Impact of Sedation on Cognitive Function in Mechanically Ventilated Patients.

The practice of sedation dosing strategy in mechanically ventilated patient has a profound effect on cognitive function. We conducted a comprehensive review of outcome of sedation on mental health function in critically ill patients on mechanical ventilation in the intensive care unit (ICU). We specifically evaluated current sedative dosing strategy and the development of delirium, post-traumatic stress disorders (PTSDs) and agitation. Based on this review, heavy dosing sedation strategy with benzodiazepines contributes to cognitive dysfunction. However, outcome for mental health dysfunction is mixed in regard to newer sedatives agents such as dexmedetomidine and propofol. Moreover, studies that examine the impact of sedatives for persistence of PTSD/delirium and its long-term cognitive and functional outcomes for post-ICU patients are frequently underpowered. Most studies suffer from low sample sizes and methodological variations. Therefore, larger randomized controlled trials are needed to properly assess the impact of sedation dosing strategy on cognitive function.

Applications of Nasal High-Flow Oxygen Therapy in Critically ill Adult Patients.

The use of nasal high-flow oxygen therapy (NHFOT) has become increasingly common in hospitals across Europe, Asia, and North America. These high utility devices provide an efficient and comfortable access points for providing supplemental oxygen to patients with variety of respiratory disorders. They are relatively easy to set up, and clinicians and patients alike give very positive feedback about their ease of use and comfort for patients in the hospital setting. However, it remains uncertain whether NHFOT improves patient survival or even reduces respiratory complications. Outcome data in adult populations are few and frequently underpowered to guide physicians for their widespread use in hospital setting. In this article, we present a review of the current technology and available studies pertinent to NHFOT.

Survival benefit of CPAP favors hypercapnic patients with the overlap syndrome.

BACKGROUND: Patients with the combination of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), known as the "overlap syndrome," have a substantially greater risk of morbidity and mortality compared to those with either COPD or OSA alone. The study's objective was to report on the long-term outcome of hypercapnic (PaCO2 ≥ 45 mmHg) and normocapnic patients with the overlap syndrome treated with continuous positive airway pressure (CPAP). METHODS: A nonconcurrent cohort of consecutive patients with the overlap syndrome was followed for a median duration of 71 months (range 1-100) at a VA sleep center. All patients were managed according to the prevailing recommendations of both diseases. The end point of the study was all-cause mortality. RESULTS: Of the 271 patients identified, 104 were hypercapnic (PaCO2 = 51.6 ± 4.3 mmHg). Both normocapnic and hypercapnic patients had comparable apnea-hypopnea indexes (AHI) (29.2 ± 23.8 and 35.2 ± 29.2/h, respectively; p = 0.07) and similar adherence rates to CPAP (43 and 42 %, respectively, p = 0.9). Survival analysis revealed that hypercapnic patients who were adherent to CPAP had reduced mortality compared to nonadherent hypercapnic patients (p = 0.04). In contrast, the cumulative mortality rate for normocapnic patients was not significantly different between the adherent and the nonadherent group (p = 0.42). In multivariate analysis, the comorbidity index was the only independent predictor of mortality in normocapnic patients with the overlap syndrome [hazard ratio (HR) 1.68; p < 0.001] while CPAP adherence was associated with improved survival (HR 0.65; p = 0.04). CONCLUSIONS: CPAP mitigates the excess risk of mortality in hypercapnic patients but not in normocapnic patients with the overlap syndrome.

Cardiovascular mortality in obstructive sleep apnoea treated with continuous positive airway pressure or oral appliance: an observational study.

