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Impact Of ABCB1 Polymorphisms on Lacosamide Serum Concentrations In Uygur Pediatric Patients with Epilepsy in China

Ther Drug Monit. 2021 Oct 1. doi: 10.1097/FTD.0000000000000927. Online ahead of print.

ABSTRACT

PURPOSE: P-glycoprotein, encoded by ABCB1 (or MDR1), may contribute to drug resistance in epilepsy by limiting gastrointestinal absorption and brain access to antiseizure medications (ASMs). The study aimed to evaluate the impact of ABCB1 polymorphisms on lacosamide (LCM) serum concentrations in Uygur pediatric epileptic patients.

METHODS: The serum concentrations of LCM were determined by ultra-performance liquid chromatography, and the ABCB1 polymorphism was analyzed via polymerase chain reaction-fluorescence staining in situ hybridization. The chi-squared test and Fisher’s exact test were used to analyze the allelic and genotypic distributions of ABCB1 polymorphisms between the drug-resistant and drug-responsive patient groups. Differences in steady-state and dose-corrected LCM serum concentrations between different genotypes were analyzed using the One-Way Analysis of Variance (ANOVA) and Mann-Whitney test.

RESULTS: A total of 131 Uygur children with epilepsy were analyzed, and of them, 41 demonstrated drug resistance. The frequency of the GT genotype of ABCB1 G2677T/A was significantly higher in the drug-resistant group than that in the drug-responsive group (p < 0.05, OR = 1.966, 95% CI = 1.060-3.647). Patients with the G2677T/A- AT genotype had a statistically significantly lower concentration-to-dose (CD) value than patients with the G2677T/A-GG genotype (mean: 0.6 ± 0.2 vs 0.8 ± 0.5 μg/ml per mg/kg, p < 0.001). Significantly lower LCM serum concentrations were observed in ABCB1 C3435T CT and TT genotype carriers than those in the CC carriers (p = 0.008 and p = 0.002), and a significantly lower LCM CD value was observed in ABCB1 C3435T CT genotype carriers than that in the CC carriers (p = 0.042).

CONCLUSION: ABCB1 G2677T/A and C3435T polymorphisms may affect LCM serum concentrations and treatment efficacy in Uygur pediatric patients with epilepsy, leading to drug resistance in pediatric patients.

PMID:34610620 | DOI:10.1097/FTD.0000000000000927

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Preoperative Conization May Have a Positive Impact on Survival in Early-Stage Cervical Cancer: A Propensity-Matched Study

Oncol Res Treat. 2021 Oct 5:1-8. doi: 10.1159/000519646. Online ahead of print.

ABSTRACT

INTRODUCTION: A recent prospective randomized study demonstrated that minimally invasive surgery (MIS) was inferior to open surgery in disease survival in early-stage cervical cancer. Our aim was to investigate whether there were survival benefits of preoperative conization prior to MIS for early-stage cervical cancer.

METHODS: We retrospectively analyzed patients who eventually underwent definitive MIS with stage IA2 to IB1 (no >2 cm) squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma. Preoperatively, the patients were separated into 2 groups: one managed with conization and the other undergoing biopsy without conization. Propensity scoring weight and matching were used to reduce the influence of possible allocation biases. The Cox regression model was used for univariate and multivariate analyses of disease recurrence and survival.

RESULTS: 227 patients were contained in this study (99 patients in the conization group and 128 patients in the nonconization group). The 5-year DFS of the conization group was statistically better than that of the nonconization group (98.4% vs. 91.8%, p = 0.011). By univariate analysis, conization (HR = 0.11, 95% CI = 0.01-0.87, p = 0.03) and histologic cell type (p = 0.01) were considered as risk factors for recurrence. Multivariate analysis further confirmed conization (HR = 0.04, 95% CI = 0.01-0.51, p = 0.01) and histologic cell type (p < 0.01) correlated with DFS. After propensity score matching (1:1), 84 patients were included in the conization and nonconization groups, respectively, with 5-year DFS still higher in the conization group (98.3% vs. 92.9%, p = 0.037). The results after univariate and multivariate analyses were consistent with those prior to propensity score matching.

