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The New England Journal of Medicine May 2015In previous phase 1-2 clinical trials involving older adults, a subunit vaccine containing varicella-zoster virus glycoprotein E and the AS01B adjuvant system (called... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In previous phase 1-2 clinical trials involving older adults, a subunit vaccine containing varicella-zoster virus glycoprotein E and the AS01B adjuvant system (called HZ/su) had a clinically acceptable safety profile and elicited a robust immune response.
METHODS
We conducted a randomized, placebo-controlled, phase 3 study in 18 countries to evaluate the efficacy and safety of HZ/su in older adults (≥50 years of age), stratified according to age group (50 to 59, 60 to 69, and ≥70 years). Participants received two intramuscular doses of the vaccine or placebo 2 months apart. The primary objective was to assess the efficacy of the vaccine, as compared with placebo, in reducing the risk of herpes zoster in older adults.
RESULTS
A total of 15,411 participants who could be evaluated received either the vaccine (7698 participants) or placebo (7713 participants). During a mean follow-up of 3.2 years, herpes zoster was confirmed in 6 participants in the vaccine group and in 210 participants in the placebo group (incidence rate, 0.3 vs. 9.1 per 1000 person-years) in the modified vaccinated cohort. Overall vaccine efficacy against herpes zoster was 97.2% (95% confidence interval [CI], 93.7 to 99.0; P<0.001). Vaccine efficacy was between 96.6% and 97.9% for all age groups. Solicited reports of injection-site and systemic reactions within 7 days after vaccination were more frequent in the vaccine group. There were solicited or unsolicited reports of grade 3 symptoms in 17.0% of vaccine recipients and 3.2% of placebo recipients. The proportions of participants who had serious adverse events or potential immune-mediated diseases or who died were similar in the two groups.
CONCLUSIONS
The HZ/su vaccine significantly reduced the risk of herpes zoster in adults who were 50 years of age or older. Vaccine efficacy in adults who were 70 years of age or older was similar to that in the other two age groups. (Funded by GlaxoSmithKline Biologicals; ZOE-50 ClinicalTrials.gov number, NCT01165177.).
Topics: Adjuvants, Immunologic; Aged; Double-Blind Method; Female; Herpes Zoster; Herpes Zoster Vaccine; Humans; Injections, Intramuscular; Male; Middle Aged; Treatment Outcome; Vaccines, Subunit
PubMed: 25916341
DOI: 10.1056/NEJMoa1501184 -
Molecular Cancer Apr 2021
Topics: Biomarkers, Tumor; Cancer-Associated Fibroblasts; Colonic Neoplasms; Exosomes; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Staging; Prognosis; Tumor Microenvironment
PubMed: 33926453
DOI: 10.1186/s12943-021-01367-x -
Clinical Microbiology Reviews Jan 2014The agents of human treponematoses include four closely related members of the genus Treponema: three subspecies of Treponema pallidum plus Treponema carateum. T.... (Review)
Review
The agents of human treponematoses include four closely related members of the genus Treponema: three subspecies of Treponema pallidum plus Treponema carateum. T. pallidum subsp. pallidum causes venereal syphilis, while T. pallidum subsp. pertenue, T. pallidum subsp. endemicum, and T. carateum are the agents of the endemic treponematoses yaws, bejel (or endemic syphilis), and pinta, respectively. All human treponematoses share remarkable similarities in pathogenesis and clinical manifestations, consistent with the high genetic and antigenic relatedness of their etiological agents. Distinctive features have been identified in terms of age of acquisition, most common mode of transmission, and capacity for invasion of the central nervous system and fetus, although the accuracy of these purported differences is debated among investigators and no biological basis for these differences has been identified to date. In 2012, the World Health Organization (WHO) officially set a goal for yaws eradication by 2020. This challenging but potentially feasible endeavor is favored by the adoption of oral azithromycin for mass treatment and the currently focused distribution of yaws and endemic treponematoses and has revived global interest in these fascinating diseases and their causative agents.
Topics: Animals; Disease Eradication; Disease Models, Animal; Endemic Diseases; Treponema; Treponemal Infections
PubMed: 24396138
DOI: 10.1128/CMR.00070-13 -
Transactions of the Royal Society of... Oct 2014The endemic treponemal diseases, consisting of yaws, bejel (endemic syphilis) and pinta, are non-venereal infections closely related to syphilis, and are recognized by...
The endemic treponemal diseases, consisting of yaws, bejel (endemic syphilis) and pinta, are non-venereal infections closely related to syphilis, and are recognized by WHO as neglected tropical diseases (NTDs). Despite previous worldwide eradication efforts the prevalence of yaws has rebounded in recent years and the disease is now a major public health problem in 14 countries. Adequate data on the epidemiology of bejel and pinta is lacking. Each disease is restricted to a specific ecological niche but all predominantly affect poor, rural communities. As with venereal syphilis, the clinical manifestations of the endemic treponemal diseases are variable and can be broken down in to early stage and late stage disease. Current diagnostic techniques are unable to distinguish the different causative species but newer molecular techniques are now making this possible. Penicillin has long been considered the mainstay of treatment for the endemic treponemal diseases but the recent discovery that azithromycin is effective in the treatment of yaws has renewed interest in these most neglected of the NTDs, and raised hopes that global eradication may finally be possible.
