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Materials and methods | PMC9821721 | |||
Participants | A priori power analyses (software package, G* Power 3.1.9.7: University of Dusseldorf, Germany) conducted using the results from studies by Hazime et al. [ | PMC9821721 | ||
Experimental design | This study utilized a fully randomized, crossover, repeated measures design, with all participants completing four protocols. The four protocols involved the participant receiving: 1) a-tDCS targeting the left M1, with testing of the contralateral (right) leg, 2) a-tDCS targeting the left M1 with testing of the ipsilateral (left) leg, 3) sham tDCS (s-tDCS) targeting the left M1, with testing of the contralateral (right) leg, and 4) s-tDCS targeting the left M1 with testing of the ipsilateral (left) leg. At least one week of recovery was allocated between each session to ensure that no effects from prior stimulations carried over to the next session ( | PMC9821721 | ||
Experimental design. | knee extensors | CONTRACTION | Abbreviations: KE: knee extensors, KF: knee flexors, MVC: maximal voluntary isometric contraction, tDCS: transcranial direct current stimulation. | PMC9821721 |
tDCS intervention | A similar stimulation protocol as the only other study to test ipsilateral tDCS effects [ | PMC9821721 | ||
MVC and fatigue tests | fatigue | CONTRACTION | Prior to any performance measurements, participants completed a five-minute warm up using a cycle ergometer at 70 revolutions per minute and 1 kilopond.To measure force, a cuff with a non-extensible strap was attached to a strain gauge (Omega Engineering Inc., LCCA 500 pounds; sensitivity = 3 mV/V, OEI, Canada) and placed around the ankle of the participant. Knee joint angles were measured using a goniometer (90Following the post-tDCS MVC, participants performed a repeated contraction (fatigue) protocol consisting of 12 KE MVCs with a work to rest ratio of 5:10 seconds [ | PMC9821721 |
tDCS blinding questionnaire | itching, tingling, scalp irritation | Before and after receiving tDCS (either a-tDCS or s-tDCS), participants were given a questionnaire, where they were asked to rate perceived sensations (e.g., itching, tingling, scalp irritation) on a scale from 1–10 (Likert scale: 1 = absent, 10 = severe) [ | PMC9821721 | |
Statistical analysis | blurred vision, scalp irritation, fatigue, anxiety, itching, burning sensation, headache, acute mood, neck pain | Statistical analyses were calculated using SPSS software (Version 27.0, SPSS, Inc. Chicago, IL). Normality and homogeneity of variances tests were conducted for all dependent variables. If the assumption of sphericity was violated, the Greenhouse-Geiser correction was employed. For absolute MVC force, a three-way repeated measures ANOVA (2x2x2) with factors including time (pre-/post-tDCS), tDCS protocol (anodal/sham), and tested leg ((ipsilateral to tDCS) / contralateral to tDCS) was conducted. Sex was not included in the absolute data analysis as it is well established that men typically exert greater forces than women. However, for relative measures, sex was incorporated as a factor. For the fatigue index, a three-way repeated measures ANOVA (2x2x2) with factors including sex, tDCS protocol (anodal/sham), and leg tested was also completed. For the fatigue test, another 3-way repeated measures ANOVA (2x2x2) with factors including first and last (12) repetition, two legs and tDCS protocol (anodal/sham).If significant interactions were detected, post-hoc t-tests corrected for multiple comparisons were conducted to determine differences between values. Significance was set at p ≤ 0.05. Cohen’s Friedman’s ANOVA was utilized to detect significant effects for scales related to headache, neck pain, blurred vision, scalp irritation, tingling, itching, burning sensation, acute mood change, fatigue, and anxiety. For significant effects post-hoc Wilcoxon Signed Ranks tests corrected for multiple comparisons were performed. | PMC9821721 | |
Results | PMC9821721 | |||
Absolute force measures | Coefficient of variations (CV) less than 10% of the mean and excellent reliability described as an ICC: >0.9 were found between pre-test measurements for the contralateral (α = 0.943, a-tDCS CV: 31.6 = 6.5% of mean, s-tDCS CV: 30.5 = 6.3% of mean) and ipsilateral (α = 0.964, a-tDCS: 36.4 = 7.5% of mean, s-tDCS: 36.2 = 7.4% of mean) KE.There was a significant [A significant [ | PMC9821721 | ||
Mean participant absolute contralateral and ipsilateral knee extensor force following anodal transcranial direct current stimulation (a-tDCS) or sham tDCS (s-tDCS). | (* denotes statistical significance at | PMC9821721 | ||
Relative (normalized) MVC force | A significant interaction effect for condition x leg tested [ | PMC9821721 | ||
Fatigue test | fatigue | There were no significant main or interaction effects for fatigue index force ( | PMC9821721 | |
Participant contralateral and ipsilateral knee extensor force fatigue index following anodal transcranial direct current stimulation (a-tDCS) or sham tDCS (s-tDCS). | (* denotes statistical significance at | PMC9821721 | ||
Mean participant contralateral and ipsilateral knee extensor (KE) force for each contraction of the fatigue protocol. | Asterisk highlights a significant (p<0.0001) decrease in force from repetition #1 to #12. Columns and bars represent mean force values and standard deviations in Newtons. | PMC9821721 | ||
tDCS blinding questionnaire data | fatigue, scalp irritation, itching, burning sensation, headache | MINOR | Only minor side effects were reported following tDCS, including headache, scalp irritation, tingling, itching, burning sensation, and fatigue. Friedman’s ANOVA revealed no significant differences in these variables between the four protocols (all p values ≥ 0.056) suggesting that participants were sufficiently blinded to which type of stimulation they were receiving. | PMC9821721 |
Discussion | fatigue, muscle fatiguability | The main objective of this study was to determine if a-tDCS targeting the left M1 could modulate maximal force production or muscle fatiguability in either the right (contralateral to tDCS) or left (ipsilateral to tDCS) quadriceps. This study demonstrated significant force impairments (s-tDCS with testing of contralateral KE MVC, and a-tDCS with testing of ipsilateral KE MVC) and no significant changes (a-tDCS with testing of the contralateral KE MVC and s-tDCS with testing of the ipsilateral KE MVC) in discrete (single repetition) MVC tests.Since four meta-analyses [The anodal and sham tDCS post-test protocols were conducted after approximately 10 minutes of physical inactivity. While the pre-test MVCs were performed shortly after a warm-up, the beneficial effects of this warm-up may have been reduced after 10 minutes of inactivity [While a-tDCS in the literature has shown the ability to increase M1 excitability, it has also been hypothesized that a-tDCS could attenuate the reduction in output from the M1 contributing to supraspinal fatigue [This study found no significant differences between male and female participants for relative force production or fatigue index. This suggests that tDCS affects male and female participants to a similar extent. A review by Dedoncker [ | PMC9821721 | |
