Erie County Medical Center

(cKp). hvKp usually infects individuals from the community, who are often healthy. Infections are more common in the Asian Pacific Rim but are occurring globally. hvKp infection frequently presents at multiple sites or subsequently metastatically spreads, often requiring source control. hvKp has an increased ability to cause central nervous system infection and endophthalmitis, which require rapid recognition and site-specific treatment. The genetic factors that confer hvKp's hypervirulent phenotype are present on a large virulence plasmid and perhaps integrative conjugal elements. Increased capsule production and aerobactin production are established hvKp-specific virulence factors. Similar to cKp, hvKp strains are becoming increasingly resistant to antimicrobials via acquisition of mobile elements carrying resistance determinants, and new hvKp strains emerge when extensively drug-resistant cKp strains acquire hvKp-specific virulence determinants, resulting in nosocomial infection. Presently, clinical laboratories are unable to differentiate cKp from hvKp, but recently, several biomarkers and quantitative siderophore production have been shown to accurately predict hvKp strains, which could lead to the development of a diagnostic test for use by clinical laboratories for optimal patient care and for use in epidemiologic surveillance and research studies.

WATTS, HUGH G. M.D.†, LOS ANGELES, CALIFORNIA; LIFESO, ROBERT M. M.D.‡, BUFFALO, NEW YORK Author Information

The etiology of severe pneumonia requiring mechanical ventilation in the very elderly has been imprecise because of lack of comprehensive studies and low yield of diagnostic approach. Overall, 104 patients 75 yr of age and older with severe pneumonia were studied prospectively at two university-affiliated hospitals. Microbial investigation included blood culture, serology, pleural fluid, and bronchoalveolar secretions. Streptococcus pneumoniae (14%), gram-negative enteric bacilli (14%), Legionella sp. (9%), Hemophilus influenzae (7%), and Staphylococcus aureus (7%) were the predominant pathogens in community-acquired pneumonia (CAP). Staphylococcus aureus (29%), gram-negative enteric bacilli (15%), Streptococcus pneumoniae (9%), and Pseudomonas aeruginosa (4%) accounted for most isolates of nursing home-acquired pneumonia (NHAP). The case fatality rate was 55% (53% for CAP and 57% for NHAP; p > 0.5). Activity of Daily Living (ADL) Index, pulmonary, endocrine and central nervous system (CNS) comorbidities were associated with distinct microbial etiology. By multivariate analysis, hospital mortality was associated independently with 24-h urine output (odds ratio [OR], 5.6; 95% confidence interval [CI], 2.5 to 7.9; p < 0.001), septic shock (OR, 4.3; 95% CI, 1.9 to 8.9; p = 0.0059), radiographic multilobar involvement (OR, 3.7; 95% CI, 1.8 to 15.6; p = 0.02), and inadequate antimicrobial therapy (OR, 2.6; 95% CI, 1.4 to 23.9; p = 0.034). Further studies should focus on identifying effective antimicrobial regimens in randomized trials.

Establishing a clinical diagnosis of infection in residents of long-term-care facilities (LTCFs) is difficult. As a result, deciding when to initiate antibiotics can be particularly challenging. This article describes the establishment of minimum criteria for the initiation of antibiotics in residents of LTCFs. Experts in this area were invited to participate in a consensus conference. Using a modified delphi approach, a questionnaire and selected relevant articles were sent to participants who were asked to rank individual signs and symptoms with respect to their relative importance. Using the results of the weighting by participants, a modification of the nominal group process was used to achieve consensus. Criteria for initiating antibiotics for skin and soft-tissue infections, respiratory infections, urinary infections, and fever where the focus of infection is unknown were developed.

