating a lack of reward-related behavior. Taken together this data provides evidence that the novel pain therapeutic, MS15203, has minimal reward liability. Therefore, GPR171 deserves further exploration as a pain target. SIGNIFICANCE STATEMENT: MS15203, a drug that activates the receptor GPR171, was previously shown to increase morphine analgesia. The authors use in vivo and histological techniques to show that it fails to activate the rodent reward circuitry, providing support for the continued exploration of MS15203 as a novel pain drug, and GPR171 a novel pain target.

PMID:36933620 | DOI:10.1016/j.pbb.2023.173543

J Neurosurg Pediatr. 2023 Mar 17:1-9. doi: 10.3171/2023.1.PEDS22341. Online ahead of print.

ABSTRACT

OBJECTIVE: Programmable valves have gained increasing popularity in the complex treatment of pediatric hydrocephalus. Over the last decade, adjustable serial valves have gradually replaced fixed-pressure valves in the authors’ department. The present study investigates this development by analyzing shunt- and valve-related outcomes for this vulnerable population.

METHODS: A retrospective analysis of all shunting procedures between January 2009 and January 2021 in children younger than 1 year of age was performed at the authors’ single-center institution. Postoperative complications and surgical revisions were set as outcome parameters. Shunt and valve survival rates were evaluated. Statistical analysis compared children who underwent implantation of the Miethke proGAV/proSA programmable serial valves with those who underwent implantation of the fixed-pressure Miethke paediGAV system.

RESULTS: Eighty-five procedures were evaluated. The paediGAV system was implanted in 39 cases and the proGAV/proSA in 46 cases. The mean ± SD follow-up was 247.7 ± 140 weeks. In 2009 and 2010, paediGAV valves were used exclusively, but by 2019, the use of proGAV/proSA had evolved into the first-line therapy. The paediGAV system was significantly more often revised (p < 0.05). The main indication for revision was proximal occlusion, with or without impairment to the valve. The valve and shunt survival rates of proGAV/proSA were significantly prolonged (p < 0.05). The surgery-free valve survival of proGAV/proSA was 90% after 1 year and 63% after 6 years. There were no overdrainage-related revisions of proGAV/proSA valves.

CONCLUSIONS: Favorable shunt and valve survival validates the increasing use of programmable proGAV/proSA serial valves in this delicate population. Potential benefits in postoperative treatment should be addressed in prospective multicenter studies.

PMID:36933264 | DOI:10.3171/2023.1.PEDS22341

J Neurosurg Pediatr. 2023 Mar 17:1-6. doi: 10.3171/2023.2.PEDS22569. Online ahead of print.

ABSTRACT

OBJECTIVE: Hemispherectomy is a complex surgical intervention for medically refractory epilepsy, and its surgical sequelae continue to be defined. The incidence, timing, and predictors of postoperative hydrocephalus are not well understood. Correspondingly, the aim of this study was to define the natural history of the development of hydrocephalus after hemispherectomy based on the authors’ institutional experience.

METHODS: The authors performed a retrospective review of their departmental database for all relevant cases between 1988 and 2018. Demographic and clinical results were abstracted and analyzed using regression analyses to identify predictors of postoperative hydrocephalus.

RESULTS: Of the 114 patients who satisfied selection criteria, there were 53 females (46%) and 61 males (53%) with mean ages of 2.2 and 6.5 years at first seizure and at hemispherectomy, respectively. There were 16 patients (14%) with a history of previous seizure surgery. In terms of surgery, the mean estimated blood loss was 441 ml, with a mean operative time of 7 hours, and 81 patients (71%) required intraoperative transfusions. A planned postoperative external ventricular drain (EVD) was placed in 38 patients (33%). The most common procedural complications were infection and hematoma, occurring in 7 patients (6%) each. Overall, there were 13 patients (11%) with postoperative hydrocephalus requiring permanent CSF diversion, occurring at a median of 1 year (range 0.1-5 years) after surgery. On multivariable analysis, a postoperative EVD (OR 0.12, p < 0.01) was significantly associated with a decreased likelihood of postoperative hydrocephalus, whereas previous surgery history (OR 4.32, p = 0.03) and postoperative infection complication (OR 5.14, p = 0.04) were significantly associated with increased likelihood of postoperative hydrocephalus.

CONCLUSIONS: Postoperative hydrocephalus mandating permanent CSF diversion following hemispherectomy can be expected in approximately 1 in 10 cases, presenting months after surgery on average. A postoperative EVD appears to reduce this likelihood, whereas postoperative infection and previous history of seizure surgery were shown to statistically increase this likelihood. These parameters should be carefully considered in the management of pediatric hemispherectomy for medically refractory epilepsy.

PMID:36933263 | DOI:10.3171/2023.2.PEDS22569

J Neurosurg Spine. 2023 Mar 17:1-8. doi: 10.3171/2023.2.SPINE221071. Online ahead of print.

