Host Factors and Biomarkers Associated with Poor Outcomes in Adults with Invasive Pneumococcal Disease

BackgroundInvasive pneumococcal disease (IPD) causes considerable morbidity and mortality. We aimed to identify host factors and biomarkers associated with poor outcomes in adult patients with IPD in Japan, which has a rapidly-aging population.MethodsIn a large-scale surveillance study of 506 Japanese adults with IPD, we investigated the role of host factors, disease severity, biomarkers based on clinical laboratory data, treatment regimens, and bacterial factors on 28-day mortality.ResultsOverall mortality was 24.1%, and the mortality rate increased from 10.0% in patients aged ˂50 years to 33.1% in patients aged ≥80 years. Disease severity also increased 28-day mortality, from 12.5% among patients with bacteraemia without sepsis to 35.0% in patients with severe sepsis and 56.9% with septic shock. The death rate within 48 hours after admission was high at 54.9%. Risk factors for mortality identified by multivariate analysis were as follows: white blood cell (WBC) count <4000 cells/μL (odds ratio [OR], 6.9; 95% confidence interval [CI], 3.7–12.8, p < .001); age ≥80 years (OR, 6.5; 95% CI, 2.0–21.6, p = .002); serum creatinine ≥2.0 mg/dL (OR, 4.5; 95% CI, 2.5–8.1, p < .001); underlying liver disease (OR, 3.5; 95% CI, 1.6–7.8, p = .002); mechanical ventilation (OR, 3.0; 95% CI, 1.7–5.6, p < .001); and lactate dehydrogenase ≥300 IU/L (OR, 2.4; 95% CI, 1.4–4.0, p = .001). Pneumococcal serotype and drug resistance were not associated with poor outcomes.ConclusionsHost factors, disease severity, and biomarkers, especially WBC counts and serum creatinine, were more important determinants of mortality than bacterial factors.     

Blood Lead Levels and Cause-Specific Mortality of Inorganic Lead-Exposed Workers in South Korea

The objective of this study was to identify the association of blood lead level (BLL) with mortality in inorganic lead-exposed workers of South Korea. A cohort was compiled comprising 81,067 inorganic lead exposed workers working between January 1, 2000, and December 31, 2004. This cohort was merged with the Korean National Statistical Office to follow-up for mortality between 2000 and 2008. After adjusting for age and other carcinogenic metal exposure, all-cause mortality (Relative risk [RR] 1.36, 95% confidence interval [CI] 1.03–1.79), digestive disease (RR 3.23, 95% CI 1.33–7.86), and intentional self-harm (RR 2.92, 95% CI 1.07–7.81) were statistically significantly higher in males with BLL >20 μg/dl than of those with BLL ≤10μg/dl. The RR of males with BLL of 10–20 μg/dl was statistically higher than of those with BLL ≤10μg/dl in infection (RR 3.73. 95% CI, 1.06–13.06). The RRs of females with 10–20 μg/dl BLL was statistically significantly greater than those with BLL <10μg/dl in all-cause mortality (RR 1.93, 95% CI 1.16–3.20) and colon and rectal cancer (RR 13.42, 95% CI 1.21–149.4). The RRs of females with BLL 10–20 μg/dl (RR 10.45, 95% CI 1.74–62.93) and BLL ≥20 μg/dl (RR 12.68, 95% CI 1.69–147.86) was statistically significantly increased in bronchus and lung cancer. The increased suicide of males with ≥20 μg/dl BLLs, which might be caused by major depression, might be associated with higher lead exposure. Also, increased bronchus and lung cancer mortality in female workers with higher BLL might be related to lead exposure considering low smoking rate in females. The kinds of BLL-associated mortality differed by gender.     

Early Standard Electroencephalogram Abnormalities Predict Mortality in Septic Intensive Care Unit Patients