The association between support elements (ventilator days = Vd, enteral protein = EnP, number of antibiotics per day = AB/d) and the magnitude of the septic state (SSS) and its bacteriologic manifestations (bacti. log) in 66 patients with blunt multiple trauma (mean HTI-ISS = 40) over 1649 days have been studied retrospectively. SSS is measured by summing the standard deviation units of change in the septic direction for the 16 measurements taken every day in the intensive care unit. Increasing Vd is tightly associated with an increasing SSS (r = +0.52), after day 10 an increasing bacti. log (r = +0.21 to +0.32), and an increasing AB/d (r = +0.26) (all p less than 0.001, N = 1615 - 1626). The independent variables that best predicted Vd were delayed operations (DORS), day of rising EnP, and total positive blood cultures (TPC) (adj. R sq. = 0.84, F = 104, dF = 3/59). An increasing AB/d was associated with an increasing SSS (r = +0.38), increasing Vd (r = +0.26), and an increased bacti. log (r = +0.14 to +0.18) (all p less than 0.001, N = 1615). Only an increased EnP was consistently associated with a reduced SSS (r = -0.38) and a reduction in bacti. log (r = -0.10 to -0.21) (all p less than 0.001, N = 1626-1636). The independent variables Vd, EnP, AB/d, and TPC best predicted SSS for all surviving patients (adj. R sq. = 0.42, F = 268, dF = 4/1496). The patients who died of sepsis were not different in terms of bacti. log from those with equal Vd but were distinguished by zero EnP, high AB/d, and persistent ventilatory support. In conclusion, DORS is tightly associated with increased Vd, SSS, AB/d, and zero EnP. If Vd exceeds 10, there is an increasing bacti. log and evidence of infection probably from the gut. This responds only to increased EnP and not to AB/d. Death due to sepsis is not associated with increased bacti. log but with zero EnP and high AB/d and their consequences.

Hypertension is the most common medical disorder encountered during pregnancy. Hypertensive disorders are one of the major causes of pregnancy-related maternal deaths in the United States. We will present a comprehensive update of the literature pertinent to hypertension in pregnancy. The paper begins by defining and classifying hypertensive disorders in pregnancy. The normal vascular and renal physiological changes which occur during pregnancy are detailed. We will summarize the intriguing aspects of pathophysiology of preeclampsia, emphasizing on recent advances in this field. The existing diagnostic tools and the tests which have been proposed for screening preeclampsia are comprehensively described. We also highlight the short- and long-term implications of preeclampsia. Finally, we review the current management guidelines, goals of treatment and describe the potential risks and benefits associated with various antihypertensive drug classes. Preeclampsia still remains an enigma, and the present management focuses on monitoring and treatment of its manifestations. We are hopeful that this in depth critique will stimulate the blossoming research in the field and assist practitioners to identify women at risk and more effectively treat affected individuals.

This study conducted a systematic review to assess the quality of existing literature on psychological treatments for irritable bowel syndrome and to quantify the evidence for their efficacy. Three independent reviewers (2 from England, 1 from the United States) coded the quality of 32 studies, 17 of which provided data suitable for meta-analysis. Meta-analysis of efficacy data (50% reduction of symptoms) gave an odds ratio of 12 (95% confidence interval = 5.56-25.96) and a number needed to treat of 2. Psychological treatments are, as a class of interventions, effective in reducing symptoms compared with a pooled group of control conditions. Questions regarding the relative superiority of specific psychological treatments and influence of active versus nonspecific treatment effects remain unanswered.

Fifty-six blunt multiple trauma patients (HTI-ISS 22-57) were studied for the effects of immediate versus delayed internal fixation of a femur or acetabular fracture on the pulmonary failure septic state. The pulmonary failure septic state may be defined as an alveolar arterial oxygen tension difference greater than 100, plus fever and leukocytosis. These patients were divided into four groups. Group I (N = 20) had immediate internal fixation, postoperative ventilatory support, and was sitting up at 30 hours. Group II (N = 20) had 10 days of femur traction and postoperative ventilatory support. Group III (N = 9) was immediately extubated after surgery and had 30 days of femur traction. Group IV (N = 7) had special circumstances that should increase the duration of the pulmonary failure septic state. These four groups of patients were statistically identical by 20 different criteria on admission except that Group I had more recognized chest injuries than Group II (12 vs. 9). Group I required 3.4 +/- 2.6 days of ventilator support and 7.5 +/- 3.8 intensive care unit (ICU) days; they had 12 +/- 8.8 elevated white counts, 3.8 +/- 4 febrile days, 0.05 positive blood cultures per patient, four fracture complications out of 93 fractures, 59 injections of narcotics, and 23 +/- 8.6 acute care days. Ten days of femur traction doubled the duration of the pulmonary failure septic state relative to Group I at a statistically significant level for nine out of 10 criteria, while increasing the number of positive blood cultures by a factor of 10, the number of fracture complications by a factor of 3.5, and the use of injectable narcotics by a factor of 2. Thirty days of femur traction increased the duration of the pulmonary failure septic state relative to Group I by a factor of 3 to 5 for all criteria at a statistically significant level, while increasing fracture complications by a factor of 17, positive blood cultures by a factor of 74, and the use of narcotics by a factor of 2. Group IV, which had four out of seven immediate internal fixations, behaved similarly to Group II. Femoral shaft traction should be avoided in the blunt multiple trauma patients because it greatly increases the cost of care and the risk of multiple systems organ failure.(ABSTRACT TRUNCATED AT 400 WORDS)

