Isometric Exercise Training and Arterial Hypertension: An Updated Review.

Hypertension is recognised as a leading attributable risk factor for cardiovascular disease and premature mortality. Global initiatives towards the prevention and treatment of arterial hypertension are centred around non-pharmacological lifestyle modification. Exercise recommendations differ between professional and scientific organisations, but are generally unanimous on the primary role of traditional aerobic and dynamic resistance exercise. In recent years, isometric exercise training (IET) has emerged as an effective novel exercise intervention with consistent evidence of reductions in blood pressure (BP) superior to that reported from traditional guideline-recommended exercise modes. Despite a wealth of emerging new data and endorsement by select governing bodies, IET remains underutilised and is not widely prescribed in clinical practice. This expert-informed review critically examines the role of IET as a potential adjuvant tool in the future clinical management of BP. We explore the efficacy, prescription protocols, evidence quality and certainty, acute cardiovascular stimulus, and physiological mechanisms underpinning its anti-hypertensive effects. We end the review with take-home suggestions regarding the direction of future IET research.

Effects of isometric leg training on ambulatory blood pressure and morning blood pressure surge in young normotensive men and women.

Despite the reported association between diurnal variations in ambulatory blood pressure (BP) and elevated cardiovascular disease risk, little is known regarding the effects of isometric resistance training (IRT), a practical BP-lowering intervention, on ambulatory BP and morning BP surge (MBPS). Thus, we investigated whether (i) IRT causes reductions in ambulatory BP and MBPS, in young normotensives, and (ii) if there are any sex differences in these changes. Twenty normotensive individuals (mean 24-h SBP = 121 ± 7, DBP = 67 ± 6 mmHg) undertook 10-weeks of bilateral-leg IRT (4 × 2-min/2-min rest, at 20% maximum voluntary contraction (MVC) 3 days/week). Ambulatory BP and MBPS (mean systolic BP (SBP) 2 h after waking minus the lowest sleeping 1 h mean SBP) was measures pre- and post-training. There were significant reductions in 24-h ambulatory SBP in men (- 4 ± 2 mmHg, P = 0.0001) and women (- 4 ± 2 mmHg, P = 0.0001) following IRT. Significant reductions were also observed in MBPS (- 6 ± 8 mmHg, p = 0.044; - 6 ± 7 mmHg, P = 0.019), yet there were no significant differences between men and women in these changes, and 24-h ambulatory diastolic BP remained unchanged. Furthermore, a significant correlation was identified between the magnitude of the change in MBPS and the magnitude of changes in the mean 2-h SBP after waking for both men and women (men, r = 0.89, P = 0.001; women, r = 0.74, P = 0.014). These findings add further support to the idea that IRT, as practical lifestyle intervention, is effective in significantly lowering ambulatory SBP and MBPS and might reduce the incidence of adverse cardiovascular events that often occur in the morning.

Handgrip strength and health outcomes: Umbrella review of systematic reviews with meta-analyses of observational studies.

PURPOSE: The aim of the present study was to assess both the credibility and strength of evidence arising from systematic reviews with meta-analyses of observational studies on handgrip strength and health outcomes. METHODS: An umbrella review of systematic reviews with meta-analyses of observational studies was conducted. We assessed meta-analyses of observational studies based on random-effect summary effect sizes and their p values, 95% prediction intervals, heterogeneity, small-study effects, and excess significance. We graded the evidence from convincing (Class I) to weak (Class IV). RESULTS: From 504 articles returned in a search of the literature, 8 systematic reviews were included in our review, with a total of 11 outcomes. Overall, nine of the 11 of the outcomes reported nominally significant summary results (p < 0.05), with 4 associations surviving the application of the more stringent p value (p < 10-6). No outcome presented convincing evidence. Three associations showed Class II evidence (i.e., highly suggestive): (1) higher handgrip values at baseline were associated with a minor reduction in mortality risk in the general population (n = 34 studies; sample size = 1,855,817; relative risk = 0.72, 95% confidence interval (95%CI): 0.67-0.78), (2) cardiovascular death risk in mixed populations (n = 15 studies; relative risk = 0.84, 95%CI: 0.78-0.91), and (3) incidence of disability (n = 7 studies; relative risk = 0.76, 95%CI: 0.66-0.87). CONCLUSION: The present results show that handgrip strength is a useful indicator for general health status and specifically for early all-cause and cardiovascular mortality, as well as disability. To further inform intervention strategies, future research is now required to fully understand mechanisms linking handgrip strength scores to these health outcomes.

