Effect of non-vascularized fibular harvest on the donor limb: radiological evaluation at a mean follow-up of twelve point eight years.

PURPOSE: The study is aimed at evaluating the long-term (at a minimum follow-up of 10 years) impact of non-vascularized fibular harvest on the donor limbs. METHODS: There were 27 donor limbs (n = 19 children) available for retrospective radiological review. The graft was obtained bilaterally in eight patients. The following parameters were evaluated in the follow-up radiographs: continuity/non-continuity of fibular regenerate, width of the regenerated fibula, distal fibular station, medial proximal tibial angle, posterior proximal tibial angle, lateral distal tibial angle (LDTA), anterior distal tibial angle, and tibia diaphyseal angulation (interphyseal angles). For analysis and comparisons, the donor limbs were compared to the healthy limbs (controls) of the children with unilateral harvest. Additionally, the impact of continuous and non-continuous fibular regeneration was separately analyzed. RESULTS: The mean child's age at the time of fibular harvest was four years. The mean follow-up was 12.8 years. The fibula was found regenerated in continuity in 22 limbs of 15 children (81.5%). When analyzed as a combined group (both continuous and non-continuous fibular regenerations), all the donor limb radiological parameters matched those of healthy limbs except LDTA (p = 0.04). In the subgroup analysis between non-continuous and continuous fibulae, significant abnormalities were again obvious in LDTA (p = 0.0001). The non-continuous fibulae were significantly lesser in width. All limbs with non-continuous fibular regeneration manifested ankle valgus. CONCLUSIONS: The non-vascularized fibula emerged as a relatively safe procedure in the long term with minimal affections of the knee, ankle, or tibial anatomy when longitudinal integrity of fibula was restored. The non-regenerations of the fibula may be prone to developing ankle valgus.

Results of a phase 2 trial of an oral CXCR4 antagonist, mavorixafor, for treatment of WHIM syndrome.

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare primary immunodeficiency caused by gain-of-function mutations in the CXCR4 gene. We report the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of mavorixafor from a phase 2 open-label dose-escalation and extension study in 8 adult patients with genetically confirmed WHIM syndrome. Mavorixafor is an oral small molecule selective antagonist of the CXCR4 receptor that increases mobilization and trafficking of white blood cells from the bone marrow. Patients received escalating doses of mavorixafor, up to 400 mg once daily. Five patients continued on the extension study for up to 28.6 months. Mavorixafor was well tolerated with no treatment-related serious adverse events. At a median follow-up of 16.5 months, we observed dose-dependent increases in absolute neutrophil count (ANC) and absolute lymphocyte count (ALC). At doses ≥300 mg/d, ANC was maintained at >500 cells per microliter for a median of 12.6 hours, and ALC was maintained at >1000 cells per microliter for up to 16.9 hours. Continued follow-up on the extension study resulted in a yearly infection rate that decreased from 4.63 events (95% confidence interval, 3.3-6.3) in the 12 months prior to the trial to 2.27 events (95% confidence interval, 1.4-3.5) for patients on effective doses. We observed an average 75% reduction in the number of cutaneous warts. This study demonstrates that mavorixafor, 400 mg once daily, mobilizes neutrophil and lymphocytes in adult patients with WHIM syndrome and provides preliminary evidence of clinical benefit for patients on long-term therapy. The trial was registered at www.clinicaltrials.gov as #NCT03005327.

Physiologic lead placement with electroanatomic mapping: A case series.

INTRODUCTION: His bundle pacing (HBP) and left bundle branch area pacing (LBBAP) have emerged as attractive alternatives to traditional biventricular pacing to achieve cardiac resynchronization therapy. Early reported results have been inconsistent, particularly amongst patients in whom initial placement with traditional approaches has been unsuccessful or those with complex anatomy or congenital abnormalities. In this report, we describe the use of three-dimensional electroanatomic mapping (EAM) in five selected cases. METHODS: Five patients from multiple clinical sites underwent EAM-guided HBP or LBBAP by highly trained electrophysiologists with significant experience with conduction system pacing. Each patient in this series underwent EAM-guided conduction system pacing due to complex anatomy and/or prior failed lead implantation. RESULTS: EAM-guided lead implantation was successful in all five cases. Capture thresholds were relatively low and patients continued to have evidence of successful lead implantation with minimum 1-month follow-up. The fluoroscopy time varied, likely owing to the variable complexity of the cases. CONCLUSIONS: The use of EAM, in combination with traditional intracardiac electrograms with or without fluoroscopy, allows more targeted and precise placement of leads for HBP and LBBAP pacing. Further investigation is needed to determine this strategy's long-term performance and to optimize patient selection.