BACKGROUND: Depression is a prevalent and disabling mental disorder that frequently co-occurs with a wide range of chronic conditions. Evidence has suggested that depression could be associated with excess all-cause mortality across different settings and populations, although the causality of these associations remains unclear. METHODS: We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, PsycINFO, and Embase electronic databases were searched through January 20, 2018. Systematic reviews and meta-analyses that investigated associations of depression and all-cause and cause-specific mortality were selected for the review. The evidence was graded as convincing, highly suggestive, suggestive, or weak based on quantitative criteria that included an assessment of heterogeneity, 95% prediction intervals, small-study effects, and excess significance bias. RESULTS: A total of 26 references providing 2 systematic reviews and data for 17 meta-analytic estimates met inclusion criteria (19 of them on all-cause mortality); data from 246 unique studies (N = 3,825,380) were synthesized. All 17 associations had P < 0.05 per random effects summary effects, but none of them met criteria for convincing evidence. Associations of depression and all-cause mortality in patients after acute myocardial infarction, in individuals with heart failure, in cancer patients as well as in samples from mixed settings met criteria for highly suggestive evidence. However, none of the associations remained supported by highly suggestive evidence in sensitivity analyses that considered studies employing structured diagnostic interviews. In addition, associations of depression and all-cause mortality in cancer and post-acute myocardial infarction samples were supported only by suggestive evidence when studies that tried to adjust for potential confounders were considered. CONCLUSIONS: Even though associations between depression and mortality have nominally significant results in all assessed settings and populations, the evidence becomes weaker when focusing on studies that used structured interviews and those that tried to adjust for potential confounders. A causal effect of depression on all-cause and cause-specific mortality remains unproven, and thus interventions targeting depression are not expected to result in lower mortality rates at least based on current evidence from observational studies.

Plasma levels of cortisol were sampled for 24 hours in 32 endogenously depressed (ED) patients and 72 normal controls who also underwent the dexamethasone suppression test. The ED patients had significantly higher mean 24-hour plasma levels of cortisol (means 24h PC). However, means 24h PC values of subjects in both groups were normally distributed, with a marked overlap between the two. Only seven ED patients had means 24h PC values higher than 2 SDs from the normal mean (greater than 10 micrograms/dL). An abnormal dexamethasone suppression test result was only partially related to basal cortisol levels. The mean plasma level of cortisol between 1 and 4 PM was found to be highly correlated with the means 24h PC value in ED patients, as has been previously reported in normal subjects and patients with various other diseases (in which it also powerfully discriminated between hypersecretors and normosecretors). This finding supports the use of mean cortisol levels between 1 and 4 PM as a reliable and convenient indication of cortisol secretion.

Despite common findings suggesting that lack of negative life events should be optimal, recent work has revealed a curvilinear pattern, such that some cumulative lifetime adversity is instead associated with optimal well-being. This work, however, is limited in that responses to specific stressors as they occurred were not assessed, thereby precluding investigation of resilience. The current research addressed this critical gap by directly testing the relationship between adversity history and resilience to stressors. Specifically, we used a multimethod approach across two studies to assess responses to controlled laboratory stressors (respectively requiring passive endurance and active instrumental performance). Results revealed hypothesized U-shaped relationships: Relative to a history of either no adversity or nonextreme high adversity, a moderate number of adverse life events was associated with less negative responses to pain and more positive psychophysiological responses while taking a test. These results provide novel evidence in support of adversity-derived propensity for resilience that generalizes across stressors.

INTRODUCTION: Dental plaque biofilms are colonized by respiratory pathogens in mechanically-ventilated intensive care unit patients. Thus, improvements in oral hygiene in these patients may prevent ventilator-associated pneumonia. The goal of this study was to determine the minimum frequency (once or twice a day) for 0.12% chlorhexidine gluconate application necessary to reduce oral colonization by pathogens in 175 intubated patients in a trauma intensive care unit. METHODS: A randomized, double-blind, placebo-controlled clinical trial tested oral topical 0.12% chlorhexidine gluconate or placebo (vehicle alone), applied once or twice a day by staff nurses. Quantitation of colonization of the oral cavity by respiratory pathogens (teeth/denture/buccal mucosa) was measured. RESULTS: Subjects were recruited from 1 March, 2004 until 30 November, 2007. While 175 subjects were randomized, microbiologic baseline data was available for 146 subjects, with 115 subjects having full outcome assessment after at least 48 hours. Chlorhexidine reduced the number of Staphylococcus aureus, but not the total number of enterics, Pseudomonas or Acinetobacter in the dental plaque of test subjects. A non-significant reduction in pneumonia rate was noted in groups treated with chlorhexidine compared with the placebo group (OR = 0.54, 95% CI: 0.23 to 1.25, P = 0.15). No evidence for resistance to chlorhexidine was noted, and no adverse events were observed. No differences were noted in microbiologic or clinical outcomes between treatment arms. CONCLUSIONS: While decontamination of the oral cavity with chlorhexidine did not reduce the total number of potential respiratory pathogens, it did reduce the number of S. aureus in dental plaque of trauma intensive care patients.

