Impact of vitamin D replacement in adults and elderly in the Middle East and North Africa: a systematic review and meta-analysis of randomized controlled trials.

In the Middle East and North Africa (MENA), a vitamin D dose ≥2000 IU/day may be needed to allow to the majority of the population to reach the target 25-hydroxyvitamin D (25(OH)D) level ≥20 ng/ml. Data in the region on the effect of vitamin D supplementation on various skeletal and extra-skeletal effects are scarce. INTRODUCTION: Hypovitaminosis D is prevalent worldwide, more so in the Middle East and North Africa (MENA). This study aims to determine the effects of vitamin D replacement on the mean difference in 25-hydroxyvitamin D [25(OH)D] level reached and other outcomes, in the MENA. METHODS: This is a meta-analysis of randomized trials from the MENA, administering vitamin D supplementation for at least 3 months, without language or time restriction. We conducted a comprehensive search in seven databases until July 2015. We abstracted data from published reports, independently and in duplicate. We calculated the mean difference (MD) and 95 % CI of 25(OH)D level reached for eligible comparisons, and pooled data using RevMan version 5.3. RESULTS: We identified 2 studies in elderly and 17 in adults; for the latter, 11 were included in the meta-analysis. Comparing a high vitamin D dose (>2000 IU/day) to placebo (nine studies), the MD in 25(OH)D level achieved was 18.3 (CI 14.1; 22.5) ng/ml; p value < 0.001; I 2 = 92 %. Comparing an intermediate dose (800-2000 IU/day) to placebo (two studies), the MD in 25(OH)D level achieved was 14.7 (CI 4.6; 24.9) ng/ml; p value 0.004; I 2 = 91 %. Accordingly, 89 and 71 % of participants, in the high and intermediate dose groups, respectively, reached the desirable level of 20 ng/ml. The risk of bias in the included studies was unclear to high, except for three studies. CONCLUSION: In the MENA region, vitamin D doses ≥2000 IU/day may be needed to reach the target 25(OH)D level ≥20 ng/ml. The long-term safety and the efficacy of such doses on various outcomes are unknown.

BRAF mutational epidemiology in dysplastic nevi: does different solar UV radiation exposure matter?

BACKGROUND: Proto-oncogene B-Raf (BRAF) mutation rates have been reported in nevi and melanomas of homogeneous Caucasian cohorts. OBJECTIVE: To study the demographics of BRAF mutations in dysplastic nevi of populations with differing potential solar UV radiation exposure. METHODS: Extended BRAF testing for 9 mutations in 125 dysplastic nevi from 101 patients, derived from populations with differing potential UV radiation exposure rates (Lebanon and Saudi Arabia), was performed. Clinical and microscopic parameters were recorded. RESULTS: BRAF mutation status was carried out for 101/125 (80.8%) cases with an overall mutation rate of 62.4% (63/101). V600E (c.1799T > A) was the predominant mutation, found in 61/63 (96.8%) cases. BRAF mutation rate differed significantly by potential UV radiation exposure (Lebanon: 53.4%, Saudi Arabia: 74.4%, P < 0.05). A 43.8% discordant mutation rate (7/16 patients) was found in patients with multiple nevi, including 2 patients with different BRAF mutations. Microscopic examination subdivided the dysplasia into mild (n = 24), moderate (n = 60) and severe (n = 41) with trunk predominance (72.8%). Higher rates of pigment in the stratum corneum were identified in Saudi Arabia (P < 0.05). No statistical significant increase in BRAF mutation rate was noted with advanced architectural and cytological atypia. Parameters associated with a negative BRAF mutation status included upper extremity location, regression, cohesiveness and presence of suprabasal melanocytes (P < 0.05). Positive BRAF mutation status was reasonably predicted by multivariate binary logistic regression by 2 independent predictors: Geographic location and compound nevus type. CONCLUSIONS: In our Near Eastern cohort, the BRAF mutation rate varied significantly by geographic location. In patients with multiple dysplastic nevi examined, discordant BRAF mutation status potentially negates an underlying constitutional predilection.