Limitations | RECRUITMENT | It might be suggested that the recruitment of 16 participants in this study involving a more variable intervention might have led to low statistical power even though the power analysis indicated that 8–10 participants should provide sufficient power. This lower power may have diminished the possibility of revealing any sex differences. Furthermore, as only the KE (quadriceps) were tested, future studies should aim to determine if other muscle groups ipsilateral to the site of stimulation are affected in a similar manner, while also utilizing transcranial magnetic stimulation (TMS) to determine potential changes in corticospinal excitability. When combined with transmastoid electrical stimulation which activates axons in the spinal cord, effects can be distinguished between cortical and spinal excitability or inhibition. Finally, as reviewed by Savoury et al. [ | PMC9821721 | |
Conclusions | fatigue | This study found that 10 minutes of 2 mA of a-tDCS is not an effective or consistent method for increasing maximal force production or reducing fatigue in the KE either contralateral or ipsilateral to the stimulated M1. Furthermore, the decrements with the contralateral s-tDCS also contributed to the inconsistent findings with tDCS. With many athletes looking to devices such as those for administering tDCS to provide performance enhancements, it is important to caution that tDCS may not be beneficial but could instead be detrimental to exercise performance.The experiments comply with the current laws of the country in which they were performed. | PMC9821721 | |
Methods | PMC10616990 | |||
Enrollment | thirty-nine, allergy | MAY, TRIGGER FINGER, ALLERGY | Institutional review board approval was obtained prior to initiation of the study. Four hundred and thirty-nine patients, 18 years of age and older, undergoing carpal tunnel release by three certified hand surgeons at a single academic institution were screened for eligibility between May 2019 and October 2021. Participants were enrolled at either their preoperative clinic visit or on the day of surgery. Adults unable to provide informed consent, paediatric or adolescent patients, pregnant women and prisoners were excluded from this study. Patients undergoing simultaneous procedures on the ipsilateral extremity, such as trigger finger or cubital tunnel release, and patients with a documented allergy to adhesives or tape were also excluded. One hundred and twenty-five participants were randomized to either the subcuticular Monocryl or traditional nylon group using a digital randomizer application (CONSORT flow chart reporting the number of patients through the enrollment, intervention, allocation, follow-up and data analysis phases of the trial. | PMC10616990 |
Technique | Surgeries were performed by three experienced or highly-experienced fellowship-trained hand surgeons (RMS, COB, RHA) in practice for a minimum of 10 years ( | PMC10616990 | ||
Data collection | itching, itchiness, scars, pain | SCAR | Patients returned for two postoperative follow-up appointments, at 10–12 days and 6 weeks after surgery. Nylon sutures were removed at the first postoperative visit. At each visit, the incisions were evaluated by trained research personnel. The treating surgeon did not perform these evaluations to ensure interobserver reliability and eliminate bias. Both the patients and research personnel evaluated the incisions via direct visualization and palpation, after which they completed POSAS evaluation. Patients assessed their scars on the criteria of pain, itchiness, colour, stiffness, thickness and irregularity, while observers rated the vascularity, pigmentation, thickness, relief, pliability and surface area of the scars. Both were also asked to provide their overall opinion of the scar. Each item was rated on a 10-point scale, with the lowest score ‘1’ corresponding to normal skin (i.e. normal pigmentation, no itching) and the highest score ‘10’ corresponding to the largest difference from normal skin (i.e. the worst imaginable scar or sensation). The scores are summed separately, with lower scores indicating closer resemblance to normal skin. | PMC10616990 |
Statistical analysis | Based on previously published data ( | PMC10616990 | ||
Results | SCAR, REGRESSION, SCAR | A total of 104 patients completed the first postoperative visit at 2 weeks, and 62 patients completed the second postoperative visit at 6 weeks. At 2 weeks, 48 patients in the Monocryl group and 56 patients in the nylon group successfully completed the questionnaires. At 6 weeks, 31 patients in the Monocryl group and 31 patients in the nylon group successfully completed the questionnaires (Average patient assessments of their scars are reported in Mean Patient Scar Assessment Scale at 2-week and 6-week postoperative visits.Significant Average observer assessments of the scars are reported in Mean Observer Scar Assessment Scale at 2-week and 6-week postoperative visits.Significant Changes in patient and observer scar assessments between 2 and 6 weeks are reported for each suture type in Changes in (a) patient and (b) observer ratings for each suture type from 2 weeks to 6 weeks.Significant Linear regression models depicting the effect of timepoint and suture type on overall opinion and total scores. While patients and observers rated the appearance of scars closed with Monocryl similarly between 2 and 6 weeks, they noted significant improvement in the appearance of scars closed with nylon between these timepoints. No differences were noted between Monocryl and nylon at 6 weeks. Confidence intervals are shown at 95%. | PMC10616990 | |
Discussion | inflammation, scars, pain, tightness, tenderness, carpal tunnel | SCAR, INFLAMMATION, ADVERSE REACTION, PROLIFERATIVE, SCAR, COMPLICATIONS | Although carpal tunnel release is the most performed elective procedure in the hand, debate remains regarding the optimal suture type and method for wound closure. There is emerging evidence that suture material and closure technique can influence the ultimate outcome (Several studies have pointed to the advantages conferred by using absorbable sutures for closure of carpal tunnel incisions. Two groups found that patients who received absorbable sutures had significantly less pain in the immediate postoperative period compared with patients who received non-absorbable sutures (Prior economic analyses have suggested that use of absorbable sutures offers a significant opportunity for cost reduction. A Cochrane report determined that if all surgeons in the United Kingdom used non-absorbable sutures after carpal tunnel release, then the cost to the healthcare system for a nursing visit to remove sutures would be over 3 million British pounds (GBP) per year (Prior studies have highlighted potential drawbacks of absorbable sutures, namely increased residual wound inflammation and persistent scar tenderness (We found no differences in patient or observer assessment of any category between the Monocryl or nylon groups at 6 weeks, although our study was underpowered to reveal if there actually would be a difference in observer ratings at this timepoint. No patient in our study developed a delayed adverse reaction to Monocryl. No patients developed any surgical site complications. This suggests that delayed tissue reaction or inflammation is not a major concern at 6 weeks following Monocryl use and that absorbable and non-absorbable sutures produce comparable scars in the long-term. Furthermore, our findings challenge the classic teaching that non-absorbable sutures cause less inflammation and therefore result in a better scar. Scar appearance following Monocryl (a) and nylon (b) wound closures immediately postoperative and at 2 weeks.Our study has limitations. Based on our a priori power analysis, our study was underpowered to detect