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1.
Isr Med Assoc J ; 23(9): 563-568, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34472231

RESUMO

BACKGROUND: Infants born very prematurely have functionally and structurally immature gastrointestinal tracts. OBJECTIVES: To assess the safety and tolerability of administration of enteral recombinant human (rh) insulin on formula fed preterm infants and to assess whether enteral administration of rh-insulin enhances gastrointestinal tract maturation by reducing the time to reach full enteral feeding. METHODS: A phase 2, multicenter, double-blind, placebo-controlled, randomized study was conducted. Premature infants (26-33 weeks gestation) were randomized 1:1 to receive insulin 400 µU/ml mixed with enteral feeding or placebo added to their formula. The primary efficacy outcome measure was the number of days required to achieve full enteral feeding. Safety outcomes included adverse events and blood glucose levels. RESULTS: The study consisted of 33 infants randomized for the safety population and 31 for efficacy analysis. The mean time to full enteral feeding was 6.37 days (95% confidence interval [95%CI] 4.59-8.15) in the enteral rh-insulin treatment group (n=16) and 8.00 days (95%CI 6.20-9.80) in the placebo group (n=15), which represents a statistically significant reduction of 1.63 days (95%CI 0.29-2.97; P = 0.023). There was no difference in blood glucose levels between the groups and none of the participants experienced hypoglycemia. Adverse events occurred in 9/17 (53%) infants in the enteral rh-insulin group and 12/16 (75%) in the placebo group. CONCLUSIONS: Our trial demonstrated that administration of enteral rh-insulin as supplement to enteral nutrition significantly reduced time to achieve full enteral feeding in preterm infants with a gestational age of 26-33 weeks.


Assuntos
Nutrição Enteral/estatística & dados numéricos , Hipoglicemiantes/administração & dosagem , Recém-Nascido Prematuro , Insulina/administração & dosagem , Glicemia/efeitos dos fármacos , Método Duplo-Cego , Feminino , Idade Gestacional , Humanos , Hipoglicemiantes/efeitos adversos , Recém-Nascido , Insulina/efeitos adversos , Masculino , Fatores de Tempo
2.
Shanghai Kou Qiang Yi Xue ; 30(3): 312-315, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34476452

RESUMO

PURPOSE: To investigate the effect of toothpaste containing emulsifier 30 and sodium lauryl sulfate surfactant on the integrity of oral epithelium. METHODS: Sixty individuals equally divided into 2 groups by random number table methods. Group A received toothpaste containing emulsifier 30, while group B received fluoride toothpaste containing sodium lauryl sulfate (SLS) surfactant. The exfoliation of oral soft tissue was evaluated before, 30 minutes and 4 days after the test. The fluoride concentration in plaque and saliva was compared between the two groups. The data were processed with SPSS 22.0 software package. RESULTS: The scores of oral soft tissue exfoliation at 30 min and 4 d after the test were increased significantly (P<0.05). The scores of subgingival, supragingival, oral apex and oral soft tissue exfoliation of group A at 30 min after using the paste were significantly lower than those 4 days after using the paste(P<0.05), while no significant change was observed in the score of oral soft tissue exfoliation at the dorsal tongue(P>0.05). The total scores of subgingival, supragingival, dorsal tongue, ventral tongue and oral soft tissue exfoliation in group B 30 min after using the paste were significantly higher than those at 4 d after use, and the score of oral soft tissue exfoliation at oral apex was significantly lower than that at 4 d after use (P<0.05).The total scores of subgingival, supragingival, dorsal tongue, ventral tongue and oral soft tissue exfoliation in group B at 30 min after using the paste were significantly higher than those of group A, while the score of oral soft tissue exfoliation at oral apex was significantly lower than that of group A(P<0.05).The total scores of subgingival, supragingival, ventral tongue and oral soft tissue exfoliation in group B at 4 d after using the paste were significantly higher than those of group A(P<0.05). The scores of oral soft tissue exfoliation at oral apex and dorsal tongue at 4 d after use had no significant difference between the two groups (P>0.05). The fluoride concentration in plaque and saliva was increased significantly in both groups after test(P<0.05). CONCLUSIONS: Both fluoride toothpaste containing emulsifier 30 and SLS surfactant cause a certain degree of oral soft tissue exfoliation. In comparison, fluoride toothpaste containing emulsifier 30 has less oral soft tissue damage; moreover, the two fluoride toothpastes can effectively inhibit acid production of plaque bacteria and prevent occurrence of caries.


Assuntos
Tensoativos , Cremes Dentais , Método Duplo-Cego , Epitélio , Fluoretos , Humanos , Dodecilsulfato de Sódio , Fluoreto de Sódio
3.
Trials ; 22(1): 585, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479619

RESUMO

BACKGROUND: Major depressive disorder is the second leading cause of years lost to disability worldwide. Anyu Peibo Capsule has been shown to be effective and safe in phase II trials. METHODS: This clinical study is a multi-center, randomized, double-blinded, placebo-controlled, parallel-group, phase III trial of Anyu Peibo Capsule in China. The aim is to test whether the administration of Anyu Peibo Capsule compared to placebo improves clinical outcomes in adults (aged 18 to 65 years) with MDD. Patients will receive an 8-week treatment of Anyu Peibo Capsule 1.6 g per day or placebo. The primary outcome will be the change from baseline in the total score for the Montgomery-Asberg Depression Rating Scale at the end of the 8-week treatment. DISCUSSION: The trial aims to provide pivotal evidence for the efficacy and safety of Anyu Peibo Capsule in patients with major depressive disorder. TRIAL REGISTRATION: ClinicalTrials.gov NCT04210973 . Registered on December 26, 2019.