Current recommendations for management of obese patients post-extubation are based on clinical experience and expert opinions. It was hypothesised that the application of noninvasive ventilation (NIV) during the first 48 h after extubation in severely obese patients would reduce post-extubation failure and avert the need for reintubation. Following protocol-driven weaning trials, 62 consecutive severely obese patients (body mass index > or =35 kg x m(-2)) were assigned to NIV via nasal mask immediately post-extubation and compared with 62 historically matched controls who were treated with conventional therapy. The primary end-point was the incidence of respiratory failure in the first 48 h post-extubation. Compared with conventional therapy, the institution of NIV resulted in 16% (95% confidence interval 2.9-29.3%) absolute risk reduction in the rate of respiratory failure. There was a significant difference in the intensive care unit and lengths of hospital stay between the two groups. Subgroup analysis of hypercapnic patients showed reduced hospital mortality in the NIV group compared with the control group. In conclusion, noninvasive ventilation may be effective in averting respiratory failure in severely obese patients when applied during the first 48 h post-extubation. In selected patients with chronic hypercarbia, early application of noninvasive ventilation may confer a survival benefit.

OBJECTIVES: To determine in older people the relation between auditory dysfunction and cognitive dysfunction, and if central auditory test abnormalities predict the onset of clinical dementia or cognitive decline. DESIGN: Prospective population-based cohort study. SETTING: Framingham Heart Study outpatient biennial examinations 18 and 21. PARTICIPANTS: Members of the Framingham Heart Study cohort with normal findings from cognitive screening tests at biennial examination 18. MEASUREMENTS: Peripheral audiometric thresholds and word recognition in quiet; Synthetic Sentence Identification with Ipsilateral Competing Message (SSI-ICM); Mini-Mental State Examination; and detailed neuropsychological testing of subjects with abnormal findings from the Mini-Mental State Examination. Relative risk of dementia was determined using age-adjusted Cox proportional hazards regression models. RESULTS: Hearing loss significantly lowered performance on the verbal parts of the Mini-Mental State Examination. The relative risk of subsequent clinical dementia or cognitive decline was 6 in subjects with very poor scores (< 50%) in one ear on the SSI-ICM (P = .02); the relative risk was 12.5 if the poor scores were present in both ears (P = .001). CONCLUSIONS: Central auditory dysfunction precedes senile dementia in a significant number of cases and may be an early marker for senile dementia. Hearing tests should be included in the evaluation of persons older than 60 years and in those suspected of having cognitive dysfunction.

We performed a retrospective study of a large cohort of patients who had episodes of Staphylococcus aureus bacteremia (SAB) from January 1995 through February 1999 at 1 medical center to identify predictors of 30-day mortality in SAB. Among 293 patients with episodes of SAB, 68 died (23.2%) within 30 days of onset. There was no significant difference in 30-day mortality associated with treatment with vancomycin, a beta-lactam, or a miscellaneous group of antimicrobial agents (P=.180). By logistic regression, an acute physiology score (a component of the acute physiology and chronic health evaluation [APACHE III]) >60 at onset of SAB was the most important predictor of 30-day mortality (odds ratio [OR], 15.7). Other significant predictors were lung (OR, 5.8) or unknown (OR, 4.1) focus of SAB, age > or =65 years (OR, 2.0), and diabetes mellitus (OR, 2.4). Future investigators of SAB should take into consideration acute severity of illness at onset as well as other factors when evaluating or comparing outcomes.