Pharmacokinetic and pharmacodynamic evaluation of Solid self-nanoemulsifying delivery system (SSNEDDS) loaded with curcumin and duloxetine in attenuation of neuropathic pain in rats.

The present investigation is focused on improving oral bioavailability of poorly soluble and lipophilic drugs, curcumin (CRM) and duloxetine (DXH), through the solid self-nanoemulsifying drug delivery system (S-SNEDDS) and identifying their potential against attenuation of NP in chronic constriction injury (CCI)-induced rats through the solid self-nanoemulsifying drug delivery system (S-SNEDDS). The optimized batch of S-SNEDDS reported was containing CRM and DXH (30 mg each), castor oil (20% w/w), tween-80 (40% w/w), transcutol-P (40% w/w), and syloid 244 FP (1 g). The high dose of each of naïve CRM (NCH), naïve DXH (NDH), physical mixture of DXH and CRM (C-NCM-DXH), S-SNEDDS-CRM (SCH), S-SNEDDS-DXH (SDH), and S-SNEDDS-CRM-DXH (C-SCH-SDH) was subjected for MTT assay. The developed formulations were subjected to pharmacokinetic studies and results showed about 8 to 11.06 and 2-fold improvement in oral bioavailability of CRM and DXH through S-SNEDDS. Furthermore, CCI-induced male Wistar rats were treated with SSNEDDS containing CRM and DXH, S-SNEDDS containing individual drug, individual naïve forms, and their combination from the day of surgery for 14 days and evaluated for behavioral at pre-determined time intervals. On the terminal day, animals were sacrificed to assess tissue myeloperoxidase, superoxide anion, protein, tumor necrosis factor-α, total calcium levels, and histopathological changes. Pronounced effect was observed in rats treated with S-SNEDDS containing both drugs with respect to rats receiving any of other treatments owing to enhanced oral bioavailability through S-SNEDDS. Therefore, it can be concluded that S-SNEDDS of both drugs and their coadministration can accelerate the prevention of NP.

Systematic Development of Transethosomal Gel System of Piroxicam: Formulation Optimization, In Vitro Evaluation, and Ex Vivo Assessment.

Piroxicam is used in the treatment of rheumatoid arthritis, osteoarthritis, and other inflammatory diseases. Upon oral administration, it is reported to cause ulcerative colitis, gastrointestinal irritation, edema and peptic ulcer. Hence, an alternative delivery system has been designed in the form of transethosome. The present study describes the preparation, optimization, characterization, and ex vivo study of piroxicam-loaded transethosomal gel using the central composite design. On the basis of the prescreening study, the concentration of lipids and ethanol was kept in the range of 2-4% w/v and 0-40% v/v, respectively. Formulation was optimized by measuring drug retention in the skin, drug permeation, entrapment efficiency, and vesicle size. Optimized formulation was incorporated in hydrogel and compared with other analogous vesicular (liposomes, ethosomes, and transfersomes) gels for the aforementioned responses. Among the various lipids used, soya phosphatidylcholine (SPL 70) and ethanol in various percentages were found to affect drug retention in the skin, drug permeation, vesicle size, and entrapment efficiency. The optimized batch of transethosome has shown 392.730 µg cm-2 drug retention in the skin, 44.312 µg cm-2 h-1 drug permeation, 68.434% entrapment efficiency, and 655.369 nm vesicle size, respectively. It was observed that the developed transethosomes were found superior in all the responses as compared to other vesicular formulations with improved stability and highest elasticity. Similar observations were noted with its gel formulation.

Stable Co-crystals of Glipizide with Enhanced Dissolution Profiles: Preparation and Characterization.