BACKGROUND AND OBJECTIVE: The objective of this study was to evaluate the long-term cardiovascular mortality in patients with severe obstructive sleep apnoea (OSA) treated with either continuous positive airway pressure (CPAP) or mandibular advancing device (MAD). METHODS: A non-concurrent cohort study of 570 subjects with severe OSA (apnoea/hypopnoea index (AHI) ≥ 30/h) and a control group of 269 subjects (AHI < 5/h) were followed up for a median of 79 months (interquartile range 76-88 months). All patients received CPAP initially. MAD was offered for those who were non-adherent to CPAP. The endpoint was cardiovascular death. RESULTS: Two hundred and eight control subjects, 177 patients treated with CPAP, 72 with MAD and 212 who declined treatment were analysed. Forty-two patients had a fatal cardiovascular event during the course of the study. The non-apnoeic group had the lowest cardiovascular death rate (0.28 per 100 person-years (95% confidence interval (CI): 0.08-0.71)) followed by the CPAP-treated (0.56 per 100 person-years (95% CI: 0.20-1.23)) and the MAD-treated OSA group (0.61 per 100 person-years (95% CI: 0.13-1.78)), with the highest cardiovascular mortality rate observed in the untreated OSA group (2.1 per 100 person-years (95% CI: 1.37-2.92)). Although residual AHI for MAD-treated patients was significantly higher than CPAP-treated patients (16.3 ± 5.1/h vs. 4.5 ± 2.3/h; P < 0.001), there was no difference in cardiovascular death rate between the two groups (hazard ratio 1.08 (95% CI: 0.55-1.74); P = 0.71). CONCLUSIONS: Both CPAP and MAD may be equally effective therapy in reducing the risk of fatal cardiovascular events in patients with severe OSA.

Toll-like receptor activity in patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) has been linked to chronic inflammation and cardiovascular diseases. Considerable evidence suggests that innate immune defense mechanisms might interact with proinflammatory pathways and contribute to atherogenesis. We hypothesized that the classical pathogen recognition receptors of the innate immune response, Toll-like receptors, are involved in modulating the inflammatory response in OSA. METHODS: Expression of TLR2 and TLR4 on circulating monocytes from 29 subjects with documented OSA and 18 controls were compared with the use of flow cytometry and reverse transcription-polymerase chain reaction at baseline and after 8 weeks of continuous positive airway pressure (CPAP). RESULTS: There was a significant increase in both TLR2 and TLR4 surface expression and mRNA levels on monocytes after adjustment for age, body mass index, and waist-to-hip ratio. This was paralleled by enhanced nuclear factor-κB nuclear binding and an increased release of IL-6, INF-γ, and TNF-α in OSA versus control subjects. Following 8 weeks of treatment, continuous positive airway pressure downregulated TLR2 and TLR4 expression and abrogated the release of inflammatory cytokines. CONCLUSION: OSA is associated with enhanced expression and signaling events downstream of TLR2 and TLR4 in circulating monocytes. These observations are mitigated by CPAP therapy, which suggest that TLR2 and TLR4 activation may be involved as a signaling mechanism in immune-mediated progression of atherosclerosis in OSA.

The prevalence of waterpipe tobacco smoking among the general and specific populations: a systematic review.

BACKGROUND: The objective of this study was to systematically review the medical literature for the prevalence of waterpipe tobacco use among the general and specific populations. METHODS: We electronically searched MEDLINE, EMBASE, and the ISI the Web of Science. We selected studies using a two-stage duplicate and independent screening process. We included cohort studies and cross sectional studies assessing the prevalence of use of waterpipe in either the general population or a specific population of interest. Two reviewers used a standardized and pilot tested form to collect data from each eligible study using a duplicate and independent screening process. We stratified the data analysis by country and by age group. The study was not restricted to a specific context. RESULTS: Of a total of 38 studies, only 4 were national surveys; the rest assessed specific populations. The highest prevalence of current waterpipe smoking was among school students across countries: the United States, especially among Arab Americans (12%-15%) the Arabic Gulf region (9%-16%), Estonia (21%), and Lebanon (25%). Similarly, the prevalence of current waterpipe smoking among university students was high in the Arabic Gulf region (6%), the United Kingdom (8%), the United States (10%), Syria (15%), Lebanon (28%), and Pakistan (33%). The prevalence of current waterpipe smoking among adults was the following: Pakistan (6%), Arabic Gulf region (4%-12%), Australia (11% in Arab speaking adults), Syria (9%-12%), and Lebanon (15%). Group waterpipe smoking was high in Lebanon (5%), and Egypt (11%-15%). In Lebanon, 5%-6% pregnant women reported smoking waterpipe during pregnancy. The studies were all cross-sectional and varied by how they reported waterpipe smoking. CONCLUSION: While very few national surveys have been conducted, the prevalence of waterpipe smoking appears to be alarmingly high among school students and university students in Middle Eastern countries and among groups of Middle Eastern descent in Western countries.

