Predictors of In-Hospital Mortality in Older Inpatients with Suspected Infection.

OBJECTIVES: To determine the rate and predictors of death in older individuals with suspected infection at any time during hospital stay in a geriatric acute ward and the prognostic ability of different tools [quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA), Modified and National Early Warning Scores (MEWS) and (NEWS)] in such population. DESIGN: Prospective observational single-center cohort study. SETTING AND PARTICIPANTS: Among patients admitted to an acute geriatric unit of an Italian University Hospital with at least 1 sepsis risk factor, all subjects with suspected infection at admission or during hospital stay (defined as antibiotic prescription and associated culture test) were considered. METHODS: A geriatric assessment including comorbidity and social, functional, and cognitive status was performed for each patient. Clinical parameters were evaluated at least twice daily throughout hospital stay; qSOFA, MEWS, and NEWS were derived, with positive cutoffs set at ≥2, ≥5, and ≥7, respectively. RESULTS: Among 305 older inpatients (median age 86.0 years, 49.2% female), 21% died during hospital stay. Sepsis was diagnosed in 31.8% of the overall sample and in 64.1% of deceased patients. Deceased patients showed a significantly higher prevalence of prior institutionalization, functional dependence, cognitive impairment, and multimorbidity. The prognostic accuracy of the qSOFA score at infection onset was only fair (area under the receiver operating characteristic curve 0.72; 95% CI, 0.65-0.79, P < .001) and comparable with that of MEWS and NEWS. After multivariable analysis, in-hospital death was positively associated with male sex [odds ratio (OR), 2.11; 95% CI, 1.01-4.44; P = .048] and abnormal white blood cells count (OR, 4.93; 95% CI, 2.36-10.29; P < .001), platelet count (OR, 2.61; 95% CI, 1.10-6.16; P = .029) and serum creatinine (OR, 2.70; 95% CI, 1.30-5.61; P = .008), along with any of the score considered, and negatively associated with autonomy in instrumental activities (OR, 0.78; 95% CI, 0.68-0.90; P < .001). CONCLUSIONS: Prognosis in older inpatients with infection or sepsis appears to be determined both by the geriatric characteristics and by the severity of the acute event, expressed by recommended tools and blood test results.

Characterization by LC-MS/MS of oxidized products identified in synthetic peptide somatostatin and cetrorelix submitted to forced oxidative stress by hydrogen peroxide: Two case studies.

In a broader scenario, the forced degradation studies provided by the ICH guidelines for Q1A, Q1B, and Q2B degradation studies allow to know the CQA of the molecule used as a drug product, to determine the appropriate analytical methods, excipients, and storage conditions ensuring the quality of the drug, its efficacy, and patient safety. In this study, we focused our attention on understanding how oxidative stress is performed by H2 O2 -impacted small synthetic peptides that do not contain residues susceptible to oxidation such as methionine. Among the amino acids susceptible to oxidation, methionine is the most reactive and depending on the structure of the protein where it is exposed, it tends to oxidize by converting into methionine sulfone or methionine sulfoxide by oxidation of its sulfur atom. Scouting experiments obtained by forced oxidative stress conditions are presented on two small synthetic peptides that do not contain any methionine residues spiked with different amounts of H2 O2 , and they are analyzed by LC-MS/MS. Less frequent oxidation products than those commonly observed on proteins/peptides-containing methionine have been characterized on both peptides. The study demonstrated that somatostatin, by means of one residue of tryptophan on the molecule, can generate traces of several oxidized products detected by UPLC-MS. Furthermore, even at a negligible level, oxidation on tyrosine and proline in cetrorelix that does not contain methionine nor tryptophan has been detected by UHPLC-MS/MS. Identification and quantification of oxidized species were achieved by high-resolution MS and MS/MS experiments. Thus, FDSs undoubtedly aid the evaluation of the CQAs as an important component of the characterization package as recommended by HAs and ICH, facilitating the understanding of unforeseen features of the studied molecule used as drugs.

Industry Perspective on the Use and Characterization of Polysorbates for Biopharmaceutical Products Part 2: Survey Report on Control Strategy Preparing for the Future.

Polysorbate (PS) 20 and 80 are the main surfactants used to stabilize biopharmaceutical products. Industry practices on various aspects of PS based on a confidential survey and following discussions by 16 globally acting major biotechnology companies is presented in two publications. Part 1 summarizes the current practice and use of PS during manufacture in addition to aspects like current understanding of the (in)stability of PS, the routine QC testing and control of PS, and selected regulatory aspects of PS.1 The current part 2 of the survey focusses on understanding, monitoring, prediction, and mitigation of PS degradation pathways in order to propose an effective control strategy. The results of the survey and extensive cross-company discussions are put into relation with currently available scientific literature.

Industry Perspective on the use and Characterization of Polysorbates for Biopharmaceutical Products Part 1: Survey Report on Current State and Common Practices for Handling and Control of Polysorbates.

Polysorbates (PS) are widely used as a stabilizer in biopharmaceutical products. Industry practices on various aspects of PS are presented in this part 1 survey report based on a confidential survey and following discussions by 16 globally acting major biotechnology companies. The current practice and use of PS during manufacture across their global manufacturing sites are covered in addition to aspects like current understanding of the (in)stability of PS, the routine QC testing and control of PS, and selected regulatory aspects of PS. The results of the survey and extensive cross-company discussions are put into relation with currently available scientific literature. Part 2 of the survey report (upcoming) will focus on understanding, monitoring, prediction, and mitigation of PS degradation pathways to develop an effective control strategy.