IntroductionSepsis is associated with increased mortality, delirium and long-term cognitive impairment in intensive care unit (ICU) patients. Electroencephalogram (EEG) abnormalities occurring at the acute stage of sepsis may correlate with severity of brain dysfunction. Predictive value of early standard EEG abnormalities for mortality in ICU septic patients remains to be assessed.MethodsIn this prospective, single center, observational study, standard EEG was performed, analyzed and classified according to both Synek and Young EEG scales, in consecutive patients acutely admitted in ICU for sepsis. Delirium, coma and the level of sedation were assessed at the time of EEG recording; and duration of sedation, occurrence of in-ICU delirium or death were assessed during follow-up. Adjusted analyses were carried out using multiple logistic regression.ResultsOne hundred ten patients were included, mean age 63.8 (±18.1) years, median SAPS-II score 38 (29–55). At the time of EEG recording, 46 patients (42%) were sedated and 22 (20%) suffered from delirium. Overall, 54 patients (49%) developed delirium, of which 32 (29%) in the days after EEG recording. 23 (21%) patients died in the ICU. Absence of EEG reactivity was observed in 27 patients (25%), periodic discharges (PDs) in 21 (19%) and electrographic seizures (ESZ) in 17 (15%). ICU mortality was independently associated with a delta-predominant background (OR: 3.36; 95% CI [1.08 to 10.4]), absence of EEG reactivity (OR: 4.44; 95% CI [1.37–14.3], PDs (OR: 3.24; 95% CI [1.03 to 10.2]), Synek grade ≥ 3 (OR: 5.35; 95% CI [1.66–17.2]) and Young grade > 1 (OR: 3.44; 95% CI [1.09–10.8]) after adjustment to Simplified Acute Physiology Score (SAPS-II) at admission and level of sedation. Delirium at the time of EEG was associated with ESZ in non-sedated patients (32% vs 10%, p = 0.037); with Synek grade ≥ 3 (36% vs 7%, p< 0.05) and Young grade > 1 (36% vs 17%, p< 0.001). Occurrence of delirium in the days after EEG was associated with a delta-predominant background (48% vs 15%, p = 0.001); absence of reactivity (39% vs 10%, p = 0.003), Synek grade ≥ 3 (42% vs 17%, p = 0.001) and Young grade >1 (58% vs 17%, p = 0.0001).ConclusionsIn this prospective cohort of 110 septic ICU patients, early standard EEG was significantly disturbed. Absence of EEG reactivity, a delta-predominant background, PDs, Synek grade ≥ 3 and Young grade > 1 at day 1 to 3 following admission were independent predictors of ICU mortality and were associated with occurence of delirium. ESZ and PDs, found in about 20% of our patients. Their prevalence could have been higher, with a still higher predictive value, if they had been diagnosed more thoroughly using continuous EEG.     

Association between Body Mass Index and Prognosis of Colorectal Cancer: A Meta-Analysis of Prospective Cohort Studies

Studies have reported conflicting results on the association between body mass index (BMI) and prognosis of colorectal cancer. Therefore, we have conducted a meta-analysis of prospective studies, which examined the association of pre- and post-diagnostic BMI with colorectal cancer-specific mortality and all-cause mortality in patients with colorectal cancer. We searched Medline and EMBASE database published between 1970 and September 2014. A total of 508 articles were identified, of which 16 prospective cohort studies were included for the current meta-analysis. The analysis included 58,917 patients who were followed up over a period ranging from 4.9 to 20 years (median: 9.9 years). We found that being underweight before cancer diagnosis was associated with increased all-cause mortality (Relative risk [RR]: 1.63, 95% CI: 1.18–2.23, p < 0.01) and being obese (BMI ≥ 30 kg/m²) before cancer diagnosis was associated with increased colorectal cancer-specific mortality (RR: 1.22, 95% CI: 1.003–1.35, p < 0.01) and all-cause mortality (RR: 1.25, 95% CI: 1.14–1.36, p < 0.01). On the other hand, being underweight (RR: 1.33, 95% CI: 1.20–1.47, p < 0.01), obese (RR: 1.08, 95% CI: 1.03–1.3, p < 0.01), and class II/III obese (BMI ≥ 35 kg/m²; RR: 1.13, 95% CI: 1.04–1.23, p < 0.01) after diagnosis were associated with significantly increased all-cause mortality. Being obese prior to diagnosis of colorectal cancer was associated with increased colorectal cancer-specific mortality and all-cause mortality, whereas being obese after diagnosis was associated with increased all-cause mortality. The associations with being underweight may reflect reverse causation. Maintaining a healthy body weight should be discussed with colorectal cancer survivors.     

Cluster Survey Evaluation of a Measles Vaccination Campaign in Jharkhand,India, 2012

IntroductionIndia was the last country in the world to implement a two-dose strategy for measles-containing vaccine (MCV) in 2010. As part of measles second-dose introduction, phased measles vaccination campaigns were conducted during 2010–2013, targeting 131 million children 9 months to <10 years of age. We performed a post-campaign coverage survey to estimate measles vaccination coverage in Jharkhand state.MethodsA multi-stage cluster survey was conducted 2 months after the phase 2 measles campaign occurred in 19 of 24 districts of Jharkhand during November 2011–March 2012. Vaccination status of children 9 months to <10 years of age was documented based on vaccination card or mother’s recall. Coverage estimates and 95% confidence intervals (95% CI) for 1,018 children were calculated using survey methods.ResultsIn the Jharkhand phase 2 campaign, MCV coverage among children aged 9 months to <10 years was 61.0% (95% CI: 54.4–67.7%). Significant differences in coverage were observed between rural (65.0%; 95% CI: 56.8–73.2%) and urban areas (45.6%; 95% CI: 37.3–53.9%). Campaign awareness among mothers was low (51.5%), and the most commonly reported reason for non-vaccination was being unaware of the campaign (69.4%). At the end of the campaign, 53.7% (95% CI: 46.5–60.9%) of children 12 months to <10 years of age received ≥2 MCV doses, while a large proportion of children remained under-vaccinated (34.0%, 95% CI: 28.0–40.0%) or unvaccinated (12.3%, 95% CI: 9.3–16.2%).ConclusionsImplementation of the national measles campaign was a significant achievement towards measles elimination in India. In Jharkhand, campaign performance was below the target coverage of ≥90% set by the Government of India, and challenges in disseminating campaign messages were identified. Efforts towards increasing two-dose MCV coverage are needed to achieve the recently adopted measles elimination goal in India and the South-East Asia region.     

