Nutritional Intervention in Chronic Fatigue Syndrome and Fibromyalgia (CFS/FMS) A Unique Porcine Serum Polypeptide Nutritional Supplement

Background: Clinical experience suggested that a unique porcine serum polypeptide extract, used in hospitals for people with severe malnutrition, serendipitously resulted in a dramatic improvement in many fibromyalgia cases. Aims: The study aims to determine the effectiveness of a unique polypeptide serum extract in improving the symptoms of CFS and fibromyalgia (CFS/FMS). Methods: An open-label prospective study of 43 people with CFS or Fibromyalgia recruited worldwide. Interventions: Four 500 mg tablets twice daily for five weeks. Outcome Measures: Assessed baseline at five weeks of treatment using a VAS(1-10 points) rating energy, sleep, cognitive function, pain, overall well-being, anxiety, and digestive health, as well as the FIQR. The primary outcome measure was the pre- and post-treatment VAS composite score for the first five symptoms. Results: 43 subjects completed the three-week treatment trial. 60.5% of subjects rated themselves as improved, with 18.6% rating themselves as much better. In the 60.5% of subjects that rated themselves as improved, the significant average improvement was seen in all categories: 1. 69.4% increase in energy(p<.001) 2. 69.2% increase in overall well-being(<.001) 3. 53.8% improvement in sleep(<.001) 4. 60.5% improvement in mental clarity(<.001) 5. 37.9% decrease in pain(<.013) 6. 34.8% decrease in anxiety(<.001) 7. 54.6% improvement in digestive symptoms(<.001) 8. FIQR 59.2 to 39.3(<.001) In six individuals who also had pre- and post IgG antibody levels, total IgG increased by 13.8% on average, with similar improvements seen in the IgG 1-4 subsets. Conclusion: Recovery Factors® resulted in markedly improved energy, sleep, cognition, pain relief, calming, digestion and overall well-being in those with CFS/FMS. Clinical Trial Registration Number: NCT04381793.

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Low dose oral ketamine treatment in chronic suicidality: An open-label pilot study

Translational Psychiatry ◽

10.1038/s41398-021-01230-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Adem T. Can ◽

Daniel F. Hermens ◽

Megan Dutton ◽

Cyrana C. Gallay ◽

Emma Jensen ◽

...

Keyword(s):

Suicidal Ideation ◽

Low Dose ◽

Suicide Ideation ◽

Well Being ◽

Primary Outcome Measure ◽

Open Label ◽

Oral Ketamine ◽

High Level ◽

Chronic Suicidality

AbstractRecently, low-dose ketamine has been proposed as a rapid-acting treatment option for suicidality. The majority of studies to date have utilised intravenous (IV) ketamine, however, this route of administration has limitations. On the other hand, oral ketamine can be administered in a range of settings, which is important in treating suicidality, although studies as to safety and feasibility are lacking. n = 32 adults (aged 22–72 years; 53% female) with chronic suicidal thoughts participated in the Oral Ketamine Trial on Suicidality (OKTOS), an open-label trial of sub-anaesthetic doses of oral ketamine over 6 weeks. Participants commenced with 0.5 mg/kg of ketamine, which was titrated to a maximum 3.0 mg/kg. Follow-up assessments occurred at 4 weeks after the final dose. The primary outcome measure was the Beck Scale for Suicide Ideation (BSS) and secondary measures included scales for suicidality and depressive symptoms, and measures of functioning and well-being. Mean BSS scores significantly reduced from a high level of suicidal ideation at the pre-ketamine (week 0) timepoint to below the clinical threshold at the post-ketamine (week 6) timepoint. The proportion of participants that achieved clinical improvement within the first 6 weeks was 69%, whereas 50% achieved a significant improvement by the follow-up (week 10) timepoint. Six weeks of oral ketamine treatment in participants with chronic suicidality led to significant reduction in suicidal ideation. The response observed in this study is consistent with IV ketamine trials, suggesting that oral administration is a feasible and tolerable alternative treatment for chronic suicidality.

