The Ottawa SAH search algorithms: protocol for a multi- centre validation study of primary subarachnoid hemorrhage prediction models using health administrative data (the SAHepi prediction study protocol).

BACKGROUND: Conducting prospective epidemiological studies of hospitalized patients with rare diseases like primary subarachnoid hemorrhage (pSAH) are difficult due to time and budgetary constraints. Routinely collected administrative data could remove these barriers. We derived and validated 3 algorithms to identify hospitalized patients with a high probability of pSAH using administrative data. We aim to externally validate their performance in four hospitals across Canada. METHODS: Eligible patients include those ≥18 years of age admitted to these centres from January 1, 2012 to December 31, 2013. We will include patients whose discharge abstracts contain predictive variables identified in the models (ICD-10-CA diagnostic codes I60** (subarachnoid hemorrhage), I61** (intracranial hemorrhage), 162** (other nontrauma intracranial hemorrhage), I67** (other cerebrovascular disease), S06** (intracranial injury), G97 (other postprocedural nervous system disorder) and CCI procedural codes 1JW51 (occlusion of intracranial vessels), 1JE51 (carotid artery inclusion), 3JW10 (intracranial vessel imaging), 3FY20 (CT scan (soft tissue of neck)), and 3OT20 (CT scan (abdominal cavity)). The algorithms will be applied to each patient and the diagnosis confirmed via chart review. We will assess each model's sensitivity, specificity, negative and positive predictive value across the sites. DISCUSSION: Validating the Ottawa SAH Prediction Algorithms will provide a way to accurately identify large SAH cohorts, thereby furthering research and altering care.

Aneurysmal SubArachnoid Hemorrhage-Red Blood Cell Transfusion And Outcome (SAHaRA): a pilot randomised controlled trial protocol.

INTRODUCTION: Anaemia is common in aneurysmal subarachnoid haemorrhage (aSAH) and is a potential critical modifiable factor affecting secondary injury. Despite physiological evidence and management guidelines that support maintaining a higher haemoglobin level in patients with aSAH, current practice is one of a more restrictive approach to transfusion. The goal of this multicentre pilot trial is to determine the feasibility of successfully conducting a red blood cell (RBC) transfusion trial in adult patients with acute aSAH and anaemia (Hb ≤100 g/L), comparing a liberal transfusion strategy (Hb ≤100 g/L) with a restrictive strategy (Hb ≤80 g/L) on the combined rate of death and severe disability at 12 months. METHODS: Design This is a multicentre open-label randomised controlled pilot trial at 5 academic tertiary care centres. Population We are targeting adult aSAH patients within 14 days of their initial bleed and with anaemia (Hb ≤110 g/L). Randomisation Central computer-generated randomisation, stratified by centre, will be undertaken from the host centre. Randomisation into 1 of the 2 treatment arms will occur when the haemoglobin levels of eligible patients fall to ≤100 g/L. Intervention Patients will be randomly assigned to either a liberal (threshold: Hb ≤100 g/L) or a restrictive transfusion strategy (threshold: Hb ≤80 g/L). Outcome Primary: Centre randomisation rate over the study period. Secondary: (1) transfusion threshold adherence; (2) study RBC transfusion protocol adherence; and (3) outcome assessment including vital status at hospital discharge, modified Rankin Score at 6 and 12 months and Functional Independence Measure and EuroQOL Quality of Life Scale scores at 12 months. Outcome measures will be reported in aggregate. ETHICS AND DISSEMINATION: The study protocol has been approved by the host centre (OHSN-REB 20150433-01H). This study will determine the feasibility of conducting the large pragmatic RCT comparing 2 RBC transfusion strategies examining the effect of a liberal strategy on 12-month outcome following aSAH. TRIAL REGISTRATION NUMBER: NCT02483351; Pre-results.

Body mass index and the risk of injury in adults: a cross-sectional study.