The Korean Clinical Research Center for End-Stage Renal Disease Study Validates the Association of Hemoglobin and Erythropoiesis-Stimulating Agent Dose with Mortality in Hemodialysis Patients

Background

Anemia is an important risk factor for mortality in hemodialysis (HD) patients. However, higher hemoglobin (Hb) is not necessarily better, as seen in several studies. This study aimed to validate the clinical use of an Hb target of 10–11 g/dL in Korean HD patients.

Methods

A total of 1,276 HD patients from the Clinical Research Center (CRC) for End-Stage Renal Disease (ESRD) were investigated in a prospective observational study. Cox proportional hazard analysis was conducted for each category of time-dependent Hb level and erythropoiesis-stimulating agent (ESA) dose, with subgroup analysis stratified by age and diabetes status.

Results

Using a reference Hb level of 10–11 g/dL, the hazard ratios (HRs) of death were 5.12 (95% confidence interval [CI], 2.62–10.02, P <0.05) for Hb level <9.0 g/dL, and 2.03 (CI, 1.16–3.69, P <0.05) for Hb level 9.0–10.0 g/dL, after adjustment for multiple clinical variables. However, an Hb level ≥11 g/dL was not associated with decreased mortality risk. In an adjusted model categorized by Hb and ESA dose, the risk of death at an Hb level <10 g/dL and a higher dose of ESA (≥126 U/kg/week) had an HR of 2.25 (CI, 1.03–4.92, P <0.05), as compared to Hb level 10–11 g/dL and a lower dose of ESA. In subgroup analysis, those older than 65 years or who were diabetic had greater risk for mortality only in Hb category <9.0 g/dL. However, there was no significant interaction between age or diabetes status and Hb.

Conclusion

Using CRC-ESRD data, we validated the association between Hb and ESA dose and mortality in Korean HD patients. The clinical practice target of an Hb of 10–11 g/dL before the new KDIGO guideline era seems reasonable considering its survival benefit in HD patients.     

Mycobacterium ulcerans in the Elderly: More Severe Disease and Suboptimal Outcomes

Background

The clinical presentation of M. ulcerans disease and the safety and effectiveness of treatment may differ in elderly compared with younger populations related to relative immune defficiencies, co-morbidities and drug interactions. However, elderly populations with M. ulcerans disease have not been comprehensively studied.

Methodology/Principal Findings

A retrospective analysis was performed on an observational cohort of all confirmed M. ulcerans cases managed at Barwon Health from 1/1/1998-31/12/2014. The cohort included 327 patients; 131(40.0%) ≥65 years and 196(60.0%) <65 years of age. Patients ≥65 years had a shorter median duration of symptoms prior to diagnosis (p<0.01), a higher proportion with diabetes (p<0.001) and immune suppression (p<0.001), and were more likely to have lesions that were multiple (OR 4.67, 95% CI 1.78–12.31, p<0.001) and WHO category 3 (OR 4.59, 95% CI 1.98–10.59, p<0.001). Antibiotic complications occurred in 69(24.3%) treatment episodes at an increased incidence in those aged ≥65 years (OR 5.29, 95% CI 2.81–9.98, p<0.001). There were 4(1.2%) deaths, with significantly more in the age-group ≥65 years (4 compared with 0 deaths, p = 0.01). The overall treatment success rate was 92.2%. For the age-group ≥65 years there was a reduced rate of treatment success overall (OR 0.34, 95% CI 0.14–0.80, p = <0.01) and when surgery was used alone (OR 0.21, 95% CI 0.06–0.76, p<0.01). Patients ≥65 years were more likely to have a paradoxical reaction (OR 2.06, 95% CI 1.17–3.62, p = 0.01).

Conclusions/Significance

Elderly patients comprise a significant proportion of M. ulcerans disease patients in Australian populations and present with more severe and advanced disease forms. Currently recommended treatments are associated with increased toxicity and reduced effectiveness in elderly populations. Increased efforts are required to diagnose M. ulcerans earlier in elderly populations, and research is urgently required to develop more effective and less toxic treatments for this age-group.     

Association of Kidney Disease Measures with Cause-Specific Mortality: The Korean Heart Study

