Antibiotic research and development: business as usual?

This article contends that poor economic incentives are an important reason for the lack of new drugs and explains how the DRIVE-AB intends to change the landscape by harnessing the expertise, motivation and diversity of its partner

Real-world burden of chemotherapy-induced myelosuppression in patients with small cell lung cancer: a retrospective analysis of electronic medical data from community cancer care providers.

AIMS: Chemotherapy-induced myelosuppression, which commonly exhibits as neutropenia, anemia, or thrombocytopenia, represents a substantial burden for patients with cancer that affects health-related quality of life and increases healthcare resource utilization (HCRU). We evaluated the burden of myelosuppression among chemotherapy-treated patients with small cell lung cancer (SCLC) using real-world data from community cancer care providers in the Western United States. MATERIALS AND METHODS: This was a retrospective, observational analysis of electronic medical records (EMRs) from Providence St. Joseph Health hospital-associated oncology clinics between January 2016 and December 2019. Patient demographics were assessed from the date of first SCLC diagnosis in adult patients with chemotherapy-induced grade ≥3 myelosuppression in first-line (1L) or second-line-and-beyond (2L+) treatment settings. Myelosuppressive adverse events (AEs), treatment patterns, and HCRU were assessed from the date of chemotherapy initiation (index date) until 12 months, date of the last visit, date of death, or study end, whichever occurred earliest. RESULTS: Of 347 eligible patients with SCLC who had received chemotherapy (mean age 66; 49% female), all had received at least 1L treatment, and 103 (29.7%) had a 2L + treatment recorded within the EMR during the study period. Of 338 evaluable patients with longitudinal laboratory data, 206 (60.9%) experienced grade ≥3 myelosuppressive AEs, most commonly neutropenia, anemia, and thrombocytopenia (44.9, 41.1, and 25.4 per 100 patients, respectively). Rates of granulocyte colony-stimulating factor use and red blood cell transfusions were 47.0 and 41.7 per 100 patients, respectively. There was a trend toward increasing the use of supportive care interventions and visits to inpatient and outpatient facilities in patients with myelosuppressive AEs in more than one cell lineage. CONCLUSIONS: Chemotherapy-induced myelosuppression places a substantial real-world burden on patients with SCLC in the community cancer care setting. Innovations to protect bone marrow from chemotherapy-induced damage have the potential to reduce this burden

Real-world burden of myelosuppression in patients with small cell lung cancer (SCLC): Retrospective, longitudinal data analysis.

Background: Myelosuppression is a common side effect of chemotherapy (CT) that can compromise patient (pt) and economic outcomes. To evaluate the overall burden of myelosuppression, a longitudinal, patterns of care analysis was conducted among pts with SCLC treated with CT in routine clinical practice. Methods: Data were obtained from Providence St. Joseph Health electronic medical records between Jan 2016 and Dec 2019. Hematologic adverse events, treatment patterns, and hospital-based healthcare resource utilization and costs were assessed during the 12 months from first diagnosis of SCLC in pts who had CT-induced grade 3/4 myelosuppression in 1st or 1st/2nd/3rd-line (1/2/3L) treatment settings. Descriptive statistics were utilized to summarize key findings. Costs of care were calculated from actual treatment costs for inpatient, outpatient, and emergency room services after first diagnosis and treatment with CT. Professional billing was not included due to variability in physician employment by the system. Results: 347 pts were eligible for analysis; mean age (SD) was 66 (9.0) years, 49% were female, and 89% were Caucasian. Prominent comorbidities included chronic obstructive pulmonary disease (52%), diabetes (23%), and peripheral vascular disease (20%). 264 pts (76%) received 1L treatment only, while an additional 83 pts (24%) had both 1L and 2/3L treatment. Of 339 evaluable pts with longitudinal laboratory data, grade 3/4 cytopenias were reported as follows: 45%, neutropenia; 41%, anemia; and 25%, thrombocytopenia. 43% and 15% of pts received red blood cell or platelet transfusions, respectively. 49% of pts received prophylaxis (6%) or treatment (43%) with G-CSF, and 4% of pts were treated with erythropoiesis-stimulating agents. Average total costs of care (post initial-diagnosis and treatment) for pts without grade 3/4 hematologic events (n = 110) were $67,802 per pt throughout the 12 months’ follow-up. On average, annual per pt costs for those with grade 3/4 hematologic events were$131,047 for neutropenia, $95,954 for anemia, and$90,053 for thrombocytopenia. Conclusions: A large and meaningful proportion of pts had grade 3/4 myelosuppression with annual incremental associated costs per pt ranging from $22,251 for pts with thrombocytopenia to$63,245 for pts with neutropenia. Despite the availability of protocols of care and various rescue treatments, CT-induced myelosuppression places a significant real-world burden on pts and the healthcare system

