Imran H. Iftikhar

Effects of continuous positive airway pressure on blood pressure in patients with resistant hypertension and obstructive sleep apnea: a meta-analysis

Objective: To systematically analyze the studies that have examined the effect of continuous positive airway pressure (CPAP) on blood pressure (BP) in patients with resistant hypertension and obstructive sleep apnea (OSA). Methods: Design – meta-analysis of observational studies and randomized controlled trials (RCTs) indexed in PubMed and Ovid (All Journals@Ovid). participants: individuals with resistant hypertension and OSA; interventions – CPAP treatment. Results: A total of six studies met the inclusion criteria for preintervention to postintervention analyses. The pooled estimates of mean changes after CPAP treatment for the ambulatory (24-h) SBP and DBP from six studies were −7.21 mmHg [95% confidence interval (CI): −9.04 to −5.38; P < 0.001; I2 58%) and −4.99 mmHg (95% CI: −6.01 to −3.96; P < 0.001; I2 31%), respectively. The pooled estimate of the ambulatory SBP and DBP from the four RCTs showed a mean net change of −6.74 mmHg [95% CI: −9.98 to −3.49; P < 0.001; I2 61%] and −5.94 mmHg (95% CI: −9.40 to −2.47; P = 0.001; I2 76%), respectively, in favor of the CPAP group. Conclusion: The pooled estimate shows a favorable reduction of BP with CPAP treatment in patients with resistant hypertension and OSA. The effects sizes are larger than those previously reported in patients with OSA without resistant hypertension.

Meta-analysis: continuous positive airway pressure improves insulin resistance in patients with sleep apnea without diabetes.

RATIONALE Obstructive sleep apnea (OSA) is an independent risk factor for the development of insulin resistance (IR). Treatment with continuous positive airway pressure (CPAP) for OSA has shown conflicting results on IR. OBJECTIVES To conduct a meta-analysis of randomized controlled trials (RCTs) that have evaluated the effect of CPAP on a validated index of IR, the homeostasis model assessment of insulin resistance (HOMA-IR). METHODS PubMed and Embase were searched through August 10, 2012. Two independent reviewers screened citations to identify trials of the effect of CPAP on HOMA-IR. Data were extracted for postintervention HOMA-IR values. MEASUREMENTS AND MAIN RESULTS A total of five studies that enrolled 244 subjects (83% male) met the inclusion criteria. None of the subjects in the included studies had diabetes. The pooled estimate of the difference in means in HOMA-IR between the CPAP and sham CPAP/control groups was -0.44 (95% confidence interval, -0.82 to -0.06; P = 0.02). The funnel plot does not suggest the presence of any publication bias. The I-squared index for the data on difference in means in HOMA-IR between the CPAP and sham CPAP/control groups was 0.00 (P = 0.61). CONCLUSIONS The pooled estimate of RCTs shows a favorable effect of CPAP on insulin resistance as measured by HOMA-IR in patients with OSA without diabetes. The effect size on HOMA-IR is modest, but not insignificant, when compared with the effects of thiazolidinedione in nondiabetic patients with metabolic syndrome. Further research and RCTs are warranted involving a larger number of patients and longer treatment periods to determine the beneficial effects of CPAP on IR.

Effect of Oral Appliances on Blood Pressure in Obstructive Sleep Apnea: A Systematic Review and Meta-analysis