CONCLUSION: Preoperative conization in conjunction with MIS seemed to be a safe and feasible approach, with results that may have implications for the reduction of recurrence. Histologic cell type also impacted survival. Therefore, more future prospective studies are warranted.

PMID:34610605 | DOI:10.1159/000519646

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Transcranial Motor-evoked Potential Alert after Supine-to-Prone Position Change during Thoracic Ossification in Posterior Longitudinal Ligament Surgery: A Prospective Multicenter Study of the Monitoring Committee of the Japanese Society for Spine Surgery and Related Research

Spine (Phila Pa 1976). 2021 Oct 4. doi: 10.1097/BRS.0000000000004246. Online ahead of print.

ABSTRACT

STUDY DESIGN: A prospective, multicenter study.

OBJECTIVE: To evaluate the usefulness of transcranial motor-evoked potentials (Tc-MEPs) during supine-to-prone position change for thoracic ossification of the posterior longitudinal ligament (T-OPLL).

SUMMARY OF BACKGROUND DATA: Supine-to-prone position change might be a risk of spinal cord injury in posterior decompression and fusion surgeries for T-OPLL.

METHODS: The subjects were 145 patients with T-OPLL surgically treated with posterior decompression and fusion using Tc-MEPs in 14 institutes. Tc-MEPs were monitored before surgery from supine-to-prone position and intraoperatively in 7 institutes and only intraoperatively in the other 7 institutes because of disapproval of the anesthesia department. In cases of Tc-MEP alert after position change, we adjusted the cervicothoracic posture. When the MEP did not recover, we reverted the position to supine and monitored the Tc-MEPs in supine position.

RESULTS: There were 83 and 62 patients with/without Tc-MEP before position change to prone (group A and B). The true-positive rate was lower in group A than group B, but without statistical significance (8.4% vs 16.1%, p = 0.12). In group A, 5 patients who had Tc-MEP alert during supine-to-prone position change were all female and had larger body mass index values and upper thoracic lesions. Among the patients, 3 underwent surgeries after cervicothoracic alignment adjustment, and 2 had postponed operations to 1 week later with halo-vest fixation because of repeated Tc-MEP alerts during position change to prone. The Tc-MEP alert at exposure was statistically more frequent in group B than in group A (p = 0.033).

CONCLUSION: Tc-MEP alert during position change is an important sign of spinal cord injury due to alignment change at the upper thoracic spine. Tc-MEP monitoring before supine-to-prone position change was necessary to prevent spinal cord injury in surgeries for T-OPLL.Level of Evidence: 4.

PMID:34610608 | DOI:10.1097/BRS.0000000000004246

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Short- and Medium-Term Impact of a Structured Medical Intervention in Adolescents with Overweight, Obesity, or Increased Waist Circumference

Obes Facts. 2021 Oct 5:1-11. doi: 10.1159/000519270. Online ahead of print.

ABSTRACT

INTRODUCTION AND OBJECTIVES: This study aimed to assess the impact of a structured medical intervention in adolescents with overweight or obesity at medical discharge and after 5 years and identify the factors responsible for the reappearance of anthropometric alterations.

METHODS: A total of 42 adolescents with overweight, obesity, and/or increased waist circumference (WC) participated in a survey on eating habits, physical exercise, and sedentary habits. Body mass index (BMI), fat mass (FM), and WC were evaluated quarterly during a structured medical intervention, with a maximum duration of 3 years (2007-2010) and 5 years after its conclusion (2015-2016). SPSS 19.0®was used for statistical analysis.

RESULTS: Initially, 23.8% adolescents were overweight, 28.6% were obese, 83.3% had increased FM, and 95.2% had high WC. A significant improvement was noted until medical discharge with respect to BMI, FM, and WC (p < 0.001) owing to an increased number of meals; reduction in the consumption of hypercaloric foods/drinks (p < 0.001); increase in the consumption of fruits, vegetables, and soup (p < 0.001); increase in physical exercise and daily walks (p < 0.001); and reduction in sedentary habits (p < 0.001). At reassessment, after 5 years, the majority had normal BMI, FM, and WC (p < 0.001), although 45.2% had abandoned sports (p < 0.001).