Present study deciphers preparation of co-crystals of lipophilic glipizide by using four different acids, oxalic, malonic, stearic, and benzoic acids, in order to achieve enhanced solubility and dissolution along with stability. All co-crystals were prepared by dissolving drug and individual acids in the ratio of 1:0.5 in acetonitrile at 60-70°C for 15 min, followed by cooling at room temperature for 24 h. FT-IR spectroscopy revealed no molecular interaction between acids and drug as the internal structure and their geometric configurations remain unchanged. Differential scanning calorimetry revealed closer melting points of raw glipizide and its co-crystals, which speculates absence of difference in crystallinity as well as intermolecular bonding of the co-crystals and drug. PXRD further revealed that all the co-crystals were having similar crystallinity as that of raw glipizide except glipizide-malonic acid co-crystals. This minor difference in the relative intensities of some of the diffraction peaks could be attributed to the crystal habit or crystal size modification. SEM revealed difference in the crystal morphology for all the co-crystals. Micromeritic, solubility, dissolution, and stability data revealed that among all the prepared co-crystals, glipizide-stearic acid co-crystals were found superior. Hence, it was concluded that glipizide-stearic acid co-crystals could offer an improved drug design strategy to overcome dissolution and bioavailability related challenges associated with lipophilic glipizide.

Modeling population heterogeneity in viral dynamics for chronic hepatitis C infection: Insights from Phase 3 telaprevir clinical studies.

Viral dynamic modelling has proven useful for designing clinical studies and predicting treatment outcomes for patients infected with the hepatitis C virus. Generally these models aim to capture and predict the on-treatment viral load dynamics from a small study of individual patients. Here, we explored extending these models (1) to clinical studies with numerous patients and (2) by incorporating additional data types, including sequence data and prior response to interferon. Data from Phase 3 clinical studies of the direct-acting antiviral telaprevir (T; total daily dose of 2250 mg) combined with pegylated-interferon alfa and ribavirin (PR) were used for the analysis. The following data in the treatment-naïve population were reserved to verify the model: (1) a T/PR regimen where T was dosed every 8 h for 8 weeks (T8(q8h)/PR) and (2) a T/PR regimen where T was dosed twice daily for 12 weeks (T12(b.i.d.)/PR). The resulting model accurately predicted (1) sustained virologic response rates for both of these dosing regimens and (2) viral breakthrough characteristics of the T8(q8h)/PR regimen. Since the observed viral variants depend on the T exposure, the second verification suggested that the model was correctly sensitive to the different T regimen even though the model was developed using data from another T regimen. Furthermore, the model predicted that b.i.d. T dosing was comparable to q8h T dosing in the PR-experienced population, a comparison that has not been made in a controlled clinical study. The methods developed in this work to estimate the variability occurring below the limit of detection for the viral load were critical for making accurate predictions.

Creation of superwetting surfaces with roughness structures.

In this work, we explored the possibility of creating superwetting surfaces, which are defined here as those with apparent contact angles of <5°, using roughness structures for the purpose of eliminating the surface tension effect on a floating small plate, which is denser than the surrounding liquid. The roughness ratio is often thought to play a critical role in generating superwetting surfaces. However, we found that the top surface ratio had more influence on apparent contact angles. When this ratio was <0.013, the resulting apparent contact angle might be less than 5°, when the intrinsic contact angle was ≥40°. Accordingly, hybrid micro- and nanostructures, which had such a small ratio, were chosen to create the superwetting surfaces. These surfaces were subsequently applied to eliminate the surface tension effect on a small plate. As a result of this elimination, the small plate sank down to the bottom of the liquid.

Combination therapy with telaprevir for chronic hepatitis C virus genotype 1 infection in patients with HIV: a randomized trial.

