Sadeq A. Quraishi

Effects of intermittent hypoxia on sympathetic activity and blood pressure in humans

Sympathetic nerve activity and arterial pressure are frequently elevated in patients with obstructive sleep apnea (OSA). The mechanisms responsible for chronic sympathetic activation and hypertension in OSA are unknown. To determine whether repetitive apneas raise sympathetic nerve activity and/or arterial pressure, awake and healthy young subjects performed voluntary end-expiratory apneas for 20 s per min for 30 min (room air apneas). To accentuate intermittent hypoxia, in a separate group of subjects, hypoxic gas (inspired O2 10%) was added to the inspiratory port for 20 s before each apnea (hypoxic apneas). Mean arterial pressure (MAP) and muscle sympathetic nerve activity (MSNA, peroneal microneurography) were determined before and up to 30 min following the repetitive apneas. Following 30 hypoxic apneas (O2 saturation nadir 83.1+/-1.2%), MSNA increased from 17.4+/-2.7 to 23.4+/-2.5 bursts/min and from 164+/-28 to 240+/-35 arbitrary units respectively (P<0.01 for both; n=10) and remained elevated while MAP increased transiently from 80.5+/-3.7 to 83.1+/-3.9 mm Hg (P<0.05; n=11). In contrast, in the subjects who performed repetitive apneas during room air exposure (O2 saturation nadir 95.1+/-0.8%), MAP and MSNA did not change (n=8). End-tidal CO2 post-apnea, an index of apnea-induced hypercapnia, was similar in the 2 groups. In a separate control group, no effect of time on MAP or MSNA was noted (n=7). Thus, repetitive hypoxic apneas result in sustained sympathetic activation and a transient elevation of blood pressure. These effects appear to be due to intermittent hypoxia and may play a role in the sympathetic activation and hypertension in OSA.

Long-term quality of life measures after functional endoscopic sinus surgery.

Background Chronic rhinosinusitis (CRS) is a common disease that has a significant impact on quality of life (QOL). The aim of this study was to evaluate the longer-term effects of combined medical and surgical therapy for CRS on overall health status and QOL. Methods We used a prospective study that utilized the Short-Form 36 Survey at baseline presentation and at a mean time of 3 years post-functional endoscopic sinus surgery to assess the general health status of patients who presented for their initial visit from 1996 to 1998. Of the 200 randomly selected patients, 150 respondents completed follow-up surveys (a 75% response rate). Results Eighty-nine (59.3%) women and 61 (40.7%) men were included in the study. Baseline QOL scores indicated significant differences between patients with CRS and published norms in 6/8 subscale parameters (role physical, bodily pain, general health, social function, vitality, and mental health). Significant improvement in all six categories was maintained at the end of the study period (p < 0.05) with QOL scores within limits of published norms for the general population. Conclusion Our data indicate that functional endoscopic sinus surgery, combined with appropriate postoperative care, is effective at maintaining a significant improvement in the overall general health status of patients for at least 3 years after surgical intervention and that the overall scores return to a range of normative values for the general population.

Clinical Implications of the Transversus Abdominis Plane Block in Adults

The transversus abdominis plane (TAP) block is a relatively new regional anesthesia technique that provides analgesia to the parietal peritoneum as well as the skin and muscles of the anterior abdominal wall. It has a high margin of safety and is technically simple to perform, especially under ultrasound guidance. A growing body of evidence supports the use of TAP blocks for a variety of abdominal procedures, yet, widespread adoption of this therapeutic adjunct has been slow. In part, this may be related to the limited sources for anesthesiologists to develop an appreciation for its sound anatomical basis and the versatility of its clinical application. As such, we provide a brief historical perspective on the TAP block, describe relevant anatomy, review current techniques, discuss pharmacologic considerations, and summarize the existing literature regarding its clinical utility with an emphasis on recently published studies that have not been included in other systematic reviews or meta-analyses.

Evidence for a U-shaped relationship between prehospital vitamin D status and mortality: a cohort study.

