scholarly journals Resveratrol improves motor function in patients with muscular dystrophies: an open-label, single-arm, phase IIa study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kentaro Kawamura ◽  
Shinobu Fukumura ◽  
Koki Nikaido ◽  
Nobutada Tachi ◽  
Naoki Kozuka ◽  
...  

AbstractMuscular dystrophies (MDs) are inherited disorders characterized by progressive muscle weakness. Previously, we have shown that resveratrol (3,5,4′-trihydroxy-trans-stilbene), an antioxidant and an activator of the protein deacetylase SIRT1, decreases muscular and cardiac oxidative damage and improves pathophysiological conditions in animal MD models. To determine whether resveratrol provides therapeutic benefits to patients with MDs, an open-label, single-arm, phase IIa trial of resveratrol was conducted in 11 patients with Duchenne, Becker or Fukuyama MD. The daily dose of resveratrol was 500 mg/day, which was increased every 8 weeks to 1000 and then 1500 mg/day. Primary outcomes were motor function, evaluated by a motor function measure (MFM) scale, muscular strength, monitored with quantitative muscle testing (QMT), and serum creatine kinase (CK) levels. Adverse effects and tolerability were evaluated as secondary outcomes. Despite the advanced medical conditions of the patients, the mean MFM scores increased significantly from 34.6 to 38.4 after 24 weeks of medication. A twofold increase was found in the mean QMT scores of scapula elevation and shoulder abduction. Mean CK levels decreased considerably by 34%. Diarrhoea and abdominal pain was noted in six and three patients, respectively. Resveratrol may provide some benefit to MD patients.

2021 ◽  
Vol 17 (3) ◽  
pp. 34-39
Author(s):  
H.V. Palahuta

Muscular dystrophies are a heterogeneous group of inherited disorders that share similar clinical features. Being a rare disease, muscular dystrophy represents a huge diagnostic problem for clinicians. Clinically, muscular dystrophies are characterized by progressive muscle weakness, muscle atrophy, and movement disorders. The combination of clinical signs and analysis of the possible type of inheritance allows one to suspect specific forms of muscular dystrophy. Clinicians increasingly need to rely on electrophysiological, imaging, and genetic data for more accurate differential diagnosis. The paper presents the results of the combined use of magnetic resonance imaging of the thigh muscles and electromyography in 17 patients with muscular dystrophy.


2020 ◽  
Vol 132 (6) ◽  
pp. 1914-1924 ◽  
Author(s):  
Liang Li ◽  
Jiantao Yang ◽  
Bengang Qin ◽  
Honggang Wang ◽  
Yi Yang ◽  
...  

OBJECTIVEHuman acellular nerve allograft applications have increased in clinical practice, but no studies have quantified their influence on reconstruction outcomes for high-level, greater, and mixed nerves, especially the brachial plexus. The authors investigated the functional outcomes of human acellular nerve allograft reconstruction for nerve gaps in patients with brachial plexus injury (BPI) undergoing contralateral C7 (CC7) nerve root transfer to innervate the upper trunk, and they determined the independent predictors of recovery in shoulder abduction and elbow flexion.METHODSForty-five patients with partial or total BPI were eligible for this retrospective study after CC7 nerve root transfer to the upper trunk using human acellular nerve allografts. Deltoid and biceps muscle strength, degree of shoulder abduction and elbow flexion, Semmes-Weinstein monofilament test, and static two-point discrimination (S2PD) were examined according to the modified British Medical Research Council (mBMRC) scoring system, and disabilities of the arm, shoulder, and hand (DASH) were scored to establish the function of the affected upper limb. Meaningful recovery was defined as grades of M3–M5 or S3–S4 based on the scoring system. Subgroup analysis and univariate and multivariate logistic regression analyses were conducted to identify predictors of human acellular nerve allograft reconstruction.RESULTSThe mean follow-up duration and the mean human acellular nerve allograft length were 48.1 ± 10.1 months and 30.9 ± 5.9 mm, respectively. Deltoid and biceps muscle strength was grade M4 or M3 in 71.1% and 60.0% of patients. Patients in the following groups achieved a higher rate of meaningful recovery in deltoid and biceps strength, as well as lower DASH scores (p < 0.01): age < 20 years and age 20–29 years; allograft lengths ≤ 30 mm; and patients in whom the interval between injury and surgery was < 90 days. The meaningful sensory recovery rate was approximately 70% in the Semmes-Weinstein monofilament test and S2PD. According to univariate and multivariate logistic regression analyses, age, interval between injury and surgery, and allograft length significantly influenced functional outcomes.CONCLUSIONSHuman acellular nerve allografts offered safe reconstruction for 20- to 50-mm nerve gaps in procedures for CC7 nerve root transfer to repair the upper trunk after BPI. The group in which allograft lengths were ≤ 30 mm achieved better functional outcome than others, and the recommended length of allograft in this procedure was less than 30 mm. Age, interval between injury and surgery, and allograft length were independent predictors of functional outcomes after human acellular nerve allograft reconstruction.