Survey instruments used in clinical and epidemiological research on waterpipe tobacco smoking: a systematic review.

BACKGROUND: The primary objective was to systematically review the medical literature for instruments validated for use in epidemiological and clinical research on waterpipe smoking. METHODS: We searched the following databases: MEDLINE, EMBASE, and ISI the Web of Science. We selected studies using a two-stage duplicate and independent screening process. We included papers reporting on the development and/or validation of survey instruments to measure waterpipe tobacco consumption or related concepts. Two reviewers used a standardized and pilot tested data abstraction form to collect data from each eligible study using a duplicate and independent screening process. We also determined the percentage of observational studies assessing the health effects of waterpipe tobacco smoking and the percentage of studies of prevalence of waterpipe tobacco smoking that have used validated survey instruments. RESULTS: We identified a total of five survey instruments. One instrument was designed to measure knowledge, attitudes, and waterpipe use among pregnant women and was shown to have internal consistency and content validity. Three instruments were designed to measure waterpipe tobacco consumption, two of which were reported to have face validity. The fifth instrument was designed to measure waterpipe dependence and was rigorously developed and validated. One of the studies of prevalence and none of the studies of health effects of waterpipe smoking used validated instruments. CONCLUSIONS: A number of instruments for measuring the use of and dependence on waterpipe smoking exist. Future research should study content validity and cross cultural adaptation of these instruments.

Predictive factors for COPD exacerbations and mortality in patients with overlap syndrome.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA)-overlap syndrome-have a substantially greater risk of morbidity and mortality, compared to those with either COPD or OSA alone. OBJECTIVES: The aim of this retrospective study was to identify clinical modifiable factors associated with COPD exacerbations and all-cause mortality in patients with overlap syndrome. METHODS: The electronic records of patients with simultaneous COPD and OSA who had a documented acute exacerbation of COPD during a 42-month period were evaluated for reviewed. A control group of overlap syndrome patients without exacerbations was matched 1:1 for age and body mass index. Vital status and cause of death were assessed through the population death registry. RESULTS: Out of 225 eligible cases, 92 patients had at least one episode of COPD exacerbation. There was no significant association between severity of airflow limitation and apnoea hypopnea index (P = .31). After adjusting for confounding variables, patients who had at least one COPD exacerbation were more likely to be active smokers (P = .01), have poorer lung function (P = .001) and less likely to adhere to continuous positive airway pressure (CPAP) use (P = .03). All-cause mortality was also correlated with low forced expiratory volume in 1 second (P = .006), CPAP use (P = .007), and burden of comorbidities (P < .001). CONCLUSION: Lung function and CPAP use were independent predictors of COPD exacerbations and all-cause mortality in a cohort of patients with overlap syndrome. These factors should be taken into account when considering the management and prognosis of these patients.

Prolonged versus Intermittent Infusion of ß-Lactams for the Treatment of Nosocomial Pneumonia: A Meta-Analysis.

BACKGROUND: The primary objective of this meta-analysis is aimed at determining whether ß-lactams prolonged infusion in patients with nosocomial pneumonia (NP) results in higher cure rate and improved mortality compared to intermittent infusion. MATERIALS AND METHODS: Relevant studies were identified from searches of MEDLINE, EMBASE, and CENTRAL from inception to September 1st, 2015. All published articles which evaluated the outcome of extended/continuous infusion of antimicrobial therapy versus intermittent infusion therapy in the treatment of NP were reviewed. RESULTS: A total of ten studies were included in the analysis involving 1,051 cases of NP. Prolonged infusion of ß-lactams was associated with higher clinical cure rate (OR 2.45, 95% CI, 1.12, 5.37) compared to intermittent infusion. However, there was no significant difference in mortality (OR 0.85, 95% CI 0.63-1.15) between the two groups. Subgroup analysis for ß-lactam subclasses and for severity of illness showed comparable outcomes. CONCLUSION: The limited data available suggest that reduced clinical failure rates when using prolonged infusions of ß-lactam antibiotics in critically ill patients with NP. More detailed studies are needed to determine the impact of such strategy on mortality in this patient population.

Pain Intensity and Opioid Utilization in Response to CPAP Therapy in Veterans with Obstructive Sleep Apnea on Chronic Opioid Treatment.

