Shorter Treatment Duration Research Articles

Once-Daily Valbenazine Is Effective for Tardive Dyskinesia in Elderly Patients (>=65 Years)

<h3>Introduction</h3> Valbenazine is a selective and potent vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia (TD), a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics or other dopamine-receptor blocking agents (DRBAs). Valbenazine is the only approved TD medication with once-daily dosing and no requirements or cautions for dosing based on age. Older adults (≥55 years) have an increased risk for TD after a shorter duration of treatment with DRBAs, and previous analyses have shown that valbenazine is effective and well tolerated in this population (Sajatovic et al, Int J Geriatr Psychiatry 2020). The current presentation includes findings from the first analyses to evaluate the effects of an approved TD medication in an elderly population, using the more conventional age cutoff of ≥65 years. <h3>Methods</h3> Data from two long-term studies (KINECT 3-extension, KINECT 4) of participants receiving up to 48 weeks of once-daily treatment with valbenazine (40 mg or 80 mg) were pooled and analyzed by age (≥65 and <65 years). Analyses included mean change from baseline (CFB) to Week 48 in Abnormal Involuntary Movement Scale (AIMS) total score. AIMS response at Week 48 was also assessed as follows: clinically meaningful response (≥30% improvement from baseline); protocol-defined response (≥50% improvement from baseline). Additional analyses included response thresholds for Clinical Global Improvement-Tardive Dyskinesia (CGI-TD) and Patient Global Impression of Change (PGIC) as follows: rating of "minimally improved" or better (score ≤3) at Week 48 (CGI-TD≤3, PGIC≤3); rating of "much improved" or "very much improved" (score ≤2) at Week 48 (CGI-TD≤2, PGIC≤2). Treatment-emergent adverse events (TEAEs) were also monitored. <h3>Results</h3> Treatment outcomes were generally robust and comparable between the age subgroups. Pooled AIMS results indicated substantial improvements in TD movements were found in both age subgroups with valbenazine 40 mg (≥65 years, n=8; <65 years, n=46) and 80 mg (≥65 years, n=20; <65 years, n=105): mean CFB (≥65 years, -6.4 and -9.8 [for 40 and 80 mg, respectively]; <65 years, -5.5 and -8.3); clinically meaningful ≥30% response (≥65 years, 75% and 95%; <65 years, 61% and 80%); and protocol-defined ≥50% response (≥65 years, 75% and 85%; <65 years, 50% and 70%). CGI-TD and PGIC response rates indicated that clinician- and patient-reported global improvements were also substantial in both age subgroups: CGI-TD≤3 (≥65 years, 88% and 100% [for 40 and 80 mg, respectively]; <65 years, 89% and 97%); CGI-TD≤2 (≥65 years, 88% and 95%; <65 years, 62% and 83%); PGIC≤3 (≥65 years, 88% and 100%; <65 years, 89% and 94%); PGIC≤2 (≥65 years, 75% and 90%; <65 years, 77% and 80%). Analyses of TEAEs indicated no statistically significant differences between age subgroups for the incidence of any TEAEs (≥65 years, 73%; <65 years, 72%) or any serious TEAEs (≥65 years, 18%; <65 years, 17%). However, discontinuations due to TEAEs were significantly more common in elderly participants (≥65 years, 26%; <65 years, 13%; <i>P</i><0.05). <h3>Conclusions</h3> These analyses, which are the first to evaluate any approved TD medication in patients ≥65 years, indicate that long-term treatment with once-daily valbenazine is appropriate and beneficial for this age group. Elderly study participants had clinically meaningful and substantial improvements in TD that were comparable to (or better than) those in the younger cohort. These results may provide clinicians with important information about the management of TD in elderly patients. <h3>This research was funded by</h3> Neurocrine Biosciences, Inc.