BACKGROUND Obstructive sleep apnea (OSA) is an independent risk factor for the development of hypertension. However the effect of continuous positive airway pressure (CPAP) on lowering systemic blood pressure (BP) in OSA patients has been conflicting. Oral appliance (OA) therapy is an important alternative therapy to CPAP for patients with mild to moderate OSA. OBJECTIVE To conduct a meta-analysis of studies which have evaluated the effect of OAs on BP in patients with OSA. DATA SOURCES Studies were retrieved by searching PubMed (all studies that were published until December 15, 2011) STUDY SELECTION Three independent reviewers screened citations to identify trials of the effect of OA on BP. DATA EXTRACTION Data from observational and randomized controlled trial (RCT) studies was extracted for pre- and post-treatment systolic, diastolic, and mean arterial blood pressure (SBP, DBP, and MAP). DATA SYNTHESIS A total of 7 studies that enrolled 399 participants met the inclusion criteria. The pooled estimate of mean changes and the corresponding 95% CIs for SBP, DBP, and MAP from each trial are -2.7 mm Hg (95% CI: -0.8 to -4.6), p-value 0.04; -2.7 mm Hg (95% CI: -0.9 to -4.6), p-value 0.004; and -2.40 mm Hg (95% CI: -4.01 to -0.80), p-value 0.003 (Figures 2-4). The pooled estimate of mean changes and the corresponding 95% CIs for nocturnal SBP, DBP, and MAP from each trial are -2.0 mm Hg (95% CI: 1.1 to -5.3), p-value 0.212; -1.7 mm Hg (95% CI: -0.1 to -3.2), p-value 0.03; and -1.9 mm Hg (95% CI: 1.3 to -5.1), p-value 0.255 (Figures 5-7) respectively. CONCLUSIONS The pooled estimate shows a favorable effect of OAs on SBP, MAP, and DBP. Most of the studies were observational. Therefore, more RCTs are warranted involving a larger number of patients and longer treatment periods to confirm the effects of OA on BP.

Meta-analyses of the Association of Sleep Apnea with Insulin Resistance, and the Effects of CPAP on HOMA-IR, Adiponectin, and Visceral Adipose Fat

OBJECTIVE We sought to conduct an updated meta-analysis of randomized controlled trials (RCTs) on the effect of continuous positive airway pressure (CPAP) on insulin resistance, as measured by homeostasis model assessment of insulin resistance (HOMA-IR), visceral abdominal fat (VAF), and adiponectin. Additionally, we performed a separate meta-analysis and meta-regression of studies on the association of insulin resistance and obstructive sleep apnea (OSA). METHODS All included studies were searched from PubMed (from conception to March 15, 2014). Data were pooled across all included RCTs as the mean difference in HOMA-IR and VAF, and as the standardized mean difference in the case of adiponectin analysis. From the included case-control studies, data on the difference of HOMA-IR between cases and controls were pooled across all studies, as the standardized mean difference (SMD). RESULTS There was a significant difference in HOMA-IR (-0.43 [95% CIs: -0.75 to -0.11], p = 0.008) between CPAP treated and non CPAP treated participants. However, there was no significant difference in VAF or adiponectin; (-47.93 [95% CI: -112.58 to 16.72], p = 0.14) and (-0.06 [95% CI: -0.28 to 0.15], p = 0.56), respectively. Meta-analysis of 16 case-control studies showed a pooled SMD in HOMA-IR of 0.51 (95% CI: 0.28 to 0.75), p ≤ 0.001, between cases and controls. CONCLUSIONS The results of our meta-analyses show that CPAP has a favorable effect on insulin resistance. This effect is not associated with any significant changes in total adiponectin levels or amount of VAF. Our findings also confirm a significant association between OSA and insulin resistance.

Sleep Duration and Metabolic Syndrome. An Updated Dose–Risk Metaanalysis

RATIONALE Several studies have reported that both short and long sleep durations are associated with the metabolic syndrome, but whether a dose-response relationship exists is unclear. OBJECTIVES We performed a metaanalysis to study the magnitude of the association between the different durations of sleep and metabolic syndrome. METHODS We searched in the databases of PubMed, Web of Science, and Ovid (all Journals@Ovid) from inception to October 4, 2014 for cross-sectional studies where an association between metabolic syndrome and sleep duration was analyzed. MEASUREMENTS AND MAIN RESULTS Eighteen studies with 75,657 participants were included. Daily sleep duration of 7 to 8 hours was used as the reference group. The odds ratio (OR) of having metabolic syndrome for short (<7 h) sleep was 1.23 (95% CI, 1.11-1.37; P < 0.001; I(2), 71%). The ORs for less than 5 hours, 5 to 6 hours, and 6 to 7 hours of sleep were 1.51 (95% CI, 1.10-2.08; P = 0.01), 1.28 (95% CI, 1.11-1.48; P < 0.001), and 1.16 (95% CI, 1.02-1.31; P = 0.02), respectively. The coefficient of sleep duration on log of ORs was -0.06 ± 0.02 (P = 0.02). The OR for long sleep duration was 1.13 (95% CI, 0.97-1.32; P = 0.10; I(2), 89%). CONCLUSIONS A dose-response relationship exists between short sleep duration and metabolic syndrome. Those who report a sleep duration of less than 5 hours have a 1.5 higher odds of having metabolic syndrome. Our study does not support the notion that long sleep is associated with metabolic syndrome.