Assuntos
Transtorno Depressivo Maior , Adulto , China , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Método Duplo-Cego , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
4.
J Int Soc Sports Nutr ; 18(1): 60, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503541

RESUMO

BACKGROUND: Numerous studies have demonstrated the efficacy of creatine supplementation for improvements in exercise performance. Few studies, however, have examined the effects of phosphocreatine supplementation on exercise performance. Furthermore, while polyphenols have antioxidant and anti-inflammatory properties, little is known regarding the influence of polyphenol supplementation on muscular strength, power, and endurance. Thus, the purpose of the present study was to compare the effects of 28 days of supplementation with phosphocreatine disodium salts plus blueberry extract (PCDSB), creatine monohydrate (CM), and placebo on measures of muscular strength, power, and endurance. METHODS: Thirty-three men were randomly assigned to consume either PCDSB, CM, or placebo for 28 days. Peak torque (PT), average power (AP), and percent decline for peak torque (PT%) and average power (AP%) were assessed from a fatigue test consisting of 50 maximal, unilateral, isokinetic leg extensions at 180°·s- 1 before and after the 28 days of supplementation. Individual responses were assessed to examine the proportion of subjects that exceeded a minimal important difference (MID). RESULTS: The results demonstrated significant (p < 0.05) improvements in PT for the PCDSB and CM groups from pre- (99.90 ± 22.47 N·m and 99.95 ± 22.50 N·m, respectively) to post-supplementation (119.22 ± 29.87 N·m and 111.97 ± 24.50 N·m, respectively), but no significant (p = 0.112) change for the placebo group. The PCDSB and CM groups also exhibited significant improvements in AP from pre- (140.18 ± 32.08 W and 143.42 ± 33.84 W, respectively) to post-supplementation (170.12 ± 42.68 W and 159.78 ± 31.20 W, respectively), but no significant (p = 0.279) change for the placebo group. A significantly (p < 0.05) greater proportion of subjects in the PCDSB group exceeded the MID for PT compared to the placebo group, but there were no significant (p > 0.05) differences in the proportion of subjects exceeding the MID between the CM and placebo groups or between the CM and PCDSB groups. CONCLUSIONS: These findings indicated that for the group mean responses, 28 days of supplementation with both PCDSB and CM resulted in increases in PT and AP. The PCDSB, however, may have an advantage over CM when compared to the placebo group for the proportion of individuals that respond favorably to supplementation with meaningful increases in muscular strength.


Assuntos
Força Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Fosfocreatina/farmacologia , Resistência Física/efeitos dos fármacos , Extratos Vegetais/farmacologia , Mirtilos Azuis (Planta)/química , Creatina , Suplementos Nutricionais , Método Duplo-Cego , Humanos , Masculino , Torque , Adulto Jovem
5.
BMJ Open ; 11(9): e047099, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475155

RESUMO

INTRODUCTION: Experimental and clinical data demonstrate that skin diseases like psoriasis are affected by psychological factors and can be modulated by interventions other than conventional drug therapy. The expectation of patients towards the benefit of a forthcoming treatment as well as treatment pre-experiences have been demonstrated as crucial factors mediating placebo responses in inflammatory skin diseases. However, it is unknown whether and to what extent treatment outcomes of psoriasis patients under therapy with monoclonal antibodies like secukinumab can be experimentally modulated at subjective and physiological levels by modifying the expectation of patients via verbal instruction or prior experience. METHODS AND ANALYSIS: Treatment expectations will be modulated in patients with moderate-to-severe psoriasis undergoing treatment with the anti-interleukin-17A monoclonal antibody secukinumab. Patients with a Psoriasis Area and Severity Index (PASI) >12 will be randomly allocated to one of three groups (N=40 each). As a standard schedule, patients in the pharmacological control group (group 1) will be treated weekly with 300 mg secukinumab, while patients in groups 2 and 3 will receive only 75 mg secukinumab (75% dose reduction) during all treatment weeks. In addition to the injections, patients in group 3 will ingest a novel tasting drink, with a cover story explaining that previous studies showed additional beneficial effects of this combination (drug and drink). Patients will be assessed and treated at nine visits over a 16-week period, during which the severity of pain and itch symptoms, skin lesions and quality of life will be analysed with standardised questionnaires and the PASI. ETHICS AND DISSEMINATION: This study was approved by the Ethics committee of the Medical Faculty of the University Duisburg-Essen. Study outcomes will be published in peer-reviewed scientific journals.