Blood pressure-lowering efficacy of a 6-week multi-modal isometric exercise intervention.

Isometric exercise training (IET) is an effective method for reducing resting blood pressure (BP). To date, no research studies have been conducted using multiple exercises within an IET intervention. Previous research has suggested that varied exercise programmes may have a positive effect on adherence. Therefore, this randomized controlled study aimed to investigate the BP-lowering efficacy of a multi-modal IET (MIET) intervention in healthy young adults. Twenty healthy participants were randomized to an MIET [n = 10; four women; SBP 117.9 ± 6.9 mmHg; DBP 66.3 ± 5.1 mmHg] or control (CON) group (n = 10; five women; SBP, 123.3 ± 10.4 mmHg; DBP, 77.3 ± 6.7 mmHg). The MIET group completed three sessions per week of 4, 2-min isometric contractions, with a 1-min rest between each contraction, for 6 weeks. Resting BP and heart rate (HR) were measured at baseline and post-intervention. Pre-to-post intervention within-group reductions in resting BP were observed (SBP: 5.3 ± 6.1 mmHg, DBP: 3.4 ± 3.7 mmHg, MAP: 4.0 ± 3.9 mmHg, HR: 4.8 ±6 .6 bpm), although clinically relevant (≥2 mmHg), these changes were not statistically significant. Significant (p < 0.05) between-group differences were found between the intervention and control groups, indicating that the MIET intervention has a greater BP-lowering effect compared to control. The clinically relevant post-training reductions in resting BP suggest that MIET may be a promising additional IET method for hypertension prevention. These findings; however, must be interpreted with caution due to the small sample size and the non-clinical cohort.

Comorbidity Associations with AATD Among Commercially Insured and Medicare Beneficiaries with COPD in the US.

Introduction: Alpha-1 antitrypsin deficiency (AATD) is often not identified in patients with chronic obstructive pulmonary disease (COPD) until advanced stages of disease, despite the availability of genetic testing. While clinical practice guidelines provide recommendations on patients who should be tested, more refined algorithms are needed to identify COPD patients who are likely candidates for AATD testing and to prevent delays in diagnosis and treatment. The objective of this study was to identify comorbid associations with AATD among patients diagnosed with COPD in the United States. Methods: Using data from the 2012-2017 PharMetrics Plus Administrative Claims Database and 2011-2014 Medicare Fee for Service 5% Sample, patients with COPD (ICD-9-CM: 491.xx, 492.xx, or 496, ICD-10-CM J41, J42, J43, J44) and AATD (ICD-9-CM: 273.4, ICD-10-CM: E88.01) were identified. Patient demographic and diagnostic characteristics were assessed. Logistic regression models were developed to identify significant predictors of AATD. Results: A cohort of 344,528 Medicare beneficiaries with COPD (of which 302 (0.09%) also had two diagnoses of AATD) and a cohort of 340,259 commercially insured patients with COPD (of which 1076 (0.3%) also had a diagnosis of AATD) were constructed. Associations with AATD identified in both models included ICD-9-CM and ICD-10-CM codes for chronic pulmonary heart disease, chronic liver disease and cirrhosis, and liver transplant. Discussion: Significant associations with a diagnosis of AATD among patients with COPD were consistently represented in each of the datasets evaluated, which suggests meaningful comorbidity implications in AATD patients. These findings reinforce the need to test individuals with COPD for AATD as early as possible to help reduce the development of associated comorbid conditions.

The Impact of Genistein Supplementation on Tendon Functional Properties and Gene Expression in Estrogen-Deficient Rats.