Health care costs in a randomized trial of antimicrobial duration among cystic fibrosis patients with pulmonary exacerbations

BackgroundThe purpose of these analyses was to determine whether overall costs were reduced in cystic fibrosis (CF) patients experiencing pulmonary exacerbation (PEx) who received shorter versus longer durations of treatment. MethodsAmong people with CF experiencing PEx, we calculated 30-day inpatient, outpatient, emergency room, and medication costs and summed these to derive total costs in 2020 USD. Using the Kaplan-Meier sample average (KMSA) method, we calculated adjusted costs and differences in costs within two pairs of randomized groups: early robust responders (ERR) randomized to receive treatment for 10 days (ERR-10 days) or 14 days (ERR-14 days), and non-early robust responders (NERR) randomized to receive treatment for 14 days (NERR-14 days) or 21 days (NERR-21 days). ResultsPatients in the shorter treatment duration groups had shorter lengths of stay per hospitalization (mean ± standard deviation (SD) for ERR-10 days: 7.9 ± 3.0 days per hospitalization compared to 10.1 ± 4.2 days in ERR-14 days; for NERR-14 days: 8.7 ± 4.9 days per hospitalization compared to 9.6 ± 6.5 days in NERR-21 days). We found statistically significantly lower adjusted mean costs (95% confidence interval) among those who were randomized to receive shorter treatment durations (ERR-10 days: $60,800 ($59,150 - $62,430) vs $74,420 ($72,610 - $76,450) in ERR-14 days; NERR-14 days: $66,690 ($65,960-$67,400) versus $74,830 ($73,980-$75,650) in NERR-21 days). ConclusionsTied with earlier evidence that shorter treatment duration was not associated with worse clinical outcomes, our analyses indicate that treating with shorter antimicrobial durations can reduce costs without diminishing clinical outcomes.

Dextroamphetamine Treatment in Children With Hypothalamic Obesity

IntroductionHypothalamic obesity (HO) in children has severe health consequences. Lifestyle interventions are mostly insufficient and currently no drug treatment is approved for children with HO. Amphetamines are known for their stimulant side-effect on resting energy expenditure (REE) and suppressing of appetite. Earlier case series have shown positive effects of amphetamines on weight in children with acquired HO. We present our experiences with dextroamphetamine treatment in the, up to now, largest cohort of children with HO.MethodsA retrospective cohort evaluation was performed of children with HO treated with dextroamphetamine at two academic endocrine pediatric clinics. Off-label use of dextroamphetamine was initiated in patients with progressive, therapy-resistant acquired or congenital HO. Anthropometrics, REE, self-reported (hyperphagic) behavior and energy level, and side effects were assessed at start and during treatment.ResultsNineteen patients with a mean age of 12.3 ± 4.0 years had been treated with dextroamphetamine. In two patients, ΔBMI SDS could not be evaluated due to short treatment duration or the simultaneous start of extensive lifestyle treatment. Mean treatment duration of the 17 evaluated patients was 23.7 ± 12.7 months. Fourteen patients (n = 10 with acquired HO, n = 4 with congenital HO) responded by BMI decline or BMI stabilization (mean ΔBMI SDS of -0.6 ± 0.8, after a mean period of 22.4 ± 10.5 months). In three patients, BMI SDS increased (mean ΔBMI SDS of +0.5 ± 0.1, after a mean period of 29.7 ± 22.6 months). In 11 responders, measured REE divided by predicted REE increased with +8.9%. Thirteen patients (68.4%) reported decreased hyperphagia, improvement of energy level and/or behavior during treatment. Two patients developed hypertension during treatment, which resulted in dosage adjustment or discontinuation of treatment. Twelve children continued treatment at last moment of follow-up.ConclusionIn addition to supportive lifestyle interventions, dextroamphetamine treatment may improve BMI in children with HO. Furthermore, dextroamphetamines have the potential to decrease hyperphagia and improve resting energy expenditure, behavior, and energy level. In patients with acquired HO, these effects seem to be more pronounced when compared to patients with congenital HO. Future studies are needed to support these results.

Development and Validation of a Prediction Model for the Treatment Time of Deformational Head Shapes Using a Cranial Remolding Orthosis

The cranial remolding orthosis (CRO) has been shown in previous studies to be an effective method of treatment for deformational head shapes. Many studies have shown younger infants achieve greater correction than older infants and generally have a shorter treatment duration. The goal of this study is to develop and validate a prediction equation for the maximum treatment time for deformational head shapes when utilizing a CRO. This retrospective study included subjects with deformational plagiocephaly (DP), deformational brachycephaly (DB), or deformational asymmetrical brachycephaly (DAB) who began CRO treatment between 3 and 18 months of gestational age. Prediction models were derived from 1250 subjects with DP, DB, and DAB and the validation used data from 210 different subjects. Actual treatment time was less than or equal to predicted treatment time in 85.19% (DP), 56.67% (DB), and 75.40% (DAB) of the cases when rounding the prediction up to the nearest month. The prediction equation has moderate accuracy for predicting the likely maximum amount of CRO treatment time for patients with DP, DB, and DAB and may be used clinically to give caregivers an estimated treatment duration for a patient who is indicated for a CRO, if treatment was initiated immediately.