Assuntos
Psoríase , Qualidade de Vida , Método Duplo-Cego , Humanos , Motivação , Dor/tratamento farmacológico , Psoríase/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento
6.
BMJ Open ; 11(9): e047142, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475156

RESUMO

INTRODUCTION: For over more than a decade, low-dose amitriptyline and mirtazapine are prescribed off-label for insomnia. However, placebo-controlled evidence on these antidepressants for insomnia is still lacking. Therefore, the present trial aims to assess the effectiveness of low-dose amitriptyline (10-20 mg/day) and mirtazapine (7.5-15 mg/day) in patients with insomnia disorder with difficulty maintaining sleep or early-morning awakening problems in general practice. METHODS AND ANALYSIS: The Drug REdiscovery: low-dose Amitriptyline and Mirtazapine for INsomnia disorder in General practice (DREAMING) study is a randomised, double-blind, placebo-controlled trial in about 50 general practices. Adults (18-85 years) with insomnia disorder (Diagnostic and Statistical Manual of Mental Disorders-5) who ask their general practitioner (GP) for sleep medication when non-pharmacological treatment is deemed not effective, are eligible. EXCLUSION CRITERIA: isolated sleep initiation problem, contraindications for or drug-drug interactions with either amitriptyline or mirtazapine. Participants (n=156) will be randomly assigned to three parallel treatment groups of 16-week treatment with either amitriptyline (one or two tablets of 10 mg/day) or mirtazapine (one or two tablets of 7.5 mg/day) or placebo (one or two tablets) alongside usual GP care. All participants start and end with single dose, but dose can be doubled following GP consultation in week 3. Questionnaire assessments will be conducted at baseline, week 6, 12, 20 and 52. The primary study outcome is self-reported insomnia severity at 6 weeks, measured with the Insomnia Severity Index (ISI) in an intention to treat analysis. Secondary outcomes include subjective sleep quality quantified by sleep indices, daytime functioning and symptoms, safety and treatment evaluation and other sleep care consumption. ETHICS AND DISSEMINATION: The Medical Ethics Committee of the VU Medical Centre Amsterdam approved this trial. The results of this trial will be published in peer-reviewed scientific journals and presented at relevant academic conferences and to key stakeholders. TRIAL REGISTRATION NUMBER: NTR7449.


Assuntos
Medicina Geral , Distúrbios do Início e da Manutenção do Sono , Adulto , Amitriptilina , Antidepressivos/uso terapêutico , Método Duplo-Cego , Humanos , Mirtazapina , Ensaios Clínicos Controlados Aleatórios como Assunto , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Resultado do Tratamento
7.
JNMA J Nepal Med Assoc ; 59(236): 365-368, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-34508534

RESUMO

INTRODUCTION: Propofol is the most frequently used anaesthetic agent. Despite various anaesthetic benefits, propofol is not without side effects, pain on injection being the most common adverse effect. This study aimed to find the grade of pain reduced due to the injection of propofol after administration of lidocaine. METHODS: A descriptive cross-sectional study was conducted from March 2015 to August 2015 in the operating theatre in a tertiary care hospital after taking ethical clearance with an ethical clearance from the Institutional Review Committee. A total of 64 participants fulfilling all inclusion criteria of both gender, age ranged from 16-65 years of American Society of Anesthesiologists physical status I and II ready for elective surgery under general anaesthesia with propofol pretreated with 60mg lidocaine with venous occlusion for one minute were observed. The pain was graded by the four-point scale (0=none, 1=mild, 2=moderate, 3=severe). Haemodynamic variables were measured until just before intubation. RESULTS: In patients pretreated with lidocaine, no pain 56 (87.5%), mild pain 8 (12.5%) and moderate pain 0 (0%) were observed. CONCLUSIONS: The grade of pain during injection of propofol was reduced in more than three-fourth of the patients after administration of pre-anaesthetic drug-like lidocaine.


Assuntos
Propofol , Adolescente , Adulto , Idoso , Anestésicos Intravenosos/efeitos adversos , Anestésicos Locais , Estudos Transversais , Método Duplo-Cego , Humanos , Lidocaína , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Dor/etiologia , Dor/prevenção & controle , Propofol/efeitos adversos , Centros de Atenção Terciária , Adulto Jovem
8.
Am J Gastroenterol ; 116(9): 1929-1937, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34465695

RESUMO

INTRODUCTION: Linaclotide improves abdominal pain and constipation in patients with constipation-predominant irritable bowel syndrome (IBS-C). Patients report additional bothersome abdominal symptoms of bloating and discomfort. The intention of this study was to evaluate linaclotide's efficacy in relieving IBS-C-related abdominal symptoms (bloating, discomfort, and pain) using a novel multi-item Abdominal Score (AS). METHODS: Patients with IBS-C with abdominal pain ≥3 (0-10 scale) were randomized to linaclotide 290 µg or placebo daily for 12 weeks. The AS, derived from the Diary for IBS Symptoms-Constipation, is the average of abdominal bloating, discomfort, and pain at their worst (0 = none, 10 = worst possible). The primary end point was overall change from baseline (CFB) in AS. Secondary end points included CFB in 12-week AS evaluated using cumulative distribution function and 6-week/12-week AS responder (AS improvement ≥2 points for ≥6-week/12-week). RESULTS: Overall, 614 patients (mean age 46.7 years; 81% female) were randomized. All prespecified end points showed significant benefit of linaclotide vs placebo. The mean overall CFB AS reduction for linaclotide was -1.9 vs -1.2 for placebo (P < 0.0001); the 6-week/12-week AS responder rate was 40.5% for linaclotide vs 23.4% for placebo (odds ratio = 2.2 [95% confidence interval, 1.55-3.12; P < 0.0001]). Diarrhea was the most common treatment-emergent adverse event (linaclotide = 4.6%, placebo = 1.6%). DISCUSSION: Linaclotide significantly reduced multiple abdominal symptoms important to patients with IBS-C (bloating, discomfort, and pain) compared with placebo, as measured by a novel multi-item AS. The AS, derived from the Diary for IBS Symptoms-Constipation, should be considered for use in future IBS-C clinical studies to measure clinically meaningful improvements beyond traditional end points.


