Objective The contribution of bacterial co-infection to critical illness associated with 2009 influenza A (H1N1) [pH1N1] virus infection remains uncertain. The objective of this study was to determine if bacterial co-infection increased the morbidity and mortality of pH1N1. Design Retrospective and Prospective cohort study Setting 35 adult U.S. intensive care units over the course of one year Patients 683 critically ill adults with confirmed or probable pH1N1 Interventions None Measurements and Main Results A confirmed or probable case was defined as a positive pH1N1 test result or positive test for influenza A that was otherwise not subtyped. Bacterial co-infection was defined as documented bacteremia or any presumed bacterial pneumonia with or without positive respiratory tract culture within 72 hours of ICU admission. The mean age was 45±16 years, mean BMI 32.5±11.1 kg/m2, and mean APACHE II score 21±9, with 76% having at least one co-morbidity. Of 207 (30.3%) patients with bacterial co-infection on ICU admission, 154 had positive cultures with Staphylococcus aureus (n=57) and Streptococcus pneumoniae (n=19) the most commonly identified pathogens. Bacterial co-infected patients were more likely to present with shock (21 vs. 10%; P=0.0001), require mechanical ventilation at the time of ICU admission (63 vs. 52%; P=0.005) and have longer duration of ICU care (median 7 vs. 6 days; P=0.05). Hospital mortality was 23%; 31% in bacterial co-infected patients and 21% in patients without co-infection (P=0.002). Immunosuppression (RR 1.57; 95% CI 1.20–2.06; P=0.0009) and Staphylococcus aureus at admission (RR 2.82; 95% CI: 1.76–4.51; P<0.0001) were independently associated with increased mortality. Conclusions Among ICU patients with pH1N1, bacterial co-infection diagnosed within 72 hours of admission, especially with Staphylococcus aureus, was associated with significantly higher morbidity and mortality.

Children with preexisting neurologic conditions and immune compromise were at increased risk of pH1N1-associated death after PICU admission. Secondary complications of pH1N1, including myocarditis, encephalitis, and clinical diagnosis of early presumed MRSA coinfection of the lung, were mortality risk factors.

ObjectiveTo assess if a coding variant in the gene encoding transient receptor potential cation channel, subfamily V, member 1 (TRPV1) is associated with genetic risk of painful knee osteoarthritis (OA).MethodsThe Ile585Val TRPV1 variant encoded by rs8065080 was genotyped in 3270 cases of symptomatic knee OA, 1098 cases of asymptomatic knee OA and 3852 controls from seven cohorts from the UK, the USA and Australia. The genetic association between the low-pain genotype Ile–Ile and risk of symptomatic and asymptomatic knee OA was assessed.ResultsThe TRPV1 585 Ile–Ile genotype, reported to be associated with lower thermal pain sensitivity, was associated with a lower risk of symptomatic knee OA in a comparison of symptomatic cases with healthy controls, with an odds ratio (OR) of 0.75 (95% CI 0.64 to 0.88; p=0.00039 by meta-analysis) after adjustment for age, sex and body mass index. No difference was seen between asymptomatic OA cases and controls (OR=1.02, 95% CI 0.82 to 1.27 p=0.86) but the Ile–Ile genotype was associated with lower risk of symptomatic versus asymptomatic knee OA adjusting for covariates and radiographic severity (OR=0.73, 95% CI 0.57 to 0.94 p=0.0136). TRPV1 expression in articular cartilage was increased by inflammatory cytokines (tumour necrosis factor α and interleukin 1). However, there were no differences in TRPV1 expression in healthy and arthritic synovial tissue.ConclusionsA genotype involved in lower peripheral pain sensitivity is significantly associated with a decreased risk of painful knee OA. This indicates a role for the pro-nociceptive gene TRPV1 in genetic susceptibility to symptomatic knee OA, which may also be influenced by a role for this molecule in cartilage function.

ABSTRACTObjective: The supply and distribution of mechanical ventilation capacity is of profound importance for planning for severe public health emergencies. However, the capability of US health systems to provide mechanical ventilation for children and adults remains poorly quantified. The objective of this study was to determine the quantity of adult and pediatric mechanical ventilators at US acute care hospitals.Methods: A total of 5752 US acute care hospitals included in the 2007 American Hospital Association database were surveyed. We measured the quantities of mechanical ventilators and their features.Results: Responding to the survey were 4305 (74.8%) hospitals, which accounted for 83.8% of US intensive care unit beds. Of the 52 118 full-feature mechanical ventilators owned by respondent hospitals, 24 204 (46.4%) are pediatric/neonatal capable. Accounting for nonrespondents, we estimate that there are 62 188 full-feature mechanical ventilators owned by US acute care hospitals. The median number of full-feature mechanical ventilators per 100 000 population for individual states is 19.7 (interquartile ratio 17.2–23.1), ranging from 11.9 to 77.6. The median number of pediatric-capable device full-feature mechanical ventilators per 100 000 population younger than 14 years old is 52.3 (interquartile ratio 43.1–63.9) and the range across states is 22.1 to 206.2. In addition, respondent hospitals reported owning 82 755 ventilators other than full-feature mechanical ventilators; we estimate that there are 98 738 devices other than full-feature ventilators at all of the US acute care hospitals.Conclusions: The number of mechanical ventilators per US population exceeds those reported by other developed countries, but there is wide variation across states in the population-adjusted supply. There are considerably more pediatric-capable ventilators than there are for adults only on a population-adjusted basis.(Disaster Med Public Health Preparedness. 2010;4:199-206)