BackgroundThe link of low estimated glomerular filtration rate (eGFR) and high proteinuria to cardiovascular disease (CVD) mortality is well known. However, its link to mortality due to other causes is less clear.MethodsWe studied 367,932 adults (20–93 years old) in the Korean Heart Study (baseline between 1996–2004 and follow-up until 2011) and assessed the associations of creatinine-based eGFR and dipstick proteinuria with mortality due to CVD (1,608 cases), cancer (4,035 cases), and other (non-CVD/non-cancer) causes (3,152 cases) after adjusting for potential confounders.ResultsAlthough cancer was overall the most common cause of mortality, in participants with chronic kidney disease (CKD), non-CVD/non-cancer mortality accounted for approximately half of cause of death (47.0%for eGFR <60 ml/min/1.73m² and 54.3% for proteinuria ≥1+). Lower eGFR (<60 vs. ≥60 ml/min/1.73m²) was significantly associated with mortality due to CVD (adjusted hazard ratio 1.49 [95% CI, 1.24–1.78]) and non-CVD/non-cancer causes (1.78 [1.54–2.05]). The risk of cancer mortality only reached significance at eGFR <45 ml/min/1.73m² when eGFR 45–59 ml/min/1.73m² was set as a reference (1.62 [1.10–2.39]). High proteinuria (dipstick ≥1+ vs. negative/trace) was consistently associated with mortality due to CVD (1.93 [1.66–2.25]), cancer (1.49 [1.32–1.68]), and other causes (2.19 [1.96–2.45]). Examining finer mortality causes, low eGFR and high proteinuria were commonly associated with mortality due to coronary heart disease, any infectious disease, diabetes, and renal failure. In addition, proteinuria was also related to death from stroke, cancers of stomach, liver, pancreas, and lung, myeloma, pneumonia, and viral hepatitis.ConclusionLow eGFR was associated with CVD and non-CVD/non-cancer mortality, whereas higher proteinuria was consistently related to mortality due to CVD, cancer, and other causes. These findings suggest the need for multidisciplinary prevention and management strategies in individuals with CKD, particularly when proteinuria is present.     

Risk and Outcome after Ablation of Isthmus-Dependent Atrial Flutter in Elderly Patients

MethodsA total of 1187 patients with a mean age 65±12 years consecutively referred for AFL ablation were retrospectively analyzed in the study.Results445 (37.5%) patients were aged ≥70 (range 70 to 93) among which 345 were aged 70 to 79 years (29.1%) and 100 were aged ≥80 (8.4%). In multivariable analysis, AFL-related rhythmic cardiomyopathy and presentation with 1/1 AFL were less frequent (respectively adjusted OR = 0.44, 0.27–0.74, p = 0.002 and adjusted OR = 0.29, 0.16–0.52, p<0.0001). AFL ablation-related major complications were more frequent in patients ≥70 although remained lower than 10% (7.4% in ≥70 vs. 4.2% in <70, adjusted OR = 1.74, 1.04–2.89, p = 0.03). After 2.1±2.7 years, AFL recurrence was less frequent in patients ≥70 (adjusted OR = 0.54, 0.37–0.80, p = 0.002) whereas atrial fibrillation (AF) occurrence was as frequent in the 70–79 and ≥80 age subsets. As expected, cardiac mortality was higher in older patients. Patients aged ≥80 also had a low probability of AFL recurrence (5.0%) and AF onset (19.0%).ConclusionsOlder patients represent 37.5% of patients referred for AFL ablation and displayed a <10% risk of ablation-related complications. Importantly, AFL recurrences were less frequent in patients ≥70 while AF occurrence was as frequent as in patients <70. Similar observations were made in patients ≥80 years. AFL ablation appears to be safe and efficient and should not be ruled out in elderly patients.     

Whole-Body CT in Haemodynamically Unstable Severely Injured Patients – A Retrospective,Multicentre Study

Background

The current common and dogmatic opinion is that whole-body computed tomography (WBCT) should not be performed in major trauma patients in shock. We aimed to assess whether WBCT during trauma-room treatment has any effect on the mortality of severely injured patients in shock.

Methods

In a retrospective multicenter cohort study involving 16719 adult blunt major trauma patients we compared the survival of patients who were in moderate, severe or no shock (systolic blood pressure 90–110,<90 or >110 mmHg) at hospital admission and who received WBCT during resuscitation to those who did not. Using data derived from the 2002–2009 version of TraumaRegister®, we determined the observed and predicted mortality and calculated the standardized mortality ratio (SMR) as well as logistic regressions.

Findings

9233 (55.2%) of the 16719 patients received WBCT. The mean injury severity score was 28.8±12.1. The overall mortality rate was 17.4% (SMR  = 0.85, 95%CI 0.81–0.89) for patients with WBCT and 21.4% (SMR = 0.98, 95%CI 0.94–1.02) for those without WBCT (p<0.001). 4280 (25.6%) patients were in moderate shock and 1821 (10.9%) in severe shock. The mortality rate for patients in moderate shock with WBCT was 18.1% (SMR 0.85, CI95% 0.78–0.93) compared to 22.6% (SMR 1.03, CI95% 0.94–1.12) to those without WBCT (p<0.001, p = 0.002 for the SMRs). The mortality rate for patients in severe shock with WBCT was 42.1% (SMR 0.99, CI95% 0.92–1.06) compared to 54.9% (SMR 1.10, CI95% 1.02–1.16) to those without WBCT (p<0.001, p = 0.049 for the SMRs). Adjusted logistic regression analyses showed that WBCT is an independent predictor for survival that significantly increases the chance of survival in patients in moderate shock (OR = 0.73; 95%CI 0.60–0.90, p = 0.002) as well as in severe shock (OR = 0.67; 95%CI 0.52–0.88, p = 0.004). The number needed to scan related to survival was 35 for all patients, 26 for those in moderate shock and 20 for those in severe shock.