Tendinopathy risk increases with menopause. The phytoestrogen genistein prevents collagen loss during estrogen deficiency (ovariectomy [OVX]). The influence of genistein on tendon function and extracellular matrix (ECM) regulation is not well known. We determined the impact of genistein on tendon function and the expression of several genes important for the regulation of tendon ECM. Eight-week-old rats (n = 42) were divided into three groups: intact, OVX, or OVX-genistein (6 mg/kg/day) for 6 weeks. Tail fascicles were assessed with a Deben tensile stage. Achilles tendon mRNA expression was determined with digital droplet polymerase chain reaction. Compared to intact, fascicle stress tended to be lower in untreated OVX rats (P = .022). Furthermore, fascicle modulus and energy density were greater in genistein-treated rats (P < .05) compared to intact. Neither OVX nor genistein altered expression of Col1a1, Col3a1, Casp3, Casp8, Mmp1a, Mmp2, or Mmp9 (P > .05). Compared to intact, Tnmd and Esr1 expression were greater and Pcna and Timp1 expression were lower in OVX rats (P < .05). Genistein treatment returned Tnmd, Pcna, and Timp1 to levels of intact-vehicle (P < .05), but did not alter Scx or Esr1 (P > .05). Several ß-catenin/Wnt signaling-related molecules were not altered by OVX or genistein (P > .05). Our findings demonstrate that genistein improves tendon function in estrogen-deficient rats. The effect of genistein in vivo was predominately on genes related to cell proliferation rather than collagen remodeling.

Relative and Cumulative Effects of Hypertension Self-Care Behaviors on Blood Pressure.

New recommendations for hypertension (HTN) diagnosis and treatment highlight the role of self-care activities in managing blood pressure (BP). This cross-sectional study investigated the predictive validity of the Hypertension Self-Care Activity Level Effects (H-SCALE) measure and examined the relative and cumulative effects of HTN self-care adherence on BP. We pooled baseline data from three studies (N = 79), resulting in a gender and racially balanced sample. Partial correlations determined the relative effects of individual self-care behaviors on BP. We modeled the relationship between adherence to self-care behaviors and BP control using logistic regression. Physical activity had the greatest correlation with systolic BP. Adherence to each additional self-care behavior increased the odds of systolic BP control by 88% (95% confidence interval (CI) = [1.20, 2.96]) and diastolic BP control by 74% (95% CI = [1.10, 2.75]). Results provide further evidence that the H-SCALE is a valid assessment tool and should be adopted by clinicians to aid in improving BP management.

"Get a Grip on Hypertension": EXPLORING THE USE OF ISOMETRIC HANDGRIP TRAINING IN CARDIOPULMONARY REHABILITATION PATIENTS.

PURPOSE: Isometric handgrip (IHG) training lowers systolic and diastolic blood pressure (SBP and DBP, respectively), but the efficacy of IHG training in cardiopulmonary rehabilitation patients is unknown. The purpose of this study was to determine if IHG decreases blood pressure in cardiopulmonary rehabilitation patients. METHODS: Cardiopulmonary rehabilitation program participants (n = 11; 50-80 yr old) were randomized to IHG (n = 6) or control (CON; no treatment; n = 5) groups. IHG participants completed an IHG training program at 30% maximal voluntary contraction, 3 d/wk for 6 wk. Resting SBP, DBP, and heart rate were assessed weekly. RESULTS: Mean regression for SBP following IHG was negative (-1.04 ± 0.80). Mean regression in the CON group was positive (0.50 ± 0.88), but there was no significant difference between groups. Separate analysis of weeks 1 to 7 yielded a negative mean regression (-1.12 ± 0.54) in the IHG group, but positive (1.2 ± 0.60) in the CON group. A Wilcoxon test of these differences yielded significance for SBP (P = .009). In 3 of 6 IHG participants, SBP was lower (mean ± SD: -16 ± 11 mm Hg; P = .12), and in 2 IHG participants, DBP was lower (-9 ± 1 mm Hg; P = .06) compared with baseline. In 2 of 5 CON participants, SBP was not significantly lower (-11 ± 7 mm Hg) and, in 3 of 5 CON participants, DBP was lower (-7 ± 4 mm Hg; P = .04). CONCLUSIONS: Our data suggest that standard IHG training may be inadequate for blood pressure management immediately following a major cardiac or pulmonary event. Future work with a larger cohort and more developed training protocol to determine the efficacy of IHG training in patients with cardiopulmonary disease is warranted.

Blood pressure lowering effects of a novel isometric exercise device following a 4-week isometric handgrip intervention.