Treatment of Wound Infections in a Mouse Model Using Zn2+-Releasing Phage Bound to Gold Nanorods.

Infections caused by drug-resistant bacteria, particularly Gram-negative organisms, are increasingly difficult to treat using antibiotics. A potential alternative is “phage therapy”, in which phages infect and lyse the bacterial host. However, phage therapy poses serious drawbacks and safety concerns, such as the risk of genetic transduction of antibiotic resistance genes, inconsistent pharmacokinetics, and unknown evolutionary potential. In contrast, metallic nanoparticles possess precise, tunable properties, including efficient conversion of electronic excitation into heat. In this work, we demonstrate that engineered phage-nanomaterial conjugates that target the Gram-negative pathogen Pseudomonas aeruginosa are highly effective as a treatment of infected wounds in mice. Photothermal heating, performed as a single treatment (15 min) or as two treatments on consecutive days, rapidly reduced the bacterial load and released Zn2+ to promote wound healing. The phage-nanomaterial treatment was significantly more effective than systemic standard-of-care antibiotics, with a >10× greater reduction in bacterial load and ∼3× faster healing as measured by wound size reduction when compared to fluoroquinolone treatment. Notably, the phage-nanomaterial was also effective against a P. aeruginosa strain resistant to polymyxins, a last-line antibiotic therapy. Unlike these antibiotics, the phage-nanomaterial showed no detectable toxicity or systemic effects in mice, consistent with the short duration and localized nature of phage-nanomaterial treatment. Our results demonstrate that phage therapy controlled by inorganic nanomaterials can be a safe and effective antimicrobial strategy in vivo.

The intention to receive tuberculosis preventive therapy in adult household contacts of pulmonary TB patients in Delhi, India.

The integration of newer tuberculosis preventive therapy regimens, which have shorter treatment duration, simpler dosing requirements, and improved safety profile, is being considered within India's national tuberculosis elimination program. However, a potential operational challenge in the successful rollout of the expanded TPT plan is the extent of its acceptability in adult household contacts of pulmonary tuberculosis patients due to possibility of lower risk perception and suboptimal perceived benefit. This study was conducted to determine the intention to accept Tuberculosis Preventive Therapy among adult household contacts of pulmonary tuberculosis patients in Delhi, India. This cross-sectional study was conducted from June-November 2020 in Delhi, India. Data were collected through face to-face interviews by trained field investigations from the high-risk adult household contacts of PTB patients. A total of 536 household contacts including 237 (44.2%) men and 299 (55.8%) women were recruited with median (IQR) age 40 (22-52) years. Risk factors for incident tuberculosis observed in the HHCs were undernourishment (32.3%), overweight (47.8%), and diabetes comorbidity (10.6%). Most of the participants had not heard of latent TB infection (97.3%) The intention to accept tuberculosis preventive therapy was reported by 394 (73.5%) participants with an absence of symptoms (33.1%), feeling completely healthy (42.9%), and drug adverse effects (27.5%) (n=142) being primary drivers of non-intention. Nearly three in four HHCs without TB disease expressed willingness to accept TPT if prescribed with caveat for the social desirability bias.

Drug-resistant tuberculosis: advances in diagnosis and management.

Purpose of reviewDiagnosis and treatment of drug-resistant tuberculosis (DR-TB) is undergoing substantial changes, owing availability of new diagnostic tools and drugs, coupled with global underdiagnosis and undertreatment. Recent developments are reviewed.Recent findingsMolecular diagnostics, for Mycobacterium tuberculosis complex detection and prediction of drug resistance, implemented in the last decade, accelerated TB diagnosis with improved case detection. Nevertheless, access and coverage of drug-resistance testing remain insufficient. Genome sequencing-technologies, based on targeted next-generation sequencing show early potential to mitigate some of the challenges in the future. The recommendation to use an all oral, bedaquiline based regimen for treatment of multidrug-resistant/rifampicin-resistant TB is major advancement in DR-TB care. TB regimen using new and repurposed TB drugs demonstrate in recent clinical trials like, NIX-TB, ZeNIX and TB PRACTECAL considerable treatment success, shorten treatment duration and reduce toxicity. Their optimal use is threatened by the rapid occurrence and spread of strains, resistant to new drugs. Children benefit only very slowly from the progress.SummaryThere is notable progress in improved diagnosis and treatment of drug-resistant TB, but complicated by the COVID-19 pandemic the majority of TB patients worldwide don’t have (yet) access to the advances.

