Enhancement of Disease and Pathology by Synergy of Trichuris Suis and Campylobacter Jejuni in the Colon of Immunologically Naive Swine

Campylobacter jejuni, a leading cause of bacterial gastroenteritis, has different age distribution and disease expression in developing and developed countries, which may be due to the endemnicity of infection and the age of acquisition of immunity. Differences in disease expression are not solely dependent on the C jejuni strain or virulence attributes. Another modulating factor in developing countries may be endemic nematode infections such as Trichuris, which drive type 2 cytokine responses and down-regulate type I immune responses. In this study, three-day-old germfree pigs given dual infections with Trichuris suis and C jejuni had more frequent, more severe diarrhea and severe pathology than pigs given no pathogens, only T. suis, or only C jejuni. These pigs had significant hemorrhage and inflammatory cell infiltrates in the proximal colon where adult worms were found, and abscessed lymphoglandular complexes in the distal colon with intracellular C jejuni. Pigs given only C jejuni had mild clinical signs and pathology, and bacteria in feces or extracellular sites. Pigs given T suis or no pathogens had no disease and minimal pathology. Thus, these agents synergized to produce significant disease and pathology, which was site specific

Genetic Diversity of Campylobacter sp. Isolates from Retail Chicken Products and Humans with Gastroenteritis in Central Michigan

Multilocus sequencing was used to compare Campylobacter sp. strains isolated from retail chicken products and humans with gastroenteritis in central Michigan. Sequence comparisons demonstrated overlapping diversity between chicken and human isolates. Campylobacter jejuni isolates from clinical sources had a greater diversity of flagellin alleles and a higher rate of quinolone resistance than isolates from retail chicken products

Inhaled Fluticasone Furoate for Outpatient Treatment of Covid-19

In a platform randomized trial, the use of inhaled fluticasone furoate did not result in a shorter time to recovery than placebo among outpatients with acute SARS-CoV-2 infection

Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial

The effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the US with mild to moderate symptomatic COVID-19 is unknown. To evaluate the efficacy of ivermectin, 400 μg/kg, daily for 3 days compared with placebo for the treatment of early mild to moderate COVID-19. ACTIV-6, an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial, was designed to evaluate repurposed therapies in outpatients with mild to moderate COVID-19. A total of 1591 participants aged 30 years and older with confirmed COVID-19, experiencing 2 or more symptoms of acute infection for 7 days or less, were enrolled from June 23, 2021, through February 4, 2022, with follow-up data through May 31, 2022, at 93 sites in the US. Participants were randomized to receive ivermectin, 400 μg/kg (n = 817), daily for 3 days or placebo (n = 774). Time to sustained recovery, defined as at least 3 consecutive days without symptoms. There were 7 secondary outcomes, including a composite of hospitalization or death by day 28. Among 1800 participants who were randomized (mean [SD] age, 48 [12] years; 932 women [58.6%]; 753 [47.3%] reported receiving at least 2 doses of a SARS-CoV-2 vaccine), 1591 completed the trial. The hazard ratio (HR) for improvement in time to recovery was 1.07 (95% credible interval [CrI], 0.96-1.17; posterior P value [HR >1] = .91). The median time to recovery was 12 days (IQR, 11-13) in the ivermectin group and 13 days (IQR, 12-14) in the placebo group. There were 10 hospitalizations or deaths in the ivermectin group and 9 in the placebo group (1.2% vs 1.2%; HR, 1.1 [95% CrI, 0.4-2.6]). The most common serious adverse events were COVID-19 pneumonia (ivermectin [n = 5]; placebo [n = 7]) and venous thromboembolism (ivermectin [n = 1]; placebo [n = 5]). Among outpatients with mild to moderate COVID-19, treatment with ivermectin, compared with placebo, did not significantly improve time to recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19. ClinicalTrials.gov Identifier: NCT04885530

Time to Sustained Recovery Among Outpatients With COVID-19 Receiving Montelukast vs Placebo: The ACTIV-6 Randomized Clinical Trial