a difference in patient and observer scar assessment scales between Monocryl and nylon at 6 weeks. However, it is our experience and impression while conducting this study that the majority of patients in both groups were fully healed by 6 weeks with only minimally noticeable difference in their scars. Indeed, many patients questioned the need for the 6-week postoperative appointment, and only 62 of the 104 patients returned to complete the 6-week study visit. We do not believe that those patients lost to follow-up would bias our results, as they likely had satisfactory healing of their scars, which would reinforce the findings that no major differences exist between Monocryl and nylon closures at 6 weeks and that similar long-term outcomes can be expected regardless of suture type or closure technique. Recruiting an additional 83 patients to power the study to detect a difference in observer scar ratings at 6 weeks did not seem like a practical endeavour. Importantly, we did find statistically significant differences between Monocryl and nylon at 2 weeks. When statistical tests are significant, it is always of sufficient power, and thus we can reject our null hypothesis that Monocryl and nylon would produce equal POSAS scores at 2 weeks. Another limitation is that we were unable to perform a multivariate analysis of other surgical variables that might have influenced scar appearance (e.g. time to suture removal, tightness of closure). A final limitation is that 6 weeks may be considered a relatively short follow-up period. However, we anticipated that because most wounds would be fully healed at this stage, it would be challenging to have patients return several months later beyond the normal follow-up period for a carpal tunnel release, which did turn out to be the case. Furthermore, at 6 weeks wounds are nearing the end of the proliferative healing phase before remodelling, and thus any differences between groups would be best highlighted in the period leading up to this timepoint ( | PMC10616990 |
Supplemental Material | PMC10616990 | |||
sj-zip-1-jhs-10.1177_17531934231178383 - Supplemental material for Prospective randomized controlled trial comparing the effect of Monocryl versus nylon sutures on patient- and observer-assessed outcomes following carpal tunnel surgery | Click here for additional data file.Supplemental material, sj-zip-1-jhs-10.1177_17531934231178383 for Prospective randomized controlled trial comparing the effect of Monocryl versus nylon sutures on patient- and observer-assessed outcomes following carpal tunnel surgery by Edward Wu, Robert Allen, Christopher Bayne and Robert Szabo in Journal of Hand Surgery (European Volume) | PMC10616990 | ||
References | PMC10616990 | |||
Key Points | PMC10116385 | |||
Question | depression | Can depression be reduced during pregnancy and before birth using a brief, safe intervention? | PMC10116385 | |
Findings | depressive disorder, depression | In this randomized clinical trial of 234 adult pregnant individuals, elevated symptoms were reported during routine obstetric care depression screening. Compared with enhanced usual care, brief interpersonal psychotherapy significantly improved depression symptoms and major depressive disorder diagnosis rate during pregnancy. | PMC10116385 | |
Meaning | depression | Brief interpersonal psychotherapy may be warranted to relieve depression in pregnant individuals with potential intergenerational benefits. | PMC10116385 | |
Importance | depression | Prenatal depression is prevalent with negative consequences for both the mother and developing fetus. Brief, effective, and safe interventions to reduce depression during pregnancy are needed. | PMC10116385 | |
Objective | depression | To evaluate depression improvement (symptoms and diagnosis) among pregnant individuals from diverse backgrounds randomized to brief interpersonal psychotherapy (IPT) vs enhanced usual care (EUC). | PMC10116385 | |
Design, Setting, and Participants | depression | A prospective, evaluator-blinded, randomized clinical trial, the Care Project, was conducted among adult pregnant individuals who reported elevated symptoms during routine obstetric care depression screening in general practice in obstetrics and gynecology (OB/GYN) clinics. Participants were recruited between July 2017 and August 2021. Repeated measures follow-up occurred across pregnancy from baseline (mean [SD], 16.7 [4.2] gestational weeks) through term. Pregnant participants were randomized to IPT or EUC and included in intent-to-treat analyses. | PMC10116385 | |
Interventions | Treatment comprised an engagement session and 8 active sessions of brief IPT (MOMCare) during pregnancy. EUC included engagement and maternity support services. | PMC10116385 | ||
Main Outcomes and Measures | depression, Depression | Two depression symptom scales, the 20-item Symptom Checklist and the Edinburgh Postnatal Depression Scale, were assessed at baseline and repeatedly across pregnancy. Structured Clinical Interview for | PMC10116385 | |
Results | MDD | Of 234 participants, 115 were allocated to IPT (mean [SD] age, 29.7 [5.9] years; 57 [49.6%] enrolled in Medicaid; 42 [36.5%] had current MDD; 106 [92.2%] received intervention) and 119 to EUC (mean [SD] age, 30.1 [5.9] years; 62 [52.1%] enrolled in Medicaid; 44 [37%] had MDD). The 20-item Symptom Checklist scores improved from baseline over gestation for IPT but not EUC ( | PMC10116385 | |
Conclusions and Relevance | MDD, depression, ’ mental health | In this study, brief IPT significantly reduced prenatal depression symptoms and MDD compared with EUC among pregnant individuals from diverse racial, ethnic, and socioeconomic backgrounds recruited from primary OB/GYN clinics. As a safe, effective intervention to relieve depression during pregnancy, brief IPT may positively affect mothers’ mental health and the developing fetus. | PMC10116385 | |
Trial Registration | ClinicalTrials.gov Identifier: | PMC10116385 | ||
Introduction | depression, Depression, disability | DISEASE | Depression is common and contributes to disability and disease burden.The US Preventive Services Task Force (USPSTF) showed that current interventions exhibit significant but small effects to prevent perinatal depression (defined broadly including pregnancy through 12 months post partum).The present study follows the USPSTF’s recommendations for investigating psychosocial interventions | PMC10116385 |
Methods | PMC10116385 | |||
Participants | mania, psychosis, blood transfusions, depression, Depression | RECRUITMENT | We randomized 234 pregnant individuals recruited primarily from obstetrics clinics at 2 major medical centers in the Denver, Colorado, metropolitan area. Recruitment began July 2017 and ended August 2021 with a pause from mid-April through mid-June 2020 due to the COVID-19 pandemic. Initial screening was performed based on medical record review. Eligibility criteria included 18 to 45 years of age, English speaking, 25 weeks’ gestational age (GA) or less, singleton pregnancy, and endorsing elevated depression symptoms when screened as part of standard of care (Edinburgh Postnatal Depression Scale [EPDS] score ≥10). Exclusion criteria included current illicit drug or methadone use and major health conditions requiring invasive treatments (eg, dialysis, blood transfusions, chemotherapy). Additional assessment for eligibility was performed at baseline to exclude (1) current or past psychosis or mania and (2) currently receiving cognitive behavioral therapy or IPT. The trial protocol is available in This study followed the Consolidated Standards of Reporting Trials ( | PMC10116385 |