Background: Hypertension is the leading risk factor for global mortality. Isometric resistance exercise training reduces blood pressure (BP). However, the protocols used are often limited by cost/immobility and the use of rigid exercise modalities. In response, a novel more versatile, isometric exercise (IE) device, the IsoBall (IB) was created. Purpose: The aim of this study was to test the BP-lowering effectiveness of this prototype. Methods: Twenty-three healthy participants (29.10±2.19 years old, 173.95±3.83 cm, 75.43±5.06 kg, SBP 127.10±10.37 mmHg, DBP 70.40±6.77 mmHg) were randomly allocated to either a control group (CON) or 2 isometric handgrip (IHG) training groups that used the Zona plus (ZON) and IB devices. The intervention groups completed 3 sessions each week of 4, 2 min IHG at 30% maximal voluntary contraction, with a 1-min rest, for 4 weeks. Resting BP, heart rate (HR) and IHG strength were measured in all groups at baseline and postintervention. Results: Postintervention systolic BP (SBP) was significantly lower in both ZON (114.5±8.2 mmHg, p = 0.000) and IB (119.9±7.0 mmHg, p = 0.000) compared to control (131.0±12.4 mmHg). Postintervention diastolic BP (DBP) was reduced in both intervention groups (ZON 66.6±7.4 mmHg, p = 0.004; IB 65.7±10.0 mmHg, p = 0.012) compared to CON (71.1±8.8 mmHg). Mean arterial pressure (MAP) was reduced in both groups (ZON 82.6±6.8 mmHg, p = 0.000; IB 84.3±9.1 mmHg, p = 0.000) compared to control (91.0±9.7 mmHg). No significant changes were seen in HR or strength (p > 0.05). Conclusion: The results of this study indicate that both the ZON and IB devices elicit significant SBP, DBP and MAP reductions. Despite the ZON group having larger reductions in BP, no significant differences were found between the two devices. Thus, this study indicates the IB device to be an effective alternative to the ZON that can also be used to perform other IE modalities.

Survival associated with chronic obstructive pulmonary disease among SEER-Medicare beneficiaries with non-small-cell lung cancer.

Objective: We investigated the impact of preexisting COPD and its subtypes, chronic bronchitis and emphysema, on overall survival among Medicare enrollees diagnosed with non-small-cell lung cancer (NSCLC). Methods: Using SEER-Medicare data, we included patients ≥66 years of age diagnosed with NSCLC at any disease stage between 2006 and 2010 and continuously enrolled in Medicare Parts A and B in the 12 months prior to diagnosis. Preexisting COPD in patients with NSCLC were identified using ICD-9 codes. Kaplan-Meier method and log-rank tests were used to examine overall survival by COPD status and COPD subtype. Multivariable Cox proportional hazards models were fit to assess the risk of death after cancer diagnosis. Results: We identified 66,963 lung cancer patients. Of these, 22,497 (33.60%) had documented COPD before NSCLC diagnosis. For each stage of NSCLC, median survival was shorter in the COPD compared to the non-COPD group (Stage I: 692 days vs 1,130 days, P<0.0001; Stage II: 473 days vs 627 days, P<0.0001; Stage III: 224 days vs 229 days; P<0.0001; Stage IV: 106 days vs 112 days, P<0.0001). For COPD subtype, median survival for patients with preexisting chronic bronchitis was shorter compared to emphysema across all stages of NSCLC (Stage I: 672 days vs 811 days, P<0.0001; Stage II 582 days vs 445 days, P<0.0001; Stage III: 255 days vs 229 days, P<0.0001; Stage IV: 105 days vs 112 days, P<0.0001). In Cox proportional hazard model, COPD patients exhibited 11% increase in risk of death than non-COPD patients (HR: 1.11, 95%CI: 1.09-1.13). Conclusion: NSCLC patients with preexisting COPD had shorter survival with marked differences in early stages of lung cancer. Chronic bronchitis demonstrated a greater association with time to death than emphysema.

Effects of isometric resistance training on resting blood pressure: individual participant data meta-analysis.