Efficacy of bronchoscopic lung volume reduction: A meta-analysis

Background Over the last several years, the morbidity, mortality, and high costs associated with lung volume reduction (LVR) surgery has fuelled the development of different methods for bronchoscopic LVR (BLVR) in patients with emphysema. In this meta-analysis, we sought to study and compare the efficacy of most of these methods. Methods Eligible studies were retrieved from PubMed and Embase for the following BLVR methods: one-way valves, sealants (BioLVR), LVR coils, airway bypass stents, and bronchial thermal vapor ablation. Primary study outcomes included the mean change post-intervention in the lung function tests, the 6-minute walk distance, and the St George’s Respiratory Questionnaire. Secondary outcomes included treatment-related complications. Results Except for the airway bypass stents, all other methods of BLVR showed efficacy in primary outcomes. However, in comparison, the BioLVR method showed the most significant findings and was the least associated with major treatment-related complications. For the BioLVR method, the mean change in forced expiratory volume (in first second) was 0.18 L (95% confidence interval [CI]: 0.09 to 0.26; P<0.001); in 6-minute walk distance was 23.98 m (95% CI: 12.08 to 35.88; P<0.01); and in St George’s Respiratory Questionnaire was -8.88 points (95% CI: −12.12 to −5.64; P<0.001). Conclusion The preliminary findings of our meta-analysis signify the importance of most methods of BLVR. The magnitude of the effect on selected primary outcomes shows noninfe-riority, if not equivalence, when compared to what is known for surgical LVR.

Predictors of efficacy for endobronchial valves in bronchoscopic lung volume reduction A meta-analysis

Over the last several years, numerous trials have been carried out to check the efficacy of one-way valves in the management of advanced emphysema. While the design of the valves has not altered much, by selectively studying these valves in a select group of participants, such as those with and without intact fissures (FI+ and FI−), and by using different procedural techniques, our understanding of the valves has evolved. In this meta-analysis, we sought to study the effect of these factors on the efficacy of one-way valves. From PubMed and Embase, we included only those studies that provided separate data on fissure integrity or collateral ventilation. Our study outcomes included the mean change in forced expiratory volume in first second (FEV1), 6-minute walk distance (6MWD) and the St George’s Respiratory Questionnaire (SGRQ). In the FI+ subgroup of participants, the pooled standardized mean difference in FEV1, 6MWD, and SGRQ were 0.50 (95% confidence interval (CI): 0.34 to 0.67), p ≤ 0.001, 0.29 (95% CI: 0.13 to 0.45), p ≤ 0.001 and −6.02 (95% CI: −12.12 to 0.06), p = 0.05, respectively. In comparison, these results were superior to the FI− subgroup of participants. A separate analysis of the FI+ subgroup based on lobar occlusion versus nonlobar occlusion favored the former for superior efficacy. The preliminary findings of our meta-analysis confirm that one-way valves perform better in a select group of patients who show intact fissures on lung imaging pretreatment and in those who achieve lobar occlusion.

Transbronchial Lung Cryobiopsy and Video-assisted Thoracoscopic Lung Biopsy in the Diagnosis of Diffuse Parenchymal Lung Disease. A Meta-analysis of Diagnostic Test Accuracy

Rationale: Transbronchial lung cryobiopsy is increasingly being used for the assessment of diffuse parenchymal lung diseases. Several studies have shown larger biopsy samples and higher yields compared with conventional transbronchial biopsies. However, the higher risk of bleeding and other complications has raised concerns for widespread use of this modality. Objectives: To study the diagnostic accuracy and safety profile of transbronchial lung cryobiopsy and compare with video‐assisted thoracoscopic surgery (VATS) by reviewing available evidence from the literature. Methods: Medline and PubMed were searched from inception until December 2016. Data on diagnostic performance were abstracted by constructing two‐by‐two contingency tables for each study. Data on a priori selected safety outcomes were collected. Risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool. Random effects meta‐analyses were performed to obtain summary estimates of the diagnostic accuracy. Results: The pooled diagnostic yield, pooled sensitivity, and pooled specificity of transbronchial lung cryobiopsy were 83.7% (76.9‐88.8%), 87% (85‐89%), and 57% (40‐73%), respectively. The pooled diagnostic yield, pooled sensitivity, and pooled specificity of VATS were 92.7% (87.6‐95.8%), 91.0% (89‐92%), and 58% (31‐81%), respectively. The incidence of grade 2 (moderate to severe) endobronchial bleeding after transbronchial lung cryobiopsy and of post‐procedural pneumothorax was 4.9% (2.2‐10.7%) and 9.5% (5.9‐14.9%), respectively. Conclusions: Although the diagnostic test accuracy measures of transbronchial lung cryobiopsy lag behind those of VATS, with an acceptable safety profile and potential cost savings, the former could be considered as an alternative in the evaluation of patients with diffuse parenchymal lung diseases.