OBJECTIVE The objective of the study was to examine the association between prehospital serum 25-hydroxyvitamin D [25(OH)D]and the risk of mortality after hospital admission. DESIGN We performed a retrospective cohort study of adults hospitalized for acute care between 1993 and 2011. SETTING The study was conducted at two Boston teaching hospitals. PATIENTS A total of 24,094 adult inpatients participated in the study. INTERVENTION There was no intervention. MEASUREMENTS All patients had serum 25(OH)D measured before hospitalization. The exposure of interest was 25(OH)D categorized as less than 10 ng/mL, 10-19.9 ng/mL, 20-29.9 ng/mL, 30-49.9 ng/mL, 50-59.9 ng/mL, 60-69.9 ng/mL, and 70 ng/mL or greater. The main outcome measure was 90-day mortality. Adjusted odds ratios (ORs) were estimated by multivariable logistic regression with inclusion of potential confounders. RESULTS After adjustment for age, gender, race (white vs nonwhite), patient type (surgical vs medical), season of 25(OH)D draw, and the Deyo-Charlson index, patients with 25(OH)D levels less than 30 ng/mL or 60 ng/mL or greater had higher odds of 90-day mortality compared with patients with levels of 30-49.9 ng/mL [adjusted OR (95% confidence interval) for 25(OH)D <10 ng/mL, 10-19.9 ng/mL, 20-29.9 ng/mL, 50-59.9 ng/mL, 60-69.9 ng/mL, and ≥70 ng/mL was 2.01 (1.68-2.40), 1.89 (1.64-2.18), 1.34 (1.16-1.56), 0.94 (0.69-1.26), 1.52 (1.03-2.25), and 1.69 (1.09-2.61), respectively, compared with patients with 25(OH)D levels 30-49.9 ng/mL]. LIMITATIONS A causal relationship between either low or high 25(OH)D levels and increased mortality can not necessarily be inferred from this observational study. CONCLUSIONS Analysis of 24 094 adult patients showed that 25(OH)D levels less than 20 ng/mL and 60 ng/mL or greater before hospitalization were associated with an increased odds of 90-day mortality. Although previous reports have suggested an association between low vitamin D status and mortality, these data raise the issue of potential harm from high serum 25(OH)D levels, provide a rationale for an upper limit to supplementation, and emphasize the need for caution in the use of extremely high doses of vitamin D among patients.

Prospective Study of Vitamin D Status at Initiation of Care in Critically Ill Surgical Patients and Risk of 90-Day Mortality

Objectives:1) To characterize vitamin D status at initiation of critical care in surgical ICU patients and 2) to determine whether this vitamin D status is associated with the risk of prolonged hospital length of stay, 90-day readmission, and 90-day mortality. Design:Prospective cohort study. Setting:A teaching hospital in Boston, MA. Patients:Hundred surgical ICU patients. Interventions:None. Measurements and Main Results:Mean (± SD) serum total 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were 17 ± 8 ng/mL and 32 ± 19 pg/mL, respectively. Mean calculated bioavailable 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were 2.5 ± 2.0 ng/mL and 6.6 ± 5.3 pg/mL, respectively. Receiver-operating characteristic curve analysis demonstrated that all of four vitamin D measures predicted the three clinical outcomes; total 25-hydroxyvitamin D was not inferior to the other measures. Median (interquartile range) hospital length of stay was 11 days (8–19 d). Poisson regression analysis, adjusted for biologically plausible covariates, demonstrated an association of total 25-hydroxyvitamin D with hospital length of stay (incident rate ratio per 1 ng/mL, 0.98; 95% CI, 0.97–0.98). The 90-day readmission and mortality rates were 24% and 22%, respectively. Even after adjustment for biologically plausible covariates, there remained significant associations of total 25-hydroxyvitamin D with readmission (odds ratio per 1 ng/mL, 0.84; 95% CI, 0.74–0.95) and mortality (odds ratio per 1 ng/mL, 0.84; 95% CI, 0.73–0.97). Conclusions:Serum 25-hydroxyvitamin D levels within 24 hours of ICU admission may identify patients at high risk for prolonged hospitalization, readmission, and mortality. Randomized trials are needed to assess whether vitamin D supplementation can improve these clinically relevant outcomes in surgical ICU patients.

