A systematic review of randomised clinical trials for oralantibiotic treatment of acute pyelonephritis

AbstractThere is increasing resistance to the oral antibiotics currently recommended for the treatment of pyelonephritis, and increasedhealthcare costs are associated with the reliance on alternative intravenous agents.We, therefore, performed a systematic reviewof randomised controlled trials to determine the clinical efficacy and safety of oral antibiotics for the treatment of pyelonephritisin adults. A search of four major medical databases (MEDLINE, Embase+ Embase classic, CENTRAL and Cochrane Databasefor Systematic Reviews) in addition to manual reference searching of relevant reviews was conducted. Clinical cure and adverseevent rates were reported, and trial quality and bias were assessed. A total of 277 studies were reviewed; five studies matched alleligibility criteria and were included. Antibiotics included were cefaclor, ciprofloxacin, gatifloxacin, levofloxacin, lomefloxacin,loracarbef, norfloxacin, rufloxacin and trimethoprim-sulfamethoxazole. In included studies, the clinical success of the outpatienttreatment of pyelonephritis by cefaclor, ciprofloxacin and norfloxacin at 4 to 6 weeks was comparable at between 83 to 95%.Relatively high rates of adverse events were noted in a trial of ciprofloxacin (24%) and trimethoprim-sulfamethoxazole (33%).Significant heterogeneity between all aspects of the trial designs was identified, with all studies having a potential for bias. Thisreview demonstrates a need for high-quality clinical trials into the oral antibiotic treatment of pyelonephritis, with more consistentdesigns and reporting of outcomes. There are data to support further research into oral norfloxacin and cefaclor for the outpatienttreatment of pyelonephritis in adults.Keywords Pyelonephritis . Urinary tract infection . Antibiotic . Resistance . Ora

MelRisk: Using the neutrophil-to-lymphocyte ratio to improve risk prediction models for metastatic cutaneous melanoma in the sentinel lymph node

Background: Identifying metastatic melanoma in the sentinel lymph node (SLN) is important because 80% of SLN biopsies are negative and 11% of patients develop complications. The neutrophil-to-lymphocyte ratio (NLR), a biomarker of micrometastatic disease, could improve prediction models for SLN status. We externally validated existing models and developed ‘MelRisk’ prognostic score to better predict SLN metastasis. Methods: The models were externally validated using data from a multicenter cohort study of 1,251 adults. Additionally, we developed and internally validated a new prognostic score `MelRisk’, using candidate predictors derived from the extant literature. Results: The Karakousis model had a C-statistic of 0.58 (95% CI, 0.54–0.62). The Sondak model had a C-statistic of 0.57 (95% CI 0.53–0.61). The MIA model had a C-statistic of 0.60 (95% CI. 0.56–0.64). Our ‘MelRisk’ model (which used Breslow thickness, ulceration, age, anatomical site, and the NLR) showed an adjusted C-statistic of 0.63 (95% CI, 0.56–0.64). Conclusion: Our prediction tool is freely available in the Google Play Store and Apple App Store, and we invite colleagues to externally validate its performance

Real-world experience of SARS-CoV-2 antibody assays in UK healthcare workers

Background The seroprevalence of antibodies to SARS-CoV-2 in healthcare workers is variable throughout the world. This study compares the use of two antibody assays among large cohorts of healthcare workers in southern England. Methods This cohort study includes data obtained from staff at Western Sussex Hospitals NHS Foundation Trust (WSHT) and Brighton and Sussex University Hospitals (BSUH) during voluntary antibody testing, using Abbott and Roche SARS-CoV-2 antibody assays at each Trust respectively. Results The observed seroprevalence level was 7.9% for the WSHT/Abbott cohort versus 13% for the BSUH/Roche cohort. Based on a previous positive PCR, we find that the false-negative rate of the Abbott and Roche assays were 60.2% and 19% respectively, implying sensitivity levels of 39.8% and 81%. Within these cohorts, seropositivity was most strongly associated with those of South Asian ethnicity, allied health professionals and male sex (p<0.0001). Conclusions In this real-world study, neither antibody test performed to the specification level stated by the manufacturer. More rigorous testing of these and other assays in target populations is recommended prior to widespread usage if they are to provide data that might be useful to control the pandemic

The neutrophil–lymphocyte ratio and locoregional melanoma: a multicentre cohort study