CONSORT Flow Diagram | Participants allocated to interpersonal psychotherapy and designated as “did not receive intervention” did not attend any prenatal intervention sessions. | PMC10116385 | ||
Procedures | MDD | Participants completed a baseline evaluation, including interview and questionnaire assessments. Eligible individuals were then randomly assigned to IPT or EUC using a computer-generated random numbers sequence. Participants were randomized in blocks of 2 and stratified on current MDD (assessed via the Structured Clinical Interview for | PMC10116385 | |
Intervention Conditions | depression, psychiatric | MomCare is a culturally relevant, collaborative care intervention that provides brief IPT.All IPT therapists and collaborative care team members completed a 3-day training and were certified by Nancy Grote, PhD, a leading brief IPT expert for antenatal depression. IPT therapists were doctoral-level clinicians who followed detailed treatment manuals and received supervised training. Adherence checklists ensured that MOMCare was delivered with fidelity. Fidelity ratings were very high (mean, 1.90; scale ranged from 0 [needs work] to 2 [done well]) across sessions independently rated by MOMCare developers Nancy Grote, PhD, and Mary C. Curran, MSW. All participants had at least 1 session reviewed; 25% to 40% of sessions across active IPT were reviewed (eMethods 2 in EUC augmented the usual standard of care pregnant individuals received within OB/GYN clinics through their obstetric clinicians and/or social workers. EUC consisted of maternity support services, which provides mental health counseling integrated within the obstetric setting and 1-on-1 consultation session with doctoral-level clinicians. Through maternity social services, pregnant individuals were offered mental health support, based on patient preferences, including prepartum depression care (eclectic counseling [not IPT or cognitive behavioral therapy] or psychiatric consultation including medication) and other community services. During this 1-on-1 sixty-minute consultation session, the clinician reviewed written psychoeducational materials on perinatal depression so participants could better recognize mood symptoms during pregnancy and discussed with the participant ways to talk with partners or other supports about depression to elicit help. Clinicians conducted ongoing monitoring with participants and provided referrals to patients to overcome barriers and when care was needed. Extensive community resources were provided, including information on additional alternative community mental health and counseling services, essential items and housing programs, and local resource centers for pregnancy and postpartum support. Overall, 58 participants (48.8%) reported using additional counseling. EUC occurred during the same time frame as MOMCare. | PMC10116385 | |
Measures and Outcomes | depression | The 20-item Symptom Checklist (SCL-20) measures depression symptoms from the full Symptom Checklist-90-R.EPDS is used to screen maternal depression across the peripartum period. Research shows reliability and validity in pregnancy.Prior to randomization, trained independent evaluators administered the SCID-5 at baseline to determine participants’ diagnostic status using | PMC10116385 | |
Sociodemographic and Obstetric Characteristics | Research staff blinded to condition collected sociodemographic and obstetric characteristics. Birth date, socioeconomic status, cohabitation with partner, marital status, educational attainment, race (categories: American Indian/Alaska Native, Asian, Black or African American, European, Middle Eastern, Native Hawaiian or Other Pacific Islander, North African, White, or more than 1 race), and ethnicity (Chicana, Hispanic, Latine, or Mexican) were collected via interview. Income to needs ratio was calculated by dividing the total reported household income for the past year by the poverty threshold for that year corresponding to the number of persons living in the household, specified by the US Census Bureau. Two research staff performed medical record reviews, which were assigned by an independent staff member with 50% overlap in records reviewed to ensure consistency across the 2 reviewers. GA was calculated from medical record review using early ultrasonography measures and/or date of last menstrual period applying the American College of Obstetricians and Gynecologists guidelines. | PMC10116385 | ||
Data Analytic Strategy | reduced depression, depression | All models were fit using SAS statistical software version 9.4 (SAS Institute). All analyses were conducted with the full intention-to-treat sample. We compared differences by condition on baseline demographic and clinical characteristics using To test hypotheses that participants assigned to IPT would experience reduced depression symptoms across pregnancy, we implemented hierarchical linear modelingStatistical power was calculated for the between-groups design (IPT vs EUC) using estimates based on prior IPT perinatal depression intervention studies. | PMC10116385 | |
Results | PMC10116385 | |||
Preliminary Analyses | Of 234 individuals, 119 were allocated to EUC and 115 assigned to IPT (106 of whom received intervention, and 9 participated in no intervention sessions). Participants reported their race and ethnicity as 10 (4.3%) Asian, 21 (9%) Black, 43 (18.4%) Latine, 1 (0.4%) Native Hawaiian or Pacific Islander, 101 (43.2%) non-Hispanic/Latine White, and 58 (24.8%) multiracial or multiethnic ( | PMC10116385 | ||
Descriptive Information for the Study Sample | MDD, depressive disorder | Abbreviations: EUC, enhanced usual care; IPT, interpersonal psychotherapy; MDD, major depressive disorder (diagnosis per Structured Clinical Interview using Effect sizes for continuous measures are Cohen Retention rates through prenatal assessments were 88% (101 of 115) in IPT and 87% (104 of 119) in EUC (χ | PMC10116385 | |
Intervention Effects | PMC10116385 | |||
SCL-20 | depression | There was a differential rate of change in depression symptoms assessed via SCL-20 between IPT and EUC from randomization through the end of gestation ( | PMC10116385 | |
Model-Based Estimated Depression Symptoms Over Time for IPT and EUC | depressive disorder, Depression | Abbreviations: EPDS, Edinburgh Postnatal Depression Scale; EUC, enhanced usual care; IPT, interpersonal psychotherapy; SCL-20, 20-item Symptom Checklist.Mean estimates and standard error derived from the fitted hierarchical linear modeling adjusted for covariates and the variance-covariance structure. Test of significance are based on linear contrasts at respective time within each hierarchical linear modeling model. Week 0 = time of randomization.SCL-20 scores below 20 are consistent with no major depressive disorder diagnosis.EPDS scores at or below 9 are consistent with no major depressive disorder diagnosis. | PMC10116385 | |
Effect of Intervention on Depression Symptom Trajectories Over Pregnancy | Depressive | The color shaded regions represent 95% CIs. Hierarchical linear modeling (HLM) results with full sample for intent-to-treat analyses included 115 individuals in the interpersonal psychotherapy (IPT) group and 119 in the enhanced usual care (EUC) group. A, Depressive symptoms were measured by the 20-item Symptom Checklist (SCL-20) and showed significant intervention × time interaction ( | PMC10116385 | |
EPDS | A differential rate of change over time between IPT and EUC groups was observed for EPDS ( | PMC10116385 | ||