Assuntos
Dor Abdominal/tratamento farmacológico , Constipação Intestinal/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Agonistas da Guanilil Ciclase C/uso terapêutico , Peptídeos/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento
9.
Medicine (Baltimore) ; 100(35): e26873, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477120

RESUMO

ABSTRACT: Meloxicam is commonly administrated to control postoperative pain in orthopedic surgery, while its efficacy in total knee arthroplasty (TKA) is not clear. Therefore, this study aimed to explore the postoperative analgesic effect and tolerance of meloxicam in knee osteoarthritis (OA) patients undergoing TKA.Totally, 128 knee OA patients scheduled for TKA were enrolled in this randomized, controlled, double-blind study, then randomized into meloxicam group (N = 65) and control group (N = 63) as 1:1 ratio. Patients took meloxicam or placebo from 4 hours (h) to 72 h after TKA. Patients were followed up at 6 h, 12 h, day (D)1, D2, D3, D7, month (M)1, and M3.Pain visual analog scale score at rest was decreased in meloxicam group at 12 h, D1 and D3 compared to control group; pain visual analog scale score at flexion was reduced in meloxicam group at 6 h, 12 h, D1, D2, and D3 compared to control group. Additional and total consumption of patient-controlled analgesia were both attenuated in meloxicam group compared to control group. Furthermore, patient satisfaction score was higher on D1, D2, D3 in meloxicam group compared to control group. However, no difference of hospital for special surgery knee score score at M1 or M3 was found between the 2 groups. Moreover, the occurrence of adverse events was similar between the 2 groups.Meloxicam displays good effect on controlling postoperative pain and improving patient satisfaction, while does not affect long-term knee function recovery or safety profile in knee OA patients undergoing TKA.


Assuntos
Meloxicam/normas , Osteoartrite do Joelho/tratamento farmacológico , Idoso , Anti-Inflamatórios não Esteroides/normas , Anti-Inflamatórios não Esteroides/uso terapêutico , Artroplastia do Joelho/métodos , Artroplastia do Joelho/estatística & dados numéricos , Distribuição de Qui-Quadrado , Método Duplo-Cego , Feminino , Humanos , Masculino , Meloxicam/uso terapêutico , Pessoa de Meia-Idade , Manejo da Dor/métodos , Manejo da Dor/estatística & dados numéricos , Medição da Dor/métodos , Recuperação de Função Fisiológica
10.
J Refract Surg ; 37(9): 582-589, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34506240

RESUMO

PURPOSE: To compare the efficacy of oral codeine plus acetaminophen versus oxycodone plus acetaminophen for severe pain control following photorefractive keratectomy (PRK). METHODS: This single-center trial randomized 200 patients to receive codeine 30 mg/acetaminophen 325 mg (codeine group) or oxycodone 5 mg/acetaminophen 325 mg (oxycodone group)every 4 hours as needed for severe pain for 4 days following PRK. Patients recorded postoperative pain, tablet consumption, and tetracaine use. Patients were monitored at postoperative 1 day, 1 week, and 1, 3, and 6 months for visual acuity and follow-up. Study outcomes were mean postoperative pain, treatment and tetracaine use, and visual acuity. RESULTS: Analysis of 197 patients who completed the trial (97 codeine group and 100 oxycodone group) showed mean pain scores were lower in the codeine group throughout the intervention period. Mean pain scores were higher in the oxycodone group than the codeine group on postoperative days 2 and 4 (P = .017 and P = .034, respectively). The oxycodone group consumed more tablets than the codeine group, with a difference on postoperative day 2 (P = .019), and used a greater number of tetracaine drops (P = .015). Repeated measures analysis of variance showed significant improvement in visual acuity in both groups with no difference in visual outcomes (P = .81). CONCLUSIONS: Codeine/acetaminophen is as effective and safe as oxycodone/acetaminophen for pain control following PRK, with no clinical difference in overall pain control and long-term visual outcomes. This implies that treating postoperative pain after PRK with a Schedule III opioid (codeine) is effective and potentially decreases the risk of misuse by a higher regulated Schedule II opioid (oxycodone), lowering the potential for abuse and dependence. [J Refract Surg. 2021;37(9):582-589.].