Cost minimization using an artificial neural network sleep apnea prediction tool for sleep studies.

RATIONALE More than a million polysomnograms (PSGs) are performed annually in the United States to diagnose obstructive sleep apnea (OSA). Third-party payers now advocate a home sleep test (HST), rather than an in-laboratory PSG, as the diagnostic study for OSA regardless of clinical probability, but the economic benefit of this approach is not known. OBJECTIVES We determined the diagnostic performance of OSA prediction tools including the newly developed OSUNet, based on an artificial neural network, and performed a cost-minimization analysis when the prediction tools are used to identify patients who should undergo HST. METHODS The OSUNet was trained to predict the presence of OSA in a derivation group of patients who underwent an in-laboratory PSG (n = 383). Validation group 1 consisted of in-laboratory PSG patients (n = 149). The network was trained further in 33 patients who underwent HST and then was validated in a separate group of 100 HST patients (validation group 2). Likelihood ratios (LRs) were compared with two previously published prediction tools. The total costs from the use of the three prediction tools and the third-party approach within a clinical algorithm were compared. MEASUREMENTS AND MAIN RESULTS The OSUNet had a higher +LR in all groups compared with the STOP-BANG and the modified neck circumference (MNC) prediction tools. The +LRs for STOP-BANG, MNC, and OSUNet in validation group 1 were 1.1 (1.0-1.2), 1.3 (1.1-1.5), and 2.1 (1.4-3.1); and in validation group 2 they were 1.4 (1.1-1.7), 1.7 (1.3-2.2), and 3.4 (1.8-6.1), respectively. With an OSA prevalence less than 52%, the use of all three clinical prediction tools resulted in cost savings compared with the third-party approach. CONCLUSIONS The routine requirement of an HST to diagnose OSA regardless of clinical probability is more costly compared with the use of OSA clinical prediction tools that identify patients who should undergo this procedure when OSA is expected to be present in less than half of the population. With OSA prevalence less than 40%, the OSUNet offers the greatest savings, which are substantial when the number of sleep studies done annually is considered.

Food and Drug Administration Regulation of Drugs That Raise Blood Pressure

Although it is recognized that a systolic blood pressure (SBP) increase ≥2 mm Hg or a diastolic blood pressure (DBP) increase ≥1 mm Hg increases the risk of heart attacks and strokes in middle-aged adults, the Food and Drug Administration (FDA) lacks an adequate policy for regulating medications that increase blood pressure (BP). Some FDA reviewers consider a clinically significant increase in BP to occur only if a drug raises SBP ≥20 mm Hg or if a drug raises DBP ≥10 to 15 mm Hg. In recent years, numerous drugs have been regulated or taken off the market due to cardiovascular safety concerns. The list includes rofecoxib (Vioxx), valdecoxib (Bextra), nonselective nonsteroidal anti-inflammatory drugs, sibutramine (Meridia), and phenylpropanolamine. It is probable that the hypertensive effect of these drugs explains why they increase the risk of adverse cardiovascular events. Other drugs, notably serotonin–norepinephrine reuptake inhibitors and drugs used to treat attention deficit hyperactivity disorder, were approved without cardiovascular safety data despite the fact that they raise BP comparable to valdecoxib and sibutramine. It is the responsibility of the FDA to ensure that drugs are properly labeled regarding risk. Even if a drug raises BP only modestly, FDA guidelines for new drug approvals should include a requirement for cardiovascular safety data. However, such guidelines will not address the problem of how to obtain cardiovascular safety data for the many already approved drugs that increase BP. The FDA should play a role in obtaining cardiovascular safety data for such drugs.