STUDY OBJECTIVES: Sleep fragmentation has been linked to poor pain tolerance and lowered pain threshold. Little evidence exists on whether continuous positive airway pressure (CPAP) adherence in veterans with obstructive sleep apnea (OSA) who are taking opioids for non-malignant pain would ameliorate pain and reduce consumption of opioids. METHODS: A retrospective case-control study was performed at a VA sleep center. Pain intensity was assessed using the Numerical Categorical Scale prior to CPAP treatment and 12-mo follow-up. Opioids intake was assessed using the morphine equivalent daily dose (MEDD). Adherence to CPAP was evaluated with the built-in meter. RESULTS: We reviewed 113 patients with OSA (apnea-hypopnea index [AHI] 35.9 ± 29.5) using a MEDD of 61.6 mg (range 5-980 mg) and a control group of 113 veterans with OSA (AHI 33.4 ± 27.3) on no opioids treatment. CPAP adherence was significantly lower at 12 mo in opioid-treated patients compared to controls (37% versus 55%; p = 0.01). Greater pain intensity was the only independent variable associated with CPAP non-adherence at 12-mo follow-up (p = 0.03). Compared to baseline, no significant difference was observed in pain intensity or consumption of opioids in CPAP adherent patients. CONCLUSIONS: CPAP treatment did not reduce pain intensity or consumption of opioids in veterans with chronic pain who have coexisting OSA. CPAP adherence was lower in opioid-treated veterans with OSA compared to opioid-free veterans with OSA. Pain intensity was the only determinant of CPAP adherence. Future studies are needed to evaluate pain management program on adherence to CPAP.

Sleep-disordered breathing in patients with post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) and sleep-disordered breathing (SDB) are shared by many patients. They both affect sleep and the quality of life of affected subjects. A critical review of the literature supports an association between the two disorders in both combat-related and non-combat-related PTSD. The exact mechanism linking PTSD and SDB is not fully understood. A complex interplay between sleep fragmentation and neuroendocrine pathways is suggested. The overlap of symptoms between PTSD and SDB raises diagnostic challenges that may require a novel approach in the methods used to diagnose the coexisting disorders. Similar therapeutic challenges face patients and providers when treating concomitant PTSD and SDB. Although continuous positive airway pressure therapy imparts a mitigating effect on PTSD symptomatology, lack of both acceptance and adherence are common. Future research should focus on ways to improve adherence to continuous positive airway pressure therapy and on the use of alternative therapeutic methods for treating SDB in patients with PTSD.

A comparison between time to clinical stability in community-acquired aspiration pneumonia and community-acquired pneumonia.

Antimicrobial therapy has been the main stay of therapy of community-acquired aspiration pneumonia (CAAP), but the duration of treatment has not been established. The objective of this study was to describe the time to reach clinical stability in patients with aspiration pneumonia compared to community-acquired pneumonia (CAP). A retrospective case control study at two university affiliated centers encompassing 329 consecutive patients admitted with CAAP and 329 consecutive patients with CAP was conducted between 2007 and 2011. While the median time to stability for patients with CAP was distributed around a median of 4 days, there was a bimodal distribution for time to clinical stability in patients with CAAP with dual peaks at days 2 and 5, respectively. CAAP patients who required more than 2 days to achieve clinical stability had a higher mortality rate compared to those with 2 days or less [odds ratio (OR) 5.95, 95% CI 2.85-12.4], and a longer hospital stay (6.6 ± 5.8 vs. 3.9 ± 1.2 days; p < 0.001). None of the CAAP patients who achieved clinical stability in 2 days or less was transferred to a higher level of care. In a multivariate analysis, time to clinical stability was found to be an independent predictor of outcome in patients with CAAP (OR 2.59, 95% CI 2.02-3.32). Normalization of vital signs in aspiration pneumonia follows a distinct pattern from that of patients with CAP. Time to achieve clinical stability may assist in identifying CAAP patients who are likely to require a shorter hospital stay and a shorter course of antimicrobial therapy.

Postoperative complications in patients with obstructive sleep apnea: a meta-analysis.