BACKGROUND: Previous meta-analyses based on aggregate group-level data report antihypertensive effects of isometric resistance training (IRT). However, individual participant data meta-analyses provide more robust effect size estimates and permit examination of demographic and clinical variables on IRT effectiveness. METHODS: We conducted a systematic search and individual participant data (IPD) analysis, using both a one-step and two-step approach, of controlled trials investigating at least 3 weeks of IRT on resting systolic, diastolic and mean arterial blood pressure. RESULTS: Anonymized individual participant data were provided from 12 studies (14 intervention group comparisons) involving 326 participants (52.7% medicated for hypertension); 191 assigned to IRT and 135 controls, 25.2% of participants had diagnosed coronary artery disease. IRT intensity varied (8-30% MVC) and training duration ranged from 3 to 12 weeks. The IPD (one-step) meta-analysis showed a significant treatment effect for the exercise group participants experiencing a reduction in resting SBP of -6.22 mmHg (95% CI -7.75 to -4.68; P < 0.00001); DBP of -2.78 mmHg (95% CI -3.92 to -1.65; P = 0.002); and mean arterial blood pressure (MAP) of -4.12 mmHg (95% CI -5.39 to -2.85; P < 0.00001). The two-step approach yielded similar results for change in SBP -7.35 mmHg (-8.95 to -5.75; P < 0.00001), DBP MD -3.29 mmHg (95% CI -5.12 to -1.46; P = 0.0004) and MAP MD -4.63 mmHg (95% CI -6.18 to -3.09: P < 0.00001). Sub-analysis revealed that neither clinical, medication, nor demographic participant characteristics, or exercise program features, modified the IRT treatment effect. CONCLUSION: This individual patient analysis confirms a clinically meaningful and statistically significant effect of IRT on resting SBP, DBP and mean arterial blood pressure.

Differences in Patient Demographics and Healthcare Costs of Patients with PIDD Receiving Intravenous or Subcutaneous Immunoglobulin Therapies in the United States.

BACKGROUND: Primary immune-deficiency disease (PIDD) is a rare, debilitating disease of the immune system that predisposes the affected individual to infection, autoimmune conditions, and neoplasm. A major component of the cost of treating PIDD is the high price of immunoglobulin drugs, which can be administered via an intravenous (IV) or subcutaneous (SC) route. OBJECTIVE: To compare real-world costs for patients with PIDD who are receiving IV immunoglobulin (IVIG) or SC immunoglobulin (SCIG) treatment, from a US payer perspective, using a large claims database. METHODS: Based on 2011 to 2013 data from the PharMetrics Plus database, a large national healthcare claims database, patients who were newly diagnosed with PIDD were included in the study if they had ≥2 claims for PIDD that were ≥90 days apart, and if they were treatment-naïve for a minimum of 1 year before the study period. Patients who switched the route of immunoglobulin administration were excluded, with the exception of patients who received SCIG who could initially receive ≤2 IV-loading infusions, as directed by treatment guidelines. We used propensity score analysis to match the patients in the SCIG cohort to patients in the IVIG cohort based on age, sex, and all Elixhauser comorbidities. We compared the patient characteristics and direct medical costs (all-cause, PIDD-related, and pharmacy-related) before and after matching, using t-tests for continuous variables, chi-square test for categorical variables, and Wilcoxon rank-sum test for differences in medians. RESULTS: A total of 1639 patients with PIDD (986 who received IVIG and 653 who received SCIG) met all the study inclusion criteria. Compared with the patients who received IVIG, the patients who received SCIG were predominantly female (58% vs 63%, respectively) and significantly younger (mean age, 49.1 vs 40.3 years, respectively). Significantly fewer patients who received SCIG than those receiving IVIG had claims with International Classification of Diseases, Ninth Revision codes for Elixhauser comorbidities, including cardiovascular and pulmonary conditions, diabetes, renal failure, liver disease, cancers, weight loss, fluid and electrolyte disorders, and psychoses (P <.05 for all), and their Charlson Comorbidity Index scores were lower than those receiving IVIG (1.74 vs 3.01, respectively; P ≤.05 for all). After matching the 2 cohorts (N = 553 in each), the 1-year postindex median total PIDD-related costs were significantly lower in the IVIG group than in the SCIG group ($38,064 vs $43,266, respectively; P = .002). CONCLUSIONS: In matched analyses, PIDD-related treatment costs were higher for patients who received SCIG than for those who received IVIG. Furthermore, patients who received SCIG were significantly younger and had significantly less comorbidities than their counterparts who received IVIG, suggesting that patient characteristics that reflect a desire and greater capacity for autonomy may affect physicians' choice of the route of administration for immunoglobulin.