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Long- versus short-term androgen deprivation therapy with high-dose radiotherapy for biochemical failure after radical prostatectomy: a randomized controlled trial

Future Oncology ◽

10.2217/fon-2020-0390 ◽

2020 ◽

Vol 16 (27) ◽

pp. 2035-2044

Author(s):

Charlien Berghen ◽

Steven Joniau ◽

Annouschka Laenen ◽

Gaetan Devos ◽

Kato Rans ◽

...

Keyword(s):

Radical Prostatectomy ◽

Androgen Deprivation Therapy ◽

Controlled Trial ◽

Locally Advanced ◽

Lymph Node Involvement ◽

Androgen Deprivation ◽

High Dose ◽

Open Label ◽

Clinical Trial Registration ◽

Substantial Risk

Radical prostatectomy is a well-established treatment option in the management of localized and locally advanced prostate cancer. An extended lymphadenectomy is performed in case of substantial risk for lymph node involvement. When biochemical recurrence (BCR) occurs, salvage radiotherapy (SRT) is performed. The benefit in terms of BCR-free survival (FS) and metastasis-FS by adding 6 months of androgen deprivation therapy (ADT) compared with SRT only has already been established. Retrospective evidence suggests that a longer schedule of ADT may be more beneficial compared with 6 months. This multicenter open-label randomized trial will include patients who need SRT after experiencing BCR post-radical prostatectomy with lymphadenectomy and pN0-status. Patients will be randomized for ADT duration (6 vs 24 months). Primary end point is distant metastasis-FS. Clinical Trial Registration: NCT04242017 ( ClinicalTrials.gov )

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Phase I first-in-human study of HLX07, a novel and improved recombinant anti-EGFR humanized monoclonal antibody, in patients with advanced solid cancers

Investigational New Drugs ◽

10.1007/s10637-021-01099-1 ◽

2021 ◽

Author(s):

Ming-Mo Hou ◽

Ching-Liang Ho ◽

Hsuan-Yu Lin ◽

Yunting Zhu ◽

Xiaodi Zhang

Keyword(s):

Phase I ◽

Standard Therapy ◽

Human Study ◽

Growth Factor Receptor ◽

Systemic Exposure ◽

Open Label ◽

Dose Escalation Study ◽

Clinical Trial Registration ◽

Humanized Monoclonal Antibody ◽

Open Label Phase

SummaryPurpose This study aimed to evaluate the safety and pharmacokinetic (PK) profiles of HLX07, a novel, recombinant, humanized anti-epidermal growth factor receptor (EGFR) antibody, in patients with advanced solid cancers who had failed standard therapy or for whom no standard therapy was available. Methods In this prospective, open-label, Phase I dose escalation study, patients aged ≥18 years (≥20 years for patients in Taiwan) with histologically-confirmed metastatic or recurrent epithelial carcinoma that had no K-RAS or B-RAF mutations were enrolled in a ‘3 + 3’ escalation design. HLX07 was administered weekly by 2-h intravenous infusion at doses ranging from 50 to 800 mg. The primary endpoint was summary listing of participants reporting treatment-emergent adverse events (TEAEs). Secondary endpoints included PK analysis, serum anti-HLX07 antibody assessments and efficacy. Results In total, 19 patients were enrolled between 1 October 2016 and 16 July 2019 to receive HLX07 at doses of 50 (n = 3), 100 (n = 3), 200 (n = 3), 400 (n = 3), 600 (n = 3) and 800 (n = 4) mg per week. All patients experienced at least one TEAE, most commonly fatigue (68.4%), nausea (47.4%), paronychia (31.6%) and vomiting (31.6%). Serious TEAEs were reported in 11 patients but only one serious TEAE (dyspnea in 600 mg cohort) was regarded as possibly related to study treatment. No dose limiting toxicity (DLT) was reported. Systemic exposure to HLX07 increased proportionally with dose. Anti-HLX07 antibodies were not detected in any patients. Conclusion HLX07 was well tolerated (at dose levels up to 800 mg/week) and promising in patients with advanced solid cancers.Clinical Trial Registration: The study was registered at ClinicalTrials.gov: NCT02648490 (Jan 7, 2016).