Vitamin D in acute stress and critical illness

Purpose of reviewThe pleotropic effects of vitamin D on chronic diseases have received significant attention; however, its role in acute illness is less understood. The purpose of this review is to summarize the current evidence regarding the role of vitamin D in acute stress and critical illness. Recent findings25-Hydroxyvitamin D levels may affect risk of developing acute illnesses (e.g. respiratory infections), and low concentrations are associated with unfavorable outcomes during critical care. Inflammatory changes alone do not explain the observed deterioration in vitamin D status following acute stress. Hemodilution, interstitial extravasation, decreased synthesis of binding proteins, and renal wasting of 25-hydroxyvitamin D, all appear to play a more significant role in the regulation of vitamin D status during critical illness. SummarySingle-point assessments of 25-hydroxyvitamin D following acute stress may provide an inaccurate assessment of vitamin D status. In such cases, measurement of binding proteins and free vitamin D metabolites may be essential to create a more realistic approximation of vitamin D status. Variations in patient responses to acute stress and critical illness may depend not only on the degree of systemic vitamin D insufficiency, but also on the individual tissue requirements.

Association between prehospital vitamin D status and hospital-acquired bloodstream infections

BACKGROUND Alterations in immune function can predispose patients to nosocomial infections. Few studies have explored potentially modifiable host factors that may improve immune function and decrease risk of hospital-acquired bloodstream infection (HABSI). Vitamin D is a key regulator of innate and adaptive immune systems that may influence host susceptibility to infections. OBJECTIVE We investigated the association between prehospital serum 25-hydroxyvitamin D [25(OH)D] concentrations and risk of HABSI. DESIGN We performed a retrospective cohort study of 2135 adult patients from 2 Boston teaching hospitals. All patients had 25(OH)D concentrations measured before hospitalization between 1993 and 2010. The main outcome measure was HABSI, which was defined as positive blood cultures from samples drawn 48 h after hospital admission. Coagulase-negative Staphylococcus isolates were not considered to be bloodstream infections. Associations between 25(OH)D groups and HABSI were estimated by using bivariable and multivariable logistic regression models. Adjusted ORs were estimated with the inclusion of covariate terms thought to plausibly interact with both 25(OH)D concentration and HABSI. RESULTS Compared with patients with 25(OH)D concentrations ≥30 ng/mL, patients with concentrations <30 ng/mL had higher odds of HABSI. For 25(OH)D concentrations <10 ng/mL, the OR was 2.33 (95% CI: 1.45, 3.74); for 25(OH)D concentrations from 10 to 19.9 ng/mL, the OR was 1.60 (95% CI: 1.04, 2.46); and for 25(OH)D concentrations from 20 to 29.9 ng/mL, the OR was 1.13 (95% CI: 0.69, 1.84). After adjustment for age, sex, race (nonwhite compared with white), patient type (medical compared with surgical), and Deyo-Charlson index, the ORs of HABSI were 1.95 (95% CI: 1.22, 3.12), 1.36 (95% CI: 0.89, 2.07), and 0.98 (95% CI: 0.60, 1.62), respectively. CONCLUSIONS The analysis of 2135 adult patients showed that 25(OH)D concentrations <10 ng/mL before hospitalization were associated with significantly increased odds of developing HABSI. These data support the initiation of randomized trials to test the role of vitamin D supplementation in HABSI prevention.

Vitamin D status and community-acquired pneumonia: results from the third National Health and Nutrition Examination Survey.

Objective To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] level and history of community-acquired pneumonia (CAP). Patients and Methods We identified 16,975 individuals (≥17 years) from the third National Health and Nutrition Examination Survey (NHANES III) with documented 25(OH)D levels. To investigate the association of 25(OH)D with history of CAP in these participants, we developed a multivariable logistic regression model, adjusting for demographic factors (age, sex, race, poverty-to-income ratio, and geographic location), clinical data (body mass index, smoking status, asthma, chronic obstructive pulmonary disease, congestive heart failure, diabetes mellitus, stroke, chronic kidney disease, neutropenia, and alcohol consumption), and season. Locally weighted scatterplot smoothing (LOWESS) was used to depict the relationship between increasing 25(OH)D levels and the cumulative frequency of CAP in the study cohort. Results The median [interquartile range (IQR)] serum 25(OH)D level was 24 (IQR 18–32) ng/mL. 2.1% [95% confidence interval (CI): 1.9–2.3] of participants reported experiencing a CAP within one year of their participation in the national survey. After adjusting for demographic factors, clinical data, and season, 25(OH)D levels <30 ng/mL were associated with 56% higher odds of CAP [odds ratio 1.56; 95% confidence interval: 1.17–2.07] compared to levels ≥30 ng/mL. LOWESS analysis revealed a near linear relationship between vitamin D status and the cumulative frequency of CAP up to 25(OH)D levels around 30 ng/mL. Conclusion Among 16,975 participants in NHANES III, 25(OH)D levels were inversely associated with history of CAP. Randomized controlled trials are warranted to determine the effect of optimizing vitamin D status on the risk of CAP.