Conclusions

WBCT during trauma resuscitation significantly increased the survival in haemodynamically stable as well as in haemodynamically unstable major trauma patients. Thus, the application of WBCT in haemodynamically unstable severely injured patients seems to be safe, feasible and justified if performed quickly within a well-structured environment and by a well-organized trauma team.     

Seroprevalence of IgG antibodies against SARS-CoV-2 among the general population and healthcare workers in India,June–July 2021: A population-based cross-sectional study

BackgroundIndia began COVID-19 vaccination in January 2021, initially targeting healthcare and frontline workers. The vaccination strategy was expanded in a phased manner and currently covers all individuals aged 18 years and above. India experienced a severe second wave of COVID-19 during March–June 2021. We conducted a fourth nationwide serosurvey to estimate prevalence of SARS-CoV-2 antibodies in the general population aged ≥6 years and healthcare workers (HCWs).Methods and findingsWe did a cross-sectional study between 14 June and 6 July 2021 in the same 70 districts across 20 states and 1 union territory where 3 previous rounds of serosurveys were conducted. From each district, 10 clusters (villages in rural areas and wards in urban areas) were selected by the probability proportional to population size method. From each district, a minimum of 400 individuals aged ≥6 years from the general population (40 individuals from each cluster) and 100 HCWs from the district public health facilities were included. The serum samples were tested for the presence of IgG antibodies against S1-RBD and nucleocapsid protein of SARS-CoV-2 using chemiluminescence immunoassay. We estimated the weighted and test-adjusted seroprevalence of IgG antibodies against SARS-CoV-2, along with 95% CIs, based on the presence of antibodies to S1-RBD and/or nucleocapsid protein. Of the 28,975 individuals who participated in the survey, 2,892 (10%) were aged 6–9 years, 5,798 (20%) were aged 10–17 years, and 20,285 (70%) were aged ≥18 years; 15,160 (52.3%) participants were female, and 21,794 (75.2%) resided in rural areas. The weighted and test-adjusted prevalence of IgG antibodies against S1-RBD and/or nucleocapsid protein among the general population aged ≥6 years was 67.6% (95% CI 66.4% to 68.7%). Seroprevalence increased with age (p < 0.001) and was not different in rural and urban areas (p = 0.822). Compared to unvaccinated adults (62.3%, 95% CI 60.9% to 63.7%), seroprevalence was significantly higher among individuals who had received 1 vaccine dose (81.0%, 95% CI 79.6% to 82.3%, p < 0.001) and 2 vaccine doses (89.8%, 95% CI 88.4% to 91.1%, p < 0.001). The seroprevalence of IgG antibodies among 7,252 HCWs was 85.2% (95% CI 83.5% to 86.7%). Important limitations of the study include the survey design, which was aimed to estimate seroprevalence at the national level and not at a sub-national level, and the non-participation of 19% of eligible individuals in the survey.ConclusionsNearly two-thirds of individuals aged ≥6 years from the general population and 85% of HCWs had antibodies against SARS-CoV-2 by June–July 2021 in India. As one-third of the population is still seronegative, it is necessary to accelerate the coverage of COVID-19 vaccination among adults and continue adherence to non-pharmaceutical interventions.

Manoj Murhekar and co-workers report on the seroprevalence of anti-SARS-CoV-2 antibodies in India.     

Mortality of IgA Nephropathy Patients: A Single Center Experience over 30 Years

Research on the prognosis of IgA nephropathy (IgAN) has focused on renal survival, with little information being available on patient survival. Hence, this investigation aimed to explore long-term patient outcome in IgAN patients. Clinical and pathological characteristics at the time of renal biopsy were reviewed in 1,364 IgAN patients from 1979 to 2008. The outcomes were patient death and end stage renal disease (ESRD) progression. Overall, 71 deaths (5.3%) and 277 cases of ESRD (20.6%) occurred during 13,916 person-years. Ten-, 20-, and 30-year patient survival rates were 96.3%, 91.8%, and 82.7%, respectively. More than 50% patient deaths occurred without ESRD progression. Overall mortality was elevated by 43% from an age/sex-matched general population (GP) (standardized mortality ratio [SMR], 1.43; 95% confidence interval [CI], 1.04–1.92). Men had comparable mortality to GP (SMR, 1.22; 95% CI, 0.82–1.75), but, in women, the mortality rate was double (SMR, 2.17; 95% CI, 1.21–3.57). Patients with renal risk factors such as initial renal dysfunction (estimated glomerular filgration rate <60 ml/min per 1.73m²; SMR, 1.70; 95% CI, 1.13–2.46), systolic blood pressure ≥140 mmHg (SMR, 1.88; 95% CI, 1.19–2.82) or proteinuria ≥1 g/day (SMR, 1.66; 95% CI, 1.16–2.29) had an elevated mortality rate. Patients with preserved renal function, normotension, and proteinuria <1 g/day, however, had a similar mortality rate to GP. When risk stratification was performed by counting the number of major risk factors present at diagnosis, low-risk IgAN patients had a mortality rate equal to that of GP, whereas high-risk patients had a mortality rate higher than that of GP. This investigation demonstrated that overall mortality in IgAN patients was higher than that of GP. Women and patients with renal risk factors had a higher mortality than that of GP, Therefore, strategies optimized to alleviate major renal risk factors are warranted to reduce patient mortality.     

