Five recommended reads for the Armistice Day Centenary

To mark the he centenary of the Armistice that ended the First World War, LSE Book Reviews recommend five recent academic books that explore different aspects of the conflict, ranging from the significance of 1917, the crucial role played by women scientists and the often neglected experiences of Muslim combatants

Reading list: 5 recommended reads for the Armistice Day centenary

11 November 2018 is the centenary of the Armistice that ended World War One. To mark the occasion, we recommend five recent academic books that explore different aspects of the conflict, ranging from the significance of 1917, the crucial role played by women scientists and the often neglected experiences of Muslim combatants

Survival impact of postoperative therapy modalities according to margin status in non–small cell lung cancer patients in the United States

Objective Unlike complete (R0) resection guidelines, current National Comprehensive Cancer Network (NCCN) adjuvant therapy guidelines after incomplete (R1/R2) resection of non–small cell lung cancer (NSCLC) are based on low-level evidence. We attempted to validate them. Methods Patients with pathologic stage I-IIIA NSCLC from 2004 to 2011 in the National Cancer Database were stratified by margin status, NCCN-specified stage groupings, and adjuvant therapy exposure (none, radiotherapy, chemotherapy, or both). Five-year overall survival (OS) and hazard ratios, adjusted for patient and institutional characteristics, were compared. We used a parallel analysis of R0 resections to validate our methodology. Results We analyzed 3461 R1/R2, and 78,979 R0 resections. After R0 resection, the NCCN-recommended option was associated with the best survival across all stage groups, supporting our analytic approach. Patients with R1/R2 stage IA treated with radiation had a 26% OS, compared with 58% with no treatment (P = .003). In patients with stage IB/IIA(N0) R1/R2, radiation was associated with a 25% OS compared with 47% with no treatment (P = .025) and 62% with chemotherapy (P < .007). Chemoradiation was not associated with a survival benefit in either group. Patients with IIA(N1)/IIB and IIIA had better survival with chemotherapy or chemoradiation. No group had a survival benefit with radiation alone. Conclusions NCCN adjuvant therapy guidelines after complete resection, based on high-level evidence, are validated, but not guidelines for patients with incompletely resected early-stage NSCLC, which are based on low-level evidence. Monomodality postoperative radiotherapy was not validated for any stage. Specific studies are needed to determine optimal management after incomplete resection

Prognostic value of lymph node ratio in patients with pathological N1 non-small cell lung cancer: A systematic review with meta-analysis

Background: Non-small cell lung cancer (NSCLC) patients with N1 disease have variable outcomes, and additional prognostic factors are needed. The number of positive lymph nodes (LNs) has been proposed as a prognostic indicator. However, the number of positive LNs depends on the number of LNs examined from the resection specimen. The lymph node ratio (LNR) can circumvent this limitation. The purpose of this study is to evaluate LNR as a predictor of survival and recurrence in patients with pathologic N1 NSCLC. Methods: We systematically reviewed studies published before March 17, 2016, on the prognostic value of LNR in patients with pathologic N1 NSCLC. The hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to combine the data. We also evaluated heterogeneity and publication bias. Results: Five studies published between 2010 and 2014 were eligible for this systematic review with metaanalysis. The total number of patients included was 6,130 ranging from 75 to 4,004 patients per study. The combined HR for all eligible studies evaluating the overall survival (OS) and disease-free survival (DFS) of N1 LNR in patients with pathologic N1 NSCLC was 1.53 (95% CI: 1.22-1.85) and 1.64 (95% CI: 1.19-2.09), respectively. We found no heterogeneity and publication bias between the reports. Conclusions: LNR is a worthy predictor of survival and cancer recurrence in patients with pathological N1 NSCLC

NEOADJUVANT WEEKLY NAB-PACLITAXEL PLUS CARBOPLATIN FOLLOWED BY DOXORUBICIN PLUS CYCLOPHOSPHAMIDE WITH BEVACIZUMAB ADDED CONCURRENTLY TO CHEMOTHERAPY FOR OPERABLE TRIPLE-NEGATIVE INVASIVE BREAST CANCER