Variants associated with Bedaquiline (BDQ) resistance identified in Rv0678 and efflux pump genes in Mycobacterium tuberculosis isolates from BDQ na\xefve TB patients in Pakistan

BackgroundMutations in the Rv0678, pepQ and atpE genes of Mycobacterium tuberculosis (MTB) have been reported to be associated with reduced antimycobacterial susceptibility to bedaquiline (BDQ). Resistance conferring mutations in treatment naïve MTB strains is likely to have implications for BDQ based new drug regimen that aim to shorten treatment duration. We therefore investigated the genetic basis of resistance to BDQ in MTB clinical isolates from BDQ naïve TB patients from Pakistan. In addition, mutations in genes associated with efflux pumps were investigated as an alternate mechanism of resistance.MethodsBased on convenience sampling, we studied 48 MTB clinical isolates from BDQ naïve TB patients. These isolates (from our strain bank) included 38 MDR/pre-XDR/XDR (10 BDQ resistant, 8 BDQ intermediate and 20 BDQ susceptible) and 10 pan drug susceptible MTB isolates. All strains were subjected to whole genome sequencing and genomes were analysed to identify variants in Rv0678, pepQ, atpE, Rv1979c, mmpLS and mmpL5 and drug resistance associated efflux pump genes.ResultsOf the BDQ resistant and intermediate strains 44% (8/18) had variants in Rv0678 including; two reported mutations S63R/G, six previously unreported variants; L40F, R50Q and R107C and three frameshift mutations; G25fs, D64fs and D109fs.Variants in efflux pumps; Rv1273c (G462K), Rv0507c (R426H) and Rv1634c (E198R) were found to be present in drug resistant isolates including BDQ resistant and intermediate isolates. E198R in efflux pump gene Rv1634c was the most frequently occurring variant in BDQ resistant and intermediate isolates (n = 10).ConclusionWe found RAVs in Rv0678 to be commonly associated with BDQ resistance. Further confirmation of the role of variants in efflux pump genes in resistance is required so that they may be incorporated in genome-based diagnostics for drug resistant MTB.

Stereotactic Body Radiation Therapy versus Concurrent Chemoradiotherapy for Locally Advanced Pancreatic Cancer: A Propensity Score-Matched Analysis.

Simple SummaryIn the lack of direct comparative evidence of stereotactic body radiation therapy, we reviewed one of the largest locally advanced pancreatic cancer cohort homogeneously treated in a tertiary cancer center. Our propensity score–matched analysis shows comparable outcomes between stereotactic body radiation therapy and concurrent chemoradiotherapy in terms of survival, local control, and treatment-related toxicities. Considering the advantages of SBRT such as short treatment duration, better tolerance, easy combination with systemic treatment, and the potential for dose escalation, further investigation of the feasibility of SBRT as an alternative to CCRT in treating locally advanced pancreatic cancer is required.In locally advanced pancreatic cancer (LAPC), stereotactic body radiation therapy (SBRT) has been applied as an alternative to concurrent chemoradiotherapy (CCRT); however, direct comparative evidence between these two modalities is scarce. The aim of this study was to compare the clinical outcomes of SBRT with CCRT for LAPC. We retrospectively reviewed the medical records of patients with LAPC who received SBRT (n = 95) or CCRT (n = 66) with a concurrent 5-FU-based regimen between January 2008 and July 2016. The clinical outcomes of freedom from local progression (FFLP), progression-free survival (PFS), overall survival (OS), and toxicities were analyzed before and after propensity score (PS) matching. After a median follow-up duration of 15.5 months (range, 2.3–64.5), the median OS, PFS, and FFLP of the unmatched patients were 17.3 months, 11 months, and 19.6 months, respectively. After PS matching, there were no significant differences between the SBRT and CCRT groups in terms of the 1-year rates of OS (66.7% vs. 80%, p = 0.455), PFS (40.0% vs. 54.2%, p = 0.123), and FFLP (77.2% and 87.1%, p = 0.691). Our results suggest SBRT could be a feasible alternative to CCRT in treating patients with LAPC.