Abstract Objectives The neutrophil–lymphocyte ratio (NLR) is an inflammatory biomarker which is useful in cancer prognostication. We aimed to investigate the differences in baseline NLR between patients with localised and metastatic cutaneous melanoma and how this biomarker changed over time with the recurrence of disease. Methods This multicentre cohort study describes patients treated for Stage I–III cutaneous melanoma over 10 years. The baseline NLR was measured immediately prior to surgery and again at the time of discharge or disease recurrence. The odds ratios (OR) for sentinel node involvement are estimated using mixed-effects logistic regression. The risk of recurrence is estimated using multivariable Cox regression. Results Overall 1489 individuals were included. The mean baseline NLR was higher in patients with palpable nodal disease compared to those with microscopic nodal or localised disease (2.8 versus 2.4 and 2.3, respectively; p &lt; 0.001). A baseline NLR ≥ 2.3 was associated with 30% higher odds of microscopic metastatic melanoma in the sentinel lymph node [adjusted OR 1.3 (95% CI 1.3, 1.3)]. Following surgery, 253 patients (18.7%) developed recurrent melanoma during surveillance although there was no statistically significant association between the baseline NLR and the risk of recurrence [adjusted HR 0.9 (0.7, 1.1)]. Conclusion The NLR is associated with the volume of melanoma at presentation and may predict occult sentinel lymph metastases. Further prospective work is required to investigate how NLR may be modelled against other clinicopathological variables to predict outcomes and to understand the temporal changes in NLR following surgery for melanoma. </jats:sec

A Retrospective Study Assessing the Effect of Diabetes on Mortality in Patients With COVID-19 at a Teaching Hospital in the United Kingdom.

Aim The aim of the study was to compare the clinical characteristics and outcomes (mortality, intensive care admission, mechanical ventilation, and length of stay, LoS) of patients with and without diabetes with confirmed COVID-19.  Methods This retrospective study evaluated clinical and laboratory variables in adult inpatients from Brighton and Sussex University Hospitals NHS Trust with laboratory-confirmed COVID-19 between March 10, 2020, and June 30, 2020. Univariate and multivariate analyses were performed to compare the outcomes of patients with and without diabetes.  Results Over 457 patients were included in this study (140 with diabetes and 317 without diabetes), of which 143 (31.9%) died. The median age was 80 years and were predominantly males (59.1%). Baseline characteristics at the time of COVID-19 diagnosis demonstrated that the patients with diabetes were younger than those without diabetes (p=0.008). Mortality increased with age. There was no difference in adverse outcomes in those with and without diabetes. However, subgroup analysis of patients aged ≤60 years demonstrated a significantly increased mortality in those with diabetes (p=0.016). Patients with diabetes had an increased length-of-stay compared to those without diabetes, which was more evident in those aged ≤60 years. Conclusion Age is the most important predictor of mortality. Patients with diabetes did not have increased mortality from COVID-19, which is likely due to their younger age in our cohort. More patients with diabetes stayed in the hospital longer than seven days than those without diabetes.</p

Baseline Neutrophil–Lymphocyte and Platelet–Lymphocyte Ratios as Biomarkers of Survival in Cutaneous Melanoma: A Multicenter Cohort Study

Background: In the peripheral blood, the neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) change in response to malignancy. These biomarkers are associated with adverse outcomes in numerous cancers, but the evidence is limited in relation to melanoma. This study sought to investigate the association between these biomarkers and survival in Stages I–III cutaneous melanoma. Methods: This multicenter cohort study investigated a consecutive series of patients who underwent wide excision of biopsy-proven cutaneous melanoma and sentinel lymph node biopsy during a 10-year period. The baseline NLR and PLR were calculated immediately before sentinel lymph node biopsy. Adjusted hazard ratios (HRs) for overall and melanoma-specific survival were generated. Results: Overall, 1351 patients were included in the study. During surveillance, 184 of these patients died (14%), with 141 of the deaths (77%) attributable to melanoma. Worse overall survival was associated with a baseline NLR lower than 2.5 [HR 2.2; 95% confidence interval (CI) 2.0 to 2.3; p < 0.001] and a baseline PLR lower than 100 (HR 1.8; 95% CI 1.7 to 1.8; p < 0.001). Melanoma-specific survival also was worse, with a baseline NLR lower than 2.5 (HR 1.9; 95% CI 1.6 to 2.2; p < 0.001) and a baseline PLR lower than 100 (HR 1.9; 95% CI 1.7 to 2.2; p < 0.001). The 5-year survival for patients with sentinel lymph node metastases and a low NLR and PLR was approximately 50%. Conclusion: This study provides important new data on biomarkers in early-stage melanoma, which contrast with biomarker profiles in advanced disease. These biomarkers may represent the host inflammatory response to melanoma and therefore could help select patients for adjuvant therapy and enhanced surveillance