The effect of montelukast in reducing symptom duration among outpatients with mild to moderate COVID-19 is uncertain.ImportanceThe effect of montelukast in reducing symptom duration among outpatients with mild to moderate COVID-19 is uncertain.To assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19.ObjectiveTo assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19.This randomized clinical trial (Accelerating COVID-19 Therapeutic Interventions and Vaccines [ACTIV]-6) was conducted from January 27 through June 23, 2023, during the circulation of Omicron subvariants. Participants aged 30 years or older with confirmed SARS-CoV-2 infection and 2 or more acute COVID-19 symptoms for less than 7 days were included across 104 US sites.Design, Setting, and ParticipantsThis randomized clinical trial (Accelerating COVID-19 Therapeutic Interventions and Vaccines [ACTIV]-6) was conducted from January 27 through June 23, 2023, during the circulation of Omicron subvariants. Participants aged 30 years or older with confirmed SARS-CoV-2 infection and 2 or more acute COVID-19 symptoms for less than 7 days were included across 104 US sites.Participants were randomized 1:1 to receive montelukast, 10 mg once daily, or matched placebo for 14 days.InterventionsParticipants were randomized 1:1 to receive montelukast, 10 mg once daily, or matched placebo for 14 days.The primary outcome was time to sustained recovery (defined as ≥3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of health care utilization events (hospitalization, urgent care clinic visit, emergency department visit, or death); COVID-19 clinical progression scale score; and difference in mean time unwell. A modified intention-to-treat approach was used for the analysis.Main Outcomes and MeasuresThe primary outcome was time to sustained recovery (defined as ≥3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of health care utilization events (hospitalization, urgent care clinic visit, emergency department visit, or death); COVID-19 clinical progression scale score; and difference in mean time unwell. A modified intention-to-treat approach was used for the analysis.Among 1250 participants who were randomized and received the study drug or placebo, the median age was 53 years (IQR, 42-62 years), 753 (60.2%) were female, and 704 (56.3%) reported receiving 2 or more doses of a SARS-CoV-2 vaccine. Among 628 participants who received montelukast and 622 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [AHR], 1.02; 95% credible interval [CrI], 0.92-1.12; P = .63 for efficacy). Unadjusted median time to sustained recovery was 10 days (95% CI, 10-11 days) in both groups. No deaths occurred, and hospitalizations were reported for 2 participants (0.3%) in each group; the composite of health care utilization events was reported for 18 participants (2.9%) in the montelukast group and 18 (2.9%) in the placebo group (AHR, 1.01; 95% CrI, 0.45-1.84; P = .48 for efficacy). Five participants (0.4%) experienced serious adverse events (3 [0.5%] in the montelukast group and 2 [0.3%] in the placebo group).ResultsAmong 1250 participants who were randomized and received the study drug or placebo, the median age was 53 years (IQR, 42-62 years), 753 (60.2%) were female, and 704 (56.3%) reported receiving 2 or more doses of a SARS-CoV-2 vaccine. Among 628 participants who received montelukast and 622 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [AHR], 1.02; 95% credible interval [CrI], 0.92-1.12; P = .63 for efficacy). Unadjusted median time to sustained recovery was 10 days (95% CI, 10-11 days) in both groups. No deaths occurred, and hospitalizations were reported for 2 participants (0.3%) in each group; the composite of health care utilization events was reported for 18 participants (2.9%) in the montelukast group and 18 (2.9%) in the placebo group (AHR, 1.01; 95% CrI, 0.45-1.84; P = .48 for efficacy). Five participants (0.4%) experienced serious adverse events (3 [0.5%] in the montelukast group and 2 [0.3%] in the placebo group).In this randomized clinical trial of outpatients with mild to moderate COVID-19, treatment with montelukast did not reduce duration of COVID-19 symptoms. These findings do not support the use of montelukast for the treatment of mild to moderate COVID-19.Conclusions and RelevanceIn this randomized clinical trial of outpatients with mild to moderate COVID-19, treatment with montelukast did not reduce duration of COVID-19 symptoms. These findings do not support the use of montelukast for the treatment of mild to moderate COVID-19.ClinicalTrials.gov Identifier: NCT04885530.Trial RegistrationClinicalTrials.gov Identifier: NCT04885530

Higher-Dose Fluvoxamine and Time to Sustained Recovery in Outpatients With COVID-19: The ACTIV-6 Randomized Clinical Trial