OBJECTIVES: To investigate the association between body mass index (BMI) and the risk of nonfatal body injury. METHODS: We analyzed data from 113,203 adults who participated in the Canadian Community Health Survey conducted in 2009-2010. Log-binomial models were used to estimate crude and adjusted relative risks of the association between BMI and the risk of body injury for men and women. RESULTS: Of 113,203 adult participants, 15,194 had self-reported body injuries during the past 12 months, with a 12-month cumulative incidence of 13.7% (weighted to Canadian population). There was a significant interaction between gender and BMI in relation to the risk of body injury, and therefore, analyses were stratified by gender. For women, we found a significant association between BMI and an increased risk of body injury. Women with an increased BMI had a significant increased risk of body injuries as compared with those with normal weight (adjusted relative risk: 1.13, 95% confidence interval (CI)=1.02-1.25 for BMI 30.0-34.9 kg m(-)(2); 1.17, 95% CI=1.00-1.37 for BMI 35.0-39.9 kg m(-)(2); 1.41, 95% CI=1.16-1.69 for BMI ⩾ 40 kg m(-)(2)). A reduced risk of injury was observed in underweight women. There was no significant association between BMI and the risk of body injury for men. Obese persons of both gender were more likely to suffer injuries to the knee and lower leg, and in less demanding activities such as household chores or using the stairs. CONCLUSIONS: We therefore conclude that increased BMI may be a risk factor for body injury in women, but not in men.

Absolute branching fraction measurements of exclusive D+ semileptonic decays.

Using data collected at the psi(3770) resonance with the CLEO-c detector at the Cornell e+e- storage ring, we present improved measurements of the absolute branching fractions of D+decays to K0e+ve, pi0e+ve, K*0e+ve, and p0e+ve, and the first observation and absolute branching fraction measurement of D+ --> omega e+ve. We also report the most precise tests to date of isospin invariance in semileptonic D0 and D+ decays.

Study of the semileptonic charm decays D(0)-->pi(-)l(+)nu and D(0)-->K(-)l(+)nu.

We investigate the decays D(0)-->pi(-)l(+)nu and D(0)-->K(-)l(+)nu, where l is e or mu, using approximately 7 fb(-1) of data collected with the CLEO III detector. We find R(0) identical with B(D(0)-->pi(-)e(+)nu)/B(D(0)-->K(-)e(+)nu)=0.082+/-0.006+/-0.005. Fits to the kinematic distributions of the data provide parameters describing the form factor of each mode. Combining the form factor results and R(0) gives |f(pi)(+)(0)|(2)|V(cd)|(2)/|f(K)(+)(0)|(2)|V(cs)|(2)=0.038(+0.006+0.005)(-0.007-0.003).

Measurement of the muonic branching fractions of the narrow upsilon resonances.

The decay branching fractions of the three narrow Upsilon resonances to mu(+)mu(-) have been measured by analyzing about 4.3 fb(-1) e(+)e(-) data collected with the CLEO III detector. The branching fraction B(Upsilon(1S)-->mu(+)mu(-))=(2.49+/-0.02+/-0.07)% is consistent with the current world average, but B(Upsilon(2S)-->mu(+)mu(-))=(2.03+/-0.03+/-0.08)% and B(Upsilon(3S)-->mu(+)mu(-))=(2.39+/-0.07+/-0.10)% are significantly larger than prior results. These new muonic branching fractions imply a narrower total decay width for the Upsilon(2S) and Upsilon(3S) resonances and lower other branching fractions that rely on these decays in their determination.

Search for X(3872) in gammagamma fusion and radiative production at CLEO.

We report on a search for the recently reported X(3872) state using 15.1 fb(-1) of e(+)e(-) data taken in the sqrt[s] = 9.46-11.30 GeV region. Separate searches for the production of the X(3872) in untagged gammagamma fusion and e(+)e(-) annihilation following initial state radiation are made by taking advantage of the unique angular correlation between the leptons from the decay J/psi --> l(+)l(-) in X(3872) decay to pi(+)pi(-)J/psi. No signals are observed in either case, and 90% confidence upper limits are established as (2J+1)Gamma(gammagamma)(X(3872))B(X --> pi(+)pi(-)J/psi) < 12.9 eV and Gamma(ee)(X(3872))B(X- -> pi(+)pi(-)J/psi) < 8.3 eV.

