Study sheds more light on delamanid role in treating MDR-TB

first_imgA phase 3 trial of delamanid, a newer oral drug for treating multidrug-resistant tuberculosis (MDR-TB), found no statistically significant reduction in time to sputum culture conversion when compared to placebo, but that it was safe and well tolerated.Delamanid is one of the newer drugs for treating TB, but there are lingering concerns about side effects, including an increase in the QT interval, which can cause heart rhythm problems. The World Health Organization (WHO) has classified delamanid as a group C drug, because though phase 2 and 3 clinical trials have shown that it effective and well tolerated, strong evidence for its use as a priority drug is still lacking.An international research group published its findings of the trial, which spanned four global regions, on Jan 7 in an early online edition of The Lancet Respiratory Medicine.Sensitivity analysis favors delamanid inclusionThe study took place at 17 sites in seven countries (Estonia, Latvia, Lithuania, Moldova, Peru, the Philippines, and South Africa), enrolling adults with pulmonary MDR-TB who received either delamanid (100 milligram [mg]) twice a day for 2 months, followed by a 200-mg once-daily dose for 4 months or placebo. Both groups received their usual optimized background treatment regimen.Of patients screened between September 2011 and November 2013, 511 were randomly assigned—342 to delamanid and 170 to placebo. Of the group, 327 patients were culture-positive for MDR-TB at baseline and made up the efficacy analysis: 226 in the delamanid group and 101 in the placebo group.The median time to sputum culture conversion was 51 days in those who received delamanid and 57 days in patients who got placebo, which was nonsignificant based on a hazard ratio of 1.7 (95% confidence interval, 0.91 to 1.51, P = 0.2157).However, post hoc sensitivity analyses showed differences that favored treatments that included delamanid. Also, treatment outcome based on WHO definitions showed high success rates (81.3% for delamanid and 84.2% for placebo) and low mortality rates for both groups (5.3% for delamanid and 4.7% for placebo).The researchers also looked at newly acquired drug resistance in the two groups, which showed small numbers for both. Adverse events didn’t vary between the two groups, but 96 (28.2%) of 341 patients in the delamanid group had effects, mainly gastrointestinal, compared with 38 (22.4%) of 170 people in the placebo group. The team saw no difference in QT prolongation between the two groups.Drug’s role still emerging, but safety findings keyIn a related commentary, three experts from Italy wrote that the study is notable for its sample size, geographical heterogeneity, and comprehensive design. The experts are Rosella Centis, BScEcon, and Giovanni Battista Migliori, MD, with ICS Maugeri, a hospital group, and Giovanni Sotgiu, MD, PhD, with the University of Sassari.They wrote that suboptimal statistical power could explain the nonsignificant findings, nothing that the sensitivity analysis showed a better efficacy profile for delamanid, but they said more trials are needed to better understand the drug’s role in treating patients with MDR-TB.Though delamanid seems to be safe and well tolerated, the results from the well-conducted study don’t support including it as a priority drug for use in current regimens, the three wrote. They said more evidence is needed to fully understand the ability of delamanid and other new drugs to treat TB and possibly the latent form of the disease.In a Lancet audio interview, study coauthor Rajesh Gupta, MD, MPH, with Stanford University School of Medicine, said experts struggle to understand what overall benefit, if any, the important new drugs offer to patients. He added that, although aggregating data from programatic use is useful, it can’t replace the rigor or evidence gathered from randomized clinical trials.He said the study didn’t clarify the role for delamanid in MDR-TB treatment, and Gupta notes that any drug added to an optimized background regimens in MDR-TB treatment centers of excellence settings, a feature of the study sites, will likely not show additional benefit from an efficacy perspective.However, he said the safety findings solidify delamanid as perhaps one of the safest MDR-TB drugs.As a whole, the positive findings in the current study and from earlier phase 2 trial points in the same direction in terms of delamanid’s benefit, he noted. “The challenge, however, is to really understand how effective is delamanid in the currently evolving standard of care,” Gupta said, which factor in shorter regimens, fixed nonoptimized longer regimens, and regimens to reduce toxicity.See also:Jan 7 Lancet Respir Med abstractJan 7 Lancet Respir Med audio fileJan 7 Lancet Respir Med commentarylast_img read more

