Incidence of lung cancer following pneumonia in smokers: a population-based study.

BACKGROUND: Pneumonia is more common in smokers compared with non-smokers. A high 1-year prevalence of lung cancer following hospitalization for pneumonia was demonstrated in heavy smokers. AIM: To assess the association between hospitalization for pneumonia among ever-smokers and subsequent lung cancer risk. DESIGN: Retrospective analysis. METHODS: The study cohort included all ever-smokers aged 55-80 hospitalized for pneumonia between the years 2010-15 covered by a large medical insurer in Israel. Controls were matched to cases by age in a 4:1 ratio. The primary outcome was the association between hospitalization for pneumonia and subsequent 1-year incidence of lung cancer, adjusted for gender, smoking status (past/current) and pack years. Pre-specified sensitivity analyses excluded heavy smokers (smoking history of more than 30 pack years) and patients diagnosed with lung cancer within 30 days of hospitalization, as they probably had clinical or radiological findings suggestive of lung cancer, making them ineligible for screening. RESULTS: Lung cancer was identified in 275 of 12 807 (2.1%) patients following hospitalization for pneumonia and in 44 of 51 228 (0.1%) controls (adjusted odds ratio 22.46, 95% CI 16.29-30.96, P < 0.001). Among patients hospitalized for pneumonia, 1-year lung cancer incidence remained high after excluding heavy smokers and patients diagnosed within 30 days of the index date (1.3% and 1.4%, respectively). CONCLUSIONS: Hospitalization for pneumonia is associated with high 1-year incidence of lung cancer in ever-smokers, supporting the important role of the widely used practice of performing follow up imaging post-pneumonia to exclude occult malignancy.

Reporting infections in clinical trials of patients with haematological malignancies.

BACKGROUND: Infections are common among patients treated for haematological malignancies and are associated with significant morbidity and mortality. The completeness of reporting infectious complications in randomized controlled trials (RCTs) assessing treatments for haematological malignancies is unknown. OBJECTIVES: We aimed to evaluate the completeness of reporting infectious complications in RCTs assessing treatments for haematological malignancies. DATA SOURCE: A systematic literature search was performed in PubMed database. STUDY ELIGIBILITY CRITERIA AND PARTICIPANTS: All primary published phase II/III RCTs between September 2016 and September 2018 evaluating treatments for haematological malignancies in adult patients were included. INTERVENTION: Reporting infectious complications. METHODS: A systematic review was conducted to evaluate the completeness of reporting. Study characteristics and data concerning reporting of infectious complications were collected by two independent reviewers. Quality of reporting was assessed using a modification of the CONSORT extension checklist for harms, including 15 items. RESULTS: One-hundred and seven RCTs were included. Most trials (97; 91%) provided some report on infections. Approximately half reported on each of pneumonia, sepsis and neutropenic fever; 12 trials (11%) reported on fungal infections. Only nine trials (8%) listed infections by type of pathogen (i.e. bacterial, fungal or viral) and 48 (45%) by source/type of infection (i.e. pneumonia, urinary tract infection, etc.). Most trials did not address infections in their title, abstract, introduction or discussion. Median number of items of the CONSORT modification reported was 7 points, (interquartile range (IQR) 6-9) for all included trials, with lower median for 34 acute leukaemia trials (median 6, IQR 5-8). CONCLUSIONS: Most trials evaluating treatment for haematological malignancies provide some data relating to infectious complications. The reports are mostly incomplete and rarely provided in a structured presentation.

Comparison of reporting phase III randomized controlled trials of antibiotic treatment for common bacterial infections in ClinicalTrials.gov and matched publications.