Effect of Intervention on Major Depressive Disorder (MDD) | With full sample for intent-to-treat analyses (interpersonal psychotherapy [IPT]: n = 115; enhanced usual care [EUC]: n = 119), between-groups analysis showed significant difference (χ | PMC10116385 | ||
Moderator Analyses | MDD, SCL-20 | We evaluated baseline MDD and GA at randomization as potential a priori moderators of treatment effects on primary study outcomes. Neither baseline MDD (SCL-20: | PMC10116385 | |
Discussion | MDD, depression, elevated depression | There is critical need to reduce depression during pregnancy given consequences for both mother and developing fetus. We initiated the Care Project to tackle this unaddressed challenge of decreasing depression for pregnant individuals with elevated depression (MDD and symptoms). Study findings demonstrated that a safe, prenatal intervention (MOMCare, brief IPT) substantially reduced depression symptoms and led to a considerable reduction in MDD diagnosis relative to pregnant individuals receiving EUC from general OB/GYN clinics.Results of this RCT with pregnant individuals, recruited for exhibiting elevated depression symptoms at standard OB/GYN screening, showed that brief IPT significantly decreased depression, including symptoms ( | PMC10116385 | |
Strengths and Limitations | MDD, depression | Strengths of the present work enhance confidence in the findings. The USPSTFRegarding limitations, inclusion of only English-speaking participants limits generalizability. Our intentional focus on the prenatal period precludes evaluating persistence of depression improvement after pregnancy. Further, depression symptom measures were self-reported. Objective depression changes in MDD remittance were observed using SCID-5 interview, partially addressing potential concerns with self-report. | PMC10116385 | |
Conclusions | MDD, depression, neurodevelopmental delays | Prenatal maternal depression is one of the strongest contributors to intergenerational transmission of depression, other forms of psychopathology, and neurodevelopmental delays.From an implementation perspective, it is encouraging that IPT reduced depression relatively quickly after starting treatment and that recipients benefited from treatment regardless of baseline MDD status or GA at randomization. Such findings inform inclusivity of care for those who do not receive early obstetric care or depression screening and show they can still benefit from brief IPT. | PMC10116385 | |
References | psychiatric | SENSITIVITY | Trial protocolClick here for additional data file.eMethods 1. Additional details on CONSORT diagram for exclusionseMethods 2. Adherence and fidelity ratingseFigure. Depiction of general Care Project RCT timeline, with the time points and study elements occurring when they tended to happen on average for modal participantseAppendix. MOMCare VignetteeResults 1. Change over time detailseResults 2. ModerationeResults 3. Therapist or site effectseResults 4. COVID differenceseResults 5. Sensitivity analyses for psychiatric medication useClick here for additional data file.Data sharing statementClick here for additional data file. | PMC10116385 |
Methods | This was a phase III, observer-blind, randomized, non-inferiority, multi-center study conducted in India among 460 infants who were followed up for safety and immunogenicity for 28 days after administration of three doses of either investigational or licensed comparator formulations at 6–8, 10–12 and 14–16 weeks of age. | PMC10426953 | ||
Results | HEPATITIS B, PERTUSSIS, HIB | The investigational formulation of DTwP-HepB-Hib vaccine was non-inferior to the licensed formulation in terms of hepatitis B seroprotection rate (% of subjects with HepB antibodies ≥10mIU/mL were 99.1% versus 99.0%, respectively, corresponding to a difference of 0.1% (95% CI, -2.47 to 2.68)) and pertussis immune responses (adjusted geometric mean concentrations of antibodies for anti-PT were 76.7 EU/mL versus 63.3 EU/mL, with a ratio of aGMTs of 1.21 (95% CI, 0.89–1.64), and for anti-FIM were 1079 EU/mL versus 1129 EU/mL, with a ratio of aGMTs of 0.95 (95% CI, 0.73–1.24), respectively). The immune responses to other valences (D, T, and Hib) in the two formulations were also similar. The safety profile of both formulations was found to be similar and were well tolerated. | PMC10426953 | |
Conclusions | The investigational DTwP-HepB-Hib vaccine formulation was immunogenic and well-tolerated when administered as three dose primary series in infants. | PMC10426953 | ||
Clinical trial registration | Clinical Trials Registry India number: | PMC10426953 | ||
Data Availability | Qualified researchers may request access to patient-level data and related study documents, including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient-level data will be anonymized, and study documents will be redacted to protect the privacy of study participants. Further details on Sanofi’s data-sharing criteria, eligible studies, and process for requesting access can be found at: | PMC10426953 | ||
Methods | PMC10426953 | |||
Study design and participants | ICH, tetanus | TETANUS, HIB | This was a phase 3, randomized, observer-blind study conducted in 8 centers across India among 460 infants who were followed up for safety and immunogenicity for 28 days after administration of three doses of either investigational or licensed comparator DTwP-HepB-Hib formulations at 6–8, 10–12 and 14–16 weeks of age. The study was performed from December 2018 to July 2019. The study was approved by the Indian National Regulatory Authority (The Drugs Controller General of India [DCGI]) and appropriate independent ethics committees and institutional review boards prior to the start of the study. The study was registered in the Clinical Trials Registry—India (CTRI/2018/12/016692). The conduct of this study was consistent with the standards established by the Declaration of Helsinki and compliant with the ICH guidelines for good clinical practice as well as with all local and / or national regulations and directives. Written signed informed consent was obtained from the subject’s parent/ legally acceptable representative (LAR) before any study procedures were performed. The entire informed consent process was audio-visually recorded as per Indian regulations.The study population included infants aged 6–8 weeks, at full term of pregnancy (≥ 37 weeks) and with a birth weight ≥ 2.5 kg, or medically stable prematurely born infants (born after a gestation period of 27–36 weeks), receiving the primary series of D, T, P, HepB and Hib vaccination as per the National Immunization schedule [Eligible subjects were randomized into two groups in 1:1 ratio to receive either the investigational DTwP-HepB-Hib vaccine formulation or the comparator (licensed) DTwP-HepB-Hib vaccine formulation. Randomization was performed using the permuted block method with stratification on centers and was managed with scratchable lists, available on site, which provided the vaccine to be administered for each enrolled participant. The study was conducted in an observer-blind manner, meaning that the subject’s parents / LAR, the study investigators and study staff, except the person in charge of the vaccination, were unaware of the group allocation throughout the study period.Each dose (0.5 mL) of both the investigational (batch number 2PLU005A18 expiring in Jan 2020) and the licensed comparator (batch number PLU015A17 expiring in Jun 2019) DTwP-HepB-Hib formulations, presented in 10-dose vials, contained diphtheria toxoid (≥ 30 IU), tetanus toxoid (≥ 60 IU), whole cell | PMC10426953 |