First observation and Dalitz analysis of the D0-->K(0)Setapi(0) decay.

Using 9.0 fb(-1) of integrated luminosity in e(+)e(-) collisions near the Upsilon(4S) mass collected with the CLEO II.V detector we report the first observation of the decay D0-->K(0)(S)etapi(0). We measure the ratio of branching fractions, BR(D0-->K(0)(S)etapi(0))BR / (D0-->K(0)(S)pi(0))=0.46+/-0.07+/-0.06. We perform a Dalitz analysis of 155 selected D0-->K(0)(S)etapi(0) candidates and find leading contributions from a(0)(980)K(0)(S) and K(*)(892)eta intermediate states.

Observation of eta'c production in gammagamma fusion at CLEO.

We report on the observation of the eta(')(c)(2(1)S0), the radial excitation of the eta(c)(1(1)S0) ground state of charmonium, in the two-photon fusion reaction gammagamma-->eta(')(c)-->K(0)(S)K+/-pi(-/+) in 13.6 fb(-1) of CLEO II/II.V data and 13.1 fb(-1) of CLEO III data. We obtain M(eta(')(c))=3642.9+/-3.1(stat)+/-1.5(syst) MeV and M(eta(c))=2981.8+/-1.3(stat)+/-1.5(syst) MeV. The corresponding values of hyperfine splittings between 1S0 and 3S1 states are DeltaM(hf)(1S)=115.1+/-2.0 MeV and DeltaM(hf)(2S)=43.1+/-3.4 MeV. Assuming that the eta(c) and eta(')(c) have equal branching fractions to K(S)Kpi, we obtain Gamma(gammagamma)(eta(')(c))=1.3+/-0.6 keV.

Mean airway pressure as an index of mean alveolar pressure.

Mean airway pressure (Pao) has been advocated as a useful index for monitoring hemodynamic performance and risk for barotrauma during mechanical ventilation. This is based on the assumption that Pao closely reflects mean alveolar pressure (Palv). In the present study we have compared Pao with Palv in 12 sedated, paralyzed, mechanically ventilated patients. External PEEP ranged from 0.3 to 8.9 cm H2O. Palv was estimated by measuring Pao after rapid flow interruptions made at different points in time of the breathing cycle, using a modification of the method of Fuhrman and coworkers (4). All subjects exhibited intrinsic PEEP (PEEPi), which ranged from 0.5 to 9.4 cm H2O. A significant negative correlation (p < 0.001) was found between Pao/Palv and PEEPi. On average, at PEEPi of 10 cm H2O, Pao underestimated Palv by about 50%. We conclude that Pao cannot be taken as an index of Palv in patients who exhibit dynamic hyperinflation and PEEPi caused by expiratory flow limitation.

A simple method to detect expiratory flow limitation during spontaneous breathing.

Patients with severe chronic obstructive pulmonary disease (COPD) often exhale along the same flow-volume curve during quiet breathing as during a forced expiratory vital capacity manoeuvre, and this has been taken as indicating flow limitation at rest. To obtain such curves, a body plethysmograph and the patient's co-operation are required. We propose a simple technique which does not entail these requirements. It consists in applying negative pressure at the mouth during a tidal expiration (NEP). Patients in whom NEP elicits an increase in flow throughout the expiration are not flow-limited. In contrast, patients in whom application of NEP does not elicit an increase in flow during most or part of the tidal expiration are considered as flow-limited. Using this technique, 26 stable COPD patients were studied sitting and supine. Eleven patients were flow-limited both seated and supine, eight were flow-limited only when supine, and seven were not flow-limited either seated or supine. Only 5 of 19 patients who were flow-limited seated and/or supine had severe ventilatory impairment (forced expiratory volume in one second (FEV1) < 40% predicted). We conclude that the NEP technique provides a simple, rapid, and reliable method for detection of expiratory flow limitation in spontaneously breathing subjects, which does not require the patient's co-operation, and can be applied in different body positions both at rest and during muscular exercise. Our results also indicate a high prevalence of flow limitation in COPD patients at rest, particularly when supine.