CONCLUSIONS: A relation exists between the improvement or normalization of BMI, FM, and WC and the number of meals, healthy eating habits, physical exercise, and less sedentary habits. The intervention was associated with an improvement in the parameters during the short and medium terms.

PMID:34610604 | DOI:10.1159/000519270

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Evaluation of an Expedited Trauma Transfer Protocol: Right Place, Right Time

J Surg Res. 2021 Oct 2;269:229-233. doi: 10.1016/j.jss.2021.08.022. Online ahead of print.

ABSTRACT

BACKGROUND: Trauma patients may initially be evaluated at non-trauma centers. This may cause a delay in treatment, which could affect their outcome. Additionally, advanced imaging may be performed which may be suboptimal or unnecessary, increase time to transfer, or unable to be viewed when the patient reaches a trauma center increasing the delays to treatment or need for repeat imaging. Rapid identification and transfer to definitive trauma care, minimizing unnecessary delays should be the priority.

METHODS: The trauma registry at a regional Level 1 Adult/Pediatric Trauma center was queried for transferred trauma patients over a 3-y period. A retrospective review was performed. Transferred trauma patients were compared prior to an expedited transfer protocol to after implementation. Demographics, mechanism of injury, injury severity score, computerized tomography scans performed prior to transfer, mortality, hospital and intensive care unit length of stay were compared using bivariate and multivariable regression statistics where appropriate.

RESULTS: Transferred trauma patients were identified, 683 in the pre-protocol group and 821 in the post-protocol group, an increase of 16.8%. There were no differences in age, sex, injury severity score, mechanism of injury, mortality, hospital, or intensive care unit length of stay (LOS) throughout the study period. There was a significant decrease in time to transfer (263 min ± 222 versus 227 ± 189, P < 0.001) and computerized tomography scans performed prior to transfer (Head 47% versus 32%, C-spine 36% versus 23%, Thorax 22% versus 16%, Abdomen/Pelvis 24% versus 14%, all P values <0.001 except CT Thorax). Interestingly, the rate of underinsured patients did not increase (21% versus 25%, P = 0.05). Risk-adjusted mortality and hospital LOS also did not change during the study period.

CONCLUSIONS: After implementation of an expedited trauma transfer protocol to a regional Level 1 trauma center there was an associated reduced time of arrival to definitive care and decreased advanced imaging done prior to transfer. However, there was no associated decrease in mortality or LOS among transferred patients. Further studies examining prehospital transport or hospital choice decisions and subsequent care provided at non-trauma facilities regarding imaging obtained, care rendered, and transfer decisions can be explored.

PMID:34610536 | DOI:10.1016/j.jss.2021.08.022

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Optimal allocation of PCR tests to minimise disease transmission through contact tracing and quarantine

Epidemics. 2021 Sep 25;37:100503. doi: 10.1016/j.epidem.2021.100503. Online ahead of print.

ABSTRACT

PCR testing is a crucial capability for managing disease outbreaks, but it is also a limited resource and must be used carefully to ensure the information gain from testing is valuable. Testing has two broad uses for informing public health policy, namely to track epidemic dynamics and to reduce transmission by identifying and managing cases. In this work we develop a modelling framework to examine the effects of test allocation in an epidemic, with a focus on using testing to minimise transmission. Using the COVID-19 pandemic as an example, we examine how the number of tests conducted per day relates to reduction in disease transmission, in the context of logistical constraints on the testing system. We show that if daily testing is above the routine capacity of a testing system, which can cause delays, then those delays can undermine efforts to reduce transmission through contact tracing and quarantine. This work highlights that the two goals of aiming to reduce transmission and aiming to identify all cases are different, and it is possible that focusing on one may undermine achieving the other. To develop an effective strategy, the goals must be clear and performance metrics must match the goals of the testing strategy. If metrics do not match the objectives of the strategy, then those metrics may incentivise actions that undermine achieving the objectives.

PMID:34610549 | DOI:10.1016/j.epidem.2021.100503

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Engaging nurses in research awareness using a new style of hospital journal club – a descriptive evaluation

Nurse Educ Today. 2021 Sep 21;108:105123. doi: 10.1016/j.nedt.2021.105123. Online ahead of print.

