Management of patients with hypertension and chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. On behalf of the European Society of Hypertension Working Group on Hypertension and the Kidney.

Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70-95%]) than MRA (20% [10-30%]), SGLT2i (30% [20-50%]) or (GLP1-RA (10% [5-15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15-40%) vs 18% [10%-25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5-5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers' dosage reduction was the usual management.

What is the context? Hypertension is a strong independent risk factor for development of chronic kidney disease (CKD) and progression of CKD to ESKD. Improved adherence to the guidelines in the treatment of CKD is believed to provide further reduction of cardiorenal events. European Society of Hypertension Excellence Centres (ESH-ECs) have been developed in Europe to provide excellency regarding management of patients with hypertension and implement guidelines. Numerous deficits regarding general practitioner CKD screening, use of nephroprotective drugs and referral to nephrologists prior to referral to ESH-ECs have been reported. In contrast, real-life management of these patients among ESH-ECs is unknown. Before implementation of strategies to improve guideline adherence in Europe, we aimed to investigate how patients with CKD are managed among the ESH-ECs.What is the study about? In this study, a survey was conducted in 2023 by the ESH to assess management of CKD patients referred to ESH-ECs. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed among their centres.What are the results? RAAS blockers are initiated in 90% of ESH-ECs in CKD patients, but the initiation of MRA and SGLT2i is less frequently done. Hyperkalemia is the main barrier for initiation or adequate dosing of RAAS blockade, and its most reported management was RAAS blockers dosage reduction. These findings will be crucial to implement strategies in order to improve management of patients with CKD and guideline adherence among ESH-ECs.

Prevalence of musculoskeletal pain and dysfunction in electrical utility workers: Practical considerations for prevention and rehabilitation in the workplace.

INTRODUCTION: This study assessed the prevalence and associations of musculoskeletal pain and dysfunction in electrical utility workers, with the aim of applying the findings to better prevent and rehabilitate workplace musculoskeletal disorders. METHODS: Employees completed an online survey recording their musculoskeletal symptoms across nine anatomical locations for the preceding 12 months. A total of 565 employees, working across eight different electrical utility organisational work units, completed the survey. CONSUMER AND COMMUNITY INVOLVEMENT: The study was collaborative and conducted in Australia's largest, wholly government owned electricity company. The study originated from the participating organisation wanting to better understand their musculoskeletal disorder (MSD) risks. RESULTS: Employees who experienced high job stress were 4.06 times (95% confidence interval [CI] = 1.78-9.29) more likely to report musculoskeletal symptoms in the shoulder compared with employees with lower reported job stress. Employees that perceived their work to have high physical demands report lower back musculoskeletal symptoms at 2.64 times the rate of those perceiving their job to be of low physical demand (95% CI = 1.44-4.84). There were significant differences in the lower back musculoskeletal symptoms according to work unit membership. CONCLUSIONS: Understanding the prevalence of MSDs is critical to implementing practical prevention and rehabilitation strategies in the workplace. This anonymous survey highlighted that a large proportion of electrical utility workers reported that musculoskeletal symptoms had impacted their ability to perform their job, housework and/or hobbies in the preceding 12 months. Early access to rehabilitation services is essential. However, many workers report barriers to disclosing MSDs; therefore, workplace rehabilitation services may need to be broadened to account for these barriers.

The effect of TRV027 on coagulation in COVID-19: A pilot randomized, placebo-controlled trial.

COVID-19 causes significant thrombosis and coagulopathy, with elevated D-dimer a predictor of adverse outcome. The precise mechanism of this coagulopathy remains unclear; one hypothesis is that loss of angiotensin-converting enzyme 2 activity during viral endocytosis leads to pro-inflammatory angiotensin-II accumulation, loss of angiotensin-1-7 and subsequent vascular endothelial activation. We undertook a double-blind randomized, placebo-controlled experimental medicine study to assess the effect of TRV027, a synthetic angiotensin-1-7 analogue on D-dimer in 30 patients admitted to hospital with COVID-19. The study showed a similar rate of adverse events in TRV027 and control groups. There was a numerical decrease in D-dimer in the TRV027 group and increase in D-dimer in the placebo group; however, this did not reach statistical significance (P = .15). A Bayesian analysis demonstrated that there was a 92% probability that this change represented a true drug effect.