BACKGROUND: Telaprevir (TVR) plus peginterferon-α2a (PEG-IFN-α2a) and ribavirin substantially increases treatment efficacy for genotype 1 chronic hepatitis C virus (HCV) infection versus PEG-IFN-α2a-ribavirin alone. Its safety and efficacy in patients with HCV and HIV-1 are unknown. OBJECTIVE: To assess the safety and efficacy of TVR plus PEG-IFN-α2a-ribavirin in patients with genotype 1 HCV and HIV-1 and to evaluate pharmacokinetics of TVR and antiretrovirals during coadministration. DESIGN: Phase 2a, randomized, double-blind, placebo-controlled study. (ClinicalTrials.gov: NCT00983853). SETTING: 16 international multicenter sites. PATIENTS: 62 patients with HCV genotype 1 and HIV-1 who were HCV treatment-naive and receiving 0 or 1 of 2 antiretroviral regimens were randomly assigned to TVR plus PEG-IFN-α2a-ribavirin or placebo plus PEG-IFN-α2a-ribavirin for 12 weeks, plus 36 weeks of PEG-IFN-α2a-ribavirin. MEASUREMENTS: HCV RNA concentrations. RESULTS: Pruritus, headache, nausea, rash, and dizziness were higher with TVR plus PEG-IFN-α2a-ribavirin during the first 12 weeks. During this period, serious adverse events occurred in 5% (2 in 38) of those receiving TVR plus PEG-IFN-α2a-ribavirin and 0% (0 in 22) of those receiving placebo plus PEG-IFN-α2a-ribavirin; the same number in both groups discontinued treatment due to adverse events. Sustained virologic response occurred in 74% (28 in 38) of patients receiving TVR plus PEG-IFN-α2a-ribavirin and 45% (10 in 22) of patients receiving placebo plus PEG-IFN-α2a-ribavirin. Rapid HCV suppression was seen with TVR plus PEG-IFN-α2a-ribavirin (68% [26 in 38 patients] vs. 0% [0 in 22 patients] undetectable HCV RNA levels by week 4). Two patients had on-treatment HCV breakthrough with TVR-resistant variants. Patients treated with antiretroviral drugs had no HIV breakthroughs; antiretroviral exposure was not substantially modified by TVR. LIMITATION: Small sample size and appreciable dropout rate. CONCLUSION: In patients with HCV and HIV-1, more adverse events occurred with TVR versus placebo plus PEG-IFN-α2a-ribavirin; these were similar in nature and severity to those in patients with HCV treated with TVR. With or without concomitant antiretrovirals, sustained virologic response rates were higher in patients treated with TVR versus placebo plus PEG-IFN-α2a-ribavirin.

Parent reported outcomes for idiopathic clubfoot children treated with the Ponseti technique: An analysis of 140 feet followed minimum 5 years.

Objective: The treated clubfoot children are often evaluated clinically during follow-up. However, patient reported outcomes (PROM) are seldom analysed for these children. We investigated 87 idiopathic clubfoot children (140 feet) treated by the Ponseti method and followed minimum 5 years to study their clinical outcomes and PROM. Material and methods: This was a cross-sectional study, based on evaluating treated clubfoot children clinically (Pirani score) and PROM (Oxford Ankle and Foot Questionnaire - Parent Version) and comparing them with the age-matched healthy controls (n = 60). The questionnaire has four main domains related to the child's physical, school and play, emotional and footwear profile. The children having persistent deformity (residual/relapse) were specifically studied for their PROM scores. Results: The mean child age at initial treatment was 2.3 months and the mean follow-up duration was 6.9 years. The PROM score of clubfoot children was statistically lower than the healthy controls (p < 0.001). Of the individual domains, the physical domain was the most affected. On calculating the Pirani scores, 10 out of 140 feet (7 %) had some form of persistent deformity. The children with persistent deformity had lower Oxford scores than healthy children or those with corrected feet. The physical domain followed by the emotional domain scored low when persistent deformity was present. Conclusions: Most children (98 %) had a plantigrade foot following Ponseti treatment at follow-up. However, PROM score of the clubfoot children did not correspond to the clinical outcome. Persistent deformity, even minor, was a cause of parental concern and resulted in a low PROM score.

Role of Magnetic Resonance Imaging in Concomitant Periarticular Infections in Septic Arthritis of Large Joints in Children: A Systematic Review.

Background: Septic arthritis associated with adjacent infections, presents a diagnostic challenge as the clinical presentation is similar to that of isolated septic arthritis, additional diagnostic tools are needed to detect these infections. The purpose of this study was to examine the effectiveness of magnetic resonance imaging (MRI) for diagnosis of concomitant infection in children with septic arthritis of large joints and its effect on patient outcome and treatment. Materials and Methods: Electronic literature research of PubMed, Cochrane and Scopus, was conducted in January 2022 using a combination of MeSH, search terms and keywords. The data extracted included the study details, demographic data, the proportion of patients having a concomitant periarticular infection, clinical presentation, blood parameters and culture findings and outcomes. Results: This review included seven studies with 499 patients. The mean age was 7.08 ± 2.38 years in the study. There was a male predominance, with 174 being males (62.36%). The most common joint involved was the hip joint (44.47%). 42.48% had concomitant periarticular infections detected by MRI. Osteomyelitis was the most common infection seen in 209 patients (41.84%). The mean duration of antibiotics given and hospital stay was significantly more in periarticular infections (P > 0.05). 32.5% of the patients with septic arthritis underwent a second surgical procedure whereas 61.11% of patients with periarticular infections underwent second procedure in this review (P > 0.05). Conclusions: The use of MRI to diagnose these complicated infections appears to be beneficial. Multi-centric randomised control trials are needed to investigate the efficacy of MRI and its impact on patient care and outcome.