Immunogenicity assessment | FHA | SECONDARY, PERTUSSIS | All subjects provided a pre-vaccination (baseline) blood sample at day 0 and a post-vaccination sample 28 days after administration of the third dose (day 84). The serological primary endpoints were assessed 28 days after the third dose of the primary series for the non-inferiority analyses. HepB seroprotection status was defined as anti-HbsAg antibody concentration ≥ 10 mIU/mL. The serological secondary endpoints assessed at baseline (day 0) and 28 days after the third dose of the primary series were antibody concentrations for each valence at each time point and above the following cut-offs: anti-D antibody concentrations ≥ 0.01 IU/mL, ≥ 0.1 IU/mL and ≥ 1.0 IU/mL; anti-T antibody concentrations ≥ 0.01 IU/ mL, ≥ 0.1 IU/mL and ≥ 1.0 IU/mL; anti-HBs antibody concentrations ≥ 10 mIU/mL and ≥ 100 mIU/mL; and anti-PRP antibody concentrations ≥ 0.15 μ/mL and ≥ 1.0 μ/mL. For the pertussis antigens, vaccine responses against PT, filamentous hemagglutinin (FHA), PRN (pertactin) and FIM antigens, were defined as subjects with post-dose 3 vaccination concentrations ≥ 4 x LLOQ if their pre-vaccination concentrations were <4 x LLOQ or with post-dose 3 vaccination concentrations ≥ the pre-vaccination concentrations if their pre-vaccination concentration were ≥ 4 x LLOQ. Vaccine seroconversion status for anti-PT, anti-FHA, anti-PRN and anti-FIM antibodies was defined as subjects with a ≥ 4-fold rise in their respective PT, FHA, PRN, FIM antibody concentrations between pre-dose 1 and post-dose 3. The ratio (post dose 3 /pre-primary) of individual Ab concentration for all Abs were also assessed.All immunological assays were carried out at one central laboratory (Global Clinical Immunology (GCI), Sanofi, Swiftwater, Pennsylvania, USA). The assays were performed on pre-dose 1 and post-dose 3 samples obtained from all the subjects. The method used for D, T, and | PMC10426953 |
Safety assessment | vomiting, abnormal crying, convulsions, drowsiness, loss of appetite, fever, erythema, pain, irritability | ADVERSE EVENTS, FEBRILE CONVULSION, ERYTHEMA, ENCEPHALOPATHY, HAND SWELLING, HYPOTONIC | Subjects were observed for 30 min after vaccination to assess the occurrence of any immediate adverse events (AEs). Participants were provided with diary cards, digital thermometers, and flexible rulers to record daily body temperature as well as solicited injection site (pain, erythema, and swelling) and systemic reactions (fever ≥ 38.0°C (≥ 100.4°F), vomiting, abnormal crying, drowsiness, loss of appetite, and irritability) up to 7 days after each and any study vaccine dose, and other unsolicited AEs up to 28 days after each and any study vaccine dose. The subject’s parents / LAR were contacted by telephone 8–10 days after each vaccination to remind them to record safety information in their diary cards. Information on unsolicited AEs was collected. Investigators assessed the causal relationship of each unsolicited systemic AE/serious AE (SAE) with vaccination. Information on SAEs was collected and assessed throughout the study, from screening on day 0 until study completion. The following adverse events of special interest (AESIs) were defined based upon the prior experience with the use of marketed pentavalent combination vaccines including anaphylaxis/hypersensitivity, convulsions, including febrile convulsion, hypotonic hyporesponsive episode (HHE), and encephalopathy. These AESIs were considered as SAEs and reported to the sponsor between day 0 and until 28 days after the last vaccination. | PMC10426953 |
Statistical analysis | HEPATITIS B, PERTUSSIS, PERTUSSIS, SECONDARY, HEP B, HEPATITIS B | For HepB, non-inferiority testing was based on the use of the two-sided 95% confidence interval (CI) of the difference of proportions of subjects with an anti-HBs Ab concentration ≥ 10 mIU/mL at day 84. The 95% CI of the difference was calculated using Wilson score method without continuity correction. Hepatitis B non-inferiority was considered demonstrated if the lower limit of the 95% CI of the difference of the two proportions (investigational formulation minus licensed formulation) was greater than minus 10%.For pertussis, non-inferiority testing was based on the use of aGMCs and their 95% CI, on both PT and FIM results. Adjusted GMCs were computed using analysis of covariance to adjust for baseline disparities and considering the correlation between pre- and post-vaccination concentration (log10-transformed), through an ANCOVA model using the pre-vaccination (day 0) concentration as a covariate for adjustment and the vaccine group. The 95% CI of ratio between vaccine groups aGMCs was calculated using normal approximation of the mean of log10-concentration. Pertussis non-inferiority was considered if the lower limits of the 95% CI of the ratio of adjusted GMCs for PT and for FIM antibodies were above 0.5 (less than a 2-fold reduction). Overall non-inferiority was concluded if both the pertussis (both PT and FIM) and Hep B non-inferiorities were demonstrated.Descriptive statistics were produced for each secondary endpoint. The safety and immunogenicity parameters were described with their 95% CI. Immunogenicity endpoints were summarized by vaccine groups and by time-points (pre and post primary series vaccination). For descriptive safety analyses, percentages were presented with their 95% CI (Clopper-Pearson method).The sample size was calculated based on primary study objectives, with an alpha level of 2.5% (one-sided hypotheses), a 10% non-inferiority clinical margin for the hepatitis B responses, a 2-fold decrease clinical margin for aGMC (aGMC ratio higher than 0.5) for pertussis responses (PT and FIM) and an assumption that 85% of enrolled subjects would fulfil the Per Protocol definitions in each group. Based on simulations, testing the null hypothesis on pertussis responses with a power of 91.5% (on aGMCs at Day 84), and assuming observed standard deviations of log10 (aGMCs) of 0.75 and 0.85, respectively on PT and FIM results, required a total of 195 evaluable subjects in each group. With such a sample size and an assumption of 95% of subjects with an anti-HBs Ab concentration ≥10 mIU/mL at D84, the power to demonstrate non-inferiority on HepB was 98.4% (using the Farrington and Manning method) meaning that the overall power of the trial was at least 90%. Considering a 15% of subjects non-evaluable at D84, a total of 460 subjects was included in the trial to reach the primary objective with an overall power of at least 90%.The primary immunogenicity analyses (non-inferiority testing) were performed on the per-protocol analysis set (PPAS) and confirmed on the full analyses set (FAS). The FAS was defined as the subset of enrolled subjects who received at least 1 dose of the study vaccines. The PPAS was defined as a subset of the FAS and comprised all subjects who had received the study vaccine and complied with all protocol-specified requirements and procedures. The secondary immunogenicity descriptive analyses were also performed on PPAS and FAS. In the FAS, subjects were analyzed by the vaccine group to which they were randomized. The safety analysis was performed on the safety analysis set (SafAS). The SafAS was defined for each stage of the trial as those subjects who have received at least 1 dose of the study vaccines. Subjects were analyzed after each dose according to the vaccine they received and after any dose according to the vaccine received at the first dose.The statistical analysis was conducted under the responsibility of Sanofi with SAS software, Version 9.4 (SAS Institute, Cary, NC, USA). | PMC10426953 | |