Predictors of quality of life among multiple sclerosis patients: a comprehensive analysis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a debilitating neurological disease of young people with substantial consequences on patients' quality of life (QOL). A variety of QOL instruments have been used to evaluate the efficacy of treatments. However, no study assessed the role of the different demographic, clinical, physical, social, economic and psychological parameters in the perception of patients with MS of their QOL. METHODS: Two-hundred and one consecutive patients attending outpatient clinics were prospectively studied and objectively assessed using Expanded Disability Status Scale (EDSS), 8-m walk test, and Symbol Digit Modality Test. Patients completed the following questionnaires: MS QOL-54, Hamilton Depression Rating Scale, Fatigue Severity Scale, Brief Pain Inventory Average Pain Score, Drug Side-Effects Severity Scale, Social Support, Religiosity, Physiotherapy and Exercise, and Socioeconomic Profile. Overall, QOL, physical (PHCS) and mental (MHCS) health composite scores were computed as outcome measures from MSQOL-54. RESULTS: Depression, social support, religiosity, education years and living area predicted overall QOL by linear regression (R(2) = 0.43). Unemployment and absence of fatigue correlated with poor and good QOL, respectively. Fatigue, pain, depression, EDSS, social support, MS type and anti-cholinergic treatment predicted PHCS (R(2) = 0.81). Fatigue, pain, depression, education years and social support predicted MHCS (R(2) = 0.70). CONCLUSION: The QOL in patients with MS is not solely determined by physical disability, but rather by the level of social support, living area, depression, level of education, employment, fatigue and religiosity. Accordingly, we suggest that these should be evaluated in every patient with MS as they may be modified by targeted interventions.

Effects of CYP2B6 genetic polymorphisms in patients receiving cyclophosphamide combination chemotherapy for breast cancer.

PURPOSE: The purpose of this study was to measure the frequency of three CYP2B6 [CYP2B6*4 (rs2279343), CYP2B6*5 (rs3211371) and CYP2B6*9 (rs3745274)] alleles in patients with breast cancer receiving cyclophosphamide (CP) therapy and test whether these variants are predictors of CP-associated toxicity and efficacy. METHODS: A total of 145 female breast cancer patients admitted to the American University of Beirut Medical Center for breast cancer-related therapy were included. Chart review was performed for collection of toxicity data. A time-to-event analysis was performed with a subset of 38 patients. RESULTS: The minor allele frequencies of CYP2B6*9, CYP2B6*4 and CYP2B6*5 were 0.27, 0.29 and 0.07, respectively. CYP2B6 *5/*6, *6/*9 or *6/*6 haplotypes were associated with a significantly shorter time to recurrence of the disease. There were no significant associations with myelo-toxicity. CONCLUSIONS: This is the first report on the pharmacogenetic profile of patients with breast cancer and the therapeutic and myelo-toxic behavior of CP in women from an Arab Middle Eastern country. Our results show that genotyping for these CYP2B6 alleles does not help in personalizing therapy from a toxicity perspective, and the association of shorter survival in these subjects with homozygous variants is interesting yet insufficient to justify routine genotyping prior to therapy, or to consider using a higher CP dose. Larger future studies or meta-analyses will be needed to further clarify the potential implication of these genetic polymorphisms.

Factors predisposing to median sternotomy complications. Deep vs superficial infection.