OBJECTIVES: Discrepancies between ClinicalTrials.gov entries and matching publications were previously described in general medicine. We aimed to evaluate the consistency of reporting in trials addressing systemic antibiotic therapy. METHODS: We searched ClinicalTrials.gov for completed phase III trials comparing antibiotic regimens until May 2017. Matched publications were identified in PubMed. Two independent reviewers extracted data and identified inconsistencies. Reporting was assessed among studies started before and after 1 July 2005, when the International Committee of Medical Journal Editors (ICMJE) required mandatory registration as a prerequisite for considering a trial for publication. RESULTS: Matching publications were identified for 75 (70%) of 107 ClinicalTrials.gov entries. Median time from study completion to publication was 26 months (interquartile range 19-42). Primary outcome definition was inconsistent between ClinicalTrials.gov and publications in seven trials (7/72, 10%) and reporting of the primary outcome timeframe was inconsistent in 14 (14/71, 20%). Secondary outcomes definitions were inconsistent in 36 trials (36/66, 55%). Reporting of inclusion criteria and study timeline were inconsistent in 17% (13/65) and 3% (2/65), respectively. Trials started after July 2005 were significantly less likely to have reporting inconsistencies and were published in higher impact factor journals. CONCLUSIONS: We found a lower inconsistency rate of outcome reporting compared with other medical disciplines. Reporting completeness and consistency were significantly better after July 2005. The ICMJE requirement for mandatory registration was associated with significant improvement in reporting quality in infectious diseases trials. Prolonged time lag to publication and missing data from unpublished trials should raise a discussion on current reporting and publishing procedures.

Comparison of published and unpublished phase I clinical cancer trials: an analysis of the CliniclTrials.gov database.

Introduction The role of phase I cancer trials is constantly evolving and they are increasingly being used in 'go/no' decisions in drug development. As a result, there is a growing need to ensure trials are published when completed. There are limited data on the publication rate and the factors associated with publication in phase I trials. Methods The ClinicalTrials.gov database was searched for completed adult phase I cancer trials with reported results. PubMed was searched for matching publications published prior to April 1, 2017. Logistic regression was used to identify factors associated with unpublished trials. Linear regression was used to explore factors associated with time lag from study database lock to publication for published trials. Results The study cohort included 319 trials. 95 (30%) trials had no matching publication. Thirty (9%) trials were not published in abstract form as well. On multivariable analysis, the most significant factor associated with unpublished trials was industry funding (odds ratio 3.3, 95% confidence interval 1.7-6.6, p=0.019). For published trials, time lag between database lock and publication was longer by 10.9 months (standard error 3.6, p<0.001) for industry funded trials compared with medical center funded trials. Conclusions Timely publishing of early cancer clinical trials results remains unsatisfactory. Industry funded phase I cancer trials were more likely to remain unpublished, and were associated with a longer time lag from database lock to publication. Policies that promote transparency and data sharing in clinical trial research might improve accountability among industry and investigators and improve timely results publication.

Comparison of reporting phase I trial results in ClinicalTrials.gov and matched publications.

Background Data on completeness of reporting of phase I cancer clinical trials in publications are lacking. Methods The ClinicalTrials.gov database was searched for completed adult phase I cancer trials with reported results. PubMed was searched for matching primary publications published prior to November 1, 2016. Reporting in primary publications was compared with the ClinicalTrials.gov database using a 28-point score (2=complete; 1=partial; 0=no reporting) for 14 items related to study design, outcome measures and safety profile. Inconsistencies between primary publications and ClinicalTrials.gov were recorded. Linear regression was used to identify factors associated with incomplete reporting. Results After a review of 583 trials in ClinicalTrials.gov , 163 matching primary publications were identified. Publications reported outcomes that did not appear in ClinicalTrials.gov in 25% of trials. Outcomes were upgraded, downgraded or omitted in publications in 47% of trials. The overall median reporting score was 23/28 (interquartile range 21-25). Incompletely reported items in >25% publications were: inclusion criteria (29%), primary outcome definition (26%), secondary outcome definitions (53%), adverse events (71%), serious adverse events (80%) and dates of study start and database lock (91%). Higher reporting scores were associated with phase I (vs phase I/II) trials (p<0.001), multicenter trials (p<0.001) and publication in journals with lower impact factor (p=0.004). Conclusions Reported results in primary publications for early phase cancer trials are frequently inconsistent or incomplete compared with ClinicalTrials.gov entries. ClinicalTrials.gov may provide more comprehensive data from new cancer drug trials.

Educational interventions encouraging appropriate use of blood transfusions.