Topics: Anti-Bacterial Agents; Developing Countries; Endemic Diseases; Humans; Pinta; Syphilis; Yaws
PubMed: 25157125
DOI: 10.1093/trstmh/tru128 -
Open Forum Infectious Diseases Oct 2022Approximately 10 years after vaccination with the recombinant zoster vaccine (RZV), an interim analysis of this follow-up study of the ZOE-50/70 trials demonstrated that...
Long-term Protection Against Herpes Zoster by the Adjuvanted Recombinant Zoster Vaccine: Interim Efficacy, Immunogenicity, and Safety Results up to 10 Years After Initial Vaccination.
Approximately 10 years after vaccination with the recombinant zoster vaccine (RZV), an interim analysis of this follow-up study of the ZOE-50/70 trials demonstrated that efficacy against herpes zoster remained high. Moreover, the safety profile remained clinically acceptable, suggesting that the clinical benefit of the RZV in ≥50-year-olds is sustained up to 10 years.
PubMed: 36299530
DOI: 10.1093/ofid/ofac485 -
JAMA Surgery Jun 2023Both elective sigmoid resection and conservative treatment are options for patients with recurrent, complicated, or persistent painful diverticulitis; understanding...
Quality-of-Life and Recurrence Outcomes Following Laparoscopic Elective Sigmoid Resection vs Conservative Treatment Following Diverticulitis: Prespecified 2-Year Analysis of the LASER Randomized Clinical Trial.
IMPORTANCE
Both elective sigmoid resection and conservative treatment are options for patients with recurrent, complicated, or persistent painful diverticulitis; understanding outcomes following each can help inform decision-making.
OBJECTIVE
To compare outcomes of elective sigmoid resection and conservative treatment for patients with recurrent, complicated, or persistent painful diverticulitis at 2-year follow-up.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter parallel open-label individually randomized clinical trial comparing elective sigmoid resection to conservative treatment in patients with recurrent, complicated, or persistent painful diverticulitis was carried out in 5 Finnish hospitals between September 2014 and October 2018. Follow-up up to 2 years is reported. Of 85 patients randomized and included, 75 and 70 were available for QOL outcomes at 1 year and 2 years, respectively, and 79 and 78 were available for the recurrence outcome at 1 year and 2 years, respectively. The present analysis was conducted from September 2015 to June 2022.
INTERVENTIONS
Laparoscopic elective sigmoid resection vs conservative treatment (patient education and fiber supplementation).
MAIN OUTCOMES AND MEASURES
Prespecified secondary outcomes included Gastrointestinal Quality of Life Index (GIQLI) score, complications, and recurrences within 2 years.
RESULTS
Ninety patients (28 male [31%]; mean [SD] age, 54.11 [11.9] years and 62 female [69%]; mean [SD] age, 57.13 [7.6] years) were randomized either to elective sigmoid resection or conservative treatment. After exclusions, 41 patients in the surgery group and 44 in the conservative group were included in the intention-to-treat analyses. Eight patients (18%) in the conservative treatment group underwent sigmoid resection within 2 years. The mean GIQLI score at 1 year was 9.51 points higher in the surgery group compared to the conservative group (mean [SD], 118.54 [17.95] vs 109.03 [19.32]; 95% CI, 0.83-18.18; P = .03), while the mean GIQLI score at 2 years was similar between the groups. Within 2 years, 25 of 41 patients in the conservative group (61%) had recurrent diverticulitis compared to 4 of 37 patients in the surgery group (11%). Four of 41 patients in the surgery group (10%) and 2 of 44 in the conservative group (5%) had major postoperative complications within 2 years. In per-protocol analyses, the mean (SD) GIQLI score was higher in the surgery group compared to the conservative treatment group by 11.27 points at 12 months (119.42 [17.98] vs 108.15 [19.28]; 95% CI, 2.24-20.29; P = .02) and 10.43 points at 24 months (117.24 [15.51] vs 106.82 [18.94]; 95% CI, 1.52-19.33; P = .02).
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, elective sigmoid resection was effective in preventing recurrent diverticulitis and improved quality of life over conservative treatment within 2 years.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02174926.
Topics: Humans; Male; Female; Middle Aged; Quality of Life; Conservative Treatment; Treatment Outcome; Neoplasm Recurrence, Local; Diverticulitis; Laparoscopy
PubMed: 37074706
DOI: 10.1001/jamasurg.2023.0466 -
JAMA Jan 2021Antibiotics are an effective and safe alternative to appendectomy for managing uncomplicated acute appendicitis, but the optimal antibiotic regimen is not known. (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Antibiotics are an effective and safe alternative to appendectomy for managing uncomplicated acute appendicitis, but the optimal antibiotic regimen is not known.