STUDY OBJECTIVES: Median sternotomy infections are a serious complication of cardiac surgery. The purpose of this study was to determine the patient characteristics and operative variables that predict incidence of sternal infection, and possibly its severity. DESIGN: Univariate and multivariate retrospective analysis comparing patient, operative, and post-operative data in patients with and without sternal infections. SETTING: Cardiac surgery program of a 580-bed private hospital in Toledo, Ohio. PATIENTS: We studied 2,317 consecutive (June 1991 to December 1994) patients undergoing cardiac surgery. RESULTS: Forty-one sternal infections were documented. Of these, 21 (0.91%) were deep infections with mediastinal involvement and 20 (0.86%) were superficial. Two patients with deep infections died (2/41, 5%). Ten variables were associated with infection by univariate analysis (p < 0.05), and of these, five were independent predictors by multivariate logistic regression. These predictors were obesity (p < 0.001), insulin-dependent diabetes (p < 0.001), use of internal mammary artery grafts (p = 0.02), surgical reexploration of the mediastinum (p = 0.003), and postoperative transfusions (p = 0.01). Predictors of deep and superficial sternal infection did not differ. Length of hospitalization was substantially longer for patients with deep (32 +/- 21 days) vs superficial infection (13 +/- 10 days). CONCLUSIONS: The present study confirms previous findings that obesity, insulin-dependent diabetes, and internal mammary artery grafting (especially bilaterally) increase the risk of sternal infection. In addition, chest surgical reexploration and blood transfusions were postoperative factors that predisposed patients with median sternotomy to infection. Unlike their associated morbidity and mortality, predictors of deep and superficial sternal infections are similar.

Total respiratory input impedance with the upper airway wall shunt minimized.

Respiratory impedances (Zrs) measured with the cheeks manually supported (Zsc) demonstrate an antiresonance (AR) at approximately 170 Hz, whereas those measured with the head generator (Zhg) have an AR at significantly lower frequencies (150 Hz). The differences in the AR between methods were previously attributed to upper airway wall (UAW) shunting in Zsc, and Zhg was believed to represent shunt-free impedance. To test this hypothesis, we measured four independent estimates of Zrs (4-256 Hz) in five healthy adults. Applying the oscillations at the mouth, we measured Zrs with the cheeks unsupported (Zuc) and when the subject's head and neck were enclosed in a rigid chamber completely filled with water (Zwa). We also measured Zhg with the oscillations applied around the head. Because water is incompressible, Zwa should minimize UAW shunt if not completely eliminate it. There were no significant differences in any of the AR features (e.g., location and bandwidth) of Zuc, Zsc, and Zwa. Conversely, all AR features of Zwa and Zhg were significantly different. To assess wall motion during both forms of oscillations (i.e., applied at the mouth and around the head), we measured two UAW local impedances by use of accelerometers placed on the cheeks (Zch) and submental (Zsm) region. Above 40 Hz, Zch and Zsm estimates were significantly dependent on the forcing method. Furthermore, Zch and Zsm made with the standard oscillations were consistent with the lumped UAW impedances measured with a head plethysmograph, whereas those made with the oscillations around the head were not. Therefore we conclude that, at > 32 Hz, Zsc more closely represents shunt-free impedance than does Zhg and hence should be preferred when Zrs are measured.

Wave propagation, input impedance, and wall mechanics of the calf trachea from 16 to 1,600 Hz.

Propagation of waves in the airways is important in flow limitation as well as in oscillation mechanics. In five excised calf tracheae, we measured phase propagation velocity (c) and input impedance with open (Zop) or closed end (Zcl) for frequencies (f) between 16 and 1,600 Hz at two axial tensions [nonstretched (TN) and stretched (TS); TS > TN]. From 16 to 64 Hz, c slightly increased because of the viscoelastic properties of the wall tissues. Between 64 and 200 Hz, c was relatively constant and less than the free-field speed of sound (c0 = 340 m/s), with values smaller at TS (140 +/- 39 m/s) than at TN (172 +/- 35 m/s). Above 200 Hz, c exceeded c0 and displayed two maxima at approximately 300 and approximately 700 Hz, with values of approximately 360 and approximately 550 m/s, respectively. For f > 1,400 Hz, c approached c0. We provide evidence that the two maxima in c were the result of the two-compartment behavior of the wall tissues, i.e., the separate cartilaginous and soft tissues. A nonrigid tube model with its wall impedance composed of two series resistance, compliance, and inertance pathways in parallel simultaneously fits c, Zop, and Zcl well and hence provides a link among these data. By use of the relationship between volumetric wall parameters and the tracheal geometry, separate material properties such as viscosity and Young's modulus of both the soft tissue (approximately 1 cmH2O.s and approximately 0.26 x 10(4) cmH2O, respectively) and the cartilage (approximately 3.7 cmH2O.s and approximately 2 x 10(4) cmH2O, respectively) were estimated. These results indicate that measures of c and Zop or Zcl data over these frequencies provide information about the dynamic mechanical properties of both the soft tissue and cartilage in the airway walls.