Results | A total of 460 subjects were enrolled between December 22, 2018, and April 08, 2019, and randomized into 2 groups, group 1 (Investigational DTwP-HepB-Hib vaccine formulation, primary series, n = 232) and group 2 (Comparator (licensed) DTwP-HepB-Hib vaccine formulation, primary series, n = 228). A total of 447 subjects completed the vaccination schedule (3-dose primary series) (225 and 222 subjects in groups 1 and 2 respectively), whereas 439 patients completed the study till D84 (221 and 218 subjects in groups 1 and 2 respectively). Protocol deviations including incomplete vaccination schedule, out of window visits, and randomization errors were reported among 45 subjects (19 and 26 subjects in groups 1 and 2 respectively); ( | PMC10426953 | ||
Subject disposition. | PMC10426953 | |||
Baseline demography of randomized group (FAS). | SD, standard deviation | PMC10426953 | ||
Immunogenicity | PMC10426953 | |||
Hepatitis B seroprotection rate (primary objective) | The investigational DTwP-HepB-Hib vaccine formulation (group 1) was non-inferior to the comparator DTwP-HepB-Hib vaccine formulation (group 2) for anti HBsAg in terms of post-dose 3 seroprotection rates in the PPAS population. Seroprotection against HepB at post-dose 3 was observed in 99.1% (95% CI, 96.6–99.9) and 99.0% (95% CI, 96.5–99.9) of subjects in the groups 1 and 2 respectively. The difference in seroprotection rates between the two groups was 0.1% (95% CI, -2.47 to 2.68). The lower limit of the 2-sided 95% CI of the difference between the 2 vaccine groups was -2.4% which was well above the lower limit of the 2-sided 95% CI of the difference defined for demonstration of non-inferiority, i.e. above -10% (minus delta). | PMC10426953 | ||
Pertussis immune responses (primary objective) | hepatitis B | HEPATITIS B, PERTUSSIS | The investigational DTwP-HepB-Hib vaccine formulation (group 1) was non-inferior to the comparator DTwP-HepB-Hib vaccine formulation (group 2) for anti-pertussis responses in terms of post-dose 3 aGMCs in the PPAS population. The aGMC for anti-PT at day 84 were 76.7 EU/mL (95% CI, 62.1–94.7) and 63.3 EU/mL (95% CI, 50.9–78.6) for groups 1 and 2 respectively. The ratio of the aGMC for anti-PT antibodies at day 84 between the 2 study groups was 1.21 (95% CI, 0.89–1.64). The lower limit of the 95% CI of the ratio of aGMC for anti-PT (0.89) was above the lower limit defined for demonstration of non-inferiority for anti-PT, i.e. above 0.5.The aGMC for anti-FIM at day 84 were 1079 EU/mL (95% CI, 898–1296) and 1129 EU/mL (95% CI, 935–1362) for Groups 1 and 2 respectively. The ratio of the aGMC for anti-FIM antibodies at day 84 between the 2 study groups was 0.95 (95% CI, 0.73–1.24). The lower limit of the 95% CI of the ratio of aGMC for anti-FIM (0.73) was above the lower limit defined for demonstration of non-inferiority for anti-FIM, i.e. above 0.5.The immunogenicity of the investigational DTwP-HepB-Hib vaccine formulation was demonstrated to be non-inferior to the comparator DTwP-HepB-Hib vaccine formulation for HepB and pertussis antigens.The results were similar in the FAS population for both hepatitis B seroprotection rate and pertussis immune responses. | PMC10426953 |
Secondary objectives | HIB | The immune responses to the antigens of the five valences (D, T, P, HepB and Hib) in the investigational and comparator vaccine groups were also similar (Tables | PMC10426953 | |
Summary of seroprotection and seronconversion rates—Pre-dose 1 and post-dose 3 (PPAS). | PERTUSSIS | n refers to the number of subjects experiencing the endpoint listed in the first three columns; M refers to the number of subjects with available data for the relevant endpoint; *Vaccine response is defined as: If the pre-primary vaccination concentration is < 4 x LLOQ, then the post-primary vaccination concentration is ≥ 4 x LLOQ; If the pre-primary vaccination concentration is ≥ 4 x LLOQ, then the post-primary vaccination concentration is ≥ the pre-primary concentration; LLOQ is 2 EU/mL for pertussis antigens for DTP-ECL assay. | PMC10426953 | |
Summary of geometric means—Pre-dose 1 and post-dose 3 (PPAS). | M refers to the number of subjects with available data for the relevant endpoint. | PMC10426953 | ||
Safety | There were no AEs leading to study discontinuation, no SAEs and no AESI reported in the study. No immediate AEs were reported after any vaccination in both investigational and comparator vaccine groups. Solicited reactions (injection site reactions and systemic reactions) within 7 days after any vaccination were reported in 71.6% (164/229) and 66.7% (148/222) of subjects of investigational and comparator vaccine groups respectively (Figs | PMC10426953 | ||
Subjects reporting solicited injection site reactions after all and each vaccination. | PMC10426953 | |||
Subjects reporting solicited systemic reactions after all and each vaccine injection. | Unsolicited AEs within 28 days after any vaccine injection were reported in 4.7% (11/233) and 4.0% (9/227) of subjects of investigational and comparator vaccine groups respectively ( | PMC10426953 | ||
Unsolicited AEs within 28 days after any vaccine injections, by system organ class and preferred term (safety analysis set). | n refers number of subjects experiencing the endpoint listed in the first column. | PMC10426953 | ||
Discussion | diphtheria, tetanus | DIPHTHERIA, PERTUSSIS, PERTUSSIS, HEP B, HIB, TETANUS | This phase 3 study conducted in India evaluated the safety and immunogenicity in 460 infants followed up for 28 days after administration of three doses of either investigational or existing vaccine formulations of the SHIPL DTwP-HepB-Hib pentavalent vaccine at 6–8 weeks, 10–12 weeks and 14–16 weeks of age when administered concomitantly with other age-recommended vaccines.Both primary objectives were met in the study. The overall non-inferiority was demonstrated because the statistical tests concluded to the non-inferiority of the investigational DTwP-HepB-Hib formulation versus the comparator DTwP-HepB-Hib formulation at day 28 post-dose 3 for immune responses to both HepB and pertussis (PT and FIM) antigens contained in the vaccines. The immune responses to antigens of the five valences (D, T, HepB, Pertussis and Hib) at day 28 post-dose 3 were also observed to be similar in the investigational and comparator DTwP-HepB-Hib groups.Pre-immunization (day 0) anti-T seroprotection rates (i.e. ≥ 0.01 IU/mL) were observed to be 100% of subjects in both the groups. This was due to the presence of maternal antibodies and points to the highly successful maternal immunization program in India by which elimination of maternal and neonatal tetanus was achieved in 2015 [The anti-HBs seroprotective rates tended to be similar irrespective of whether the study subjects received HepB vaccination at birth or not. The results are similar to those observed in other HepB containing combination vaccine studies [The demonstration of the non-inferiority of the investigational DTwP-HepB-Hib vaccine formulation versus the licensed comparator DTwP-HepB-Hib vaccine formulation for their immune responses against Vaccination with either investigational or licensed comparator DTwP-HepB-Hib vaccine formulation was found to be well tolerated. The safety profile was found to be similar in both the investigational and comparator