Cercetări arheologice în zona centrală a oraşului Tîrgovişte / Recherches archéologiques à Tîrgovişte, dans la zone centrale

Cantacuzino Gheorghe I., Diaconescu Petre, Mihăescu Gabriel. Cercetări arheologice în zona centrală a oraşului Tîrgovişte / Recherches archéologiques à Tîrgovişte, dans la zone centrale. In: Materiale şi cercetări arheologice, N°15 1983. A XV-A sesiune anuală de rapoarte, Muzeul jedeţean Braşov – 1981. pp. 508-512

Cercetări arheologice în zona centrală a oraşului Tîrgovişte / Recherches archéologiques à Tîrgovişte, au centre de la ville

Cantacuzino Gheorghe I., Diaconescu Petre, Mihăescu Gabriel. Cercetări arheologice în zona centrală a oraşului Tîrgovişte / Recherches archéologiques à Tîrgovişte, au centre de la ville . In: Materiale şi cercetări arheologice, N°16 1986. A XVI-A sesiune anuală de rapoarte, Vaslui 1982. pp. 291-293

Cadazolid for the treatment of Clostridium difficile infection: results of two double-blind, placebo-controlled, non-inferiority, randomised phase 3 trials

BACKGROUND: Cadazolid is a novel quinoxolidinone antibiotic developed for treating Clostridium difficile infection. We aimed to investigate the safety and efficacy of cadazolid compared with vancomycin in patients with C difficile infection. METHODS: IMPACT 1 and IMPACT 2 were identically designed, multicentre, double-blind, placebo-controlled, non-inferiority, randomised phase 3 trials. IMPACT 1 was done in Australia, Brazil, Canada, France, Germany, Italy, the Netherlands, Peru, Poland, Romania, Spain, and the USA, and IMPACT 2 was done in Argentina, Belgium, Brazil, Canada, Chile, Croatia, Czech Republic, Greece, Hungary, Israel, Romania, Slovakia, South Korea, the UK, and the USA. Patients (aged 18 years or older) with mild-to-moderate or severe C difficile infection (diarrhoea with positive glutamate dehydrogenase and toxin A or B enzyme immunoassays) were randomly assigned (1:1) with a randomisation list stratified by centre and C difficile infection episode type (block size of four), and allocation was masked to investigators and participants. Patients received either oral cadazolid 250 mg twice daily with vancomycin-matching placebo capsule four times daily or oral vancomycin 125 mg four times a day with cadazolid-matching placebo suspension twice daily for 10 days, with 30 days of follow-up. The primary efficacy outcome was non-inferiority (margin -10%) of cadazolid versus vancomycin for clinical cure in the modified intention-to-treat and per-protocol populations. Clinical cure was defined as resolution of diarrhoea with no additional treatment for C difficile infection. These trials are registered with ClinicalTrials.gov, numbers NCT01987895 (IMPACT 1) and NCT01983683 (IMPACT 2). FINDINGS: Between March 28, 2014, and March 24, 2017, for IMPACT 1, and Dec 13, 2013, and May 2, 2017, for IMPACT 2, 1263 participants were randomly assigned to receive cadazolid (306 in IMPACT 1 and 298 in IMPACT 2) or vancomycin (326 in IMPACT 1 and 311 in IMPACT 2). In the modified intention-to-treat population in IMPACT 1, 253 (84%) of 302 had clinical cure in the cadazolid group versus 271 (85%) of 318 in the vancomycin group. In IMPACT 2, 235 (81%) of 290 versus 258 (86%) of 301 had clinical cure. In the per-protocol population, 247 (88%) of 282 versus 264 (92%) of 288 had clinical cure in IMPACT 1 and 214 (87%) of 247 versus 237 (92%) of 259 in IMPACT 2. Non-inferiority for clinical cure to vancomycin was shown in IMPACT 1 but not in IMPACT 2 (IMPACT 1 treatment difference: -1·4 [95% CI -7·2 to 4·3] for modified intention to treat and -4·1 [-9·2 to 1·0] for per protocol; IMPACT 2: -4·7 [-10·7 to 1·3] for modified intention to treat and -4·9 [-10·4 to 0·6] for per protocol). The safety and tolerability profiles of the two antibiotics were similar. INTERPRETATION: Cadazolid was safe and well tolerated but did not achieve its primary endpoint of non-inferiority to vancomycin for clinical cure in one of two phase 3 C difficile infection trials. Therefore, further commercial development of cadazolid for C difficile infection is unlikely. FUNDING: Actelion Pharmaceuticals

The management of complicated colorectal cancer in older patients in a global perspective after COVID-19: the CO-OLDER WSES project

BACKGROUND: Colorectal (CRC) cancer is becoming a disease of the elderly. Ageing is the most significant risk factor for presenting CRC. Early diagnosis of CRC and management is the best way in achieving good outcomes and longer survival but patients aged ≥75 years are usually not screened for CRC. This group of patients is often required to be managed when they are symptomatic in the emergency setting with high morbidity and mortality rates. Our main aim is to provide clinical data about the management of elderly patients presenting complicated colorectal cancer who required emergency surgical management to improve their care. METHODS: The management of complicated COlorectal cancer in OLDER patients (CO-OLDER; ClinicalTrials.gov ID: NCT05788224; evaluated by the local ethical committee CPP EST III-France with the national number 2023-A01094-41) in the emergency setting project provides carrying out an observational multicenter international cohort study aimed to collect data about patients aged ≥75 years to assess modifiable risk factors for negative outcomes and mortality correlated to the emergency surgical management of this group of patients at risk admitted with a complicated (obstructed and perforated) CRC. The CO-OLDER protocol was approved by Institutional Review Board and released. Each CO-OLDER collaborator is asked to enroll ≥25 patients over a study period from 1st January 2018 to 30th October 2023. Data will be analyzed comparing two periods of study: before and after the COVID-19 pandemic. A sample size of 240 prospectively enrolled patients with obstructed colorectal cancer in a 5-month period was calculated. The secured database for entering anonymized data will be available for the period necessary to achieve the highest possible participation. RESULTS: One hundred eighty hospitals asked to be a CO-OLDER collaborator, with 36 potentially involved countries over the world. CONCLUSIONS: The CO-OLDER project aims to improve the management of elderly people presenting with a complicated colorectal cancer in the emergency setting. Our observational global study can provide valuable data on the effectiveness of different management strategies in improving primary assessment, management and outcomes for elderly patients with obstructed or perforated colorectal cancer in the emergency setting, guiding clinical decision-making. This information can help healthcare providers make informed decisions about the best course of action for these patients