Development and evaluation of an online surgical elective for medical students.

BACKGROUND: Decreased experiential learning opportunities exacerbated by the COVID-19 pandemic have increased development of online surgical educational courses. To what extent may such courses provide exposure to broad and accessible surgical education? METHODS: Surge is a 6-week online surgical elective hosted within a virtual learning environment, covering all surgical specialties. Course content is mapped to the Royal College of Surgeons' Undergraduate Curriculum in Surgery. Each week consultant surgeons discuss their specialty in short videos on anatomy, pathology and lifestyle of a surgeon. Students also engage with learning activities; further reading lists; formative quizzes and live sessions including suturing practice. Participants were medical students undertaking third-year electives at the University of Sheffield. Pre- and post-course questionnaires investigated student interest in surgery, understanding of steps required to pursue a surgical career and confidence in surgical environments. Qualitative data was collected via free-text responses and analysed with content analysis. Quantitative data was collected using 5-point Likert scales (1 = Strongly Disagree; 5 = Strongly Agree) and analysed using the Wilcoxon signed-rank test. RESULTS: Twenty-two students participated in Surge over five 6-week cohorts. Examination of free-text responses revealed students gained increased understanding of available surgical career options. Students felt better informed regarding different surgical specialties (median score 2.5 vs. 4, p = 0.000) and steps required to develop a surgical portfolio (median score 2 vs. 5, p = 0.000). Additionally, confidence in understanding of relevant intraoperative steps improved (median score 3 vs. 4, p = 0.000). CONCLUSION: These data demonstrate Surge increased student confidence and understanding of surgical careers despite reduced in-person opportunities to engage with surgical education. Surge will continue to be developed and evaluated on a larger scale.

Poststretch Isometric Contractions of the Hamstrings: Just a Brief Stretch to Achieve Supramaximal Isometric Force.

Hamstring strain injuries are common in sport. Supramaximal eccentric or high-intensity isometric contractions are favored in hamstring strain injury prevention. The effect of combining these contraction modes in such prevention programs as a poststretch isometric contraction is unknown. Poststretch isometric contractions incorporate an active stretch and result in greater final isometric force than isometric contractions at comparable joint angles. This study compared torque and muscle activation levels between maximal voluntary isometric contraction and maximal poststretch isometric contractions of the knee flexors. Participants (n = 9) completed baseline maximal voluntary isometric contraction at 150° knee flexion and maximal poststretch isometric contractions at 120° knee flexion actively stretching at 60°/s to 150° knee flexion for final isometric contraction. Torque of the knee flexors and surface electromyography root mean square (sEMGRMS) of biceps femoris long head were simultaneously recorded and compared between baseline and poststretch isometric at 150° knee flexion. Torque was 14% greater in the poststretch isometric condition compared with baseline maximal voluntary isometric contraction (42.45 [20.75] N·m, 14% [22.18%], P < .001) without increase in sEMGRMS of biceps femoris long head (-.03 mV, ±.06, P = .130, d = .93). Poststretch isometric contractions resulted in supramaximal levels of poststretch isometric torque without increased activation of biceps femoris long head.

Mountain Rescue Casualty Care and the Undergraduate Medical Elective.

Many UK medical curricula lack dedicated prehospital education other than first aid courses and basic life support training. In contrast, nonmedical mountain rescue team members receive advanced prehospital training addressing scene management and various clinical interventions. This article reports a condensed mountain rescue casualty care course designed for medical students by a mountain rescue team. The course was offered as part of a student-selected module during phase 3A at the University of Sheffield Medical School. Within the module, students also learned the relevant biomedical sciences and clinical skills to construct their knowledge of mountain rescue casualty care.

Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial.