Pneumonia is the most serious of the common infections that occur in nursing homes, with a high case-fatality rate and considerable mortality among survivors. Risk factors for nursing home-acquired pneumonia (NHAP) have been defined, and prediction models for death due to NHAP have been developed. The bacterial etiology of NHAP has been debated, but "typical" bacterial pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) are most important. Clinical presentation of NHAP is said to be "atypical," but this may be confounded by dementia in the nursing home resident. A recent guideline has made recommendations regarding the minimal diagnostic workup when a resident has a suspected case of pneumonia. Until recently, most guidelines for the treatment of pneumonia did not specifically address NHAP; there is some evidence that use of a quinolone alone may be an acceptable first choice of therapy for most cases. Pneumococcal and influenza vaccination have been the primary prevention measures. However, additional methods to prevent NHAP should be evaluated, including improving the oral hygiene of residents and instituting pharmacological interventions.

Milnacipran is a serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor currently available for use as an antidepressant in several countries. Phase III clinical trials are currently underway to assess its potential role in the treatment of fibromyalgia syndrome, and in pursuit of US Food and Drug Administration approval for this indication. Evidence has accumulated suggesting that in animal models, milnacipran may exert pain-mitigating influences involving NE- and 5-HT-related processes at supraspinal, spinal and peripheral levels of pain transmission. Preliminary evidence suggests that milnacipran may be useful in mitigating pain and fatigue associated with fibromyalgia. However, its role in addressing comorbidities associated with fibromyalgia, including visceral pain and migraine, has yet to be investigated.

Background Influenza infection causes considerable morbidity and mortality in patients with cardiovascular disease. We assessed the effects of the influenza vaccine on mortality and cardiovascular outcomes in patients with cardiovascular disease. Methods and Results We searched PubMed, Embase, and the Cochrane Library through January 2020 for randomized controlled trials and observational studies assessing the effects of influenza vaccine on mortality and cardiovascular outcomes in patients with cardiovascular disease. Estimates were reported as random effects risk ratios (RRs) with 95% CIs. Analyses were stratified by study design into randomized controlled trials and observational studies. A total of 16 studies (n=237 058), including 4 randomized controlled trials (n=1667) and 12 observational studies (n=235 391), were identified. Participants' mean age was 69.2±7.01 years, 36.6% were women, 65.1% had hypertension, 31.1% had diabetes mellitus, and 23.4% were smokers. At a median follow‐up duration of 19.5 months, influenza vaccine was associated with a lower risk of all‐cause mortality (RR, 0.75; 95% CI, 0.60–0.93 [ P =0.01]), cardiovascular mortality (RR, 0.82; 95% CI, 0.80–0.84 [ P &lt;0.001]), and major adverse cardiovascular events (RR, 0.87; 95% CI, 0.80–0.94 [ P &lt;0.001]) compared with control. The use of the influenza vaccine was not associated with a statistically significant reduction of myocardial infarction (RR, 0.73; 95% CI, 0.49–1.09 [ P =0.12]) compared with control. Conclusions Data from both randomized controlled trials and observational studies support the use of the influenza vaccine in adults with cardiovascular disease to reduce mortality and cardiovascular events, as currently supported by clinical guidelines. Clinicians and health systems should continue to promote the influenza vaccine as part of comprehensive secondary prevention.

Pediatricians are an important source of health care for adolescents and young adults and can play a significant role in addressing their patients’ sexual and reproductive health needs, including preventing unintended pregnancies and sexually transmitted infections (STIs), including HIV, and promoting healthy relationships. STIs, HIV, and unintended pregnancy are all preventable health outcomes with potentially serious permanent sequelae; the highest rates of STIs, HIV, and unintended pregnancy are reported among adolescents and young adults. Office visits present opportunities to provide comprehensive education and health care services to adolescents and young adults to prevent STIs, HIV, and unintended pregnancies. The American Academy of Pediatrics, other professional medical organizations, and the government have guidelines and recommendations regarding the provision of sexual and reproductive health information and services. However, despite these recommendations, recent studies have revealed that there is substantial room for improvement in actually delivering the recommended services. The purpose of this clinical report is to assist pediatricians to operationalize the provision of various aspects of sexual and reproductive health care into their practices and to provide guidance on overcoming barriers to providing this care routinely while maximizing opportunities for confidential health services delivery in their offices.

Ovarian cancer is the second most common gynecological cancer and the leading cause of death in the United States. In this article we review the diagnosis and current management of epithelial ovarian cancer which accounts for over 95 percent of the ovarian malignancies. We will present various theories about the potential origin of ovarian malignancies. We will discuss the genetic anomalies and syndromes that may cause ovarian cancers with emphasis on Breast cancer type 1/2 mutations. The pathology and pathogenesis of ovarian carcinoma will also be presented. Lastly, we provide a comprehensive overview of treatment strategies and staging of ovarian cancer, conclusions and future directions.