Airway geometry and wall mechanical properties estimated from subglottal input impedance in humans.

We measured input impedance between 16 and 2,048 Hz in intubated subjects at functional residual capacity. The corresponding subglottal impedances (ZSG) were then computed using a model where the endotracheal tube was represented by a distributed-parameter two-port network. ZSG was well described by a model based on Horsfield's asymmetric airway geometry at total lung capacity (TLC) with nonrigid walls. The walls of the cartilaginous airways included separate cartilage and soft tissue compartments, whereas the noncartilaginous airway walls had only a soft tissue compartment. Both compartments consisted of a series resistance, inertance, and compliance, the values of which were computed from airway dimensions and wall material properties (viscosity, density, and Young's modulus). Airway wall thickness was determined by scaling an airway wall area-diameter relationship. Airway lengths and diameters were scaled from the Horsfield TLC values by a single factor and by an order-dependent sigmoidal curve, respectively. The estimated soft tissue viscosity and Young's modulus were 1.04 +/- 0.21 cmH2O.s and 593 +/- 319 cmH2O, respectively. Airway lengths and tracheal diameters were not statistically different from the Horsfield values. The estimated diameters of the more peripheral airways were significantly reduced compared with the Horsfield TLC values (e.g., approximately 40% at the terminal airway), which is consistent with the reduction in airway caliber when the lung deflates from TLC to functional residual capacity. These results indicate that high-frequency ZSG is sensitive to subglottal airway geometry and wall properties and that by use of appropriate structural models one can estimate airway geometry and airway wall parameters.

Serial distribution of airway mechanical properties in dogs: effects of histamine.

We measured respiratory input impedance (Zin; 8-2,048 Hz) in five dogs (anesthetized, tracheostomized, vagotomized, and mechanically ventilated) during 80 s of apnea after a bolus intravenous injection of saline or histamine (5.0 mg). In the control case, three antiresonances in Zin were found in four of the dogs, whereas in the remaining dog only two were found. The magnitude and frequency of these antiresonances were significantly altered after bronchoconstriction. To interpret Zin, a model incorporating detailed airway geometry, asymmetrical branching, and nonrigid airway walls was developed. The model fit both the saline and histamine Zin data well and predicted a serial distribution of bronchoconstriction consistent with known effects of histamine; i.e., the diameters of the most peripheral airways were reduced (26% of their control values), whereas tracheal diameters were not significantly affected. The model provided estimates of tracheal diameters that were well correlated (r = 0.92) with direct measurements. Control estimates of soft tissue viscosity (1.63 +/- 0.42 cmH2O.s) and Young's modulus (406 +/- 125 cmH2O) compared closely with values in the literature. These results indicate that bronchoconstriction induced by histamine results in significant changes in Zin over this frequency range and that by using this data analysis approach definitive physiological parameters relative to airway geometry and wall mechanical properties can be obtained from measurements made at the airway opening.

Lung resistance and elastance in spontaneously breathing preterm infants: effects of breathing pattern and demographics.