BACKGROUND: Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications. METHODS: SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. FINDINGS: Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP -5·5 mm Hg (95% CI -9·1 to -2·0; p=0·0031), 24-h DBP -4·8 mm Hg (-7·0 to -2·6; p<0·0001), office SBP -10·0 mm Hg (-15·1 to -4·9; p=0·0004), and office DBP -5·3 mm Hg (-7·8 to -2·7; p=0·0002). No significant changes were seen in the sham-control group: 24-h SBP -0·5 mm Hg (95% CI -3·9 to 2·9; p=0·7644), 24-h DBP -0·4 mm Hg (-2·2 to 1·4; p=0·6448), office SBP -2·3 mm Hg (-6·1 to 1·6; p=0·2381), and office DBP -0·3 mm Hg (-2·9 to 2·2; p=0·8052). The mean difference between the groups favoured renal denervation for 3-month change in both office and 24-h blood pressure from baseline: 24-h SBP -5·0 mm Hg (95% CI -9·9 to -0·2; p=0·0414), 24-h DBP -4·4 mm Hg (-7·2 to -1·6; p=0·0024), office SBP -7·7 mm Hg (-14·0 to -1·5; p=0·0155), and office DBP -4·9 mm Hg (-8·5 to -1·4; p=0·0077). Baseline-adjusted analyses showed similar findings. There were no major adverse events in either group. INTERPRETATION: Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal denervation. FUNDING: Medtronic.

Residual Force Enhancement in Humans: A Systematic Review.

A systematic literature search was conducted to review the evidence of residual force enhancement (RFE) in vivo human muscle. The search, adhered to the PRISMA statement, of CINAHL, EBSCO, Embase, MEDLINE, and Scopus (inception-July 2017) was conducted. Full-text English articles that assessed at least 1 measure of RFE in vivo voluntarily contracted human skeletal muscle were selected. The methodologies of included articles were assessed against the Downs and Black checklist. Twenty-four studies were included (N = 424). Pooled Downs and Black scores ranked "fair" ([Formula: see text] [2.26]). RFE was observed in all muscles tested. Joint range of motion varied from 15° to 60°. Contraction intensities ranged from 10% to >95% maximum. Although transient force enhancement during the stretch phase may change with angular velocity, RFE in the subsequent isometric phase is independent of velocity. The magnitude of RFE was influenced by smaller stretch amplitudes and greatest at joint angles indicative of longer muscle lengths. Contraction and activation intensity influenced RFE, particularly during the initial isometric contraction phase of a poststretch isometric contraction. RFE resulted in increased torque production, reduced muscular activation, and enhanced torque production when the neuromuscular system is weakened seen in an aged population.

Binding loci of RelA-containing nuclear factor-kappaB dimers in promoter regions of PHM1-31 myometrial smooth muscle cells.

Human parturition is associated with many pro-inflammatory mediators which are regulated by the nuclear factor-kappaB (NF-κB) family of transcription factors. In the present study, we employed a ChIP-on-chip approach to define genomic loci within chromatin of PHM1-31 myometrial cells that were occupied by RelA-containing NF-κB dimers in response to a TNF stimulation of 1 h. In TNF-stimulated PHM1-31 cells, anti-RelA serum enriched 13 300 chromatin regions; importantly, 11 110 regions were also enriched by anti-RelA antibodies in the absence of TNF. DNA sequences in these regions, from both unstimulated or TNF-stimulated PHM1-31 cultures, were associated with genic regions including IκBα, COX-2, IL6RN, Jun and KCNMB3. TNF-induced binding events at a consensus κB site numbered 1667; these were represented by 112 different instances of the consensus κB motif. Of the 1667 consensus κB motif occurrences, 770 (46.2%) were identified within intronic regions. In unstimulated PHM1-31 cells, anti-RelA-serum-enriched regions were associated with sequences corresponding to open reading frames of ion channel subunit genes including CACNB3 and KCNB1. Moreover, in unstimulated cells, the consensus κB site was identified 2116 times, being defined by 103 different sequence instances of this motif. Of these 2116 consensus κB motifs, 1089 (51.5%) were identified within intronic regions. Parallel expression array analyses in PHM1-31 cultures demonstrated that TNF stimulated a >2-fold induction in 51 genes and a fold repression of >1.5 in 18 others. We identified 14 anti-RelA-serum-enriched genomic regions that correlated with 17 TNF-inducible genes, such as COX2, Egr-1, Jun, IκBα and IL6, as well as five regions associated with TNF-mediated gene repression, including Col1A2.

Regulation of GTP-binding protein (Gαs) expression in human myometrial cells: a role for tumor necrosis factor in modulating Gαs promoter acetylation by transcriptional complexes.