ImportanceThe effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain.ObjectiveTo assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19.Design, Setting, and ParticipantsThe ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19. Between August 25, 2022, and January 20, 2023, a total of 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were 30 years or older with confirmed SARS-CoV-2 infection and at least 2 acute COVID-19 symptoms for 7 days or less.InterventionsParticipants were randomized to receive fluvoxamine, 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days (n = 601), or placebo (n = 607).Main Outcomes and MeasuresThe primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID-19 clinical progression scale score; and difference in mean time unwell. Follow-up occurred through day 28.ResultsAmong 1208 participants who were randomized and received the study drug, the median (IQR) age was 50 (40-60) years, 65.8% were women, 45.5% identified as Hispanic/Latino, and 76.8% reported receiving at least 2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo included in the primary analysis, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09]; P for efficacy = .40]). Additionally, unadjusted median time to sustained recovery was 10 (95% CI, 10-11) days in both the intervention and placebo groups. No deaths were reported. Thirty-five participants reported health care use events (a priori defined as death, hospitalization, or emergency department/urgent care visit): 14 in the fluvoxamine group compared with 21 in the placebo group (HR, 0.69 [95% credible interval, 0.27-1.21]; P for efficacy = .86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo) but no deaths.Conclusions and RelevanceAmong outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms.Trial RegistrationClinicalTrials.gov Identifier: NCT04885530

Effect of Montelukast vs Placebo on Time to Sustained Recovery in Outpatients with COVID-19: The ACTIV-6 Randomized Clinical Trial

The effect of montelukast in reducing symptom duration among outpatients with mild to moderate coronavirus disease 2019 (COVID-19) is uncertain. To assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19. The ACTIV-6 platform randomized clinical trial aims to evaluate the effectiveness of repurposed medications in treating mild to moderate COVID-19. Between January 27, 2023, and June 23, 2023, 1250 participants ≥30 years of age with confirmed SARS-CoV-2 infection and ≥2 acute COVID-19 symptoms for ≤7 days, were included across 104 US sites to evaluate the use of montelukast. Participants were randomized to receive montelukast 10 mg once daily or matched placebo for 14 days. The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID clinical progression scale; and difference in mean time unwell. Among participants who were randomized and received study drug, the median age was 53 years (IQR 42-62), 60.2% were female, 64.6% identified as Hispanic/Latino, and 56.3% reported ≥2 doses of a SARS-CoV-2 vaccine. Among 628 participants who received montelukast and 622 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR] 1.02; 95% credible interval [CrI] 0.92-1.12; P(efficacy) = 0.63]). Unadjusted median time to sustained recovery was 10 days (95% confidence interval 10-11) in both groups. No deaths were reported and 2 hospitalizations were reported in each group; 36 participants reported healthcare utilization events (a priori defined as death, hospitalization, emergency department/urgent care visit); 18 in the montelukast group compared with 18 in the placebo group (HR 1.01; 95% CrI 0.45-1.84; P(efficacy)=0.48). Five participants experienced serious adverse events (3 with montelukast and 2 with placebo). Among outpatients with mild to moderate COVID-19, treatment with montelukast does not reduce duration of COVID-19 symptoms. ClinicalTrials.gov ( NCT04885530 )

EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision

Background and objectives: This second European Federation of Neurological Societies Task Force aimed at updating the existing evidence about the pharmacological treatment of neuropathic pain since 2005. Methods: Studies were identified using the Cochrane Database and Medline. Trials were classified according to the aetiological condition. All class I and II randomized controlled trials (RCTs) were assessed; lower class studies were considered only in conditions that had no top-level studies. Treatments administered using repeated or single administrations were considered, provided they are feasible in an outpatient setting. Results: Most large RCTs included patients with diabetic polyneuropathies and post-herpetic neuralgia, while an increasing number of smaller studies explored other conditions. Drugs generally have similar efficacy in various conditions, except in trigeminal neuralgia, chronic radiculopathy and HIV neuropathy, with level A evidence in support of tricyclic antidepressants (TCA), pregabalin, gabapentin, tramadol and opioids (in various conditions), duloxetine, venlafaxine, topical lidocaine and capsaicin patches (in restricted conditions). Combination therapy appears useful for TCA-gabapentin and gabapentin-opioids (level A). Conclusions: There are still too few large-scale comparative studies. For future trials, we recommend to assess comorbidities, quality of life, symptoms and signs with standardized tools and attempt to better define responder profiles to specific drug treatments