Purpose: This phase II neoadjuvant study investigated whether nab paclitaxel, carboplatin and bevacizumab given before neoadjuvant doxorubicin/cyclophosphamide (AC) produced higher pathologic complete response (pCR) rates in triple- negative breast cancer (TNBC) compared with historical results achieved with standard anthracycline/taxane regimens. Patients and Methods: Eligible patients with operable TNBC ≥2 cm received four cycles of carboplatin (area under the curve 6, day 1) plus nab-paclitaxel (100 mg/m2, days 1, 8 and 15) every 28 days, followed by four 14-day cycles of AC neoadjuvantly, with bevacizumab 10 mg/kg every 14 days for the rst 6 cycles of neoadjuvant chemotherapy, resuming postoperatively to complete 1 year of antibody treatment. In breast pCR and pCR (breast + nodes) were primary and secondary endpoints, respectively. Results: Due to slow accrual, the study was closed after enrollment of 42 of 60 planned patients. Of the 38 patients who underwent surgery (ef cacy population), 22 (58%) achieved an in-breast pCR and 19 (50%) achieved a pCR (breast + nodes). Neutropenia was the most common Grade 3/4 adverse event (57% Grade 3 and 31% Grade 4), but only 1 patient required hospitalisation and IV antibiotics for neutropenic fever. Other Grade 3/4 events included anaemia (24%), thrombocytopenia (29%) and peripheral neuropathy (Grade 3, 5%). Conclusion: Our results demonstrate a substantially higher pCR rate, both in-breast and breast + nodes, with the combination of nab paclitaxel plus carboplatin followed by AC, with concurrent bevacizumab, versus historic pCR rates with anthracycline-taxane regimens alone, supporting further investigation of this regimen, preferably in molecularly driven subsets, for the neoadjuvant treatment of patients with TNBC. Key words: Bevacizumab, breast cancer, carboplatin, nab-paclitaxel, neoadjuvant, triple-negative

Perceptions of US adolescents and adults with sickle cell disease on their quality of care

Importance: Sickle cell disease (SCD) is the most common inherited red blood cell disorder in the United States, and previous studies have shown that individuals with SCD are affected by multiple health disparities, including stigmatization, inequities in funding, and worse health outcomes, which may preclude their ability to access quality health care. This needs assessment was performed as part of the Sickle Cell Disease Implementation Consortium (SCDIC) to assess barriers to care that may be faced by individuals with SCD. Objective: To assess the SCD-related medical care experience of adolescents and adults with SCD. Design, Setting, and Participants: This one-time survey study evaluated pain interference, quality of health care, and self-efficacy of 440 adults and adolescents (aged 15 to 50 years) with SCD of all genotypes and assessed how these variables were associated with their perceptions of outpatient and emergency department (ED) care. The surveys were administered once during office visits by trained study coordinators at 7 of 8 SCDIC sites in 2018. Results: The SCDIC sites did not report the number of individuals approached to participate in this study; thus, a response rate could not be calculated. In addition, respondents were not required to answer every question in the survey; thus, the response rate per question differed for each variable. Of 440 individuals with SCD, participants were primarily female (245 [55.7%]) and African American (428 [97.3%]) individuals, with a mean (SD) age of 27.8 (8.6) years. The majority of participants (306 of 435 [70.3%]) had hemoglobin SS or hemoglobin S β0-thalassemia. Most respondents (361 of 437 [82.6%]) reported access to nonacute (usual) SCD care, and the majority of respondents (382 of 413 [92.1%]) noted satisfaction with their usual care physician. Of 435 participants, 287 (66.0%) reported requiring an ED visit for acute pain in the previous year. Respondents were less pleased with their ED care than their usual care clinician, with approximately half (146 of 287 [50.9%]) being satisfied with or perceiving having adequate quality care in the ED. Participants also noted that when they experienced severe pain or clinician lack of empathy, this was associated with a negative quality of care. Age group was associated with ED satisfaction, with younger patients (\u3c19 vs 19-30 and 31-50 years) reporting better ED experiences. Conclusions and Relevance: These results suggested that a negative perception of care may be a barrier for patients seeking care. These findings underscore the necessity of implementation studies to improve access to quality care for this population, especially in the acute care setting

Identifying barriers to evidence-based care for sickle cell disease: Results from the Sickle Cell Disease Implementation Consortium cross-sectional survey of healthcare providers in the USA

