Antibiotic development “alarmingly slow”
PROGRESS in the clinical development of new antibiotics remains “alarmingly slow” according to the authors of a report on the state of development and regulatory approval of new drugs in the US published in Clinical Infectious Diseases. The authors, members of the Infectious Diseases Society of America, conducted a literature review and investigation of the US clinical trials registry (clinicaltrials.org). They found that only two new oral antibiotics — telavancin and ceftaroline fosamil — had been approved for marketing in the US since their last report in 2009, a decline from 16 drugs approved in 1983–87. “Importantly, the number of large multinational pharmaceutical companies (ie, ‘Big Pharma’) actively developing antimicrobial drugs also continues to decline”, they wrote. “We identified 7 parenteral drugs in clinical development for treatment of infections caused by [multidrug-resistant gram-negative bacilli], and one whose phase 2 development program was recently halted.” The authors said the pace of research and development of new antibiotics must accelerate to reach the goal of 10 new systemic drugs to treat infections caused by resistant bacteria by 2020.
Tomosynthesis more accurate
INTEGRATED 2D and 3D mammography (tomosynthesis) in population-based breast cancer screening increases detection of breast cancer and can reduce false-positive recalls, according to the authors of a prospective comparison study published in The Lancet Oncology. A team of Australian and Italian researchers examined 2D and 3D screening to determine which was better at detecting cancers and reducing false positives compared with 2D screening alone. Their study involved 7292 women, with an average age of 58 years, screened in Italy. The screens were first reported using 2D mammograms, then using 2D and 3D mammograms combined. The researchers detected 59 cancers in 57 patients. Of the cancers detected 39 (66%) were found in both 2D and in integrated 2D and 3D screening; however, 20 (33%) were not found using 2D screening alone but were detected using integrated 2D and 3D screening. They also estimated that, if only patients with positive integrated 2D and 3D mammography were recalled, false positive recalls could be reduced by 17•2% without missing any of the detected cancers. “Our results do not warrant an immediate change to breast-screening practice, instead, they show the urgent need for randomised controlled trials of integrated 2D and 3D versus 2D mammography, and for further translational research in breast tomosynthesis”, the researchers wrote.
Ectopic pregnancy easy to miss
PATIENT history and clinical examination alone are not sufficient to indicate or eliminate the possibility of ectopic pregnancy, according to a meta-analysis published in JAMA. The analysis, which involved more than 12 000 patients, included prospective studies of 100 or more pregnant women with abdominal pain or vaginal bleeding that evaluated patient history, physical examination, laboratory values and sonography compared with a reference standard of either direct surgical visualisation of ectopic pregnancy or clinical follow-up for all pregnancies to prove that ectopic pregnancy was not missed. The researchers found that in a haemodynamically stable patient, an appropriate evaluation includes transvaginal sonography and quantitative (serial) serum human chorionic gonadotropin (hCG) testing. “Patients with signs and symptoms of excessive blood loss or hemodynamic collapse should immediately have gynecological evaluation”, the authors wrote.
Skin cancer may predict other cancers
PEOPLE with a history of non-melanoma skin cancer (NMSC) have a modest risk of being diagnosed with other cancers, according to prospective cohort study published in PLOS Medicine. Researchers used the Health Professionals Follow-up Study and the Nurses’ Health Study to document 29 447 incident cancer cases other than NMSC. The found a personal history of NMSC was significantly associated with a higher risk of other primary cancers excluding melanoma. Age-standardised absolute risk was 176 in men and 182 in women per 100 000 person-years. A personal history of NMSC was significantly associated with an increased risk of melanoma in men and with an increased risk of breast, lung and melanoma cancers in women. “Because our study was observational, these results should be interpreted cautiously and are insufficient evidence to alter current clinical recommendations”, the authors wrote. “Nevertheless, these data support a need for continued investigation of the potential mechanisms underlying this relationship.”
ART protects hearts of children with HIV
THE combination drug therapies now used to treat HIV appear to protect against the heart damage seen in children with HIV before combination therapies were available, according to research published in JAMA Pediatrics. Researchers compared echocardiographic measures of left ventricular structure and function between a cohort of HIV-infected children from an earlier study who were relatively unexposed to antiretroviral therapies (ART) and a more contemporary cohort of HIV-infected children who were more exposed to ART, usually highly active ART (HAART). About 45% of the children in the earlier study had an enlarged heart or substantial damage to the heart muscle, while only 4% in the HAART group had heart damage. The 325 contemporary HIV-infected children had lower viral loads, higher CD4 counts and longer durations of ART than the 70 HIV-infected children from the earlier study. “Our results indicate that the current use of combination ART, usually HAART, appears to be cardioprotective in HIV-infected children and adolescents”, the researchers wrote. “This finding is even more relevant in the developing world where the prevalence of HIV disease in children is much higher.”