Pharmacokinetic interaction between telaprevir and methadone.

Hepatitis C virus (HCV) antibody is present in most patients enrolled in methadone maintenance programs. Therefore, interactions between the HCV protease inhibitor telaprevir and methadone were investigated. The pharmacokinetics of R- and S-methadone were measured after administration of methadone alone and after 7 days of telaprevir (750 mg every 8 h [q8h]) coadministration in HCV-negative subjects on stable, individualized methadone therapy. Unbound R-methadone was measured in predose plasma samples before and during telaprevir coadministration. Safety and symptoms of opioid withdrawal were evaluated throughout the study. In total, 18 subjects were enrolled; 2 discontinued prior to receiving telaprevir. The minimum plasma concentration in the dosing interval (C(min)), the maximum plasma concentration (Cmax), and the area under the plasma concentration-time curve from h 0 (time of administration) to 24 h postdose (AUC(0-24)) for R-methadone were reduced by 31%, 29%, and 29%, respectively, in the presence of telaprevir. The AUC0-24 ratio of S-methadone/R-methadone was not altered. The median unbound percentage of R-methadone increased by 26% in the presence of telaprevir. The R-methadone median (absolute) unbound C(min) values in the absence (10.63 ng/ml) and presence (10.45 ng/ml) of telaprevir were similar. There were no symptoms of opioid withdrawal and no discontinuations due to adverse events. In summary, exposure to total R-methadone was reduced by approximately 30% in the presence of telaprevir, while the exposure to unbound R-methadone was unchanged. No symptoms of opioid withdrawal were observed. These results suggest that dose adjustment of methadone is not required when initiating telaprevir treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT00933283.).

A viral dynamic model for treatment regimens with direct-acting antivirals for chronic hepatitis C infection.

We propose an integrative, mechanistic model that integrates in vitro virology data, pharmacokinetics, and viral response to a combination regimen of a direct-acting antiviral (telaprevir, an HCV NS3-4A protease inhibitor) and peginterferon alfa-2a/ribavirin (PR) in patients with genotype 1 chronic hepatitis C (CHC). This model, which was parameterized with on-treatment data from early phase clinical studies in treatment-naïve patients, prospectively predicted sustained virologic response (SVR) rates that were comparable to observed rates in subsequent clinical trials of regimens with different treatment durations in treatment-naïve and treatment-experienced populations. The model explains the clinically-observed responses, taking into account the IC50, fitness, and prevalence prior to treatment of viral resistant variants and patient diversity in treatment responses, which result in different eradication times of each variant. The proposed model provides a framework to optimize treatment strategies and to integrate multifaceted mechanistic information and give insight into novel CHC treatments that include direct-acting antiviral agents.

The effect of CYP3A inhibitors and inducers on the pharmacokinetics of telaprevir in healthy volunteers.

AIM: To evaluate the effects of ketoconazole, rifampicin and efavirenz on the pharmacokinetics of telaprevir in healthy volunteers. METHOD: Results from three clinical studies are described. (1) Volunteers received a single 750 mg dose telaprevir with and without a single 400 mg dose ketoconazole. (2) Volunteers received (a) 1250 mg telaprevir followed by three 750 mg doses given every 8 h and (b) four 1250 mg telaprevir doses given every 8 h, with a single 400 mg dose ketoconazole given with the fourth dose of telaprevir. (3) Volunteers received either a single 750 mg dose telaprevir with or without 600 mg once daily rifampicin, or 750 mg every 8 h telaprevir with and without 600 mg once daily efavirenz. RESULTS: A single 400 mg dose of ketoconazole increased single dose telaprevir exposure: the geometric least-squares mean ratio (GLSMR, with 90% confidence limits) was 1.24 (1.10, 1.41) for C(max) and 1.62 (1.45, 1.81) for AUC(0,∞). However, after multiple doses of telaprevir, there was no discernible effect of ketoconazole on telaprevir exposure. Co-administration of rifampicin at steady-state markedly reduced single dose telaprevir exposure with GLSMRs of 0.14 (0.11, 0.18) for C(max) and 0.08 (0.07, 0.11) for AUC(0,∞), whereas efavirenz had a smaller effect on telaprevir exposure when both drugs were co-administered at steady-state, with GLSMRs of 0.91 (0.81, 1.02) for C(max) , 0.53 (0.44, 0.65) for C(min), and 0.74 (0.65, 0.84) for AUC(0,8 h). CONCLUSION: CYP3A inducers, rifampicin and efavirenz, can reduce telaprevir exposure to varying degrees based on their potency. The effect of ketoconazole as an inhibitor of telaprevir metabolism is more pronounced after a single dose of telaprevir than after repeated administration.