Suicides in Visually Impaired Persons: A Nation-Wide Register-Linked Study from Finland Based on Thirty Years of Data

Focusing on seasonality, gender, age, and suicide methods a Finnish nation-wide cohort-based study was carried out to compare suicide data between sighted, visually-impaired (WHO impairment level I-II, i.e., visual acuity >0.05, but <0.3) and blind (WHO impairment level III-V, i.e., visual acuity <0.05) victims. Standardized mortality ratios (SMR) of age- and gender-matched populations from official 1982–2011 national registers were used. Group differences in categorical variables were assessed with Pearson''s Chi-square or Fisher''s Exact test and in continuous variables with Mann-Whitney U-test. Seasonality was assessed by Chi-square for multinomials; ratio of observed to expected number of suicides was calculated with 95% confidence level. Hanging, poisoning, drowning, but rarely shooting or jumping from high places, were preferred suicide methods of the blind. Mortality was significantly increased in the visually impaired (SMR = 1.3; 95% CI 1.07–1.61), but in gender-stratified analyses the increase only affected males (1.34; 95% CI = 1.06–1.70) and not females (1.24; 95% CI 0.82–1.88). Age-stratified analyses identified blind males of working age rather than older men (as in the general population) as a high risk group that requires particular attention. The statistically significant spring suicide peak in blind subjects mirrors that of sighted victims and its possible cause in the blind is discussed.     

Cigarette Smoking and the Risk of Adult Myeloid Disease: A Meta-Analysis

Background

The adult myeloid diseases, myelodysplastic syndrome and acute myeloid leukemia, have been reported to be associated with cigarette smoking, but the results have been conflicting. Previous studies may have ignored the relationship between myelodysplastic syndrome and acute myeloid leukemia, where approximately one-third of myelodysplastic syndrome cases will progress to acute myeloid leukemia, which could induce a serious bias in independent analyses. For the purposes of researching pathogenesis, we suggest that myelodysplastic syndrome and acute myeloid leukemia should be regarded as a single class of adult myeloid disease, and herein assessed the relationship between cigarette smoking and the risk of adult myeloid disease.

Methods

The PubMed, Cochrane Library, EBSCO, and EMBASE databases were systematically searched for reports published from 1990 to 2015. Two authors independently assessed the methodological quality and the extracted data. The odds ratios and adjusted odds ratios (OR), a sensitivity analysis, and the publication bias were analyzed using the CMA v2 (Comprehensive Meta Analysis Version 2) software program.

Results

Twenty-five studies were included in this meta-analysis. The publication dates ranged from 1990 to 2014. The pooled OR in current smokers and ever-smokers showed an increased risk of adult myeloid disease, with ORs of 1.45 (95% CI, 1.30–1.62; p<0.001) and 1.23 (95% CI 1.15–1.32; p<0.001) versus non-smokers, respectively. In the subset analyses, the OR of adult myeloid disease was increased regardless of the form of disease, geographical region, NOS (Newcastle Ottawa Scale) score, and source of controls. The smoking status was divided into <20 and ≥20 cigarettes per day, and these groups had ORs of developing adult myeloid disease of 1.24 (95% CI, 1.09–1.40; p = 0.001) and 1.32 (95% CI, 1.14–1.53; p<0.001), respectively. In the groups divided based on the number of years the subjects had smoked (<20 and ≥20 years), the ORs were 1.05 (95% CI, 0.90–1.23; p = 0.25) and 1.30 (95% CI, 1.16–1.45; p<0.001), respectively. Similarly, <20 and ≥20 pack-years were associated with ORs of 1.15 (95% CI, 1.03–1.29; p = 0.017) and 1.34 (95% CI, 1.18–1.52; p<0.001), respectively.

Conclusions

This meta-analysis, for the first time, combined myelodysplastic syndrome with acute myeloid leukemia to assess the overall risk of adult myeloid disease, and it demonstrated that cigarette smoking is associated with a significantly increased risk of adult myeloid disease.     