STUDY OBJECTIVE: To determine whether a diagnosis of obstructive sleep apnea (OSA) imparts an increased risk of postoperative respiratory failure, cardiac events, and intensive care unit (ICU) transfer than patients with no OSA diagnosis. DESIGN: Systematic review and meta-analysis. SETTING: Academic Veterans Affairs Medical Center. MEASUREMENTS: PubMed, EMBASE, CINAHL, and ISI Web of Knowledge databases were searched through April 2013 for studies that examined the relationship between OSA and postoperative respiratory and cardiac complications among adults. Either fixed or random-effects models were used to calculate the pooled risk estimates. Sensitivity analysis was conducted to examine the robustness of pooled outcomes. MAIN RESULTS: Seventeen studies with a total of 7,162 patients were included. Overall, OSA was associated with significant increase in risk of respiratory failure [odds ratio (OR) 2.42; 95% confidence intervals (CI) 1.53 - 3.84; P = 0.0002] and cardiac events postoperatively (OR = 1.63; 95% CI 1.16 - 2.29; P = 0.005). Heterogeneity was low for these outcomes (I(2) = 5% and 0%, respectively). ICU transfer occurred also more frequently in patients with OSA (OR 2.46; 95% CI 1.29 - 4.68; P = 0.006). These results did not materially change in the sensitivity analyses according to various inclusion criteria. CONCLUSIONS: Surgical patients with OSA are at increased risk of postoperative respiratory failure, cardiac events, and ICU transfer.

Effects of water-pipe smoking on lung function: a systematic review and meta-analysis.

BACKGROUND: Although common in many Middle Eastern countries, water-pipe tobacco smoking, commonly known as water-pipe smoking (WPS), is increasingly popular in Western cultures. The primary objective of this study was to systematically review the effects of WPS on lung function. The secondary objective was to compare the effects of WPS and cigarette smoking on lung function. METHODS: We conducted a systematic review using the approach of the Cochrane Collaboration to search for, select, and abstract studies. We conducted two separate meta-analyses comparing water-pipe smokers with nonsmokers, and water-pipe smokers with cigarette smokers for each of three spirometric measurements (FEV1, FVC, and FEV1/ FVC). We used the standardized mean difference (SMD) to pool the results. RESULTS: Six cross-sectional studies were eligible for this review. Compared with no smoking, WPS was associated with a statistically significant reduction in FEV1 (SMD = -0.43; 95% CI, -0.58 to -0.29; equivalent to a 4.04% lower FEV1%), a trend toward lower FVC (SMD = -0.15; 95% CI, -0.34 to 0.04; equivalent to a 1.38% reduction in FVC%), and lower FEV1/ FVC (SMD = -0.46; 95% CI, -0.93 to 0.01; equivalent to a 3.08% lower FEV1/ FVC). Comparing WPS with cigarette smoking, there was no statistically significant difference in FEV1, FVC, and FEV1/ FVC. The six studies suffered from methodologic limitations. CONCLUSIONS: WPS negatively affects lung function and may be as harmful as cigarette smoking. WPS, therefore, is likely to be a cause of COPD.

Bicarbonate therapy in the treatment of septic shock: a second look.

The use of supplemental sodium bicarbonate for the treatment of patients with septic shock and elevated blood lactate levels remains a controversial therapy. We conducted a retrospective study between March 2004 and February 2009 of 36 consecutive patients diagnosed with septic shock who received continuous infusion of bicarbonate therapy. A control group was matched 1:1 for age, site of infection, and predicted mortality by APACHE II. All patients were managed according to standard protocols. The median time until reversal of shock did not achieve statistical significance between the bicarbonate group (44.5 h [95% confidence interval [CI] 34-54] and the control group (55.0 h [95% CI 39-60] (p = 0.09). The median time to liberation of mechanical ventilation was significantly reduced in the bicarbonate group (10 days [95% CI 5.0-13.0] compared to the control group (14 days [95% CI 9.0-19.0], p = 0.02). The length of intensive care unit (ICU) stay was also shorter in the surviving patients who received bicarbonate compared to controls (median 11.5 days (95% CI 6.0-16.0) vs. 16.0 days (95% CI 13.5-19.0), respectively; p = 0.01). However, there was no difference in 28-day mortality between the two study groups (28%; 95% CI 14-45% vs. 33%; 95% CI 19-51%, respectively; p = 0.79). Infusion of sodium bicarbonate in septic patients with arterial hyperlactatemia may facilitate weaning from mechanical ventilation and reduce length of ICU stay.