A unique case of cervical osteochondroma causing dysphagia.

Osteochondroma of the spine is a rare condition. It may present in solitary form or with multiple exostoses or hereditary multiple exostoses. In this article, we report a 22-year-old male case who was diagnosed with cervical osteochondroma, originating from the third and fourth cervical vertebra.

The Tug Test and Modified Ponseti Casting: A Simple and Reliable Method to Improve the Efficacy of Casting in Complex Clubfoot.

Background: The clinical entity of complex clubfoot poses a significant challenge to correction by slippage of casts which further complicates the deformity and prolongs the treatment. A static and dynamic component associated with this deformity causing cast slippage was recognized. The purpose of this study was to evaluate the clinical outcomes at the end of the casting period while addressing these issues. Methods: A retrospective study of 17 patients with 25 complex clubfeet over a period of 2 years was conducted. Tug test was used to ascertain the snugness of the cast. To address the dynamic component, distal extent of the cast was limited to metatarsal heads. Results: The mean age of patients at diagnosis was 4.41 months (2-7 months). The mean pre-casting Pirani score was 4.8 (4-6) and post casting Pirani score was 0.4 (0-1). A total of 128 casts were applied to correct 25 complex clubfeet. The average number of casts required to achieve correction by the modified Ponseti technique was 5.12 (4-7). Overall, four incidences of cast slippage occurred. Conclusion: The modified Ponseti technique is effective in the correction of complex clubfoot. Tug test can detect casts which are prone to slippage. Limiting the distal extent of the cast to the metatarsal heads can reduce cast slippage by reducing the repeated downward pressure by the toes on the cast.Level of evidence Level 4. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-023-00910-w.

Comparison of Various Joint Decompression Techniques in Septic Arthritis of the Hip in Children: A Systematic Review and Meta-Analysis.

The aim of this review is to conduct an analysis of existing literature on outcomes of application of various methods of joint decompression in management of septic arthritis of the hip in children. A search of literature in PubMed, Embase, and Google Scholar was conducted for identification of studies reporting on the outcomes of intervention for septic arthritis of the hip in children. Of the 17 articles selected, four were comparative studies; two of these were randomized controlled trials while the rest were single arm studies. Statistical difference was observed between the proportion of excellent clinical and radiological outcomes in arthrotomy (90%, 95% confidence interval [CI] 81-98%; 89%, 95% CI 80-98%), arthroscopy (95%, 95% CI 91-100%; 95%, 95% CI 90-99%), and arthrocentesis (98%, 95% CI 97-100%; 99%, 95% CI 97-100%), respectively. The highest overall rate of additional unplanned procedures was observed in the arthrocentesis group (24/207, 11.6%). Patients who underwent arthrocentesis had a statistically greater chance of excellent clinical and radiological outcomes, although the highest level of need for additional unplanned surgical intervention was observed in the arthrocentesis group, followed by the arthroscopy group and the arthrotomy group. Future conduct of a prospective multicentric study focusing on the developed and developing world, along with acquisition of data. such as delay of treatment and severity of disease will enable assessment of the efficacy of one technique over the other by surgeons worldwide.

Hemiepiphysiodesis using tension band plates: does the insertion technique or screw length influence the rate of correction?