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Bioenergetic and Proteomic Profiling of Immune Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients: An Exploratory Study

Biomolecules ◽

10.3390/biom11070961 ◽

2021 ◽

Vol 11 (7) ◽

pp. 961

Author(s):

Paula Fernandez-Guerra ◽

Ana C. Gonzalez-Ebsen ◽

Susanne E. Boonen ◽

Julie Courraud ◽

Niels Gregersen ◽

...

Keyword(s):

Chronic Fatigue Syndrome ◽

Complex Disease ◽

Mononuclear Cells ◽

Coupling Efficiency ◽

Well Being ◽

Chronic Fatigue ◽

Myalgic Encephalomyelitis ◽

Flux Analysis ◽

Proteomic Profiling ◽

Fatigue Syndrome

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous, debilitating, and complex disease. Along with disabling fatigue, ME/CFS presents an array of other core symptoms, including autonomic nervous system (ANS) dysfunction, sustained inflammation, altered energy metabolism, and mitochondrial dysfunction. Here, we evaluated patients' symptomatology and the mitochondrial metabolic parameters in peripheral blood mononuclear cells (PBMCs) and plasma from a clinically well-characterised cohort of six ME/CFS patients compared to age- and gender-matched controls. We performed a comprehensive cellular assessment using bioenergetics (extracellular flux analysis) and protein profiles (quantitative mass spectrometry-based proteomics) together with self-reported symptom measures of fatigue, ANS dysfunction, and overall physical and mental well-being. This ME/CFS cohort presented with severe fatigue, which correlated with the severity of ANS dysfunction and overall physical well-being. PBMCs from ME/CFS patients showed significantly lower mitochondrial coupling efficiency. They exhibited proteome alterations, including altered mitochondrial metabolism, centred on pyruvate dehydrogenase and coenzyme A metabolism, leading to a decreased capacity to provide adequate intracellular ATP levels. Overall, these results indicate that PBMCs from ME/CFS patients have a decreased ability to fulfill their cellular energy demands.

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Assessment of a combined strategy of seasonal malaria chemoprevention and supplementation with vitamin A, zinc and Plumpy’Doz™ to prevent malaria and malnutrition in children under 5 years old in Burkina Faso: a randomized open-label trial (SMC-NUT)

Trials ◽

10.1186/s13063-021-05320-7 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Paul Sondo ◽

Marc Christian Tahita ◽

Toussaint Rouamba ◽

Karim Derra ◽

Bérenger Kaboré ◽

...

Keyword(s):