Validity of severity scores in hospitalized patients with nursing home-acquired pneumonia.

BACKGROUND: Several severity scores have been advanced to predict a patient's outcome from community-acquired pneumonia (CAP). The purpose of this study is to compare the accuracy of confusion, urea, respiratory rate, BP (CURB); CURB plus age ≥ 65 years (CURB-65); CURB-65 minus urea (CRB-65); and systolic BP, oxygenation, age, and respiratory rate (SOAR) scoring systems in predicting 30-day mortality and ICU admission in patients with nursing home-acquired pneumonia (NHAP). METHODS: A retrospective analysis of a prospectively collected database of 457 nursing home residents hospitalized with pneumonia at two university-affiliated tertiary care facilities. Clinical and laboratory features were used to compute severity scores using the British Thoracic Society severity rules and the SOAR criteria. The sensitivity, specificity, and positive and negative predictive values were compared for need for ICU admission and 30-day mortality. RESULTS: The overall 30-day mortality and ICU admission rates were 23% and 25%, respectively. CURB, CURB-65, and CRB-65 performed similarly in predicting mortality with areas under the receiver operating characteristic curves (AUCs) of 0.605 (95% CI, 0.559-0.650), 0.593 (95% CI, 0.546-0.638), and 0.592 (95% CI, 0.546-0.638), respectively, whereas SOAR showed superior accuracy with an AUC of 0.765 (95% CI, 0.724-0.803) (P < .001). The need for ICU care was also better identified with the SOAR model compared with the other scoring rules. CONCLUSIONS: All three British Thoracic Society rules had lower performance accuracy in predicting 30-day mortality of hospitalized NHAP than SOAR. SOAR is also a superior alternative for better identification of severe NHAP. An improved rule for severity assessment of hospitalized NHAP is needed.

Biomarkers in the diagnosis of aspiration syndromes.

Recognizing and managing the different types of aspiration events remain a challenging task due to the lack of distinguishing clinical or laboratory characteristics. Numerous biomarkers in serum, sputum and bronchoalveolar lavage have been studied, and their role in the recognition of aspiration remains controversial at this time. Recent animal investigations using an array of biomarkers based on distinct pathogenic features of each aspiration event have produced promising results; however, they have not been validated in humans. Newer markers are being introduced as diagnostic and prognostic tools in conditions such as community-acquired pneumonia and sepsis, but they have not been examined in aspiration. The present review summarizes the different biomarkers that have been studied in aspiration and those who might have a potential clinical use in the future.

The effects of waterpipe tobacco smoking on health outcomes: a systematic review.

BACKGROUND: There is a need for a comprehensive and critical review of the literature to inform scientific debates about the public health effects of waterpipe smoking. The objective of this study was therefore to systematically review the medical literature for the effects of waterpipe tobacco smoking on health outcomes. METHODS: We conducted a systematic review using the Cochrane Collaboration methodology for conducting systematic reviews. We rated the quality of evidence for each outcome using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. RESULTS: Twenty-four studies were eligible for this review. Based on the available evidence, waterpipe tobacco smoking was significantly associated with lung cancer [odds ratio (OR) = 2.12; 95% confidence interval (CI) 1.32-3.42], respiratory illness (OR = 2.3; 95% CI 1.1-5.1), low birth-weight (OR = 2.12; 95% CI 1.08-4.18) and periodontal disease (OR = 3-5). It was not significantly associated with bladder cancer (OR = 0.8; 95% CI 0.2-4.0), nasopharyngeal cancer (OR = 0.49; 95% CI 0.20-1.23), oesophageal cancer (OR = 1.85; 95% CI 0.95-3.58), oral dysplasia (OR = 8.33; 95% CI 0.78-9.47) or infertility (OR = 2.5; 95% CI 1.0-6.3) but the CIs did not exclude important associations. Smoking waterpipe in groups was not significantly associated with hepatitis C infection (OR = 0.98; 95% CI 0.80-1.21). The quality of evidence for the different outcomes varied from very low to low. CONCLUSION: Waterpipe tobacco smoking is possibly associated with a number of deleterious health outcomes. There is a need for high-quality studies to identify and quantify with confidence all the health effects of this form of smoking.