Assuntos
Oxicodona , Ceratectomia Fotorrefrativa , Codeína , Método Duplo-Cego , Humanos , Medição da Dor , Dor Pós-Operatória/tratamento farmacológico , Estudos Prospectivos
11.
Trials ; 22(1): 595, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488845

RESUMO

BACKGROUND: Chronic lower limb ischemia develops earlier and more frequently in patients with type 2 diabetes mellitus. Diabetes remains the main cause of lower-extremity non-traumatic amputations. Current medical treatment, based on antiplatelet therapy and statins, has demonstrated deficient improvement of the disease. In recent years, research has shown that it is possible to improve tissue perfusion through therapeutic angiogenesis. Both in animal models and humans, it has been shown that cell therapy can induce therapeutic angiogenesis, making mesenchymal stromal cell-based therapy one of the most promising therapeutic alternatives. The aim of this study is to evaluate the feasibility, safety, and efficacy of cell therapy based on mesenchymal stromal cells derived from adipose tissue intramuscular administration to patients with type 2 diabetes mellitus with critical limb ischemia and without possibility of revascularization. METHODS: A multicenter, randomized double-blind, placebo-controlled trial has been designed. Ninety eligible patients will be randomly assigned at a ratio 1:1:1 to one of the following: control group (n = 30), low-cell dose treatment group (n = 30), and high-cell dose treatment group (n = 30). Treatment will be administered in a single-dose way and patients will be followed for 12 months. Primary outcome (safety) will be evaluated by measuring the rate of adverse events within the study period. Secondary outcomes (efficacy) will be measured by assessing clinical, analytical, and imaging-test parameters. Tertiary outcome (quality of life) will be evaluated with SF-12 and VascuQol-6 scales. DISCUSSION: Chronic lower limb ischemia has limited therapeutic options and constitutes a public health problem in both developed and underdeveloped countries. Given that the current treatment is not established in daily clinical practice, it is essential to provide evidence-based data that allow taking a step forward in its clinical development. Also, the multidisciplinary coordination exercise needed to develop this clinical trial protocol will undoubtfully be useful to conduct academic clinical trials in the field of cell therapy in the near future. TRIAL REGISTRATION: ClinicalTrials.gov NCT04466007 . Registered on January 07, 2020. All items from the World Health Organization Trial Registration Data Set are included within the body of the protocol.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Noma , Tecido Adiposo , Animais , Ensaios Clínicos Fase II como Assunto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Método Duplo-Cego , Humanos , Isquemia/diagnóstico , Isquemia/terapia , Estudos Multicêntricos como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Resultado do Tratamento
12.
BMC Psychiatry ; 21(1): 439, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488701

RESUMO

BACKGROUND: In people with intellectual disability (ID) and challenging behaviour, antipsychotics (AP) are often used off-label and for a long period. Despite a lack of evidence for efficacy for challenging behaviour and concerns about common and clinically relevant side effects, complete withdrawal often fails. We postulate three possible hypotheses for withdrawal failure: 1. Influence of subjective interpretation of behavioural symptoms by caregivers and family; 2. Beneficial effects from AP treatment on undiagnosed psychiatric illness, through improvement in sleep or a direct effect on behaviour; and 3. Misinterpretation of withdrawal symptoms as a recurrence of challenging behaviour. METHODS: To investigate our hypotheses, we have designed a multicentre double-blind, placebo-controlled randomised trial in which AP (pipamperone or risperidone) are withdrawn. In the withdrawal group, the AP dose is reduced by 25% every 4 weeks and in the control group the dose remains unaltered. Behaviour, sleep, psychiatric disorders, withdrawal symptoms and side effects will be measured and compared between the two groups. If drop-out from the protocol is similar in both groups (non-inferiority), the first hypothesis will be supported. If drop-out is higher in the withdrawal group and an increase is seen in psychiatric disorders, sleep problems and/or behavioural problems compared to the control group, this suggests effectiveness of AP, and indications for AP use should be reconsidered. If drop-out is higher in the withdrawal group and withdrawal symptoms and side effects are more common in the withdrawal group compared to the control group, this supports the hypothesis that withdrawal symptoms contribute to withdrawal failure. DISCUSSION: In order to develop AP withdrawal guidelines for people with ID, we need to understand why withdrawal of AP is not successful in the majority of people with ID and challenging behaviour. With this study, we will bridge the gap between the lack of available evidence on AP use and withdrawal on the one hand and the international policy drive to reduce prescription of AP in people with ID and challenging behaviour on the other hand. TRIAL REGISTRATION: This trial is registered in the Netherlands Trial Register (NTR 7232) on October 6, 2018 ( www.trialregister.nl ).


Assuntos
Antipsicóticos , Deficiência Intelectual , Adulto , Antipsicóticos/uso terapêutico , Sintomas Comportamentais , Método Duplo-Cego , Humanos , Deficiência Intelectual/complicações , Deficiência Intelectual/tratamento farmacológico , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Risperidona/uso terapêutico
13.
Trials ; 22(1): 508, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34332638