A comparison of blood pressure reductions following 12-weeks of isometric exercise training either in the laboratory or at home.

Isometric exercise training (IET)-induced reductions in resting blood pressure (RBP) have been achieved in laboratory environments, but data in support of IET outside the laboratory are scarce. The aim of this study was to compare 12 weeks of home-based (HOM) IET with laboratory-based, face-to-face (LAB) IET in hypertensive adults. Twenty-two hypertensive participants (24-60 years) were randomized to three conditions: HOM, LAB, or control (CON). IET involved isometric handgrip training (4 × 2 minutes at 30% maximum voluntary contraction, 3 days per week). RBP was measured every 6 weeks (0, 6, and 12 weeks) during training and 6 weeks after training (18 weeks). Clinically meaningful, but not statistically significant reductions in RBP were observed after 12 weeks of LAB IET (resting systolic blood pressure [SBP] -9.1 ± 4.1; resting diastolic blood pressure [DBP] -2.8 ± 2.1; P > .05), which was sustained for 6 weeks of detraining (SBP -8.2 ± 2.9; DBP -4 ± 2.9, P > .05). RBP was reduced in the HOM group after 12 weeks of training (SBP -9.7 ± 3.4; DBP -2.2 ± 2.0; P > .05), which was sustained for an additional 6 weeks of detraining (SBP -5.5 ± 3.4; DBP -4.6 ± 1.8; P > .05). Unsupervised home-based IET programs present an exciting opportunity for community-based strategies to combat hypertension, but additional work is needed if IET is to be used routinely outside the laboratory.

Healthcare utilization and costs associated with COPD among SEER-Medicare beneficiaries with NSCLC.

AIM: To estimate the healthcare utilization and costs in elderly lung cancer patients with and without pre-existing chronic obstructive pulmonary disease (COPD). METHODS: Using Surveillance, Epidemiology and End Results (SEER)-Medicare data, this study identified patients with lung cancer between 2006-2010, at least 66 years of age, and continuously enrolled in Medicare Parts A and B in the 12 months prior to cancer diagnosis. The diagnosis of pre-existing COPD in lung cancer patients was identified using ICD-9 codes. Healthcare utilization and costs were categorized as inpatient hospitalizations, skilled nursing facility (SNF) use, physician office visits, ER visits, and outpatient encounters for every stage of lung cancer. The adjusted analysis was performed using a generalized linear model for healthcare costs and a negative binomial model for healthcare utilization. RESULTS: Inpatient admissions in the COPD group increased for each stage of non-small cell lung cancer (NSCLC) compared to the non-COPD group per 100 person-months (Stage I: 14.67 vs 9.49 stays, p < .0001; Stage II: 14.13 vs 10.78 stays, p < .0001; Stage III: 28.31 vs 18.91 stays, p < .0001; Stage IV: 49.5 vs 31.24 stays, p < .0001). A similar trend was observed for outpatient visits, with an increase in utilization among the COPD group (Stage I: 1136.04 vs 796 visits, p < .0001; Stage II: 1325.12 vs 983.26 visits, p < .0001; Stage III: 2025.47 vs 1656.64 visits, p < .0001; Stage IV: 2825.73 vs 2422.26 visits, p < .0001). Total direct costs per person-month in patients with pre-existing COPD were significantly higher than the non-COPD group across all services ($54,799.16 vs $41,862.91). Outpatient visits represented the largest cost category across all services in both groups, with higher costs among the COPD group ($41,203 vs $31,140.08). CONCLUSION: Healthcare utilization and costs among lung cancer patients with pre-existing COPD was ∼2-3-times higher than the non-COPD group.

Healthcare Cost and Utilization before and after Diagnosis of Pseudomonas aeruginosa among Patients with Non-Cystic Fibrosis Bronchiectasis in the U.S.