Comparison of the treatment duration and effects of magnetic mandibular repositioning appliances and non-magnetic twin block in the treatment of growing patients with skeletal Class II malocclusion due to mandibular retrognathism – A systematic review

Over the past two decades, magnets have been used in orthodontics and dentofacial orthopedics and various attempts have been made to evaluate the biological implications of magnets and magnetic fields. This systematic review aims to provide a detailed comparison between magnetic mandibular repositioning appliances and non-magnetic twin blocks on mandibular growth modification. The objective was to evaluate the treatment duration and effects of magnetic mandibular repositioning appliances and non-magnetic twin block in growing children with skeletal Class II malocclusion due to mandibular retrognathism. Literature search of electronic databases and additional manual search was done till June 2021. Randomized controlled clinical trials (CCTs), non-randomized CCTs, case reports, case series, and retrospective clinical trials in which magnetic appliances and non-magnetic twin blocks were used for the correction of skeletal Class II malocclusion are included in the present review. Correction of skeletal Class II malocclusion was achieved in a shorter treatment duration with magnetic mandibular repositioning appliances. Similar dental and skeletal effects were observed with both the appliances; however, maxillary restraining effect and reduced mandibular incisor proclination was evident with magnetic mandibular repositioning appliances. Magnetic appliance is proven to be more effective in correction of skeletal Class II malocclusion with mandibular retrognathism and maxillary prognathism with proclined lower incisors. This systematic review was registered on Prospero with registration number CRD42020165297.

Mycophenolate Mofetil (CellCept®) in Combination With Low Dose Prednisolone in Moderate to Severe Graves' Orbitopathy.

Although corticosteroids are currently the first-choice drug for thyroid eye disease (TED), in 20–30% of cases, patients show poor or non-existent responses, and when the drug is withdrawn, 10–20% of patients relapse. Thus, in this study, we aimed to investigate the efficacy of the combined use of mycophenolate mofetil (CellCept®) and low dose oral prednisolone in patients with moderate to severe Graves' orbitopathy (GO). For the first time, we investigated the relationship between TED-related parameters and proptosis reduction. In a prospective, non-randomized, interventional case series, 242 patients with moderate-to-severe GO were, assigned to receive oral prednisolone (5 mg/ d) and mycophenolate mofetil (CellCept®) (one 500 mg tablet twice per day according to the therapeutic response). The patients were monitored regularly during the 3rd, 6th, 12th, and 18th month of treatment. The main outcome measures were the clinical activity score (CAS), intraocular pressure (IOP), diplopia, proptosis and visual acuity. We also assessed the relationship between the main outcomes with proptosis changes and time to improvement (months). Adverse effects were recorded during each visit. The clinical response rate increased from 67.7% on the third month to 89.2% on the sixth month, and 94.2% on the 12th month. This therapeutic response continued until the 18th month of follow-up. The CAS responses [disease inactivation (CAS <3)] improved during our study: 70.6% on the third month, 90.0% on the sixth month, and 92.5% at 12th month. These conditions continued until the 18th month of follow-up. Proptosis improvement was 52% on the third month, 71% on the sixth month, 83% on the 12th month, and 87.1% on the 18th month. Changes in IOP and visual acuity were not significant (P = 0.568 and 0.668, respectively). The patient showed significant improvement in the Gorman score. A Shorter duration of treatment was seen in patients with earlier onset of intervention, younger age, and lack of all extraocular muscle (EOM) enlargement on computed tomography (CT) scan (p < 0.05). In addition, a better response (more reduction) in proptosis was related to: younger age at disease, earlier treatment intervention (less interval from the time the diagnosis of moderate-to-severe GO was made until medication initiation), shorter treatment time (less time to improvement), less IOP, lack of EOM enlargement on CT scan, and lack of diplopia (P < 0.05). Adverse events occurred in six patients. Findings show that mycophenolate mofetil (CellCept®) plus low-dose prednisolone can be introduced as a new optimal dosing regimen in GO due to its better effect on chronic complications such as proptosis and diplopia.

Myoelectric Arm Orthosis in Motor Learning-Based Therapy for Chronic Deficits After Stroke and Traumatic Brain Injury.