Detection of expiratory flow limitation during mechanical ventilation.

Two new methods, application of negative pressure at the airway opening during expiration (NEP) and reduction of flow resistance by bypassing the expiratory line of the ventilator by exhaling into the atmosphere (ATM), were used to detect expiratory flow limitation in 12 semirecumbent (45 degree) mechanically ventilated patients, seven with chronic airway obstruction (CAO). An increase of expiratory flow with NEP or ATM, relative to the preceding control breath, was taken as indicating absence of expiratory flow limitation. By contrast, the portion of the tidal expiration over which there was no change in flow with NEP or ATM was considered as flow-limited. With NEP, nine patients exhibited flow limitation, six (all with CAO) were flow-limited over most of the tidal expiration (> 70% VT), and three at < 60% VT. Although the results with NEP and ATM were in general in good agreement, in the three non-flow-limited patients the ATM method gave erroneous results. Six patients were also studied supine, including two who were not flow-limited when semirecumbent: both became flow-limited when supine. We conclude that NEP provides a simple method to detect flow limitation in mechanically ventilated patients. The supine position enhances flow limitation.

Partitioning of work of breathing in mechanically ventilated COPD patients.

In 10 sedated paralyzed mechanically ventilated chronic obstructive pulmonary disease (COPD) patients, we measured the inspiratory mechanical work done per breath on the respiratory system (WI,rs). We measured the tracheal and esophageal pressures to assess the lung (L) and chest wall (W) components of WI and used the technique of rapid airway occlusion during constant-flow inflation to partition WI into static work [Wst, including work due to intrinsic positive end-expiratory pressure (WPEEPi)], dynamic work due to airway resistance, and the additional resistance offered by the respiratory tissues. Although the patients were hyperinflated, the slope of the static volume-pressure relationships of the lung did not decrease with inflation volume up to 0.8 liter. WI,W was similar in COPD patients and normal subjects. All components of WI,L were higher in COPD patients. The increase in Wst,rs was due entirely to WPEEPi. Our data suggest that, during spontaneous breathing, COPD patients would probably develop inspiratory muscle fatigue, unless continuous positive airway pressure were applied to reduce WPEEPi.

Flow resistance in mechanically ventilated patients with severe neurological injury.

In 5 mechanically ventilated patients with severe neurological injury (SNI), we measured the respiratory system's flow resistance (Rrs) over a range of inspiratory flows between 0.2 to 2 L/s, at inflation volumes (delta V) ranging from 0.1 to 1 L. Under baseline ventilatory conditions (V = 1 L/s; delta V = 0.95 L), we also partitioned Rrs into airway resistance (Raw) and the additional resistance offered by the tissues of the lung and chest wall (delta Rrs). At all inflation volumes, Rrs decreased hyperbolically with increasing flow but was higher than in normal anesthetized paralyzed subjects (N). At V of 1 L/s and delta V of 0.5 L, Rrs was significantly greater in SNI than in N (7.7 +/- 1.5 v 4.2 +/- 0.5 cm H2O/L/s; P < .01). This discrepancy was due to higher Raw in SNI. Indeed, at V of 1 L/s, Raw (mean +/- SEM) was significantly higher in SNI than in N (4.0 +/- 0.9 v 2.4 +/- 0.2 cm H2O/L/s; P < .001), whereas delta Rrs did not differ significantly. The increased Raw in SNI was due to the fact that these patients were therapeutically hyperventilated (PaCO2 = 30.4 +/- 4.2 mm Hg) and as a result their airways were bronchoconstricted. We conclude that in the intensive care unit setting, hyperventilated patients with severe neurological injury can not be considered to be adequate controls in terms of Rrs and Raw, because hypocapnia induces an increase of Raw and consequently also in Rrs (= Raw+delta Rrs).

Lung and chest wall mechanics in mechanically ventilated COPD patients.