RESUMO

BACKGROUND: Although Alzheimer's disease affects around 800,000 people in the UK and costs almost £23 billion per year, currently licenced treatments only offer modest benefit at best. Seizures, which are more common in patients with Alzheimer's disease than age matched controls, may contribute to the loss of nerve cells and abnormal brain discharges can disrupt cognition. This aberrant electrical activity may therefore present potentially important drug targets. The anti-seizure medication levetiracetam can reduce abnormal cortical discharges and reverse memory deficits in a mouse model of Alzheimer's disease. Levetiracetam has also been shown to improve memory difficulties in patients with mild cognitive impairment, a precursor to Alzheimer's disease. Clinical use of levetiracetam is well-established in treatment of epilepsy and extensive safety data are available. Levetiracetam thus has the potential to provide safe and efficacious treatment to help with memory difficulties in Alzheimer's disease. METHODS: The proposed project is a proof of concept study to test whether levetiracetam can help cognitive function in people with dementia. We plan to recruit thirty patients with mild to moderate Alzheimer's disease with no history of previous seizures or other significant co-morbidity. Participants will be allocated to a double-blind placebo-controlled crossover trial that tests levetiracetam against placebo. Standardised scales to assess cognition and a computer-based touchscreen test that we have developed to better detect subtle improvements in hippocampal function will be used to measure changes in memory. All participants will have an electroencephalogram (EEG) at baseline. The primary outcome measure is a change in the computer-based touchscreen cognitive task while secondary outcomes include the effect of levetiracetam on mood, quality of life and modelling of the EEG, including time series measures and feature-based analysis to see whether the effect of levetiracetam can be predicted. The effect of levetiracetam and placebo will be compared within a given patient using the paired t-test and the analysis of covariance adjusting for baseline values. DISCUSSION: This is the first study to evaluate if an anti-seizure medication can offer meaningful benefit to patients with Alzheimer's disease. If this study demonstrates at least stabilisation of memory function and/or good tolerability, the next step will be to rapidly progress to a larger study to establish whether levetiracetam may be a useful and cost-effective treatment for patients with Alzheimer's disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT03489044 . Registered on April 5, 2018.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Animais , Estudos Cross-Over , Método Duplo-Cego , Humanos , Levetiracetam/efeitos adversos , Camundongos , Estudo de Prova de Conceito , Qualidade de Vida
14.
Nutrients ; 13(7)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34371870

RESUMO

Kidney transplant recipients are at high risk of progressive bone loss and low-energy fractures in the years following transplantation. Marine n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation may have beneficial effects on bone strength. The Omega-3 fatty acids in Renal Transplantation (ORENTRA) trial was an investigator initiated, randomized, placebo-controlled trial investigating the effects of marine n-3 PUFA supplementation after kidney transplantation. Effects of supplementation on bone mineral density (BMD) and calcium metabolism were pre-defined secondary endpoints. Adult kidney transplant recipients (n = 132) were randomized to 2.6 g marine n-3 PUFA supplement or olive oil (control) from 8 to 52 weeks post-transplant. Dual energy X-ray absorptiometry was performed to assess changes in bone mineral density of hip, spine, and forearm, as well as trabecular bone score (TBS) of the lumbar spine. Student's t test was used to assess between-group differences. There were no differences in ΔBMD between the two groups (intervention vs. control) at lumbar spine (-0.020 ± 0.08 vs. -0.007 ± 0.07 g/cm², p = 0.34), total hip (0.001 ± 0.03 vs. -0.005 ± 0.04, p = 0.38), or other skeletal sites in the intention-to-treat analyses. There was no difference in the change in TBS score (0.001 ± 0.096 vs. 0.009 ± 0.102, p = 0.62). Finally, no effect on biochemical parameters of mineral metabolism was seen. Results were similar when analyzed per protocol. In conclusion, we found no significant effect of 44 weeks of supplementation with 2.6 g of marine n-3 PUFA on BMD in kidney transplant recipients.


Assuntos
Densidade Óssea/efeitos dos fármacos , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Transplante de Rim , Osteoporose/prevenção & controle , Fraturas por Osteoporose/prevenção & controle , Absorciometria de Fóton , Adulto , Idoso , Biomarcadores/sangue , Cálcio/sangue , Dinamarca , Suplementos Nutricionais/efeitos adversos , Ácidos Docosa-Hexaenoicos/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Ácido Eicosapentaenoico/efeitos adversos , Feminino , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Osteoporose/etiologia , Osteoporose/fisiopatologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
15.
Nutrients ; 13(7)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34371872

RESUMO

The aim of this exploratory study was to investigate gastrointestinal tolerance and protein absorption markers with a new enteral peptide formula (PF) compared to an isocaloric enteral intact protein standard formula (SF) containing the same amount of protein in ICU patients. Patients admitted to a cardio-thoracic intensive care unit expected to receive tube feeding for ≥5 days were randomized to receive either PF (1.5 kcal/mL) or SF in a double-blind manner for ≤14 days. Twenty-six patients were randomized (13 SF and 13 PF) and 23 (12 SF and 11 PF) completed at least 5 days of product administration. There were no statistically significant differences between the feeds during the first 5 days of intervention for diarrhea (SF:3 (23%); PF:5 (39%), p = 0.388), vomiting (SF:1 (8%); PF:2 (15%), p = 0.549), constipation (SF:7 (54%), PF:3 (23%), p = 0.115), and high gastric residual volume (>500 mL: SF:1 (8%); PF: 2 (15%), p = 0.535). There were no differences in plasma amino acids or urinary markers of protein absorption and metabolism. In conclusion, no major differences were found in tolerability and protein absorption markers between the standard intact protein formula and the peptide formula.