Vitamin A ◽

Burkina Faso ◽

Malaria Incidence ◽

Primary Outcome Measure ◽

Secondary Outcome ◽

Micronutrient Deficiencies ◽

Open Label ◽

Link Type ◽

Potential Factors ◽

Combined Strategy

Abstract Background Malaria and malnutrition represent major public health concerns worldwide especially in Sub-Sahara Africa. Despite implementation of seasonal malaria chemoprophylaxis (SMC), an intervention aimed at reducing malaria incidence among children aged 3–59 months, the burden of malaria and associated mortality among children below age 5 years remains high in Burkina Faso. Malnutrition, in particular micronutrient deficiency, appears to be one of the potential factors that can negatively affect the effectiveness of SMC. Treating micronutrient deficiencies is known to reduce the incidence of malaria in highly prevalent malaria zone such as rural settings. Therefore, we hypothesized that a combined strategy of SMC together with a daily oral nutrients supplement will enhance the immune response and decrease the incidence of malaria and malnutrition among children under SMC coverage. Methods Children (6–59 months) under SMC coverage receiving vitamin A supplementation will be randomly assigned to one of the three study arms (a) SMC + vitamin A alone, (b) SMC + vitamin A + zinc, or (c) SMC + vitamin A + Plumpy’Doz™ using 1:1:1 allocation ratio. After each SMC monthly distribution, children will be visited at home to confirm drug administration and followed-up for 1 year. Anthropometric indicators will be recorded at each visit and blood samples will be collected for microscopy slides, haemoglobin measurement, and spotted onto filter paper for further PCR analyses. The primary outcome measure is the incidence of malaria in each arm. Secondary outcome measures will include mid-upper arm circumference and weight gain from baseline measurements, coverage and compliance to SMC, occurrence of adverse events (AEs), and prevalence of molecular markers of antimalarial resistance comprising Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps. Discussion This study will demonstrate an integrated strategy of malaria and malnutrition programmes in order to mutualize resources for best impact. By relying on existing strategies, the policy implementation of this joint intervention will be scalable at country and regional levels. Trial registration ClinicalTrials.gov NCT04238845. Registered on 23 January 2020 https://clinicaltrials.gov/ct2/show/NCT04238845

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Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease

Scientific Reports ◽

10.1038/s41598-021-89444-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Manaf AlQahtani ◽

Abdulkarim Abdulrahman ◽

Abdulrahman Almadani ◽

Salman Yousif Alali ◽

Alaa Mahmood Al Zamrooni ◽

...

Keyword(s):

Standard Therapy ◽

Primary Outcome ◽

Controlled Trial ◽

Severe Disease ◽

Pilot Trial ◽

Standard Of Care ◽

Primary Outcome Measure ◽

Secondary Outcome ◽

Open Label ◽

Plasma Therapy

AbstractConvalescent plasma (CP) therapy in COVID-19 disease may improve clinical outcome in severe disease. This pilot study was undertaken to inform feasibility and safety of further definitive studies. This was a prospective, interventional and randomized open label pilot trial in patients with severe COVID-19. Twenty COVID-19 patients received two 200 ml transfusions of convalescent patient CP over 24-h compared with 20 who received standard of care. The primary outcome was the requirement for ventilation (non-invasive or mechanical ventilation). The secondary outcomes were biochemical parameters and mortality at 28 days. The CP group were a higher risk group with higher ferritin levels (p < 0.05) though respiratory indices did not differ. The primary outcome measure was required in 6 controls and 4 patients on CP (risk ratio 0.67, 95% CI 0.22–2.0, p = 0.72); mean time on ventilation (NIV or MV) did not differ. There were no differences in secondary measures at the end of the study. Two patients died in the control and one patient in the CP arm. There were no significant differences in the primary or secondary outcome measures between CP and standard therapy, although a larger definitive study is needed for confirmation. However, the study did show that CP therapy appears to be safe in hospitalized COVID-19 patients with hypoxia.Clinical trials registration NCT04356534: 22/04/2020.

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Open‐label study with the monoamine stabilizer (‐)‐OSU6162 in myalgic encephalomyelitis/chronic fatigue syndrome

Brain and Behavior ◽

10.1002/brb3.2040 ◽

2021 ◽

Vol 11 (4) ◽

Author(s):

Sara Haghighi ◽

Sara Forsmark ◽

Olof Zachrisson ◽

Arvid Carlsson ◽

Marie K. L. Nilsson ◽

...