Author(s):  
Raman R S ◽  
Vijaykumar Bhagwan Barge ◽  
Anil Kumar Darivenula ◽  
Himanshu Dandu ◽  
Rakesh R Kartha ◽  
...  

Abstract Background Currently, there is no specific drug for the treatment of COVID-19. Therapeutic benefits of intravenous immunoglobin (IVIG) have been demonstrated in wide range of diseases. The present study is conducted to evaluate the safety and efficacy of IVIG in the treatment of COVID-19 patients with moderate pneumonia. Methods An open-label, multicenter, comparative, randomized study was conducted on COVID-19 patients with moderate pneumonia. 100 eligible patients were randomized in 1:1 ratio either to receive IVIG + standard of care (SOC) or SOC. Results Duration of hospital stay was significantly shorter in IVIG group to that of SOC alone (7.7 Vs. 17.5 days). Duration for normalization of body temperature, oxygen saturation and mechanical ventilation were significantly shorter in IVIG compared to SOC. Percentages of patients on mechanical ventilation in two groups were not significantly different (24% Vs. 38%). Median time to RT-PCR negativity was significantly shorter with IVIG than SOC (7 Vs.18 days). There were only mild to moderate adverse events in both groups except for one patient (2%), who died in SOC. Conclusions IVIG was safe and efficacious as an adjuvant with other antiviral drugs in the treatment of COVID-19. The trial was registered under Clinical Trial Registry, India (CTRI/2020/06/026222).


2021 ◽  
Vol 9 (3) ◽  
pp. 232596712098688
Author(s):  
Su Cheol Kim ◽  
Jong Ho Jung ◽  
Sang Min Lee ◽  
Jae Chul Yoo

Background: There is no consensus on the ideal treatment for partial articular supraspinatus tendon avulsion (PASTA) lesions without tendon damage. Purpose: To introduce a novel “retensioning technique” for arthroscopic PASTA repair and to assess the clinical and radiologic outcomes of this technique. Study Design: Case series; Level of evidence, 4. Methods: A retrospective analysis was performed on 24 patients whose PASTA lesion was treated using the retensioning technique between January 2011 and December 2015. The mean ± SD patient age was 57.6 ± 7.0 years (range, 43-71 years), and the mean follow-up period was 57.6 ± 23.4 months (range, 24.0-93.7 months). Sutures were placed at the edge of the PASTA lesion, tensioned, and fixed to lateral-row anchors. After surgery, shoulder range of motion (ROM) and functional scores (visual analog scale [VAS] for pain, VAS for function, American Shoulder and Elbow Surgeons [ASES] score, Constant score, Simple Shoulder Test, and Korean Shoulder Score) were evaluated at regular outpatient visits; at 6 months postoperatively, repair integrity was evaluated using magnetic resonance imaging (MRI). Results: At 12 months postoperatively, all ROM variables were improved compared with preoperative values, and shoulder abduction was improved significantly (136.00° vs 107.08°; P = .009). At final follow-up (>24 months), the VAS pain, VAS function, and ASES scores improved, from 6.39, 4.26, and 40.09 to 1.00, 8.26, and 85.96, respectively (all P < .001). At 6 months postoperatively, 21 of the 24 patients (87.5%) underwent follow-up MRI; the postoperative repair integrity was Sugaya type 1 or 2 for all of these patients, and 13 patients showed complete improvement of the lesion compared with preoperatively. Conclusion: The retensioning technique showed improved ROM and pain and functional scores as well as good tendon healing on MRI scans at 6-month follow-up in the majority of patients. Thus, the retensioning technique appears to be reliable procedure for the PASTA lesion.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 442.2-443 ◽  
Author(s):  
H. Rainey ◽  
H. S. B. Baraf ◽  
A. Yeo ◽  
P. Lipsky