By use of the technique of rapid airway occlusion, the effects of inspiratory flow, volume, and time on lung and chest wall mechanics were investigated in 10 chronic obstructive pulmonary disease (COPD) patients mechanically ventilated for acute respiratory failure. We measured the interrupter resistance (Rint), which in humans reflects airway resistance; the additional resistances due to time constant inequality and viscoelastic pressure dissipations within the lungs (delta RL) and the chest wall; and the static and dynamic elastances of lung and chest wall. We observed that 1) static elastances of lung and chest wall in COPD patients were similar to those of normal subjects; 2) Rint of the lung was markedly increased and flow dependent in COPD patients, whereas Rint of the chest wall was negligible as in normal subjects; and 3) in COPD patients, delta RL was markedly increased at all inflation flows and volumes, reflecting increased time constant inequalities within the lungs and/or altered viscoelastic behavior. The results imply increased dynamic work due to Rint and delta RL and marked time dependency of pulmonary resistance and elastance in COPD patients.

Effect of PEEP on the mechanics of the respiratory system in ARDS patients.

In patients with adult respiratory distress syndrome (ARDS) we studied the effect of positive end-expiratory pressure (PEEP) on respiratory mechanics. We used the technique of rapid airway occlusion during constant flow (V) inflation to partition the total respiratory system resistance (Rrs) into the interrupter resistance (Rint,rs) and the additional resistance (delta Rrs) due to viscoelastic pressure dissipations and time constant inequalities. We also measured static (Est,rs) and dynamic (Edyn,rs) elastance of the respiratory system. The procedure was carried out in nine ARDS patients at different inspiratory V and inflation volumes (delta V) at PEEP of 0, 5, 10, and 15 cmH2O. We found that during baseline ventilation (delta V = 0.7 liter and V = 1 l/s), Est,rs, Edyn,rs, and Rint,rs did not change significantly with PEEP, whereas delta Rrs and Rrs increased significantly only with PEEP of 15 cmH2O. The increase of delta Rrs and Rrs with PEEP was positively correlated with the concomitant changes in end-expiratory lung volume (P < 0.001). At all levels of PEEP, under iso-delta V conditions, delta Rrs decreased with increasing V, whereas at a fixed V, delta Rrs increased with increasing delta V. A four-parameter model of the respiratory system failed to fully describe respiratory dynamics in the ARDS patients, probably due to nonlinearities.

Bilateral pneumothoraces hasten mortality in AIDS patients receiving secondary prophylaxis with aerosolized pentamidine. Association with a lower Dco prior to receiving aerosolized pentamidine.

We have administered aerosolized pentamidine (AP) to 48 AIDS patients for secondary prophylaxis of Pneumocystis carinii pneumonia (PCP). Pentamidine 60 mg was administered by ultrasonic nebulization (Fisoneb) five times during the first two weeks and then every two weeks. The mean follow-up was 343 +/- 22 days. PCP recurred in ten patients, 297 +/- 33 days after starting AP therapy. All responded to anti-Pneumocystis therapy but two patients died of unrelated reasons (20 percent mortality). Five patients developed bilateral pneumothoraces 260 +/- 35 days after starting AP therapy. Recurrence of PCP could be documented in only one patient. All died 66 +/- 27 days after the onset of the first pneumothorax. Only 5 of 33 patients without recurrence of pneumonia or pneumothorax died during the study period (15 percent mortality). No association was found between the development of pneumothorax and age, smoking, previous respiratory or infectious problems, time from last PCP and the initiation of AP therapy, and treatment duration of last PCP. Patients with pneumothoraces had a significantly lower Dco (58.6 +/- 2.6 percent predicted) prior to AP therapy than patients with recurrence of PCP without pneumothoraces (81.1 +/- 2.1 percent predicted) or patients with no recurrence of PCP (67 +/- 2.5 percent predicted) (p less than 0.05, ANOVA). In conclusion, bilateral pneumothoraces are associated with a hastened mortality in patients receiving AP for secondary prophylaxis of PCP. Low Dco before AP therapy is associated with an increased risk of bilateral pneumothoraces in patients treated with AP for secondary prophylaxis of PCP.