Assuntos
Estado Terminal/terapia , Proteínas na Dieta/administração & dosagem , Nutrição Enteral , Alimentos Formulados , Absorção Intestinal , Valor Nutritivo , Hidrolisados de Proteína/administração & dosagem , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Proteínas na Dieta/efeitos adversos , Método Duplo-Cego , Ingestão de Energia , Nutrição Enteral/efeitos adversos , Feminino , Alimentos Formulados/efeitos adversos , Humanos , Londres , Masculino , Pessoa de Meia-Idade , Hidrolisados de Proteína/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
16.
BMJ Open ; 11(8): e045493, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34341037

RESUMO

INTRODUCTION: Trigeminal neuralgia (TN) is characterised by a sudden, severe, electric shock like paroxysmal pain, which is almost always associated with triggers. Carbamazepine is the first-line medical management of TN. However, side effects are common. Currently, there is no ideal treatment for TN. Since there is a known abnormality of Na+ channels in the trigger zone, 5% lidocaine-medicated plaster (LMP), which can block the Na+ channels on Aδ and C fibres, is an effective treatment method in many chronic pain conditions. A case report has found the benefit of LMP for the treatment of TN without any side effects. Whether LMP is an option for the treatment of TN is worth exploring. METHODS AND ANALYSIS: The PATCH trial is a double-blind, enriched enrolment with randomised withdrawal, vehicle-controlled trial, aiming to explore the effects and safety of LMP in patients with TN. There is a 3-week initial open-label phase, followed by a 4-week double-blind treatment phase for responders. In the double-blind phase, patients will have to withdraw from this PATCH study if they meet one of the following criteria for treatment failure such as: >50% increase in pain intensity or paroxysms, lack of efficacy or side effects. The primary outcome will be the number of treatment failures. Adverse events will also be monitored throughout the study. ETHICS AND DISSEMINATION: This study protocol has been approved by the Institutional Review Board of Beijing Tiantan Hospital (approval number: KY 2020-102-02). The results will be disseminated in international academic meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04570293.


Assuntos
Lidocaína , Neuralgia do Trigêmeo , Método Duplo-Cego , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Neuralgia do Trigêmeo/tratamento farmacológico
17.
N Engl J Med ; 385(6): 516-525, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34347952

RESUMO

BACKGROUND: Cardiogenic shock is associated with substantial morbidity and mortality. Although inotropic support is a mainstay of medical therapy for cardiogenic shock, little evidence exists to guide the selection of inotropic agents in clinical practice. METHODS: We randomly assigned patients with cardiogenic shock to receive milrinone or dobutamine in a double-blind fashion. The primary outcome was a composite of in-hospital death from any cause, resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack or stroke diagnosed by a neurologist, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary composite outcome. RESULTS: A total of 192 participants (96 in each group) were enrolled. The treatment groups did not differ significantly with respect to the primary outcome; a primary outcome event occurred in 47 participants (49%) in the milrinone group and in 52 participants (54%) in the dobutamine group (relative risk, 0.90; 95% confidence interval [CI], 0.69 to 1.19; P = 0.47). There were also no significant differences between the groups with respect to secondary outcomes, including in-hospital death (37% and 43% of the participants, respectively; relative risk, 0.85; 95% CI, 0.60 to 1.21), resuscitated cardiac arrest (7% and 9%; hazard ratio, 0.78; 95% CI, 0.29 to 2.07), receipt of mechanical circulatory support (12% and 15%; hazard ratio, 0.78; 95% CI, 0.36 to 1.71), or initiation of renal replacement therapy (22% and 17%; hazard ratio, 1.39; 95% CI, 0.73 to 2.67). CONCLUSIONS: In patients with cardiogenic shock, no significant difference between milrinone and dobutamine was found with respect to the primary composite outcome or important secondary outcomes. (Funded by the Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario; ClinicalTrials.gov number, NCT03207165.).


Assuntos
Cardiotônicos/uso terapêutico , Dobutamina/uso terapêutico , Milrinona/uso terapêutico , Choque Cardiogênico/tratamento farmacológico , Agonistas Adrenérgicos beta/uso terapêutico , Idoso , Cardiotônicos/efeitos adversos , Comorbidade , Dobutamina/efeitos adversos , Método Duplo-Cego , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Milrinona/efeitos adversos , Inibidores da Fosfodiesterase 3/uso terapêutico , Choque Cardiogênico/mortalidade
18.
Trials ; 22(1): 543, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404463