Keyword(s):

Chronic Fatigue Syndrome ◽

Chronic Fatigue ◽

Myalgic Encephalomyelitis ◽

Open Label ◽

Open Label Study ◽

Label Study ◽

Fatigue Syndrome

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Comparison of efficacy and tolerability of oral desloratadine, rupatadine and ketotifen in seasonal allergic rhinitis

IP Journal of Otorhinolaryngology and Allied Science ◽

10.18231/j.ijoas.2021.021 ◽

2021 ◽

Vol 4 (3) ◽

pp. 106-114

Author(s):

Syed Khadeer ◽

B Jagannath

Keyword(s):

Allergic Rhinitis ◽

Adverse Events ◽

Nasal Congestion ◽

Primary Outcome Measure ◽

Nasal Symptom ◽

Secondary Outcome ◽

Open Label ◽

Non Allergic Rhinitis ◽

The Individual ◽

Change In Mean

Rhinitis is inflammation of nasal mucosa which characteristically presents as running nose, blocked nose, itching on nose or sneezing. Allergic rhinitis is more common than non-allergic rhinitis. Anti-histamines are the mainstay of SAR treatment. Desloratadine, rupatadine and ketotifen are the commonly prescribed anti histamines in our region. In this study, we have compared efficacy and tolerability of desloratadine, rupatadine and ketotifen in SAR. This was a prospective, randomized, three arm, open label comparative study of desloratadine, rupatadine and ketotifen in SAR, conducted at Department of ENT, Kempegowda Institute of Medical Sciences, Bangalore; between January 2014 and December 2014. Patients’ severity of SAR symptoms were assessed by TNSS, QoL was measured using Medical Outcomes Study questionnaire (SF-12). SF-12 was administered at the start of study and then at the end of study. Adverse effects were monitored during clinical examination at each visit. Study subjects were systemically randomized into three groups – desloratadine (DES), rupatadine (RUP) and ketotifen (KET). Based on the assigned group; desloratadine was given orally in dose of 10mg OD, rupatadine orally 10 mg OD and ketotifen orally 1mg BD. All medications were given for 4 weeks. Follow up was done for all patients every week during treatment period of 4 weeks. The primary outcome measure was change in mean TNSS from baseline; secondary outcome measures were changes in the individual nasal symptom scores, change in the quality of life and tolerability to the study medications. Total 150 patients were recruited for this study, divided into 3 groups. DES and RUP were equally effective but significantly better than KET in improving rhinorrhea, nasal congestion, TNSS and AEC. (p=0.05). All the drugs were equally effective with no statistically significant intergroup difference in improving sneezing, nasal itching and QoL. RUP appeared to have better tolerability as the total number of adverse events were marginally less. DES and RUP are comparatively more effective and faster acting than KET. All the study medications were well tolerated with few mild, self-limiting, transient adverse events requiring no intervention.

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Health-related quality of life (HRQOL) in patients (pts) with advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC) or esophageal adenocarcinoma (EAC): Results of nivolumab plus chemotherapy (NIVO+chemo) versus chemo from CheckMate 649.

Journal of Clinical Oncology ◽

10.1200/jco.2020.39.28_suppl.167 ◽

2021 ◽

Vol 39 (28_suppl) ◽

pp. 167-167

Author(s):

Elena Elimova ◽

Lucjan Wyrwicz ◽

Steven I. Blum ◽

Hong Xiao ◽

Mingshun Li ◽

...

Keyword(s):