Background:Pegloticase is a mammalian recombinant uricase coupled to monomethoxy polyethylene glycol that is approved in the US for treatment of patients with chronic refractory gout and causes profound reductions in serum urate. However, treatment with pegloticase is limited by the induction of anti-drug antibodies and loss of responsiveness in nearly half of treated patients.Objectives:The goal of this study was to determine whether co-therapy with azathioprine (AZA) would increase the frequency of chronic refractory gout patients who had persistent urate lowering from pegloticase therapy.Methods:This open label multicenter study enrolled subjects with chronic gout who failed to lower serum urate to <6 mg/dL despite medically indicated doses of urate lowering therapy (NCT02598596). Patients were screened for adequate levels of the AZA metabolizing enzyme thiopurine methyl transferase and then started on daily oral AZA 1.25 mg/kg for 1 week and then 2.5 mg/kg for the remainder of the trial. Blood levels of AZA metabolites 6-thioguanine and 6-methylmercaptopurine were measured biweekly. After receiving 2 weeks of AZA, patients were started on pegloticase (8 mg IV) and were treated biweekly for 24 weeks. The primary endpoint was the persistent lowering of serum urate to <6 mg/dL at the last three consecutive study visits. Patients who had an increase in serum urate to >6 mg/dL while on therapy did not receive additional pegloticase. All patients received infusion prophylaxis with hydrocortisone as well as gout flare prophylaxis.Results:To date, 12 patients have been enrolled. All patients were male, 75% white and 25% African American. Mean age was 62.4 ± 14.7 years, the mean BMI was 31.1 ± 4.5 and the mean duration of gout was 13.8 ± 9.2 years. At baseline, all patients had visible tophi; 58.3% suffered from gout flares; 81.8% had hypertension; 45.5% had dyslipidemia and 9.0% had coronary artery disease. Of the 12 patients, 6 have completed the full course of treatment with persistent urate lowering and 2 remain on treatment also with persistent urate lowering (figure). 2 patients lost the urate lowering effect, both after 2 doses of pegloticase, and did not receive additional therapy. 1 patient experienced an infusion reaction during the first dose (1 infusion reaction in 90 infusions [1.1%] in the entire trial to date) and 1 subject had subjective symptoms of AZA intolerance with no laboratory abnormalities; these subjects discontinued the study and were not evaluable for the endpoint. No adverse events related to AZA were reported and gout flares were noted in 6 subjects (mean 1.5 flares/patient with flares).Conclusion:AZA can be used safely in subjects with chronic refractory gout and appears to increase the frequency of subjects experiencing long term lowering of serum urate.References:Disclosure of Interests: :Hope Rainey: None declared, Herbert S.B. Baraf Grant/research support from: Horizon; Gilead Sciences, Inc.; Pfizer; Janssen; AbbVie, Consultant of: Horizon; Gilead Sciences, Inc.; Merck; AbbVie, Speakers bureau: Horizon, Anthony Yeo Employee of: Horizon, Peter Lipsky Consultant of: Horizon Therapeutics


2015 ◽  
Vol 35 (4) ◽  
pp. 481-489 ◽  
Author(s):  
Raja Zabaneh ◽  
Simon D. Roger ◽  
Mohamed El-Shahawy ◽  
Michael Roppolo ◽  
Grant Runyan ◽  
...  