Effect of Cholecalciferol Supplementation on Vitamin D Status and Cathelicidin Levels in Sepsis: A Randomized, Placebo-controlled Trial

Objectives:To compare changes in vitamin D status and cathelicidin (LL-37) levels in septic ICU patients treated with placebo versus cholecalciferol. Design:Randomized, placebo-controlled, trial. Setting:Medical and surgical ICUs of a single teaching hospital in Boston, MA. Patients:Thirty adult ICU patients. Interventions:Placebo (n = 10) versus 200,000 IU cholecalciferol (n = 10) versus 400,000 IU cholecalciferol (n = 10), within 24 hours of new-onset severe sepsis or septic shock. Measurements and Main Results:Blood samples were obtained at baseline (day 1) and on days 3, 5, and 7, to assess total 25-hydroxyvitamin D, as well as vitamin D–binding protein and albumin to calculate bioavailable 25-hydroxyvitamin D. Plasma LL-37 and high-sensitivity C-reactive protein levels were also measured. At baseline, median (interquartile range) plasma 25-hydroxyvitamin D was 17 ng/mL (13–22 ng/mL) and peaked by day 5 in both intervention groups. Groups were compared using Kruskal-Wallis tests. Relative to baseline, on day 5, median change in biomarkers for placebo, 200,000 IU cholecalciferol, and 400,000 IU cholecalciferol groups, respectively, were as follows: 1) total 25-hydroxyvitamin D, 3% (–3% to 8%), 49% (30–82%), and 69% (55–106%) (p < 0.001); 2) bioavailable 25-hydroxyvitamin D, 4% (–8% to 7%), 45% (40–70%), and 96% (58–136%) (p < 0.01); and 3) LL-37: –17% (–9% to –23%), 4% (–10% to 14%), and 30% (23–48%) (p = 0.04). Change in high-sensitivity C-reactive protein levels did not differ between groups. A positive correlation was observed between bioavailable 25-hydroxyvitamin D and LL-37 (Spearman &rgr; = 0.44; p = 0.03) but not for total 25-hydroxyvitamin D and LL-37. Conclusions:High-dose cholecalciferol supplementation rapidly and safely improves 25-hydroxyvitamin D and bioavailable 25-hydroxyvitamin D levels in patients with severe sepsis or septic shock. Changes in bioavailable 25-hydroxyvitamin D are associated with concomitant increases in circulating LL-37 levels. Larger trials are needed to verify these findings and to assess whether optimizing vitamin D status improves sepsis-related clinical outcomes.

The economic cost of firearm-related injuries in the United States from 2006 to 2010

BACKGROUND Estimates of the number of firearm-related injuries widely vary. Although focus has been primarily on deaths, the societal cost of caring for victims of these injuries is largely unknown. Our goal was to estimate the economic impact of nonfatal, firearm-related injuries in the United States based on recent, publically available data. METHODS We queried several national registries for hospital and emergency department (ED) discharges from 2006 to 2010 to estimate the annual incidence of firearm-related injuries. The cost of direct medical services and lost productivity from firearm-related injuries were extrapolated from recently published estimates. To identify potentially important trends, we compared the economic impact and payor mix for firearm-related injuries in 2006 with those in 2010. RESULTS During the 5-year analytic period, we identified 385,769 (SE = 29,328) firearm-related ED visits resulting in 141,914 (SE = 14,243) hospital admissions, costing more than