OBJECTIVE
To compare oral antibiotics with combined intravenous followed by oral antibiotics in the management of computed tomography-confirmed uncomplicated acute appendicitis.
DESIGN, SETTING, AND PARTICIPANTS
The Appendicitis Acuta (APPAC) II multicenter, open-label, noninferiority randomized clinical trial was conducted from April 2017 until November 2018 in 9 Finnish hospitals. A total of 599 patients aged 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis were enrolled in the trial. The last date of follow-up was November 29, 2019.
INTERVENTIONS
Patients randomized to receive oral monotherapy (n = 295) received oral moxifloxacin (400 mg/d) for 7 days. Patients randomized to receive intravenous antibiotics followed by oral antibiotics (n = 288) received intravenous ertapenem (1 g/d) for 2 days followed by oral levofloxacin (500 mg/d) and metronidazole (500 mg 3 times/d) for 5 days.
MAIN OUTCOMES AND MEASURES
The primary end point was treatment success (≥65%) for both groups, defined as discharge from hospital without surgery and no recurrent appendicitis during 1-year follow-up, and to determine whether oral antibiotics alone were noninferior to intravenous and oral antibiotics, with a margin of 6% for difference.
RESULTS
Among 599 patients who were randomized (mean [SD] age, 36 [12] years; 263 [44%] women), 581 (99.7%) were available for the 1-year follow-up. The treatment success rate at 1 year was 70.2% (1-sided 95% CI, 65.8% to ∞) for patients treated with oral antibiotics and 73.8% (1-sided 95% CI, 69.5% to ∞) for patients treated with intravenous followed by oral antibiotics. The difference was -3.6% ([1-sided 95% CI, -9.7% to ∞]; P = .26 for noninferiority), with the confidence limit exceeding the noninferiority margin.
CONCLUSION AND RELEVANCE
Among adults with uncomplicated acute appendicitis, treatment with 7 days of oral moxifloxacin compared with 2 days of intravenous ertapenem followed by 5 days of levofloxacin and metronidazole resulted in treatment success rates greater than 65% in both groups, but failed to demonstrate noninferiority for treatment success of oral antibiotics compared with intravenous followed by oral antibiotics.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03236961; EudraCT Identifier: 2015-003633-10.
Topics: Acute Disease; Administration, Intravenous; Administration, Oral; Adult; Anti-Bacterial Agents; Appendectomy; Appendicitis; Drug Therapy, Combination; Ertapenem; Female; Follow-Up Studies; Humans; Levofloxacin; Male; Metronidazole; Middle Aged; Moxifloxacin; Tomography, X-Ray Computed; Young Adult
PubMed: 33427870
DOI: 10.1001/jama.2020.23525 -
Microbes and Infection Jan 2002Treponemal diseases comprise venereal syphilis (Treponema pallidum subsp. pallidum) and the endemic (non-venereal) treponematoses, i.e. yaws (T. pallidum subsp.... (Review)
Review
Treponemal diseases comprise venereal syphilis (Treponema pallidum subsp. pallidum) and the endemic (non-venereal) treponematoses, i.e. yaws (T. pallidum subsp. pertenue), endemic syphilis (T. pallidum subsp. endemicum) and pinta (T. carateum). Treponemal diseases are distinguished on the basis of epidemiological characteristics and clinical manifestations. They are at present indistinguishable by morphological, immunological or serological methods. Several minor genetic differences have been identified among the subspecies. The endemic treponematoses have not yet been eliminated and are currently thought to affect at least 2.5 million persons. Renewed action towards the elimination of these diseases should be undertaken.
Topics: Endemic Diseases; History, 20th Century; Humans; Pinta; Syphilis; Treponemal Infections; Yaws
PubMed: 11825779
DOI: 10.1016/s1286-4579(01)01513-1 -
International Journal of Molecular... Apr 2023Colorectal cancer (CRC) is one of the most common cancers in Western countries and remains the second most common cause of cancer death worldwide. Many studies show the... (Review)
Review
Colorectal cancer (CRC) is one of the most common cancers in Western countries and remains the second most common cause of cancer death worldwide. Many studies show the importance of diet and lifestyle in the incidence of CRC, as well as in CRC prevention. However, this review summarizes those studies that analyze the impact of nutrition on tumor microenvironment modulation and cancer progression. We review the available information about the effects of specific nutrients on cancer cell progression and on the different cells within the tumor microenvironment. Diet and nutritional status in the clinical management of colorectal cancer patients are also analyzed. Finally, future perspectives and challenges are discussed, with a view to improving CRC treatments by employing nutritional approaches. These promise great benefits and will eventually improve CRC patients' survival.
Topics: Humans; Tumor Microenvironment; Colorectal Neoplasms; Diet; Life Style
PubMed: 37108477
DOI: 10.3390/ijms24087317