♦BackgroundPeginesatide is a novel, synthetic, peptide-based pegylated erythropoiesis-stimulating agent that is designed specifically to stimulate the erythropoietin receptor. The purpose of the present study was to assess, for the first time, the efficacy and safety of peginesatide in chronic kidney disease (CKD) patients receiving peritoneal dialysis (PD) and previously on epoetin treatment.♦MethodsIn this open-label multicenter study, 59 PD patients with CKD were converted from epoetin (alfa or beta) to once-monthly peginesatide. Doses were titrated to maintain hemoglobin levels between 10 g/dL and 12 g/dL during the 25 weeks of the study. The primary endpoint was change from baseline in mean hemoglobin values during the evaluation period (weeks 20 – 25).♦ResultsThe mean hemoglobin value during the evaluation period was 11.3 ± 1.07 g/dL, and the mean change from baseline was 0.10 ± 1.15 g/dL (95% confidence limits: –0.24, 0.44 g/dL). During the evaluation period, most patients maintained hemoglobin levels between 10 g/dL and 12 g/dL (63.0%) and within ±1.0 g/dL of baseline (60.9%). The median weekly epoetin dose at baseline was 96.0 U/kg, and the median starting peginesatide dose was 0.047 mg/kg. Forty-three patients (72.9%) completed the study. Six patients (10.2%) received red blood cell transfusions. The observed adverse event profile was consistent with underlying conditions in the PD patient population. The most common adverse event was peritonitis (20.3%), a complication commonly associated with PD. Four deaths occurred during the study (2 related to septic shock, and 1 each to myocardial ischemia and myasthenia gravis).♦ConclusionsIn this study, once-monthly peginesatide maintained hemoglobin levels in PD patients after conversion from epoetin.


Drug Research ◽  
2021 ◽  
Author(s):  
Budi Prasaja ◽  
Yahdiana Harahap ◽  
Monika Sandra ◽  
Irene Iskandar ◽  
Windy Lusthom ◽  
...  

AbstractIbuprofen is a widely used and well-tolerated analgesic and antipyretic. It is desirable to have a formulation with a rapid rate of absorption because it is required for rapid pain relief and temperature reduction. Previous studies have described the pharmacokinetic profiles of ibuprofen suppository and the mean peak times of ibuprofen suppository were around 1.8 hours, indicating a slower rate of absorption. The aim of this study is to compare the pharmacokinetic parameters of rectal administration of ibuprofen between enema and suppository form in order to provide evidence for the faster absorption rates of ibuprofen enema. This study was a phase-1 clinical study, open-label, randomized and two-way crossover with one-week washout period comparing the absorption profile of equal dose of ibuprofen administered rectally in two treatment phases: ibuprofen suppository and enema. Blood samples were collected post dose for pharmacokinetic analyses. Tmax was analyzed using a Wilcoxon matched paired test. A standard ANOVA model, appropriate for bioequivalence studies was used and ratios of 90% confidence intervals were calculated. This study showed that Tmax for ibuprofen enema was less than half that of ibuprofen suppository (median 40 min vs. 90 min, respectively; p-value=0.0003). Cmax and AUC0–12 for ibuprofen enema were bioequivalent to ibuprofen suppository, as the ratio of test/reference=104.52%, 90% CI 93.41–116.95% and the ratio of test/reference=98.12%, 90%CI 93.34–103.16%, respectively, which fell within 80–125% bioequivalence limit. The overall extent of absorption was similar to the both, which were all well tolerated. In terms of Tmax, Ibuprofen enema was absorbed twice as quickly as from ibuprofen suppository. Therefore it is expected that an ibuprofen enema may provide faster onset of analgesic and antipyretic benefit.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Julia Colombijn ◽  
Anna Bonenkamp ◽  
Anita Van Eck van der Sluijs ◽  
Alferso C Abrahams ◽  
Joost Bijlsma ◽  
...  