Gastric Cancer ◽

Gastroesophageal Junction ◽

Well Being ◽

Primary Analysis ◽

Open Label ◽

Cox Models ◽

Study Objective ◽

Gastroesophageal Junction Cancer ◽

Patient Reported ◽

Mean Differences

167 Background: CheckMate 649 (NCT02872116) is a randomized, open label phase 3 study in first line (1L) treatment of pts with advanced GC/GEJC/EAC. Primary analysis results showed statistically significant improvement in overall survival (OS) for NIVO+chemo vs. chemo in all randomized pts. We present HRQOL results for these pts, included as an exploratory study objective. Methods: HRQOL was assessed using EQ-5D-3L (EQ-5D) and Functional Assessment of Cancer Therapy–Gastric Cancer (FACT-Ga). Assessments were performed at baseline (BL), every 6 weeks during treatment and during follow-up. Change from BL EQ-5D Visual Analog Scale (VAS), Utility Index (UI) and FACT-Ga scores were analyzed using mixed models. Time to first symptom deterioration (TTSD), time until definitive deterioration (TuDD), and time to improvement (TTI) were estimated with Kaplan-Meier estimators and stratified Cox models; deterioration/improvement was based on prespecified meaningful change thresholds. Results: 1581 pts were randomized to NIVO+chemo (n = 789) or chemo (n = 792). Among 1359 pts with BL and post-BL patient-reported outcomes (NIVO+chemo, n = 693; chemo, n = 666), BL scores for FACT-Ga total were similar between treatment groups. Least squares mean differences from BL favored NIVO+chemo at most visits for EQ-5D, FACT-Ga total, and Gastric Cancer Subscale (GaCS), and were comparable for other subscales (not shown). TTI generally favored NIVO+chemo (most HR > 1) but was not significantly different between arms. TTSD was longer in NIVO+chemo arm compared with chemo alone (all HRs < 1), except for Emotional Well-Being (WB); only GaCS and FACT-Ga total were significantly different between arms. TuDD showed statistically significant delays in deterioration (HR with CI < 1) for all scores expect Social WB. Conclusions: Compared with chemo alone, the addition of NIVO to chemo maintained HRQoL with a decreased risk of symptom deterioration in patients with previously untreated advanced or metastatic GC/GEJC/EAC. Together with improved OS, these data support NIVO+chemo as a new 1L standard treatment for GC/GEJC/EAC. Clinical trial information: NCT02872116. [Table: see text]

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The immediate effect of Sinapis nigra and Zingiber officinale as thermogenic substances during footbaths: A Randomized Controlled Cross-over Trial

Complementary Medicine Research ◽

10.1159/000521590 ◽

2021 ◽

Author(s):

Jan Vagedes ◽

Silja Kuderer ◽

Eduard Helmert ◽

Katrin Vagedes ◽

Matthias Kohl ◽

...

Keyword(s):

Sleep Quality ◽

Zingiber Officinale ◽

Well Being ◽

Primary Outcome Measure ◽

Warm Water ◽

Long Term Effects ◽

Stimulus Perception ◽

Late Evening ◽

Short And Long Term

Objective: Warm footbaths infused with Sinapis nigra (mustard, or MU) or Zingiber officinale (ginger, or GI) are used for various thermoregulatory conditions, but little is known about how they are perceived by individuals, both short- and long-term. We analyzed the immediate and long-term effects of MU and GI on warmth and stimulus perception in healthy adults. Methods: Seventeen individuals (mean age 22.1±2.4 years; 11 female) received three footbaths (mean temperature was 40 ± 0.2 ℃, administered between 1:30-6:30pm) in a randomized order with a cross-over design: 1. with warm water only (WA), 2. with warm water and MU and 3. with warm water and GI. Warmth and stimulus perception at the feet were assessed at the 1st, 5th, 10th, 15th, and 20th minute of the footbaths, in the late evening (EVE), and the following morning (MG). We further assessed well-being (at EVE and MG) and sleep quality (at MG). The primary outcome measure was the warmth perception at the feet at the 10th minute of the footbath. Results: At the 10th minute of the footbath, warmth perception at the feet was significantly higher with MU and GI compared to WA. The immediate thermogenic effects pointed to a quick increase in warmth and stimulus perception with MU, a slower increase with GI, and a gradual decrease with WA. Regarding the long-term effects, warmth and stimulus perception were still higher after GI compared to WA at EVE and MG. No differences were seen for general well-being and sleep quality. Conclusion: Thermogenic substances can significantly alter the dynamics of warmth and stimulus perception when added to footbaths. The different profiles in the application of GI and MU could be relevant for a more differentiated and specific use of both substances in different therapeutic indications.

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