Salad kits linked to new E coli outbreak in US, Canada

first_imgThe US Centers for Disease Control and Prevention (CDC) warned consumers yesterday to avoid certain Fresh Express chopped salad kits now linked to a multistate Escherichia coli O157:H7 outbreak in the United States as well cases in five Canadian provinces.The CDC is also tracking an outbreak of E coli O157:H7 connected to romaine lettuce grown in Salinas, California. As of Dec 4, 102 people in 23 states have been sickened in that outbreak, and 58 people have been hospitalized.CDC officials are trying to determine whether romaine lettuce in the salad kits is the source of the newly reported outbreak.Three patients have kidney failureThe new outbreak has sickened eight people in three states, including three patients who developed hemolytic uremic syndrome, a type of kidney failure. No deaths have been reported. Four cases have been reported in Minnesota, three in Wisconsin, and one in North Dakota.Patients reported symptom onset from Nov 5 to 15, and they range in age from 21 to 91, with a median age of 32. Five of the patients are women, the CDC said.Of seven people who have been interviewed, all reported eating leafy greens in the week before developing symptoms, and six reported eating or maybe eating a Fresh Express Sunflower Crisp chopped salad kit.Canada reports 16 casesThe investigation is also being conducted with the Public Health Agency of Canada (PHAC), which has identified 16 cases of E coli in five eastern provinces likely linked to the same salad kits. Canadian patients reported symptom onset between Nov 5 and Nov 22, and four have been hospitalized. As in the US, no deaths have been reported.Investigations are still under way to determine what ingredient in the chopped salad kit is contaminated.”Romaine lettuce is one of the ingredients in the salad kit, but we do not know yet if this outbreak is related to a current outbreak linked to romaine lettuce from the Salinas, California, growing region,” the CDC said. “Preliminary information indicates that romaine lettuce in the salad kits eaten by some of the sick people likely came from the Salinas growing region.”Buyers and sellers should toss Fresh Express Sunflower Crisp Chopped Salad Kits, with a best-before date up to and including Dec 7, 2019, the CDC said. The kits are clearly marked on the front of the bag, and are labeled UPC 0 71279 30906 4, beginning with lot code Z.”Check your fridge for this salad kit,” the CDC said. “Don’t eat it. Throw it away. Even if some of the kit was eaten and no one got sick, throw the rest away.”See also:Dec 9 CDC noticeDec 8 PHAC noticeDec 4 CDC Salinas outbreak updatelast_img read more

Glasgow’s renaissance

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Gazprom secures €700 mln loan from Credit Agricole

first_img(L to R) Andrey Kruglov, Regis Monfront, and Erik Koebe (Image courtesy of Gazprom)Gazprom signed a five-year €700 million (Approx: US$740 million) with France’s Credit Agricole Corporate & Investment Bank.Andrey Kruglov, Gazprom’s deputy chairman, and Regis Monfront, deputy CEO of Credit Agricole CIB and Erik Koebe, president of Credit Agricole CIB (Russia) signed the agreement on Tuesday.Gazprom said it has been working with Credit Agricole since 1995. The French bank, a corporate and investment subdivision of the Credit Agricole Group, participated in a number of Gazprom deals with the purpose of attracting corporate and project financing.1 EUR = 1.05655 USD LNG World News Stafflast_img read more

Non-containerised goods down in Hamburg

first_imgNon-containerised imports were down 2.2 percent in the reporting period to 419,000 tonnes, with the growth of project cargo, timber and fruit shipments failing to offset downturns in paper, metal and vehicles.Meanwhile, exports of non-containerised goods fell 13 percent compared with the previous year at 776,000 tonnes, with growing timber, iron and steel cargoes failing to compensate for lower automobile exports.Overall, the port posted a total seaborne cargo throughput of 104.9 million tonnes for the first nine months of the year – up 0.3 percent compared with the same period of 2015. Cargo volumes in third quarter of 2016 rose 2.7 percent year-on-year to 34.7 million tonnes.Axel Mattern, joint ceo of Port of Hamburg Marketing, noted that cargo throughput at the German gateway has stabilised and is showing signs of increasing, with a “discernible” upwards trend in volumes.www.hafen-hamburg.delast_img read more