OBJECTIVES: Sickle cell disease (SCD) leads to chronic and acute complications that require specialised care to manage symptoms and optimise clinical results. The National Heart Lung and Blood Institute (NHLBI) evidence-based guidelines assist providers in caring for individuals with SCD, but adoption of these guidelines by providers has not been optimal. The objective of this study was to identify barriers to treating individuals with SCD. METHODS: The SCD Implementation Consortium aimed to investigate the perception and level of comfort of providers regarding evidence-based care by surveying providers in the regions of six clinical centres across the USA, focusing on non-emergency care from the providers\u27 perspective. RESULTS: Respondents included 105 providers delivering clinical care for individuals with SCD. Areas of practice were most frequently paediatrics (24%) or haematology/SCD specialist (24%). The majority (77%) reported that they were comfortable managing acute pain episodes while 63% expressed comfort with managing chronic pain. Haematologists and SCD specialists showed higher comfort levels prescribing opioids (100% vs 67%, p=0.004) and managing care with hydroxyurea (90% vs 51%, p=0.005) compared with non-haematology providers. Approximately 33% of providers were unaware of the 2014 NHLBI guidelines. Nearly 63% of providers felt patients\u27 medical needs were addressed while only 22% felt their mental health needs were met. CONCLUSIONS: A substantial number of providers did not know about NHLBI\u27s SCD care guidelines. Barriers to providing care for patients with SCD were influenced by providers\u27 specialty, training and practice setting. Increasing provider knowledge could improve hydroxyurea utilisation, pain management and mental health support

Ellagic Acid Derivatives from Rubus ulmifolius Inhibit Staphylococcus aureus Biofilm Formation and Improve Response to Antibiotics

Biofilms contribute to the pathogenesis of many forms of Staphylococcus aureus infection. Treatment of these infections is complicated by intrinsic resistance to conventional antibiotics, thus creating an urgent need for strategies that can be used for the prevention and treatment of biofilm-associated infections.This study demonstrates that a botanical natural product composition (220D-F2) rich in ellagic acid and its derivatives can limit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility. The source of this composition is Rubus ulmifolius Schott. (Rosaceae), a plant used in complementary and alternative medicine in southern Italy for the treatment of skin and soft tissue infections. All S. aureus clonal lineages tested exhibited a reduced capacity to form a biofilm at 220D-F2 concentrations ranging from 50-200 µg/mL, which were well below the concentrations required to limit bacterial growth (530-1040 µg/mL). This limitation was therapeutically relevant in that inclusion of 220D-F2 resulted in enhanced susceptibility to the functionally-distinct antibiotics daptomycin, clindamycin and oxacillin. Testing with kidney and liver cell lines also demonstrated a lack of host cell cytotoxicity at concentrations of 220D-F2 required to achieve these effects.These results demonstrate that extract 220D-F2 from the root of Rubus ulmifolius can be used to inhibit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility without toxic effects on normal mammalian cells. Hence, 220D-F2 is a strong candidate for development as a botanical drug for use in the prevention and treatment of S. aureus biofilm-associated infections

An Epidemiologic Evaluation of Sickle Cell Disease in the United States: Birth Prevalence, Distance as a Barrier to Care, and Potential Bias in a Clinical Trial of Hydroxyurea

Sickle cell disease (SCD) is an inherited hematologic disorder in which abnormal hemoglobin results in misshapen red blood cells. SCD results in increased morbidity including pain crises, acute chest syndrome and chronic organ damage, often requiring acute medical care and hospitalization. We conducted three epidemiologic studies related to birth prevalence, access to care, and chronic organ damage in children with SCD. First, we evaluated SCD and sickle cell trait (SCT) birth prevalence in Shelby County, TN from 2002-2012. The birth prevalence among African Americans was 3.5 (95% CI: 3.1, 3.9) per 1000 live births for SCD and 68.1 (95% CI: 66.5, 69.7) per 1000 live births for SCT. We observed higher birth prevalence of SCD and lower birth prevalence of SCT than expected based on national estimates. Next, the association between travel distance from home to St. Jude Children\u27s Research Hospital, a comprehensive sickle cell center, and the rate of clinic visits and hospitalizations among children with SCDwas studied. We found patients =35 miles, indicating distance may be a barrier to health care access. Bias analysis suggested that under-reporting could explain the observed differences in hospitalization rates if 30%of patients who lived \u3e=35 miles from the hospital under-reported six hospitalizations over six years. The final study evaluated potential bias from missing data in a previously published multi-center randomized, placebo-controlled trial of hydroxyurea therapy on spleen and kidney function among infantswith SCD. Thirteen percent and 31% of randomized subjects did not have follow-up data for the spleen and kidney objectives, respectively. We did not find evidence of bias from missing data in the kidney objective, however, the true effect of hydroxyurea on spleen function could have been underestimated due to differential attrition. Additionally, even if the effect of hydroxyurea on spleen function was attenuated substantially due to missing data, the magnitude of the effect of hydroxyurea is likely smaller than originally hypothesized in the clinical trial