Reported values of lung resistance (RL) and elastance (EL) in spontaneously breathing preterm neonates vary widely. We hypothesized that this variability in lung properties can be largely explained by both inter- and intrasubject variability in breathing pattern and demographics. Thirty-three neonates receiving nasal continuous positive airway pressure [weight 606-1,792 g, gestational age (GA) of 25-33 wk, 2-49 days old] were studied. Transpulmonary pressure was measured by esophageal manometry and airway flow by face mask pneumotachography. Breath-to-breath changes in RL and EL in each infant were estimated by Fourier analysis of impedance (Z) and by multiple linear regression (MLR). RL(MLR) (RL(MLR) = 0.85 x RL(Z) -0.43; r(2) = 0.95) and EL(MLR) (EL(MLR) = 0.97 x EL(Z) + 8.4; r(2) = 0.98) were highly correlated to RL(Z) and EL(Z), respectively. Both RL (mean +/- SD; RL(Z) = 70 +/- 38, RL(MLR) = 59 +/- 36 cm H(2)O x s x l(-1)) and EL (EL(Z) = 434 +/- 212, EL(MLR) = 436 +/- 210 cm H(2)O/l) exhibited wide intra- and intersubject variability. Regardless of computation method, RL was found to decrease as a function of weight, age, respiratory rate (RR), and tidal volume (VT) whereas it increased as a function of RR. VT and inspiratory-to-expiratory time ratio (TI/TE). EL decreased with increasing weight, age, VT and female gender and increased as RR and TI/TE increased. We conclude that accounting for the effects of breathing pattern variability and demographic parameters on estimates of RL and EL is essential if they are to be of clinical value. Multivariate statistical models of RL and EL may facilitate the interpretation of lung mechanics measurements in spontaneously breathing infants.

Respiratory impedance and multibreath N2 washout in healthy, asthmatic, and cystic fibrosis subjects.

We measured forced expiratory volume in 1 s (FEV1), respiratory impedance (Zrs) from 4 to 60 Hz, and a multibreath N2 washout (MBNW) in 6 normal, 10 asthmatic, and 5 cystic fibrosis (CF) subjects. The MBNW were characterized by the mean dilution number (MDN) derived by a moment analysis. The Zrs spectra were characterized by the minimum resistance (Rmin), the drop in resistance (Rdrop) from 4 Hz to Rmin, and the first resonance frequency (Fr1). Measurements were repeated after bronchodilation in three normal and all asthmatic subjects. Before bronchodilation, six of the asthmatic subjects showed close to normal FEV1. The Zrs in the normal subjects showed low Rmin (1.9 +/- 0.7 cmH2O.l-1.s), Rdrop (0.4 +/- 0.4), and Fr1 (10 +/- 2 Hz). Four of the mildly obstructed asthmatic subjects had normal Zrs but elevated MDNs (i.e., abnormal ventilation distribution). The other six asthmatic subjects had significantly elevated Rmin (4.1 +/- 0.8), Rdrop (6.3 +/- 5.8), and Fr1 (34 +/- 0.4 Hz) and elevated MDNs. The CF patients had elevated Zrs features and MDNs. After bronchodilation, no changes in FEV1, MDN, or Zrs occurred in the normal subjects. All asthmatic subjects showed increased FEV1 and decreased MDN, but the Zrs was unaltered in the four asthmatic subjects whose base-line Zrs was normal. For the other six asthmatic subjects, there were large decreases in the Rmin, Rdrop, and Fr1. Finally, there was a poor correlation between the MDN and the Zrs features but high correlation between the Zrs features alone. These results imply that significant nonuniform peripheral airway obstruction can exist such that ventilation distribution is abnormal but Zrs from 4 to 60 Hz is not. Abnormalities in Zrs from 4 to 60 Hz occur only after significant overall obstruction in the peripheral and more central airways. Combining Zrs and the MBNW may permit us to infer whether the disease is predominantly in the lung periphery or in the more central airways.

Detecting lung overdistention in newborns treated with high-frequency oscillatory ventilation.

Positive airway pressure (Paw) during high-frequency oscillatory ventilation (HFOV) increases lung volume and can lead to lung overdistention with potentially serious adverse effects. To date, no method is available to monitor changes in lung volume (DeltaVL) in HFOV-treated infants to avoid overdistention. In five newborn piglets (6-15 days old, 2.2-4.2 kg), we investigated the use of direct current-coupled respiratory inductive plethysmography (RIP) for this purpose by evaluating it against whole body plethysmography. Animals were instrumented, fitted with RIP bands, paralyzed, sedated, and placed in the plethysmograph. RIP and plethysmography were simultaneously calibrated, and HFOV was instituted at varying Paw settings before (6-14 cmH(2)O) and after (10-24 cmH(2)O) repeated warm saline lung lavage to induce experimental surfactant deficiency. Estimates of Delta VL from both methods were in good agreement, both transiently and in the steady state. Maximal changes in lung volume (Delta VL(max)) from all piglets were highly correlated with Delta VL measured by RIP (in ml) = 1.01 x changes measured by whole body plethysmography - 0.35; r(2) = 0.95. Accuracy of RIP was unchanged after lavage. Effective respiratory system compliance (Ceff) decreased after lavage, yet it exhibited similar sigmoidal dependence on Delta VL(max) pre- and postlavage. A decrease in Ceff (relative to the previous Paw setting) as Delta VL(max) was methodically increased from low to high Paw provided a quantitative method for detecting lung overdistention. We conclude that RIP offers a noninvasive and clinically applicable method for accurately estimating lung recruitment during HFOV. Consequently, RIP allows the detection of lung overdistention and selection of optimal HFOV from derived Ceff data.