Streptococcus pneumoniae Serotypes and Mortality in Adults and Adolescents in South Africa: Analysis of National Surveillance Data, 2003 - 2008

BackgroundAn association between pneumococcal serotypes and mortality has been suggested. We aimed to investigate this among individuals aged ≥15 years with invasive pneumococcal disease (IPD) in South Africa.MethodsIPD cases were identified through national laboratory-based surveillance at 25 sites, pre-pneumococcal conjugate vaccine (PCV) introduction, from 2003–2008. We assessed the association between the 20 commonest serotypes and in-hospital mortality using logistic regression with serotype 4 (the third commonest serotype with intermediate case-fatality ratio (CFR)) as referent.ResultsAmong 3953 IPD cases, CFR was 55% (641/1166) for meningitis and 23% (576/2484) for bacteremia (p<0.001). Serotype 19F had the highest CFR (48%, 100/207), followed by serotype 23F (39%, 99/252) and serotype 1 (38%, 246/651). On multivariable analysis, factors independently associated with mortality included serotype 1 (OR 1.9, 95%CI 1.1–3.5) and 19F (OR 2.9, 95%CI 1.4–6.1) vs. serotype 4; increasing age (25–44 years, OR 1.8, 95%CI 1.0–3.0; 45–64 years, OR 3.6, 95%CI 2.0–6.4; ≥65 years, OR 5.2, 95%CI 1.9–14.1; vs. 15–24 years); meningitis (OR 4.1, 95%CI 3.0–5.6) vs. bacteremic pneumonia; and HIV infection (OR1.7, 95%CI 1.0–2.8). On stratified multivariate analysis, serotype 19F was associated with increased mortality amongst bacteremic pneumococcal pneumonia cases, while no serotype was associated with increased mortality in meningitis cases.ConclusionMortality was increased in HIV-infected individuals, which may be reduced by increased antiretroviral therapy availability. Serotypes associated with increased mortality are included in the 10-and-13-valent PCV and may become less common in adults due to indirect effects following routine infant immunization.     

Serum IL-10 Predicts Worse Outcome in Cancer Patients: A Meta-Analysis

BackgroundIL–10 is an important immunosuppressive cytokine which is frequently elevated in tumor microenvironment. Some studies have reported that overexpression of serous IL–10 is correlated with worse outcome in patients with malignant tumor. Here, we conducted a meta-analysis to assess the prognostic impact of serous IL–10 expression in cancer patients.MethodsWe searched PubMed and EBSCO for studies in evaluating the association of IL–10 expression—in serum and clinical outcome in cancer patients. Overall survival (OS) was the primary prognostic indicator and disease-free survival (DFS) was the secondary indicator. Extracted data were computed into odds ratios (ORs) and 95% confidence interval (CI) or a P value for survival at 1, 3 and 5 years. Pooled data were weighted using the Mantel–Haenszel Fixed-effect model. All statistical tests were two-sided.ResultsA total of 1788 patients with cancer from 21 published studies were incorporated into this meta-analysis. High level of serum IL–10 was significantly associated with worse OS at 1-year (OR = 3.70, 95% CI = 2.81 to 4.87, P < 0.00001), 3-year (OR = 3.33, 95% CI = 2.53 to 4.39, P < 0.0001) and 5-year (OR = 2.80, 95% CI = 1.90 to 4.10, P < 0.0001) of cancer. Subgroup analysis showed that the correlation between serous IL–10 expression and outcome of patients with solid tumors and hematological malignancies are consistent. The association of IL–10 with worse DFS at 1-year (OR = 3.34, 95% CI = 1.40 to 7.94, P = 0.006) and 2-year (OR = 3.91, 95% CI = 1.79 to 8.53, P = 0.0006) was also identified.ConclusionsHigh expression of serous IL–10 leads to an adverse survival in most types of cancer. IL–10 is a valuable biomarker for prognostic prediction and targeting IL–10 treatment options for both solid tumors and hematological malignancies.     

A Prospective Study of Alcohol Consumption and Smoking and the Risk of Major Gastrointestinal Bleeding in Men

MethodsWe prospectively studied 48,000 men in the Health Professional follow-up Study (HPFS) who were aged 40–75 years at baseline in 1986. We identified men with major GIB requiring hospitalization and/or blood transfusion via biennial questionnaires and chart review.ResultsWe documented 305 episodes of major GIB during 26 years of follow-up. Men who consumed >30 g/day of alcohol had a multivariable relative risk (RR) of 1.43 (95% confidence interval (CI), 0.88–2.35; P for trend 0.006) for major GIB when compared with nondrinkers. Alcohol consumption appeared to be primarily related to upper GIB (multivariable RR for >30 g/day vs. nondrinkers was 1.35; 95% CI, 0.66–2.77; P for trend 0.02). Men who consumed ≥ 5 drinks/week vs. < 1 drink/month of liquor had a multivariable RR of 1.72 (95% CI, 1.26–2.35, P for trend <0.001). Wine and beer were not significantly associated with major GIB. The risk of GIB associated with NSAIDs/aspirin use increased with greater alcohol consumption (multivariable RR 1.37; 95% CI, 0.85–2.19 for 1-14g/day of alcohol, RR 1.75; 95% CI, 1.07–2.88 for ≥ 15g/day compared to nondrinkers). Smoking was not significantly associated with GIB.ConclusionsAlcohol consumption, but not smoking, was associated with an increased risk of major GIB. Associations were most notable for upper GIB associated with liquor intake. Alcohol appeared to potentiate the risk of NSAID-associated GIB.     

The Burden of Influenza and RSV among Inpatients and Outpatients in Rural Western Kenya, 2009–2012

Background

In Kenya, detailed data on the age-specific burden of influenza and RSV are essential to inform use of limited vaccination and treatment resources.