BackgroundTechnologies that enhance motor learning-based therapy and are clinically deployable may improve outcome for those with neurological deficits. The MyoPro™ is a customized myoelectric upper extremity orthosis that utilizes volitionally generated weak electromyographic signals from paretic muscles to assist movement of an impaired arm. Our purpose was to evaluate MyoPro as a tool for motor learning-based therapy for individuals with chronic upper limb weakness.MethodsThis was a pilot study of thirteen individuals with chronic moderate/severe arm weakness due to either stroke (n = 7) or TBI (n = 6) who participated in a single group interventional study consisting of 2 phases. The in-clinic phase included 18 sessions (2x per week, 27hrs of face-to-face therapy) plus a home exercise program. The home phase included practice of the home exercise program. The study did not include a control group. Outcomes were collected at baseline and at weeks 3, 5, 7, 9, 12, 15, and 18. Statistics included mixed model regression analysis.ResultsStatistically significant and clinically meaningful improvements were observed on Fugl-Meyer (+7.5 points). Gains were seen at week 3, increased further through the in-clinic phase and were maintained during the home phase. Statistically significant changes in Modified Ashworth Scale, Range of Motion, and Chedoke Arm and Hand Activity Inventory were seen early during the in-clinic phase. Orthotic and Prosthetic User's Survey demonstrated satisfaction with the device throughout study participation. Both stroke and TBI participants responded to the intervention.ConclusionsUse of MyoPro in motor learning-based therapy resulted in clinically significant gains with a relatively short duration of in-person treatment. Further studies are warranted.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT03215771.

Plasma‐Modified Coal Fly Ash Zeolites with Enhanced Catalytic Efficiency toward the Total Oxidation of Volatile Organic Compounds as Low‐Cost Substitutes for Platinum Group Metals Catalysts

The initial coal fly ash zeolites (CFAZ) are obtained from raw coal fly ash with two SiO2/Al2O3 ratios of 2.0 and 2.2 by hydrothermal activation or by two‐stage process. Microwave plasma surface treatment of CFAZ is performed to modify their surface and therefore their catalytic activity in total VOC oxidation. CHF3 and SF6 are used as plasma agents at two different treatments times—30 s and 60 s. The obtained hierarchal CFAZ are characterized by X‐ray diffraction, N2‐physisorption, temperature programmed reduction experiments, UV–vis spectroscopy and X‐ray photoelectron spectroscopy to clarify the effect of plasma treatment on the surface and reduction properties, morphology and structure of the modified samples. The catalytic performance of the modified CFAZ is investigated in a flow system toward toluene oxidation in the temperature range of 250–520 °C. It has been observed that CHF3 favors the catalytic activity of CFAZ at shorter treatment duration, while SF6 inhibits their catalytic properties. The development of efficient low‐cost catalyst will contribute to the saving of critical raw materials such as platinum group metals, and to the utilization of the enormous resource of coal ash instead of its landfilling in accordance to the development of circular economy and smart waste management.

Emerging data on rifampicin pharmacokinetics and approaches to optimal dosing in children with tuberculosis

Introduction Despite its longstanding role in tuberculosis (TB) treatment, there continues to be emerging rifampicin research that has important implications for pediatric TB treatment and outstanding questions about its pharmacokinetics and optimal dose in children. Areas covered This review aims to summarize and discuss emerging data on the use of rifampicin for: 1) routine treatment of drug-susceptible TB; 2) special subpopulations such as children with malnutrition, HIV, or TB meningitis; 3) treatment shortening. We also highlight the implications of these new data for child-friendly rifampicin formulations and identify future research priorities. Expert opinion New data consistently show low rifampicin exposures across all pediatric populations with 10-20 mg/kg dosing. Although clinical outcomes in children are generally good, rifampicin dose optimization is needed, especially given a continued push to shorten treatment durations and for specific high-risk populations of children who have worse outcomes. A pooled analysis of existing data using applied pharmacometrics would answer many of the important questions remaining about rifampicin pharmacokinetics needed to optimize doses, especially in special populations. Targeted clinical studies in children with TB meningitis and treatment shortening with high-dose rifampicin are also priorities.