Determinants of prolonged mechanical ventilation after coronary artery bypass grafting.

BACKGROUND: Early extubation of cardiac surgical patients enhances ambulation, improves cardiopulmonary function, and can lead to savings in health care costs. METHODS: We retrospectively examined the role of 48 variables in determining the period of ventilatory support in 507 patients having coronary artery bypass grafting. RESULTS: Fifteen (< 3%) of 507 patients required ventilatory support in excess of 24 hours. Among the remaining patients, extubation was achieved early (< or = 8 hours) (mean time, 5.65 +/- 1.31 hours) in 53% and late (> 8 hours) (mean time, 13.7 +/- 3.4 hours) in 47%. Logistic and linear multivariate regression analyses implicated increased age, New York Heart Association functional class IV, intraoperative fluid retention, postoperative intraaortic balloon pump requirement, and bank blood transfusions as predictors of late extubation. Also, the linear regression linked lower body weight and number of anastomoses (or grafts) to increased mechanical ventilatory support. CONCLUSIONS: Analysis of the fluid balance and cardiopulmonary bypass data suggests that earlier extubation may be achieved by actively reducing fluid retention (eg, by hemoconcentration) and time on bypass (eg, normothermia). Finally, intensive care unit stay and postoperative length of stay were significantly lower in the early versus late extubation groups without an increase in pulmonary complications.

Variables predicting reintubation after cardiac surgical procedures.

BACKGROUND: This study sought to determine patient characteristics, processes of care, and intermediate outcomes as predictors of reintubation after cardiac surgical procedures. METHODS: We performed a retrospective case-control study that included all patients undergoing cardiac surgical intervention who required reintubation and an equal number of control patients not requiring reintubation. Putative risk factors were analyzed univariately by chi2, Fisher exact, Student's t, or Mann-Whitney tests. A logistic regression model was developed using data from patients requiring reintubation for cardiorespiratory reasons. RESULTS: Of the 1,000 consecutive patients reviewed, 41 (4.1%) required reintubation (30 [3%] for cardiorespiratory reasons and 11 [1.1] for unplanned operations). Univariate predictors of reintubation (p<0.05) were older age, chronic obstructive pulmonary disease, New York Heart Association functional class IV, preoperative renal failure, lower arterial oxygen tension, insertion of intraaortic balloon pump, longer time in the operating room, longer duration of cardiopulmonary bypass times, positive fluid balance, postoperative renal failure, and worse pulmonary mechanics. Patients requiring reintubation also required a longer initial period of mechanical ventilation (median, 16.3 versus 6.0 hours; p<0.05). Excellent prediction was found with a model consisting of four variables: operating room time, respiratory rate, vital capacity, and chronic obstructive pulmonary disease. CONCLUSIONS: Patients who required reintubation were sicker and had worse respiratory function and more comorbidity. Prompt extubation did not contribute to reintubation. Patients identified as having a high risk for reintubation should be followed up closely, and interventions should be directed to treating the problems leading to reintubation.

Resource utilization in coronary artery bypass operation: does surgical risk predict cost?