Club rugby approaches business end

first_imgAthlone teams will look to overcome a difficult start in the top three leagues of the Western Province Rugby Football Union (WPRFU) season.Super Leagues A, B and C will restart in a fortnight following a three-week postponement for the Muslim holy month of Ramadaan. In the Super League A, Primrose are sitting at the bottom of the log, having lost their four opening encounters. They have a minus one point to overcome. The division newcomers had an unfavourable draw to start their run in SLA as they faced sides that are normally found in the top half of the table, the likes of UCT and Union-Milnerton (Uni-Mil).This was always going to be a problem for Primrose who are still in a rebuilding phase after losing the majority of their players from last season.Perhaps the Rose’s will finally blossom next week when they host another struggling outfit, Paarl who have not bagged a win in six games. At the weekend, they lost 19-31 to Hamilton at home. They currently occupy 11th spot with five points.In other Super League A matches, Villager were shattered 3-69 by an invincible False Bay. False Bay are undefeated in six games and currently occupy second spot, while Villager sit in 10th spot with 11 points after two wins in six games.NTK hosted Uni-Mil in a one-sided affair in the northern suburbs.The 19-62 defeat was NTK’s fifth loss of the season. They are in 13th spot with a point next to their name. Uni-Mil have now won four out of seven matches and are in third spot with 23 points. In the Super League B, Surrey Estate Rangers will look to increase their one win record when they host Bellville next weekend. Rangers are in 14th spot with four points. Bellville have 22 points and they are chasing the top spot after winning four of their five opening games and find themselves in third place.In the Super League C, Manenberg Rangers, who last played last month, will look to overcome a rusty start to the season next weekend when they face Strand United at home. Manenberg Rangers are yet to register a win in four games. They are on a minus one point in 14th position. As it stands, Strand have bagged three wins in four encounters and are currently in eighth spot with 15 points.last_img read more

Novel approach

first_imgThe irresistible combination of culture, charity and immigration law was enough to send Obiter hotfooting it across London last week to hear novelist Marina Lewycka (pictured) reading excerpts from her latest book, Various Pets Alive and Dead. Author of the improbably named bestseller A Short History of Tractors in Ukrainian, Lewycka was the star turn at an Oxfam fundraising event hosted by City immigration firm Laura Devine. A raffle of signed copies of Lewycka’s books raised more than £1,000 for an Oxfam project to help people in Malawi become self-sufficient in food and fertiliser.last_img read more

Bombardier joint venture starts work on Serbian signalling upgrading

first_imgSERBIA: Bombardier Transportation has begun work on its first signalling project in Serbia, covering the 77·6 km Resnik – Valjevo section of the route from Beograd to Bar in Montenegro, of which 287 km is in Serbia. The infrastructure work will support an increase in the maximum speed on the route from 50 to 120 km/h.RZD International is managing the modernisation project on behalf of the Serbian infrastructure manager. The signalling element is being undertaken by the Bombardier Transportation (Signal) Ltd joint venture between Bombardier and Russian Railways, which has previously supplied signalling equipment for almost 300 stations across Russia, the Baltic States, CIS, Mongolia and Eastern Europe.The Serbian project is the first to get underway since RZD International and Bombardier signed a memorandum of understanding in June covering co-operation on infrastructure projects in the international market.last_img read more

Corrupt government officials in Uganda get tough warning from Museveni

first_img“This must stop or else people will be embarrassed. You shouldn’t ask investors to pay your children’s school fees, or do this and that. If you have a problem, call a clan meeting and solve it as a family, not through corruption,” President Museveni said in a series of tweets. Museveni revealed that the World Bank has issued loans and grants of $1.8 billion but only 10% of it has been utilized.“Tough action will be taken against government officials who negligently fail to utilize these funds,” he warned. Uganda’s Yoweri Museveni has issued a “tough warning” to government officials against corruption and the underutilization of loan funds.The country’s president expressed his disgust on some government officials’ attitudes who “solicit bribes and favours from investors, frustrating them in the process” during a cabinet meeting on Friday.center_img Museveni earlier announced that Uganda has recovered from its economical downturn and the country needs to kick out poverty.He also called on the security organs to stop “negative elements infiltrating decision-making centres of government.”last_img read more