ABSTRACT

BACKGROUND: Nurses, especially nurses in Africa, face barriers when trying to access and apply literature. These challenges include paywalls; complex academic language; and journal content which is hard to translate to local realities.

OBJECTIVES: To investigate nurses’ self-reported experiences of participating in a monthly hospital wide journal club at the Red Cross War Memorial Children’s Hospital (RCWMCH).

DESIGN: This descriptive study used a researcher-designed quantitative questionnaire design. The Revised Standards for Quality Improvement Reporting Excellence (SQUIRE 2.0) guideline were used.

SETTING: Red Cross War Memorial Children’s Hospital (RCWMCH) in Cape Town, South Africa.

PARTICIPANTS: All cadres of nurses working at the Red Cross War Memorial Children’s Hospital (RCWMCH) who had attended six or more hospital journal club sessions at RCWMCH over the previous two years.

METHODS: A descriptive study using a researcher-designed quantitative questionnaire.

RESULTS: 155 participants completed the survey (96.87% response rate). Participants self-reported an improved knowledge of the main sections of a journal article (p < 0.001) and a significant increase in talking to colleagues about evidence-based nursing practice after attending journal club (p < 0.001).

CONCLUSIONS: Attendance at a journal club appears to contribute to increased access to scientific literature, personal and organisational habits of reading, and collaborative exploration of clinical practice for nurses of all cadres. Innovative facilitation methods (including large-scale graphic facilitation) may contribute to efficacy and popularity of sessions.

PMID:34610529 | DOI:10.1016/j.nedt.2021.105123

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A finger-driven disposable micro-platform based on isothermal amplification for the application of multiplexed and point-of-care diagnosis of tuberculosis

Biosens Bioelectron. 2021 Sep 22;195:113663. doi: 10.1016/j.bios.2021.113663. Online ahead of print.

ABSTRACT

Tuberculosis (TB) remains the high-risk infectious pathogen that caused global pandemic and high mortality, particularly in the areas lack in health resources. Clinical TB screening and diagnosis are so far mainly conducted on limited types of commercial platforms, which are expensive and require skilled personnel. In this work, we introduced a low-cost and portable finger-driven microfluidic chip (named Fd-MC) based on recombinase polymerase amplification (RPA) for rapid on-site detection of TB. After injection of the pre-treated sample solution, the pre-packaged buffer was driven by the pressure generated by the finger-actuated operation to accomplish sequential processes of diagnosis in a fully isolated microchannel. An in-situ fluorescence strategy based on FAM-probe was implemented for on-chip results read-out though a hand-held UV lamp. Hence, the Fd-MC proved unique advantageous for avoiding the risk of infection or environmental contamination. In addition, the Fd-MC was designed for multiplexed detection, which is able to not only identify TB/non-TB infection, but also differentiate between human Mycobacterium tuberculosis and Mycobacterium bovis. The platform was verified in 37 clinical samples, statistically with 100% specificity and 95.2% sensitivity as compared to commercial real-time RPA. Overall, the proposed platform eliminates the need on external pumps and skilled personnel, holding promise to POC testing in the resource-limited area.

PMID:34610534 | DOI:10.1016/j.bios.2021.113663

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“Trends and Perioperative Outcomes Across Elective Benign Hysterectomy Procedures from the ACS-NSQIP 2007-2017”

J Minim Invasive Gynecol. 2021 Oct 2:S1553-4650(21)01178-X. doi: 10.1016/j.jmig.2021.09.714. Online ahead of print.

ABSTRACT

STUDY OBJECTIVE(S): In this study, we describe trends of all three routes of hysterectomy, patient demographics, and perioperative morbidity among women undergoing surgery for benign indications between 2007-2017. We also sought to compare the rates of ELOS and readmission rates among the laparoscopic, abdominal, and transvaginal routes.

STUDY DESIGN: Retrospective cohort study STUDY SETTING: National Database study PATIENTS: American College of Surgeons- National Surgical Quality Improvement Program (ACS-NSQIP) database to identify patients who underwent an elective hysterectomy for benign indication between 2007-2017.