BACKGROUND: Current healthcare trends may render financial risk of cardiac operation a key component of clinical decision making. It has been suggested, based on large cohorts of patients stratified by clinical risk, that the cost of operation can be predicted from models of clinical risk since length of stay (LOS) is highly correlated to clinical risk, and LOS is correlated to hospital costs and charges. Direct correlation of actual surgical costs with surgical risk are lacking. METHODS: Variable direct costs, LOS, and The Society of Thoracic Surgeons predicted mortality risk [STS risk (%)] were collected and analyzed in 628 consecutive patients undergoing coronary artery bypass grafting (CABG) at our institution in 1997. RESULTS: Cost of CABG had a near-normal distribution, and cost in 21 outlier patients (cost > two standard deviations above the mean) was an average 5.3 times normal (median cost). For individual patients, cost was well correlated to LOS (R2 = 0.48) but not with STS risk (R2 = 0.12). LOS was also poorly predicted by STS risk (R2 = 0.09). However, despite its poor prediction of cost, STS risk was an unbiased estimator over the entire population. A result manifested, when patients were grouped into similar risk (<1%, 1-2%, 2+ -3%, 3+ -5%, 5+ -10%, and >10%) cohorts, by high correlation between cost and STS risk (R2 = 0.99), cost and LOS risk (R2 = 0.99), and LOS and STS risk (R2 = 0.97). CONCLUSIONS: Our data demonstrated that, in large CABG cohorts, surgical risk models can accurately predict cost of CABG. However, despite a trend for increasing cost with increasing STS risk, surgical risk models based on preoperative data are poor predictors of cost in individual patients. Use of these models should be limited to analysis of cost trends in cardiac operation, but not for predicting financial risk in individual patients during clinical decision making.

Effects of body size on operative, intermediate, and long-term outcomes after coronary artery bypass operation.

BACKGROUND: To investigate the role of body size, if any, on operative and longer term outcomes following coronary artery surgery. METHODS: A total of 3,560 consecutive patients undergoing coronary artery bypass grafting from 1991 to 1997, including 2,401 (67%) males and a mean +/- SD age of 63 +/- 10 years were ranked based on their body mass index (BMI). The association in these patients of preoperative, long-term, and economic data with variations in BMI were studied using regression analyses. Long-term survival was studied using 5-year Kaplan-Meier survival analysis. RESULTS: Operative mortality, myocardial infarction, cerebrovascular accidents, blood transfusions, and length of hospital stay were all increased in the smallest patients (BMI < or = 24 kg/m2). Obesity did not increase adverse operative outcomes except for a greater rate of sternal wound infections occurring with increasing severity of obesity. Direct variable costs were lowest in patients clustered around normal BMI, with cost increasing similarly at low and high extremes. This effect was correlated with similar BMI effects on ventilatory and intensive care requirements. Excluding operative mortality, 5-year survival trends were similarly worse for the smallest (BMI < or = 24) and most severely obese (BMI > 34) patients. Mild obesity (BMI > or = 30 to BMI < 34) did not affect long-term survival. CONCLUSIONS: Among study patients, immediate operative outcomes were adversely affected by small body size, which reflected older age (66 +/- 10 years) and an exaggerated adverse impact of cardiopulmonary bypass. Younger age and smaller effects of cardiopulmonary bypass lead to better operative outcomes in the obese. Long-term outcomes were, however, suboptimal in severely obese patients although that group was the youngest (60 +/- 10 years). In addition to their large body habitus, other factors, including substantial prevalence of diabetes, insulin dependence and hypertension, probably played a significant role in the poor long-term outcome in the severely obese.

Effects of rate and amplitude of breathing on respiratory system elastance and resistance during growth of healthy children.