DTwP-HepB-Hib vaccine groups. There were no safety concerns observed during this study. As seen from previous studies, safety profile of investigational vaccine in the current study was not different from the safety profile of other pentavalent vaccines when evaluated in Indian infants [Limitation of this study were that it was conducted only in India, where Hep B vaccine is recommended at birth, so very few datapoints could be generated without a Hep B birth dose. The non-inferiority was assessed in the absence of demonstrated correlates of protection for some antigens, and therefore based on the data distribution.Our study highlights the importance of international collaboration for the development of multivalent vaccines. For our investigational pentavalent vaccine, 3 components (diphtheria, tetanus and HiB) are manufactured in India using standard technology; the hepB component was sourced from the manufacturing facility in Argentina, while the wP component was manufactured in India after successful technology transfer including the seed strains. This suggests that for the purpose of investigational vaccine development countries need not be limited by their geographical boundaries.Our results also add to the knowledge of evaluating and comparing immune responses to pertussis components in clinical trial settings, especially for wP containing combination vaccines. In the absence of well-defined correlates of serological protection and standardized assays or methods, the results from this study will provide guidance to researchers. | PMC10426953 |
Conclusions | PERTUSSIS, HIB | The study demonstrated that the investigational DTwP-HepB-Hib vaccine formulation was non-inferior to the licensed comparator DTwP-HepB-Hib vaccine formulation both in terms of HepB seroprotection rate and in terms of pertussis immune responses. The immune responses to all the antigens (D, T, P, HepB and Hib) in both the DTwP-HepB-Hib vaccine formulations were also similar.Overall, vaccination with either the investigational or the licensed comparator DTwP-HepB-Hib vaccine formulation was found to be well tolerated among the infants administered the 3-dose vaccine primary series (at 6–8 weeks, 10–12 weeks and 14–16 weeks of age) along with other age-recommended vaccines. | PMC10426953 | |
Supporting information | PMC10426953 | |||
CONSORT 2010 checklist of information to include when reporting a randomised trial*. | SBKS | (DOC)Click here for additional data file.(PDF)Click here for additional data file.The authors would like to thank the parents of all study subjects for consenting to participate in this research study; all the investigators and their site staff of the Departments of Paediatrics, Mysore Medical College, Mysore, KLES Dr Prabhakar Kore Hospital, Belagavi, Government Victoria Hospital, Visakhapatnam, Prakhar Hospital Pvt. Ltd., Kanpur, SBKS Medical College, Vadodara, Christian Medical College & Hospital, Ludhiana, Department of Pharmacology, SRM Medical College Hospital, Chennai, and Department of Community Medicine, Kalinga Institute of Medical Sciences, Bhubaneswar; the staff of Zifo Technologies, India (for data management) and Global Clinical Immunology, Sanofi, Swiftwater, USA (for laboratory analysis). | PMC10426953 | |
Abbreviations | HEPATITIS B, PERTUSSIS | antibody; AE, adverse eventAEs of special interestadjusted geometric mean concentrationsconfidence intervaldiphtheriaDrugs Controller General of IndiaDTP immunoassay by multiplexed Electro Chemiluminescent methodfull analyses set; FHA, filamentous hemagglutininfimbriaegeometric mean concentrationsgeometric mean concentration ratiohepatitis Bhypotonic hyporesponsive episode
inactivated poliovirus vaccinelegally acceptable representativelower limit of quantificationMarcy l’EtoileMesoScale Discovery ElectroChemiLuminescence immunoassayoral poliovirus vaccineoral rotavirus vaccineper-protocol analysis setpertactinpertussis toxinradioimmunoassayrecombinant Hepatitis B surface Antigenserious AE; SafAS, safety analyses settetanusWorld Health OrganizationWHO Pre-Qualificationwhole-cell pertussis | PMC10426953 | |
References | PMC10426953 | |||
Background | hand dexterity, early-phase motor learning | CORTEX | The left dorsolateral prefrontal cortex (DLPFC) is involved in early-phase manual dexterity skill acquisition when cognitive control processes, such as integration and complexity demands, are required. However, the effectiveness of left DLPFC transcranial direct current stimulation (tDCS) on early-phase motor learning and whether its effectiveness depends on the cognitive demand of the target task are unclear. This study aimed to investigate whether tDCS over the left DLPFC improves non-dominant hand dexterity performance and determine if its efficacy depends on the cognitive demand of the target task. | PMC9951449 |
Methods | In this randomized, double-blind, sham-controlled trial, 70 healthy, right-handed, young adult participants were recruited. They were randomly allocated to the active tDCS (2 mA for 20 min) or sham groups and repeatedly performed the Purdue Pegboard Test (PPT) left-handed peg task and left-handed assembly task three times: pre-tDCS, during tDCS, and post tDCS. | PMC9951449 | ||
Results | The final sample comprised 66 healthy young adults (mean age, 22.73 ± 1.57 years). There were significant interactions between group and time in both PPT tasks, indicating significantly higher performance of those in the active tDCS group than those in the sham group post tDCS (p < 0.001). Moreover, a greater benefit was observed in the left-handed assembly task performance than in the peg task performance (p < 0.001). No significant correlation between baseline performance and benefits from tDCS was observed in either task. | PMC9951449 | ||
Supplementary Information | The online version contains supplementary material available at 10.1186/s12967-023-03989-9. | PMC9951449 | ||
Keywords | PMC9951449 | |||
Background | upper-limb motor learning, human behavior | Motor skill learning is crucial for optimizing human behavior and essential in a variety of daily life situations. The motor learning theory of Fitts and Posner [Moreover, the DLPFC is highly activated during the performance of unfamiliar or complex fine motor skill tasks with bimanual and unimanual non-dominant hands [Transcranial direct current electrical stimulation (tDCS) is a noninvasive brain stimulation technique that can modulate neuronal excitability in cortical and subcortical areas by inducing polarity-specific membrane potential changes. Depending on stimulus intensity and duration, anodal tDCS stimulation has generally been shown to increase neuronal excitability and to promote spontaneous neuronal firing and long-term potentiation, whereas cathodal stimulation has been shown to induce the opposite effect [Most previous studies evaluating tDCS effects in upper-limb motor learning in healthy individuals targeted the cortical motor areas and cerebellum [Commonly, these studies targeting the DLPFC demonstrated significantly improved performance in the active tDCS group compared to the sham group; meanwhile, the results of most previous studies targeting the other cortical motor areas and cerebellum were extremely inconsistent [Therefore, we hypothesized that anodal tDCS on the left DLPFC might enhance early manual dexterity skill acquisition of the non-dominant hand and would lead to greater learning gain in tasks with high cognitive demand. | PMC9951449 | |
Methods | PMC9951449 |
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