Methods

We analyzed surveillance data from August 2009 to July 2012 for hospitalized severe acute respiratory illness (SARI) and outpatient influenza-like illness (ILI) at two health facilities in western Kenya to estimate the burden of influenza and respiratory syncytial virus (RSV). Incidence rates were estimated by dividing the number of cases with laboratory-confirmed virus infections by the mid-year population. Rates were adjusted for healthcare-seeking behavior, and to account for patients who met the SARI/ILI case definitions but were not tested.

Results

The average annual incidence of influenza-associated SARI hospitalization per 1,000 persons was 2.7 (95% CI 1.8–3.9) among children <5 years and 0.3 (95% CI 0.2–0.4) among persons ≥5 years; for RSV-associated SARI hospitalization, it was 5.2 (95% CI 4.0–6.8) among children <5 years and 0.1 (95% CI 0.0–0.2) among persons ≥5 years. The incidence of influenza-associated medically-attended ILI per 1,000 was 24.0 (95% CI 16.6–34.7) among children <5 years and 3.8 (95% CI 2.6–5.7) among persons ≥5 years. The incidence of RSV-associated medically-attended ILI was 24.6 (95% CI 17.0–35.4) among children <5 years and 0.8 (95% CI 0.3–1.9) among persons ≥5 years.

Conclusions

Influenza and RSV both exact an important burden in children. This highlights the possible value of influenza vaccines, and future RSV vaccines, for Kenyan children.     

Research Activity and the Association with Mortality

IntroductionThe aims of this study were to describe the key features of acute NHS Trusts with different levels of research activity and to investigate associations between research activity and clinical outcomes.MethodsNational Institute for Health Research (NIHR) Comprehensive Clinical Research Network (CCRN) funding and number of patients recruited to NIHR Clinical Research Network (CRN) portfolio studies for each NHS Trusts were used as markers of research activity. Patient-level data for adult non-elective admissions were extracted from the English Hospital Episode Statistics (2005-10). Risk-adjusted mortality associations between Trust structures, research activity and, clinical outcomes were investigated.ResultsLow mortality Trusts received greater levels of funding and recruited more patients adjusted for size of Trust (n = 35, 2,349 £/bed [95% CI 1,855–2,843], 5.9 patients/bed [2.7–9.0]) than Trusts with expected (n = 63, 1,110 £/bed, [864–1,357] p<0.0001, 2.6 patients/bed [1.7–3.5] p<0.0169) or, high (n = 42, 930 £/bed [683–1,177] p = 0.0001, 1.8 patients/bed [1.4–2.1] p<0.0005) mortality rates. The most research active Trusts were those with more doctors, nurses, critical care beds, operating theatres and, made greater use of radiology. Multifactorial analysis demonstrated better survival in the top funding and patient recruitment tertiles (lowest vs. highest (odds ratio & 95% CI: funding 1.050 [1.033–1.068] p<0.0001, recruitment 1.069 [1.052–1.086] p<0.0001), middle vs. highest (funding 1.040 [1.024–1.055] p<0.0001, recruitment 1.085 [1.070–1.100] p<0.0001).ConclusionsResearch active Trusts appear to have key differences in composition than less research active Trusts. Research active Trusts had lower risk-adjusted mortality for acute admissions, which persisted after adjustment for staffing and other structural factors.     

Risk Factors for Death in 632 Patients with Sickle Cell Disease in the United States and United Kingdom

Background

The role of pulmonary hypertension as a cause of mortality in sickle cell disease (SCD) is controversial.

Methods and Results

We evaluated the relationship between an elevated estimated pulmonary artery systolic pressure and mortality in patients with SCD. We followed patients from the walk-PHaSST screening cohort for a median of 29 months. A tricuspid regurgitation velocity (TRV)≥3.0 m/s cuttof, which has a 67–75% positive predictive value for mean pulmonary artery pressure ≥25 mm Hg was used. Among 572 subjects, 11.2% had TRV≥3.0 m/sec. Among 582 with a measured NT-proBNP, 24.1% had values ≥160 pg/mL. Of 22 deaths during follow-up, 50% had a TRV≥3.0 m/sec. At 24 months the cumulative survival was 83% with TRV≥3.0 m/sec and 98% with TRV<3.0 m/sec (p<0.0001). The hazard ratios for death were 11.1 (95% CI 4.1–30.1; p<0.0001) for TRV≥3.0 m/sec, 4.6 (1.8–11.3; p = 0.001) for NT-proBNP≥160 pg/mL, and 14.9 (5.5–39.9; p<0.0001) for both TRV≥3.0 m/sec and NT-proBNP≥160 pg/mL. Age >47 years, male gender, chronic transfusions, WHO class III–IV, increased hemolytic markers, ferritin and creatinine were also associated with increased risk of death.

Conclusions

A TRV≥3.0 m/sec occurs in approximately 10% of individuals and has the highest risk for death of any measured variable.

The study is registered in ClinicalTrials.gov with identifier

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