Intrinsic properties of lung and chest wall tissues can lead to breathing rate (frequency [f]) and amplitude (tidal volume [VT]) dependence of respiratory system resistance (R) and elastance (E). To explore these dependencies on R and E within physiological limits of tidal volume and breathing frequencies during early childhood. we measured airway opening pressure (Pao) and flow (V'ao) in 15 anesthetized, paralyzed, intubated, and mechanically ventilated healthy children (age 1 day to 72 months; weight 2.5-21 kg) at multiple combinations of VT (6, 10, and 14 mL/kg) and frequency (10, 20, and 30 breaths/min). In each instance, R and E were estimated by multiple linear regression applied to the tracheal pressure, flow, and volume (V), assuming a simple series R-E model. R decreased substantially with increasing frequency and weight (Wt), but was unaffected by changes in VT (R = 764Wt(-0.91) x f(-0.57)). E decreased sharply with increasing Wt, was lower at higher VT, and was slightly, yet significantly, increased at higher frequency (E = 2,905Wt(-1.38) x VT(-0.18) x f(0.11)). Such frequency dependence of R and E is consistent with stress adaptive, or viscoelastic, properties of respiratory tissues. The small V dependence of E is similar to that observed in other species under healthy conditions and presumably reflects the combined nonlinear pressure-volume relationships of the healthy parenchymal and chest wall tissues. Lack of VT dependence of R at high inspiratory flow rates suggests that turbulent flows are either not an important form of energy dissipation in the lower airways of children or they are counterbalanced by a decrease in tissue damping at high VT. The above regression models represent the first attempt to quantify simultaneously the separate effects of lung growth as well as rate and amplitude of breathing on R and E. Similar equations based on a larger sample of healthy subjects can provide normative R and E values for comparison with mechanically ventilated children with lung disease.

Delayed primary closure of deep sternal wound infections.

Deep infections of the sternum and mediastinum, with prevalence of osteomyelitis and tissue necrosis, were documented in 38 of 8,056 patients (0.47%) who underwent open-heart surgery (1975 through 1994) in our service. The incidences of insulin-dependent diabetes, obesity, and emergency surgery in these patients were relatively high at 39%, 47%, and 18%, respectively. Treatment with antibiotics, débridement, open packing, and delayed closure was administered to 33 patients (87%), with 100% healing. There were no deaths in this group. Flap reconstruction was indicated in 5 gravely ill patients (13%) in whom excessively large wound defects did not allow reapproximation. There were 2 deaths in this group, and 4 reoperations were necessary in the surviving patients because of sequelae arising from flap reconstruction. The overall mortality was 5.3% and the median period of hospitalization was 29 days. The length of stay decreased substantially over the period of this study (median = 21 days, year > or = 1987). Accordingly, we believe that treatment of deep sternal infections with delayed primary closure is safe and effective. Also, given the increased potential for complications and long-term sequelae, we believe that flap reconstruction should be used selectively and should be limited to patients with large defects, uncontrolled mediastinal bleeding, or both.

Predictors of gastrointestinal complications in cardiac surgery.

Gastrointestinal problems are infrequent but serious complications of cardiac surgery, with high rates of morbidity and mortality. Predictors of these complications are not well developed, and the role of fundamental variables remains controversial. In a retrospective review of our cardiac surgery experience from July 1991 through December 1997 we found that postoperative gastrointestinal complications were diagnosed in 86 of 4,463 consecutive patients (1.9%). We categorized these 86 patients into 2 groups--Surgical and Medical--according to the method of treatment used for their complications. In the Medical group, 9 of 52 patients (17%) died; in the Surgical group, 17 of 34 (50%) died. By logistic multivariate analysis, we identified 8 parameters that predicted gastrointestinal complications: age greater than 70 years, duration of cardiopulmonary bypass, need for blood transfusions, reoperation, triple-vessel disease, New York Heart Association functional class IV, peripheral vascular disease, and congestive heart failure. Postoperative re-exploration for bleeding was a predictor specific to the Surgical group. Use of an intraaortic balloon pump was markedly higher in the Gastrointestinal group than in the Control group (30% vs 10%, respectively), as was the use of inotropic support in the immediate postoperative period (27% vs 5.6%). Our results suggest that intra-abdominal ischemic injury is a likely contributing factor in most gastrointestinal complications. In turn, the ischemia is probably caused by hypoperfusion due to low cardiac output, hypotension due to blood loss, and intra-abdominal atheroemboli. The derived models are useful for identifying patients whose risk of gastrointestinal complications after cardiac surgery may be reduced by clinical measures designed to counter these mechanisms.