Non-cystic fibrosis bronchiectasis (NCFBE) is a rare, chronic lung disease characterized by bronchial inflammation and permanent airway dilation. Chronic infections with P. aeruginosa have been linked to higher morbidity and mortality. To understand the impact of P. aeruginosa in NCFBE on health care costs and burden, we assessed healthcare costs and utilization before and after P. aeruginosa diagnosis. Using data from 2007 to 2013 PharMetrics Plus administrative claims, we included patients with ≥2 claims for bronchiectasis and >1 claim for P. aeruginosa; then excluded those with a claim for cystic fibrosis. Patients were indexed at first claim for P. aeruginosa and were required to have >12 months before and after the index P. aeruginosa. The mean differences in utilization and costs were assessed using paired Student's t-tests for statistical significance. Mean total healthcare costs per patient were $36,213 pre-P. aeruginosa diagnosis versus $67,764 post-P. aeruginosa, an increase of 87% (p < 0.0001). Inpatient costs represented the largest proportion of total healthcare costs post-P. aeruginosa (54%) with an increase of four hospitalizations per patient (p < 0.0001). NCFBE patients with evidence of P. aeruginosa incur substantially greater healthcare costs and utilization after P. aeruginosa diagnosis. Future research should explore methods of earlier identification of NCFBE patients with P. aeruginosa, as this may lead to fewer severe exacerbations, thereby resulting in a reduction in hospitalizations and healthcare costs.

One-year Prevalence, Comorbidities, and Cost of Hospitalizations for Alpha-1 Antitrypsin Deficiency among Patients with Chronic Obstructive Pulmonary Disease in the United States.

Objectives: Little is known about severe chronic obstructive pulmonary disease (COPD) exacerbations among patients with Alpha-1 Antitrypsin Deficiency (AATD). We assessed inpatients with AATD and COPD among a sample of COPD inpatients to ascertain demographic, clinical and economic differences in the course of disease and treatment. Methods: Using data from the 2009 Nationwide Inpatient Sample (NIS), we identified COPD (ICD-9-CM: 491.xx, 492.xx, or 496.xx) patients with AATD (273.4). We compared patient demographics and healthcare outcomes (eg, length of stay, inpatient death, type and number of procedures, and cost of care) between COPD patients with and without alpha-1 antitrypsin deficiency. Frequencies and percentages for patient demographics were compared using bivariate statistics (eg, chi-square test). Recognizing the non-parametric nature of length of stay and cost, we calculated median values and interquartile ranges for these variables for each group of patients. Finally, the risk of inpatient death was estimated using logistic regression. Results: Of 840 242 patients with COPD (10.8% of the NIS sample population), 0.08% (684) had a primary or secondary diagnosis code for AATD. COPD+AATD were younger (56 vs 70, p<0.0001) and as a result, less likely to be covered by Medicare (44% vs 62%, p<0.0001). AATD patients were also more likely to have comorbid non-alcoholic liver disease (7% vs 2%, p<0.0001), depression (17% vs 13%, p=0.0328), and pulmonary circulation disorders (7% vs 4%, p=0.0299). Patients with AATD had a 14% longer length of stay (IRR = 1.14, 95% CI 1.07, 1.21) and a mean cost of $1487 (p=0.0251) more than COPD inpatients without AATD. Conclusions: AATD is associated with increased mean length of stay and cost, as well as higher frequency of comorbid non-alcoholic liver disease, depression, and pulmonary circulation disorders. Future research should assess other differences between AATD and the general COPD population such as natural history of disease, treatment responsiveness and disease progression.

Influence of acute and chronic streptozotocin-induced diabetes on the rat tendon extracellular matrix and mechanical properties.