Comparison of Diagnostic Accuracies of qSOFA, NEWS, and MEWS to Identify Sepsis in Older Inpatients With Suspected Infection.

OBJECTIVES: To determine and compare the accuracies of the quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) and Modified and National Early Warning Scores (NEWS and MEWS) to identify sepsis in older inpatients with suspected infection. DESIGN: Prospective diagnostic accuracy study. SETTING AND PARTICIPANTS: Patients admitted to an acute geriatric unit of an Italian University Hospital with at least one sepsis risk factor and suspected infection defined as antibiotic prescription and associated culture test during hospital stay. METHODS: Sepsis diagnosis was defined as the presence on discharge documents of International Classification of Diseases, Ninth revision, Clinical Modification codes for severe sepsis, septic shock, or for infection and acute organ disfunction. For each patient, clinical parameters were evaluated at least twice daily throughout hospital stay; qSOFA, NEWS, and MEWS were derived, and worst scores recorded. Positive cutoffs were set at ≥2, ≥7, and ≥5, respectively. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and positive and negative likelihood ratios, as well as areas under the receiver operating characteristic curve (AUROCs) were calculated. RESULTS: Among 230 geriatric patients with suspected infection at risk for sepsis (median age 86 years, 49% women), 30.9% had a sepsis diagnosis. A qSOFA ≥2 was recorded in 111 (48.3%) patients, a MEWS ≥5 in 65 (28.3%), and a NEWS ≥7 in 115 (50.0%). The qSOFA showed the highest sensitivity [81.7%, 95% confidence interval (CI) 71.7%-89.5%], but low specificity (66.7%, 95% CI 59.1%-73.7%), resulting in a high NPV (89.1%; 95% CI 82.7%-93.8%) and poor PPV (52.3%, 95% CI 43.0%-61.4%). The AUROC for qSOFA was 0.76 (95% CI 0.69-0.83), comparable with that of NEWS (0.74, 95% CI 0.67-0.81, P = .44), but significantly higher than that of MEWS (0.70, 95% CI 0.63-0.77, P = .04). CONCLUSIONS AND IMPLICATIONS: Repeated qSOFA determinations are useful to rule out sepsis in geriatric inpatients with suspected infection, but poorly support its diagnosis due to low specificity. More complex MEWS and NEWS do not perform better. Implementation of clinical scores to reliably identify sepsis in older patients is urgently needed.

Red cell distribution width predicts mid-term prognosis in patients hospitalized with acute heart failure: the RDW in Acute Heart Failure (RE-AHF) study.

The aim of the study was to evaluate the prognostic role of red cell distribution width (RDW) in a broad population of patients hospitalized for acute heart failure (AHF). In a retrospective cohort observational study, 451 consecutive patients discharged for AHF were categorized in patients with low RDW (≤ 14.8%) and high RDW (> 14.8%). The rates of death from all causes or of hospital readmission for worsening heart failure and death were determined after a median follow-up of 18 months. The overall population has a median age of 80 years (IQR 72-85), 235 patients (52%) were males. Patients with a higher RDW have more comorbidities and a higher Charlson Index. At follow-up, 200 patients (44%) had died and 247 (54%) had died or were readmitted for HF: in the cohort with low RDW, 70 patients (36.4%) had died, whereas in the cohort with high RDW, 165 patients (63.7%) had died: the unadjusted risk ratio of patients with high RDW was 2.03 (log-rank test: p < 0.0001). In a multivariate Cox regression model, the hazard ratio for death from any cause in the 'high RDW' cohort is 1.73 (95% confidence interval 1.2-2.48; p = 0.003); the RDW adds prognostic information beyond that provided by conventional predictors, including age; etiology of HF; anemia; hyponatremia; estimated glomerular filtration rate; NT-proBNP levels; Charlson comorbidity score, atrial fibrillation, functional status, therapy with renin-angiotensin-aldosterone system inhibitors, beta-blockers. RDW is a powerful marker of worse long-term outcomes in patients with AHF, and its prognostic value is maintained beyond that provided by other well-established risk factors or biomarkers.

Characteristics and management of pyogenic liver abscess: A European experience.

Pyogenic liver abscess (PLA) are space-occupying lesions in the liver associated with high morbidity and mortality. The aim of this study is to review an Italian hospital experience in epidemiological, clinical patterns, and management of PLA.We performed a retrospective, descriptive case series at a single center assessing demographic characteristics, presentation patterns, etiological factors, microbiological etiology, and management for patients treated for PLA between 2000 and 2016.Around 109 patients were identified. The majority of patients presented with fever (73%); right upper abdominal pain in 63.3%, vomiting and nausea in 28.4%. The most common laboratory abnormality among included items was increased C-reactive protein and fibrinogen blood levels, respectively, in 98% and 93.9% of cases. Abdominal ultrasound was the diagnostic investigation in 42.4% of cases; CT scan and MR imaging were performed in 51.1% and 3.3% of cases respectively. We observed blood or pus culture study in 99 cases of which only 53.5% came with positive microbial reports. The most common organism identified was Escherichia coli (26.5%), followed by Streptococcus spp (13.2%). Early antibiotic treatment started on all patients and 66.7% of cases required different approaches, Ultrasound or CT-guided needle aspiration of PLA was performed in 13 patients (11%) and percutaneous abscess drainage was performed on 72 patients (67%).PLA is a diagnostically challenging problem due to nonspecific presenting characteristics. The microbiological yield identified was a typical European spectrum with a preponderance of Escherichia coli infections. Once recognized, percutaneous drainage and antibiotic treatment are the mainstay of management for PLA.