We retrospectively studied the effect of certain characteristics of the insertion technique and the construct of tension band plates on its angular correction rates. The study included 68 physes in 28 children. The following preoperative radiological parameters were measured: interscrew angle; the length of the epiphyseal screw, its distance and angle (screw trajectory angle) with respect to the physis. Additionally, changes in the mechanical lateral distal femoral angle and medial proximal tibial angle were calculated from the follow-up radiographs. The statistical calculations involved correlating the above-mentioned parameters and correction rates using a correlation coefficient. The mean patient age at the time of surgery was 8.6 years and the follow-up was 12.1 months. The mean screw trajectory angle was 13.4 degrees, the interscrew angle 18.9 degrees and the proportion of screw length was 41.3%. The mean correction rate recorded was 1.1 degrees/ month. The child's age (R = -0.13), screw trajectory angle (R = -0.13), interscrew angle (R = -0.02), distance of screw from physis (R = 0.04), and length of screw (R = 0.07) did not show statistically significant correlation with the angular correction rates. The correction rate produced by the tension band plate was found nearly independent of the parameters recorded for insertion technique (screw trajectory angle, interscrew angle, distance of screw from the physis) or construct (length of the epiphyseal screw). It functions as long as the physis is tethered by a side plate adequately secured by appropriate length screws.

A prospective study on the role of foot evertor muscle activity in recurrence of clubfoot.

BACKGROUND: Even after corrective casting and bracing, clubfoot recurrence is challenging throughout childhood, with around 14-40 % recurrence rates. Most of the literature on recurrence was attributed to various factors, and minimal research was conducted to know the role of foot evertor muscle activity and its stimulation benefits. This study aimed to assess the role of foot evertor muscle activity in idiopathic congenital clubfoot recurrence by using clinical, sonographic, and electromyographic parameters. METHODS: A prospective cohort study was conducted at our tertiary care hospital from 2020 to 2022. The patient's demographic data, Pirani, Dimeglio, Clinical Evertor Muscle Activity scores, sonographic cross-sectional areas of leg muscle, and evertor motor activity using surface electromyography were recorded in adherence to the pre-defined intervals. RESULTS: In total, 51 patients (51 feet) were included in the study, and the overall recurrence rate was 27.5 % (14/51). In this study, around 47 % (24/51) of children had mild or poor clinical evertor activity; among them, 58 % (14/24) children had a recurrence, and the insufficient clinical evertor activity and recurrence were strongly correlated (p = 0.01). Evertor muscle cross-sectional area ratio, motor unit potentials, and recruitment were comparatively less in the recurred group; however, only the cross-sectional area ratio was statistically significant (p = 0.02). CONCLUSION: Early detection of evertor muscle weakness can help to individualize the treatment plans by predicting recurrence. Therefore, it should be included in routine clinical evaluations. Further research is required to determine the advantages of evertor muscle-strengthening activities in preventing idiopathic clubfoot deformity. LEVEL OF CLINICAL EVIDENCE: A prospective cohort study, Level of evidence-II.

Effect of telaprevir on the pharmacokinetics of buprenorphine in volunteers on stable buprenorphine/naloxone maintenance therapy.

This was an open-label, single-sequence trial in hepatitis C virus-negative volunteers on stable, individualized, buprenorphine maintenance therapy. Telaprevir at 750 mg every 8 h was coadministered with buprenorphine/naloxone (4:1 ratio as sublingual tablets) for 7 days with food. Pharmacokinetic profiles of buprenorphine, norbuprenorphine, and naloxone were measured over the 24-hour dosing interval on day -1 (buprenorphine/naloxone alone, reference) and day 7 of telaprevir coadministration (test). Geometric least-squares mean ratios and associated 90% confidence intervals of treatment ratios (test/reference) were calculated using log-transformed pharmacokinetic parameters. Opioid withdrawal symptoms were evaluated throughout the study (via questionnaires and pupillometry). Pharmacokinetic data were available for 14 and 13 volunteers on day -1 and day 7, respectively. The area under the concentration-time curve (AUC) for buprenorphine was unchanged and the maximum concentration of drug in serum (C(max)) for buprenorphine, C(max) and AUC for norbuprenorphine, and C(max) naxolone were modestly decreased during coadministration with telaprevir. Geometric least-squares mean ratios (90% confidence intervals) for buprenorphine were 0.80 (0.69, 0.93) for the C(max) and 0.96 (0.84, 1.10) for the AUC from 0 to 24 h (AUC(0-24)); for norbuprenorphine, values were 0.85 (0.66, 1.09) for C(max) and 0.91 (0.71, 1.16) for AUC(0-24); for naloxone, the C(max) was 0.84 (0.62, 1.13). Coadministration of telaprevir did not increase withdrawal symptom frequency, and there were no serious adverse events reported during or after completion of telaprevir coadministration. Results suggest dose adjustment may not be necessary when telaprevir and buprenorphine/naloxone are coadministered.