Abstract Background and Aims Dialysis patients are often prescribed a large number of medications to improve metabolic control and manage co-existing comorbidities. However, several studies suggest that a large number of medications can also detrimentally affect their health-related quality of life (HRQoL). Therefore, this study aims to provide insight in the association between the number of medications and various aspects of HRQoL in dialysis patients. Method A multicentre study was conducted among dialysis patients from Dutch dialysis centres three months after initiation of dialysis as part of the ongoing prospective DOMESTICO study. The number of medications, defined as the number of concomitantly prescribed types of drugs, was obtained from electronic patient records. Primary outcome was HRQoL measured with the Physical Component Summary (PCS) score and Mental Component Summary (MCS) score (range 0-100) of the Short Form 12. Secondary outcomes were number of symptoms (range 0-30) measured with the Dialysis Symptoms Index and self-rated health (range 0-100) measured with the visual analogue scale of the EuroQol-5D-5L. Data were analysed using linear regression and adjusted for possible confounders, including age, sex, dialysis modality, and comorbidity. Analyses for MCS and number of symptoms were performed after categorising patients in tertiles according to their number of medications because assumptions of linearity were violated for these outcomes. Results A total of 162 patients were included. Mean age of patients was 58 ± 17 years, 35% were female, and 80% underwent haemodialysis. The mean number of medications was 12.2 ± 4.5. Mean PCS and MCS were 36.6 ± 10.2 and 46.8 ± 10.0, respectively. The mean number of symptoms was 12.3 ± 6.9 and mean self-rated health 60.1 ± 20.6. In adjusted analyses, PCS was 0.6 point lower for each additional medication (95%CI -0.9 – -0.2; p=0.002). MCS was 4.9 point lower (95%CI -8.8 – -1.0; p=0.01) and 1.0 point lower (95%CI -5.1 – 3.1; p=0.63) for the highest and middle tertiles of medications, respectively, compared to the lowest tertile. Patients in the highest tertile of medications reported 4.1 more symptoms compared to the lowest tertile (95%CI 1.5 – 6.6; p=0.002) but no significant difference in the number of symptoms was observed between the middle and lowest tertile. Self-rated health was 1.5 point lower for each medication (95%CI -2.2 – -0.7; p&lt;0.001). Conclusion After adjustment for comorbidity and other confounders, a higher number of medications was associated with a lower PCS, MCS, and self-rated health in dialysis patients and with more symptoms. This suggests that it may be relevant to weigh expected therapeutic benefits of medication against their possible harmful effects on HRQoL. An unfavourable balance between expected benefits and impact on HRQoL might be ground to deviate from clinical guidelines, especially for patients with a limited life-expectancy and for whom a kidney transplant is unattainable.


1990 ◽  
Vol 4 (7) ◽  
pp. 468-471 ◽  
Author(s):  
MG Robinson ◽  
DL Decktor

The efficacy of 4 g 5-aminosalicylic acid (5-ASA, mesalamine) enemas was assessed in 666 patients with distal ulcerative colitis. Patients were enrolled in an open-label compassionate use program. One 4 g 5-ASA enema was administered each night for a period of four weeks and the disease activity index was assessed at baseline and on days 14 and 28. On days 14 and 28, 78.0% and 88.1% of patients, respectively, demonstrated an improvement in disease activity index. The mean decline in disease activity index on day 14 was 40.7% (P=0.0001) and on day 28 it was 55.4% (P=0.0001). Efficacy was similar whether the disease was confined to or extended beyond 30 cm from the anus. There was no difference in efficacy in patients suffering their first episode of disease compared to patients suffering subsequent attacks. In conclusion, high dose 5-ASA enemas are a highly effective treatment for distal ulcerative colitis.


2014 ◽  
Vol 22 (1) ◽  
Author(s):  
Robert Cooperstein ◽  
Morgan Young

Abstract Background Upright examination procedures like radiology, thermography, manual muscle testing, and spinal motion palpation may lead to spinal interventions with the patient prone. The reliability and accuracy of mapping upright examination findings to the prone position is unknown. This study had 2 primary goals: (1) investigate how erroneous spine-scapular landmark associations may lead to errors in treating and charting spine levels; and (2) study the interexaminer reliability of a novel method for mapping upright spinal sites to the prone position. Methods Experiment 1 was a thought experiment exploring the consequences of depending on the erroneous landmark association of the inferior scapular tip with the T7 spinous process upright and T6 spinous process prone (relatively recent studies suggest these levels are T8 and T9, respectively). This allowed deduction of targeting and charting errors. In experiment 2, 10 examiners (2 experienced, 8 novice) used an index finger to maintain contact with a mid-thoracic spinous process as each of 2 participants slowly moved from the upright to the prone position. Interexaminer reliability was assessed by computing Intraclass Correlation Coefficient, standard error of the mean, root mean squared error, and the absolute value of the mean difference for each examiner from the 10 examiner mean for each of the 2 participants. Results The thought experiment suggesting that using the (inaccurate) scapular tip landmark rule would result in a 3 level targeting and charting error when radiological findings are mapped to the prone position. Physical upright exam procedures like motion palpation would result in a 2 level targeting error for intervention, and a 3 level error for charting. The reliability experiment showed examiners accurately maintained contact with the same thoracic spinous process as the participant went from upright to prone, ICC (2,1) = 0.83. Conclusions As manual therapists, the authors have emphasized how targeting errors may impact upon manual care of the spine. Practitioners in other fields that need to accurately locate spinal levels, such as acupuncture and anesthesiology, would also be expected to draw important conclusions from these findings.


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