Diabetes is a major risk factor for tendinopathy, and tendon abnormalities are common in diabetic patients. The purpose of the present study was to evaluate the effect of streptozotocin (60 mg/kg)-induced diabetes and insulin therapy on tendon mechanical and cellular properties. Sprague-Dawley rats (n = 40) were divided into the following four groups: nondiabetic (control), 1 wk of diabetes (acute), 10 wk of diabetes (chronic), and 10 wk of diabetes with insulin treatment (insulin). After 10 wk, Achilles tendon and tail fascicle mechanical properties were similar between groups (P > 0.05). Cell density in the Achilles tendon was greater in the chronic group compared with the control and acute groups (control group: 7.8 ± 0.5 cells/100 µm(2), acute group: 8.3 ± 0.4 cells/100 µm(2), chronic group: 10.9 ± 0.9 cells/100 µm(2), and insulin group: 9.2 ± 0.8 cells/100 µm(2), P < 0.05). The density of proliferating cells in the Achilles tendon was greater in the chronic group compared with all other groups (control group: 0.025 ± 0.009 cells/100 µm(2), acute group: 0.019 ± 0.005 cells/100 µm(2), chronic group: 0.067 ± 0.015, and insulin group: 0.004 ± 0.004 cells/100 µm(2), P < 0.05). Patellar tendon collagen content was ∼32% greater in the chronic and acute groups compared with the control or insulin groups (control group: 681 ± 63 µg collagen/mg dry wt, acute group: 938 ± 21 µg collagen/mg dry wt, chronic: 951 ± 52 µg collagen/mg dry wt, and insulin group: 596 ± 84 µg collagen/mg dry wt, P < 0.05). In contrast, patellar tendon hydroxylysyl pyridinoline cross linking and collagen fibril organization were unchanged by diabetes or insulin (P > 0.05). Our findings suggest that 10 wk of streptozotocin-induced diabetes does not alter rat tendon mechanical properties even with an increase in collagen content. Future studies could attempt to further address the mechanisms contributing to the increase in tendon problems noted in diabetic patients, especially since our data suggest that hyperglycemia per se does not alter tendon mechanical properties.

Intensity-dependent reductions in resting blood pressure following short-term isometric exercise training.

To reduce resting blood pressure, a minimum isometric exercise training (IET) intensity has been suggested, but this is not known for short-term IET programmes. We therefore compared the effects of moderate- and low-intensity IET programmes on resting blood pressure. Forty normotensive participants (22.3 ± 3.4 years; 69.5 ± 15.5 kg; 170.2 ± 8.7 cm) were randomly assigned to groups of differing training intensities [20%EMGpeak (~23%MVC, maximum voluntary contraction, or 30%EMGpeak (~34%MVC)] or control group; 3 weeks of IET at 30%EMGpeak resulted in significant reductions in resting mean arterial pressure (e.g. -3.9 ± 1.0 mmHg, P < 0.001), whereas 20%EMGpeak did not (-2.3 ± 2.9 mmHg; P > 0.05). Moreover, after pooling all female versus male participants, IET induced a 6.9-mmHg reduction in systolic blood pressure in female participants, but only a 1.5-mmHg reduction in systolic blood pressure in male participants, although the difference was not significant. An IET intensity between 20%EMGpeak and 30%EMGpeak is sufficient to elicit significant resting blood pressure reductions in a short-term training period (3 weeks). In addition, sexual dimorphism may exist in the magnitude of reductions, but further work is required to confirm this possibility, which could be important in understanding the mechanisms responsible.

Immediate post-isometric exercise cardiovascular responses are associated with training-induced resting systolic blood pressure reductions.

PURPOSE: The purpose of this study was twofold: (1) to investigate the effect of 4 weeks of bilateral-leg isometric exercise training on the immediate isometric post-exercise cardiovascular responses, and (2) to ascertain whether any changes in immediate post-exercise cardiovascular responses may be associated with training-induced adaptations in resting blood pressure. METHODS: Thirteen normotensive males completed both isometric exercise training (IET) and control conditions, which were separated by 6 weeks. Participants performed a total of twelve training sessions; 4 × 2-min bilateral-leg isometric exercise bouts separated by 3-min rest periods, 3 days week(-1). RESULTS: Four weeks of bilateral-leg IET resulted in a reduction in resting SBP (120 ± 12-115 ± 12 mmHg, p = 0.01). The intercept of the 5-min post-exercise systolic blood pressure slope was lower (p = 0.015) following the 4-week training intervention. Individual changes in immediate post-exercise response SBP were also significantly correlated with reductions in resting SBP following 4 weeks of training. There were significant differences in the slopes of the first vs. final post-exercise BRS response (p = 0.009), and the intercepts of the HRR slopes (p = 0.04) recorded during the 5-min post-exercise periods. CONCLUSIONS: Four weeks of IET altered immediate cardiovascular responses to an individual IET session. Altered immediate responses were also associated with training-induced reductions in resting SBP. To our knowledge, this is the first evidence suggesting that very short-term (immediate) cardiovascular responses may be important in defining chronic reductions in resting blood pressure following a period of IET.