RESUMO

BACKGROUND: One key pathological finding in giant cell arteritis (GCA) is the presence of interferon-gamma and interleukin (IL)-17 producing T helper (Th) 1 and Th17 cells in affected arteries. There is anecdotal evidence of successful induction and maintenance of remission with the monoclonal anti-IL-17A antibody secukinumab. Inhibition of IL-17A could therefore represent a potential new therapeutic option for the treatment of GCA. METHODS: This is a randomized, parallel-group, double-blind, placebo-controlled, multi-center, phase II study in which patients, treating physicians, and the associated clinical staff as well as the sponsor clinical team are blinded. It is designed to evaluate efficacy and safety of secukinumab compared to placebo in combination with an open-label prednisolone taper regimen. Patients included are naïve to biological therapy and have newly diagnosed or relapsing GCA. Fifty patients are randomly assigned in a 1:1 ratio to receive either 300 mg secukinumab or placebo subcutaneously at baseline, weeks 1, 2 and 3, and every 4 weeks from week 4. Patients in both treatment arms receive a 26-week prednisolone taper regimen. The study consists of a maximum 6-week screening period, a 52-week treatment period (including the 26-week tapering), and an 8-week safety follow-up, with primary and secondary endpoint assessments at week 28. Patients who do not achieve remission by week 12 experience a flare after remission or cannot adhere to the prednisolone tapering will enter the escape arm and receive prednisolone at a dose determined by the investigator's clinical judgment. The blinded treatment is continued. Two optional imaging sub-studies are included (ultrasound and contrast-media enhanced magnetic resonance angiography [MRA]) to assess vessel wall inflammation and occlusion before and after treatment. The primary endpoint is the proportion of patients in sustained remission until week 28 in the secukinumab group compared to the proportion of patients in the placebo group. A Bayesian approach is applied. DISCUSSION: The trial design allows the first placebo-controlled data collection on the efficacy and safety of secukinumab in patients with GCA. TRIAL REGISTRATION: ClinicalTrials.gov NCT03765788 . Registration on 5 December 2018, prospective registration, EudraCT number 2018-002610-12; clinical trial protocol number CAIN457ADE11C.


Assuntos
Arterite de Células Gigantes , Anticorpos Monoclonais Humanizados , Teorema de Bayes , Ensaios Clínicos Fase II como Assunto , Método Duplo-Cego , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/tratamento farmacológico , Humanos , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
19.
J Med Food ; 24(8): 883-893, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34406877

RESUMO

During constipation, indigestible foods, such as probiotics, prebiotics, and dietary fiber, may improve the bowel environment and activity. In this randomized, double-blind, and placebo-controlled study, the effects of ID-HWS1000, composed of Lactobacillus and Bifidobacterium species, xylooligosaccharide, and dietary fiber, were evaluated to determine whether it improves the perception of bowel activity or cause changes in the gut microbiome. Thirty Korean adults with "functional constipation" according to the Rome III criteria were randomly assigned to the following groups: 20 in the ID-HWS1000 group and 10 in the placebo group. ID-HWS1000 or the placebo was consumed by the participants for 4 weeks. To assess the changes in the perception of bowel activity, clinical data and gut microbiome analyses were conducted before and after the experiment. There were significant differences between the groups in the response to 9 of the 12 survey questions (the number and duration of bowel movements, amount of feces, number of irritant bowel movements, number of times bowel movements felt incomplete, shape of the feces, amount of gas in the gut, discomfort after defecation, and discomfort owing to constipation) (P < .05). There was a decrease in the proportion of Firmicutes (Ruminococcaceae and Lachnospiraceae) and an increase in Bacteroidetes (Bacteroidaceae) (P < .05). Moreover, ID-HWS1000 directly improved the discomfort associated with bowel movements, decreased the proportion of Lachnospiraceae, and increased the proportion of Bacteroidaceae. These results confirmed that ID-HWS1000 improves the perception of bowel activity and exerts positive changes in individuals with functional constipation.


Assuntos
Microbioma Gastrointestinal , Probióticos , Adulto , Constipação Intestinal , Defecação , Método Duplo-Cego , Humanos , Percepção , Resultado do Tratamento
20.
Trials ; 22(1): 545, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34407832

RESUMO

BACKGROUND: Proton pump inhibitor (PPI) is effective for the treatment of nonerosive gastroesophageal reflux (NERD), but long-term use of PPI is prone to have complications and recurrence after withdrawal. Traditional Chinese medicine (TCM) can relieve the symptoms of reflux and improve the quality of life. The purpose of this study is to evaluate the safety and efficacy of Hewei Jiangni recipe (HWJNR) in the treatment of NERD with cold-heat complex syndrome, and clarify the mechanism of HWJNR on NERD based on the correlation analysis of intestinal flora and metabolites. METHODS: This is a single-center, randomized controlled, double-blind, placebo-controlled clinical trial in which 72 eligible participants with NERD and TCM syndrome of intermingled heat and cold will be randomly allocated in the ratio of 1:1 to two groups: TCM group and western medicine group. The TCM group will receive HWJNR with omeprazole enteric-coated tablets placebo, while the western medicine group will receive omeprazole enteric-coated tablets with HWJNR placebo. Each group will be treated for 8 weeks. The primary outcome is the score of gastroesophageal reflux disease (GERD) health-related quality of life questionnaire (GERD-Q). Secondary outcomes include SF-36 quality of life scale (SF-36), patient-reported outcomes (PRO) self-rating scale score, syndrome score of TCM, and adverse events. Mechanistic outcome is the correlation analysis of intestinal flora and metabolites from healthy individuals and NERD participants before and after the treatment respectively. DISCUSSION: The goal of this trial is to investigate the efficacy and safety of HWJNR in the treatment of NERD with cold-heat complex syndrome, and to study the composition structure and metabolite expression profile of intestinal flora in patients with NERD through 16SrRNA sequencing and metabolomic correlation analysis of fecal flora, which makes us identify the dominant links of treatment and reveal the potential mechanism of HWJNR. ChiCTR2000041225 . Registered on 22 December 2020.


Assuntos
Medicamentos de Ervas Chinesas , Qualidade de Vida , China , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Temperatura Alta , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
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