Efficacy of vision therapy for unilateral refractive amblyopia in children aged 7\u201310\u2009years

BackgroundThere is a critical period for visual development, conventionally considered to be the first 6 years of life. Children aged 7 years and older are significantly less responsive to amblyopia treatment. This study investigated the efficacy of binocular vision therapy in amblyopic children aged 7–10 years.MethodsThis retrospective study enrolled 36 children with unilateral amblyopia who were divided into a case group (receiving vision therapy, optical correction, and part-time patching of the weaker eye) and a control group (receiving optical correction and part-time patching of the weaker eye). Visual acuity (VA) was measured at baseline, at the 3-month, 6-month, and 9-month visits, and 3 months after cessation of treatment.ResultsThere were 19 subjects in the case group and 17 subjects in the control group. Mean VA in the case group improved from 0.39 ± 0.24 logMAR at baseline to 0.10 ± 0.23 logMAR at the endpoint of treatment (p < 0.001, paired t-test). Mean VA in the control group improved from 0.64 ± 0.30 logMAR at baseline to 0.52 ± 0.27 logMAR at the endpoint of treatment (p = 0.015, paired t-test). The improvement was significantly greater in the case group than in the control group (p = 0.006, two-samples independent t-test). All subjects underwent follow-up examinations within 6 to 12 months. There was no regression of VA in the case group 3 months after cessation of vision therapy. The patients in the case group who received visual therapy were with better VA improvement then patients with only optic correction and patching.ConclusionsVision therapy combined with conventional treatment (optical correction and part-time patching) is more effective than conventional treatment alone in children aged 7–10 years with unilateral refractive amblyopia. The treatment results not only in greater vision gain, but also in shorter duration of treatment.

Real-world outcomes with second-line therapy in advanced esophageal squamous cell carcinoma using SEER-Medicare data.

Aim: To characterize real-world patterns of second-line treatment and outcomes in older patients with advanced/metastatic esophageal squamous cell carcinoma (ESCC). Patients and methods: Patients aged ≥66years diagnosed with advanced/metastatic ESCC between 2010 and 2015 and followed through 2016 were included in this retrospective analysis using SEER-Medicare data. Results: Of 756 patients with advanced/metastatic ESCC, 104 (14%) received second-line therapy; median duration of treatment was 1.5months. Median overall survival was 5.7months for all patients receiving second-line treatment, and 4.5, 5.6and 8.5months, respectively, for patients receiving taxane monotherapy, taxane combination therapyand nontaxane therapy. Conclusion: A small proportion of patients with advanced/metastatic ESCC received second-line therapy, which was associated with short duration of treatment and poor overall survival.

Pantoea dispersa rhinosinusitis: clinical aspects of a rare sinonasal pathogen.

There is no report in the literature targeting the role of Pantoea dispersa in rhinosinusitis and P. dispersa has not been identified as a commensal bacterium in the sinonasal cavity. We aimed to investigate the role of P. dispersa in rhinosinusitis. We retrospectively reviewed the data of patients diagnosed with rhinosinusitis at a medical center in Taiwan. A total of 274 rhinosinusitis patients underwent sinus culture between July 2017 and July 2019. All 23 patients with acute P. dispersa rhinosinusitis experienced purulent rhinorrhea; three (13%) had nasal obstruction, but none had olfactory dysfunction, facial pressure/pain and nasal polyp. The patients with P. dispersa received a significantly shorter duration of antibiotic treatment (19.9 ± 2.6 vs. 28.9 ± 2.5days, P = 0.015) and had lower surgery rate (0% vs. 16.7%, P = 0.043) than other patients. Patients with olfactory dysfunction were more likely to receive surgical treatment (P = 0.018). Acute rhinosinusitis caused by P. dispersa resulted in less surgical interventions and shorter treatment durations. Olfactory dysfunction may imply longer course and possibility for surgical intervention in chronic rhinosinusitis. The present study revealed that P. dispersa had the potential to colonize in human sinonasal cavities and cause rhinosinusitis.

P301 Relapse rates after withdrawal of thiopurines in patients with Inflammatory Bowel Disease