BACKGROUND AND OBJECTIVES: The integration of a restrictive packed red blood cells (PRBC) transfusion strategy into daily clinical practice presents a challenge. This study describes the effect of an intervention including educational presentations and computerized alerts on PRBC utilization at a tertiary hospital. MATERIALS AND METHODS: During December 2014, lectures describing recommended PRBC transfusion indications were presented to all non-intensive care departments. Starting from January 2015, an alert was added to the electronic drug ordering system recommending transfusions at a haemoglobin (Hb) level <7 g/dl or Hb < 8 g/dl in symptomatic patients. The physician was not required to acknowledge the alert. Data regarding measured Hb preceding transfusions were collected. The primary end-point was defined as the percentage of PRBC administered at Hb ≥ 8 g/dl in 2015 compared with 2014. Secondary end-points were the percentage of PRBC administered to patients with Hb < 7 g/dl and the absolute number of PRBC transfused in 2015 compared with 2014. RESULTS: Compared to 2014, in 2015, the percentage of PRBC transfused when the Hb ≥ 8 g/dl was reduced by 18·8% (P < 0·001) and made up 29% of the total PRBC transfused. The absolute number of PRBC transfused decreased by 7·7%. The percentage of PRBC transfused when the Hb < 7 g/dl increased by 25·9% (P < 0·001). CONCLUSIONS: Following the described intervention, there was a significant improvement in the appropriateness of PRBC transfusions in our medical centre. These changes occurred despite the lack of interruption of the physician's workflow from the computerized alert. This simple strategy might be of use in implementing a restrictive PRBC transfusion strategy.

Malignancy associated SIADH: Characterization and clinical implications.

PURPOSE: To determine the distribution of etiologies for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in hospitalized patients with active malignancies and to characterize them according to the different etiologies. METHODS: A single center retrospective study including all patients with active malignancies diagnosed with SIADH in a large community hospital and tertiary center between 1 January 2007 and 1 January 2013. Two physicians reviewed every patient's medical file for predetermined relevant clinical data. RESULTS: The study cohort included 204 patients. 74.4% of those with solid tumors had metastatic disease. Most patients (149, 73%) had malignancy associated SIADH, while 55 (27%) had SIADH due to other etiologies. All of the major malignancy types were implicated in SIADH. Patients with breast cancer without lung or brain involvement were significantly less likely to be diagnosed with malignancy associated SIADH compared with other malignancies [Odds ratio (OR) 0.031, 95% CI 0.003-0.25, p < 0.001]. Patients with malignancy associated SIADH had lower serum sodium concentrations on short-term follow-up (p = 0.024) and significantly shorter median survival (58 vs. 910 days, p < 0.001). Short-term hyponatremia correction was associated with better survival. CONCLUSIONS: SIADH is associated with most malignancy types. Physicians caring for patients with breast cancer without lung or brain involvement diagnosed with SIADH without an obvious etiology should consider obtaining lung and brain imaging to rule out undiagnosed metastatic spread. Patients with malignancy associated SIADH have considerably worse outcomes compared to cancer patient with SIADH due to other etiologies. Short-term sodium concentration can be used as a prognostic marker for these patients.

Prediction and prevention of autoimmune diseases: additional aspects of the mosaic of autoimmunity.

Autoimmune connective tissue diseases are chronic, potentially life threatening complex multisystem disorders. Their etiology is unknown but genetic, hormonal and environmental factors are important. The clinical disease is preceded by a long period of time (sometimes many years) when the patients can be identified by characteristic antibodies in their serum. When such a patient is identified he is usually followed and treated if clinical disease manifests itself. However, other factors besides the existence of autoantibodies have a predictive value for those disorders; some of them hereditary or genetic, and can be used only to predict likelihood of future disease, and others, connected to lifestyle and environment, could be modified in order to try and prevent it. Several non-randomized small scale studies have suggested that autoimmune disease could be prevented if treated aggressively prior to manifestations of symptoms. However, if such is the case, criteria would have to be formalized for selection of patients for this preventive treatment. Only patients whose probability to develop clinical disease is higher then a certain threshold should be treated while asymptomatic. The aim of this article is to review the major risk factors for autoimmune disease, both hereditary and environmental, and so to help define those future criteria. Individuals who are at risk to develop an autoimmune disease should be advised to refrain from activities and lifestyle which endangers their health and quality of life.