A retrospective observational analysis of post-pandemic influenza-related outcomes in the United Kingdom, 2010–2014

This study set out to evaluate influenza- and respiratory-related illnesses recorded during primary care physician consultations in England following the H1N1 pandemic in 2009 and to enable the development of a dynamic disease model. Data were obtained from the Clinical Practice Research Datalink of primary care records over four influenza seasons (2010–2014). The primary outcome of the study was incidence of influenza- and respiratory-related diagnoses, calculated per practice and by season and age group. Upper respiratory tract infection diagnoses were most frequently recorded (mean seasonal practice level incidence; 3,762 consultations per 100,000 [SD = 1,989]), and influenza-related diagnoses were least frequently recorded across all seasons, except one. Incidence rates for the under 18 population were higher than those for the general population, in particular for upper respiratory tract infection (range of 8,024–9,950 versus 3,228–4,120, respectively) and otitis media diagnoses (2,668–3,652 versus 782–1,057, respectively). For influenza-related diagnoses, the 65+ age group, the 0 to <2 and 2 to <4 groups had a higher risk (risk ratio = 1.33, 1.12 and 1.16, respectively) than other age groups. This study provides valuable insight into the incidence of influenza- and respiratory-related diagnoses in the primary care setting in England, and suggests a higher burden of disease in young children and the elderly. The study also indicates that some influenza illness is likely to be reported under respiratory-related diagnoses, given the low incidence of influenza-related diagnoses in the study

European and Russian physician awareness of best management approaches for infections due to antibiotic-resistant Gram-negative bacteria

<p><b>Objectives:</b> The rapid spread of infections due to antibiotic-resistant, Gram-negative bacteria in Europe and surrounding regions requires a heightened level of awareness among physicians within their practice settings.</p> <p><b>Methods:</b> We surveyed 800 physicians who treat these infections across France, Germany, Spain, Italy, and Russia to assess their awareness of best management approaches.</p> <p><b>Results:</b> We found that more than two-thirds do not consider themselves highly aware of best management practices. The respondents are facing these resistant infections as evidenced by the antibiotics they report using and their stated interest in newer agents. Respondents indicated that precious time is lost waiting for culture results, but also said they will need more information about accuracy, use, and costs for adopting rapid molecular testing.</p> <p><b>Conclusions:</b> The survey further identified the need for treatment guidelines and clinical decision support tools that can be applied at the bedside.</p

Futibatinib for FGFR2 -Rearranged Intrahepatic Cholangiocarcinoma

Background: Alterations in fibroblast growth factor receptor 2 (FGFR2) have emerged as promising drug targets for intrahepatic cholangiocarcinoma, a rare cancer with a poor prognosis. Futibatinib, a next-generation, covalently binding FGFR1-4 inhibitor, has been shown to have both antitumor activity in patients with FGFR-altered tumors and strong preclinical activity against acquired resistance mutations associated with ATP-competitive FGFR inhibitors. Methods: In this multinational, open-label, single-group, phase 2 study, we enrolled patients with unresectable or metastatic FGFR2 fusion-positive or FGFR2 rearrangement-positive intrahepatic cholangiocarcinoma and disease progression after one or more previous lines of systemic therapy (excluding FGFR inhibitors). The patients received oral futibatinib at a dose of 20 mg once daily in a continuous regimen. The primary end point was objective response (partial or complete response), as assessed by independent central review. Secondary end points included the response duration, progression-free and overall survival, safety, and patient-reported outcomes. Results: Between April 16, 2018, and November 29, 2019, a total of 103 patients were enrolled and received futibatinib. A total of 43 of 103 patients (42%; 95% confidence interval, 32 to 52) had a response, and the median duration of response was 9.7 months. Responses were consistent across patient subgroups, including patients with heavily pretreated disease, older adults, and patients who had co-occurring TP53 mutations. At a median follow-up of 17.1 months, the median progression-free survival was 9.0 months and overall survival was 21.7 months. Common treatment-related grade 3 adverse events were hyperphosphatemia (in 30% of the patients), an increased aspartate aminotransferase level (in 7%), stomatitis (in 6%), and fatigue (in 6%). Treatment-related adverse events led to permanent discontinuation of futibatinib in 2% of the patients. No treatment-related deaths occurred. Quality of life was maintained throughout treatment. Conclusions: In previously treated patients with FGFR2 fusion or rearrangement-positive intrahepatic cholangiocarcinoma, the use of futibatinib, a covalent FGFR inhibitor, led to measurable clinical benefit