INTERVENTIONS: Patients were identified using Current Procedural Terminology (CPT) codes and excluded if their indication for surgery included cancer and pelvic organ prolapse diagnoses based on International Classification of Disease (ICD) codes. Collected variables of interest included age, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) classification, uterine weight > 250 grams, and operative time. Our outcomes of interest included ELOS and readmission within thirty days. ELOS was defined as a hospital admission of two days or more after laparoscopic and transvaginal hysterectomy, and greater than three days for an abdominal hysterectomy. Summary statistics were used to evaluate shifts in patient characteristics and postoperative outcomes by hysterectomy route and year of surgery. Multivariable logistic regression analysis, stratified by year, comparing laparoscopic to transvaginal and abdominal hysterectomies, was performed.

MEASUREMENTS AND MAIN RESULTS: 224,357 patients that met the inclusion and exclusion criteria. Of those, 132,567 (59.1%) underwent a laparoscopic hysterectomy; 30,105 (13.4%) a vaginal hysterectomy; and 61,685 (27.5%) an abdominal hysterectomy. The rate of laparoscopic hysterectomy increased by more than 200% between 2007-2017, while the rates of transvaginal and abdominal hysterectomies steadily decreased (-58%, -42%, respectively]). The mean age, median obesity, and ASA classification increased amongst women undergoing hysterectomy across all routes with the sharpest increase within the laparoscopic hysterectomy group (% increase in mean age [2.1%, 1.3%, 0.7%] and mean BMI [9.1%, 4.3%, 3.7%] for laparoscopic, transvaginal and abdominal routes, respectively). In 2017 the odds of ELOS were 29% lower for those who received laparoscopic compared to those who received abdominal hysterectomy (P<0.001). Comparing the rates of readmission between the laparoscopic and abdominal hysterectomy groups shows that the odds of readmission is significantly lower for patients who receive a laparoscopic hysterectomy across all eleven years (P<0.001).

CONCLUSION(S): The rates of laparoscopic hysterectomy have been steadily increasing over the past eleven years. This large retrospective study confirms the lowest rates of readmission and extended length of stay within the laparoscopic hysterectomy group despite the rising medical complexity of the patients.

PMID:34610464 | DOI:10.1016/j.jmig.2021.09.714

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Time to readmission in psychiatric inpatients with a therapeutic leave

J Psychiatr Res. 2021 Sep 24;144:102-109. doi: 10.1016/j.jpsychires.2021.09.050. Online ahead of print.

ABSTRACT

AIMS: Interventions to decrease readmissions in psychiatric patients are urgently needed. In Switzerland therapeutic leave (TL) composes a cornerstone of inpatient treatment. TL is a planned time-limited absence from the inpatient ward giving patients the opportunity to test their resilience in their usual environment. Evidence of its applicability as an intervention reducing readmissions is lacking. Therefore, our objective was to examine the association between TL and readmission risk.

METHODS: Using the Kaplan-Meier curve we compared the time to readmission of 3’302 inpatients at the UPK Basel with and without TL. Cox regression was applied, integrating other covariates associated with readmission.

RESULTS: The Kaplan-Meier curve indicated longer cumulative survival in patients with TL. The log-rank test implied statistical significance (χ2(1) = 18.8, p < .05). The Cox regression showed a reduced hazard for patients with TL (HR = 0.735, CI 95% = [0.639, 0.846], p < .001) and for involuntarily hospitalized patients (HR = 0.760, CI 95% = [0.618, 0.934], p < .01). A higher readmission risk was found for a history of psychiatric admissions (HR = 1.005, CI 95% = [1.004, 1.005], p < .001), higher severity of symptoms at admission (HR = 1.029, CI 95% = [1.018, 1.040], p < .001), comorbidity (HR = 1.178, CI 95% [1.024, 1.355], p = .022), and a diagnosis with schizophrenia-spectrum disorders (HR = 1.401, CI 95% [1.164, 1.687], p = .001).

CONCLUSION: Linking TL with readmission risk, our results imply an easy way to improve quality of care, with possible implications for practice, policies and quality interventions. TL might be suitable to enhance recovery, reduce readmissions and health care costs. RCTs are needed for validation.

PMID:34610513 | DOI:10.1016/j.jpsychires.2021.09.050