The fall 2009 pandemic period substantially impacted US hospitals, mostly through increased ED visits. For a small proportion of hospitals that experienced a high surge in inpatient admissions, increased mortality from selected clinical conditions was associated with both prepandemic outcomes and surge, highlighting the linkage between daily hospital operations and disaster preparedness.

Objectives To assess if genetic variation in the PACE4 gene, PCSK6, influences the risk for symptomatic knee OA. Methods Ten PCSK6 single nucleotide polymorphisms (SNP) were tested for association in a discovery cohort of radiographic knee OA (n= 156 asymptomatic and 600 symptomatic cases). Meta-analysis of the minor allele at rs900414 was performed in three additional independent cohorts (total n=674 asymptomatic and 2068 symptomatic). Pcsk6 knockout (KO) mice and wildtype C57BL/6 mice were compared in a battery of algesiometric assays, including hypersensitivity in response to intraplantar substance P; pain behaviours in response to intrathecal substance P; and pain behaviour in the abdominal constriction test. Results In the discovery cohort of radiographic knee OA, an intronic SNP at rs900414 was significantly associated with symptomatic OA. Replication in three additional cohorts confirmed that the minor allele at rs900414 was consistently increased among asymptomatic compared to symptomatic radiographic knee OA cases in all four cohorts. A fixed-effects meta-analysis yielded an odds ratio =1.35 (95% CI 1.17, 1.56; p-value 4.3×10−5 and no significant between-study heterogeneity). Studies in mice revealed that Pcsk6 knockout (KO) mice were significantly protected against pain in a battery of algesiometric assays. Conclusions These results suggest that a variant in PCSK6 is strongly associated with protection against pain in knee OA, offering some insight as to why in the presence of the same structural damage, some individuals develop chronic pain and others are protected. Studies in Pcsk6 null mutant mice further implicate PACE4 in pain.

Objective. To assess the genetic association of pain in patients with knee osteoarthritis (OA) and those with multiple regional pain with the R1150W variant in the ␣-subunit of the voltage-gated sodium channel Na V 1.7. Methods. Knee OA patients from 2 UK cohorts (1,411 from the Genetics of Osteoarthritis and Lifestyle study and 267 from the Hertfordshire Cohort Study; 74% with symptomatic OA) with Western Ontario and McMaster Universities OA Index (WOMAC) pain scores were genotyped for rs6746030 (encoding the R1150W change). One hundred seventy-six knee OA patients (53% symptomatic) from the Clearwater Osteoarthritis Study were also tested. A total of 4,295 samples (both affected and unaffected OA) from all 3 studies with data on multiple regional pain were tested. Fixed-effects meta-analyses were carried out with the WOMAC, symptomatic OA (adjusting for radiographic severity), and multiple regional pain as outcomes. Conclusion. We find evidence that the R1150W amino acid change in the Na V 1.7 ␣-chain is associated with multiple regional pain. This variant is confirmed to be involved in genetic susceptibility to pain, but it does not appear to have a major role in OA-specific pain.

SUMMARY:We explored nonsteroidal anti-inflammatory drug (NSAID) and aspirin (ASA) use and mortality in the U.S. Department of Health and Human Services' registry of 683 adult and 838 pediatric critically ill pandemic 2009 H1N1 influenza (pH1N1) patients. Among adults, 88 (12.9z) and 101 (14.8z) reported pre-admission use of an NSAID and ASA, respectively; mortality was similar (23-24z) regardless of NSAID or ASA use. Mortality among 89 pediatric NSAID users and 749 nonusers did not differ significantly (10.1z and 8.8z, respectively). One of 16 pediatric ASA users died. Among pediatric patients, the adjusted relative risk estimate for NSAID use and 90-day mortality was higher when influenza vaccination was included in the model (risk ratio [RR] ＝ 1.5; 95z confidence interval, 0.7-3.2), although not statistically significant. Among adults, RR estimates did not change appreciably after adjusting for age, sex, health status, or vaccine status. We found no compelling evidence that NSAID or ASA use influenced mortality in severe pH1N1.