ABSTRACT

OBJECTIVE: Bertolotti syndrome is a clinical diagnosis given to patients with low-back pain arising from a lumbosacral transitional vertebra (LSTV). While biomechanical studies have demonstrated abnormal torques and range of motion occurring at and above this type of LSTV, the long-term effects of these biomechanical changes on the LSTV adjacent segments are not well understood. This study examined degenerative changes at segments superjacent to the LSTV in patients with Bertolotti syndrome.

METHODS: This study involved a retrospective comparison of patients between 2010 and 2020 with an LSTV and chronic back pain (Bertolotti syndrome) and control patients with chronic back pain with no LSTV. The presence of an LSTV was confirmed on imaging, and the caudal-most mobile segment above the LSTV was assessed for degenerative changes. Degenerative changes were assessed by grading the intervertebral disc, facets, degree of spinal stenosis, and spondylolisthesis using well documented grading systems. All computations were performed in R, version 4.1.0. All tests were two-sided, and p values < 0.05 was considered statistically significant. Separate logistic regression analyses were run with the associated dependent variables for each aim, with age at MRI and sex included as covariates. Odds ratios and 95% confidence intervals were computed.

RESULTS: A total of 172 patients were included, 101 with Bertolotti syndrome and 71 controls. Control patients consisted of patients with low-back pain but no diagnosis of Bertolotti syndrome or an LSTV. Fifty-six Bertolotti (55.4%) and 27 control (38.0%) patients were female, (p = 0.03). After adjusting for age at MRI and sex, Bertolotti patients had pelvic incidence (PI) that was 9.83° greater than control patients (95% CI 5.15°-14.50°, p < 0.001). Sacral slope was not significantly different between the Bertolotti and control groups (beta estimate 3.10°, 95% CI -1.07° to 7.27°; p = 0.14). Bertolotti patients had 2.69 times higher odds of having a high disc grade at L4-5 (3-4 vs 0-2), compared with control patients (OR 2.69, 95% CI 1.28-5.90; p = 0.01). There were no significant differences between Bertolotti patients and controls for spondylolisthesis, facet grade, or spinal stenosis grade.

CONCLUSIONS: Patients with Bertolotti syndrome had a significantly higher PI and were more likely to have adjacent-segment disease (ASD; L4-5) compared with control patients. However, after controlling for age and sex, PI and ASD did not appear to have a significant association within the cohort of Bertolotti patients. The altered biomechanics and kinematics in this condition may be a causative factor in this degeneration, although proof of causation is not possible in this study. This association may warrant closer follow-up protocols for patients being treated for Bertolotti syndrome, but further prospective studies are needed to establish if radiographic parameters can serve as an indicator for biomechanical alterations in vivo.

PMID:36933261 | DOI:10.3171/2023.2.SPINE221071

J Neurosurg. 2023 Mar 17:1-11. doi: 10.3171/2023.1.JNS222269. Online ahead of print.

ABSTRACT

OBJECTIVE: Characterizing changes in the geographic distribution of neurosurgeons in the United States (US) may inform efforts to provide a more equitable distribution of neurosurgical care. Herein, the authors performed a comprehensive analysis of the geographic movement and distribution of the neurosurgical workforce.

METHODS: A list containing all board-certified neurosurgeons practicing in the US in 2019 was obtained from the American Association of Neurological Surgeons membership database. Chi-square analysis and a post hoc comparison with Bonferroni correction were performed to assess differences in demographics and geographic movement throughout neurosurgeon careers. Three multinomial logistic regression models were performed to further evaluate relationships among training location, current practice location, neurosurgeon characteristics, and academic productivity.

RESULTS: The study cohort included 4075 (3830 male, 245 female) neurosurgeons practicing in the US. Seven hundred eighty-one neurosurgeons practice in the Northeast, 810 in the Midwest, 1562 in the South, 906 in the West, and 16 in a US territory. States with the lowest density of neurosurgeons included Vermont and Rhode Island in the Northeast; Arkansas, Hawaii, and Wyoming in the West; North Dakota in the Midwest; and Delaware in the South. Overall, the effect size, as measured by Cramér’s V statistic, between training stage and training region is relatively modest at 0.27 (1.0 is complete dependence); this finding was reflected in the similarly modest pseudo R2 values of the multinomial logit models, which ranged from 0.197 to 0.246. Multinomial logistic regression with L1 regularization revealed significant associations between current practice region and residency region, medical school region, age, academic status, sex, or race (p < 0.05). On subanalysis of the academic neurosurgeons, the region of residency training correlated with an advanced degree type in the overall neurosurgeon cohort, with more neurosurgeons than expected holding Doctor of Medicine and Doctor of Philosophy degrees in the West (p = 0.021).

CONCLUSIONS: Female neurosurgeons were less likely to practice in the South, and neurosurgeons in the South and West had reduced odds of holding academic rather than private positions. The Northeast was the most likely region to contain neurosurgeons who had completed their training in the same locality, particularly among academic neurosurgeons who did their residency in the Northeast.

PMID:36933250 | DOI:10.3171/2023.1.JNS222269