Abstract Background Withdrawal of thiopurines after remission has been shown to be associated with an increased risk of relapse in patients with inflammatory bowel disease. However, long-term data on thiopurine withdrawal is limited especially from developing countries. Methods We retrospectively analyzed data of patients with IBD on thiopurine monotherapy who had stopped and were not on any other immunomodulator or biologics at the time of stopping thiopurines. All these were in clinical remission at the time of withdrawal. Results Among, 1264 patients of IBD who were treated with thiopurines, a total of, 461 patients had to stop thiopurine because of various reasons. Among these, 218 (UC=179; CD=39) patients were eligible for further study (Table-1). Overall, 36.7% (n=80) had relapsed after a median duration of months of, 20 months (IQR:, 9–49). There was no difference in relapse rate between UC and CD (39.6% vs, 23%; P:, 0.055). The overall cumulative probabilities of relapse were, 17%, 34%, and, 44% at the end of, 1, 3, and, 5 years respectively (Figure-1). The cumulative probabilities of relapse at, 1, 3, and, 5 years after thiopurine withdrawal were significantly lower in patients who had received azathioprine for at least, 48 months (14%, 20%, and, 31%) in comparison to those who had received for less than, 48 months (28%, 45%, and, 54%) respectively (P=0.007) (Figure-2). On multivariate Cox regression analysis, male sex [(HR:, 1.7 (1.1–2.7), P=0.014] and short duration of therapy with thiopurines [HR:, 0.98 (0.98–0.99), P=0.003] before withdrawal were associated with increased risk of relapse (Table-2). Conclusion Approximately, 50% of patients with IBD will relapse within, 5 years of thiopurine withdrawal. Male sex and shorter treatment duration (&amp;lt;, 4 years) predict relapse after thiopurine withdrawal. Treatment should be continued even beyond, 4 years in patients who tolerate and maintain remission on thiopurines.

Therapy Switches in Fingolimod-Treated Patients with Multiple Sclerosis: Long-Term Experience from the German MS Registry.

IntroductionsTherapy switches in patients with multiple sclerosis (MS) receiving treatment with fingolimod occur frequently in clinical practice but are not well represented in real-world data. The aim of this study was to identify and characterize treatment switches and reveal sociodemographic/clinical changes over time in fingolimod-treated people with MS (PwMS).MethodsData on 2536 fingolimod-treated PwMS extracted from the German MS Registry during different time periods were analyzed (2010–2019).ResultsOverall, 28.3% of PwMS were treatment-naïve before fingolimod initiation. Interferon beta (30.7%) was the most common pre-fingolimod treatment. Ocrelizumab (19.8%) was the most frequent subsequent treatment in the 944 patients on fingolimod who switched. Between 2010 and 2019, median disease duration at fingolimod initiation decreased from 8.5 to 7.1 years (p < 0.001), and patients taking fingolimod for ≥ 1 year after treatment initiation decreased from 89.6 to 80.5% (p < 0.001). Females (p < 0.001) and young patients (p = 0.003) showed a shorter time on fingolimod. The most frequent reason for switching was disease activity (relapse/MRI) despite treatment. The annualized relapse rate increased from 0.37 in patients on fingolimod to 0.47 after treatment cessation, decreasing to 0.19 after treatment with a subsequent disease-modifying drug (DMD) was initiated.ConclusionTreatment switches from fingolimod to subsequent DMDs currently occur after shorter treatment durations than 10 years ago, possibly due to the growing treatment spectrum. Planning adequate washout periods is essential and should be done on an individualized basis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-021-00320-w.

Treatment of stable nonsegmental vitiligo using transdermal delivery of 5-fluorouracil by fractional CO2 laser versus intralesional injection of 5-fluorouracil, both followed by narrow-band type ultraviolet B (UVB): A comparative study.

Updates of treatment methods of stable vitiligo are needed to give better outcomes with a shorter duration of treatment. To test the effect of transdermal 5-fluorouracil (5-FU) delivery using fractional CO2 (FrCO2 ) laser versus intralesional 5-FU injection, with narrow-band type ultraviolet B (UVB) (NB-UVB) therapy after both, in the treatment of stable vitiligo. The present study comprised 40 patients with nearly symmetrical stable vitiligo lesions. The left side was treated with FrCO2 laser followed by topical 5-FU (FrCO2 +5-FU), while the right side was treated with 5-FU intradermal injection. Both procedures were done at 2-week intervals for 3sessions followed by 24sessions of narrow-band UVB for both sides. Repigmentation was demonstrated on the left side of 90% of patients and the right side of 85% of patients. As much as >50% improvement was demonstrated on the left side of 50% of patients, and the right side of 55% of patients. Intralesional 5-FU showed a statistically significant difference in repigmentation compared to FrCO2 +5-FU. Both 5-FU injection and FrCO2 +5-FU were effective therapeutic modalities for vitiligo. Patients were more compliant with FrCO2 +5-FU.