The onset of parturition is associated with a number of proinflammatory mediators that are themselves regulated by the nuclear factor κB (NF-κB) family of transcription factors. In this context, we previously reported that the RelA NF-κB subunit represses transcription and mRNA expression of the proquiescent Gαs gene in human myometrial cells following stimulation with the proinflammatory cytokine TNF. In the present study, we initially defined the functional consequence of this on myometrial contractility. Here we show that, contrary to our initial expectations, TNF did not induce myometrial contractility but did inhibit the relaxation produced by the histone deacetylase inhibitor trichostatin A, an effect that in turn was abolished by the NF-κB inhibitor N(4)-[2-(4-phenoxyphenyl)ethyl]-4,6-quinazolinediamine. This result suggested a role for TNF in regulating Gαs expression via activating NF-κB and modifying histone acetylation associated with the promoter region of the gene. In this context, we show that the -837 to -618 region of the endogenous Gαs promoter is occupied by cAMP-response element-binding protein (CREB), Egr-1, and Sp1 transcription factors and that CREB-binding protein (CBP) transcriptional complexes form within this region where they induce histone acetylation, resulting in increased Gαs expression. TNF, acting via NF-κB, did not change the levels of CREB, Sp1, or Egr-1 binding to the Gαs promoter, but it induced a significant reduction in the level of CBP. This was associated with increased levels of histone deacetylase-1 and surprisingly an increase in H4K8 acetylation. The latter is discussed herein.

Predicting repeat power ability through common field assessments: is repeat power ability a unique physical quality?

Background: The repeat power ability (RPA) assessment is used to test the ability to repeatedly produce maximal ballistic efforts with an external load. The underpinning physical qualities influencing RPA are undetermined. This study aimed to gain further insight into the physical qualities that determine RPA by analysing the association between physical qualities and an assessment of RPA. Materials and methods: Ten well-trained male field hockey players performed an RPA assessment consisting of 20 repetitions of loaded countermovement jumps (LCMJ20), with a percent decrement score of peak power output calculated. Over a two-week period, each participant performed the YoYo Intermittent Recovery Test 2 (IRT2), a repeated speed ability assessment incorporating a 180° change of direction (RSA180), a 40-meter linear speed test (40 mST), an isometric mid-thigh pull (IMTP), a countermovement jump (CMJ), and a 3-repetition maximum half squat (HS) assessment. Pearson's correlation analysis was used to determine the strength of relationships between each assessment variable and the LCMJ20. The assessment variables with the strongest relationships within each assessment were used in a stepwise multiple linear regression analysis to determine the best predictor model of LCMJ20. Results: RSA180percent decrement score (RSA180% had a very strong, significant relationship with LCMJ20 (r = 0.736: p < 0.05). HS relative strength (HSrel) was found to have a significant and very strong, negative relationship with LCMJ20 (r =  - 0.728: p < 0.05). Stepwise multiple linear regression analysis showed RSA180 to explain 48.4% of LCMJ20 variance (Adjusted R2 = 0.484) as the only covariate included in the model. Conclusion: The findings indicate that RSA180 as a repeated high intensity effort (RHIE) task is strongly related to LCMJ20 and is also the best predictor of LCMJ20. This may suggest that RPA can provide practitioners with information on RHIE performance. The variance between assessment methods indicates that RPA may be a distinct physical quality, future research should assess other physical capacities to better understand the factors contributing to RPA.

'Legacy publication of a 2009 validation of the Riester Big Ben Square Desk aneroid device for blood pressure measurement according to the European Society of Hypertension International Protocol for validation of blood pressure measuring devices in adults (2002)'.

OBJECTIVE: To report a validation of the Riester Big Ben Square Desk Aneroid Sphygmomanometer according to the international protocol developed by the Working Group on Blood Pressure Monitoring of the European Society of Hypertension 2002 (ESH-IP 2002) in the interest of transparency. This legacy publication is intended to assure users that the device satisfied the requirements in place at that time. METHODS: Performance of the device was assessed by participants' age, sex, arm circumference and entry SBP/DBP. Validation was performed in 33 participants. The sphygmomanometer was assessed according to the ESH-IP, which defines zones of accuracy compared to the mercury standard as ≤5, ≤10, ≤15 mmHg or more. RESULTS: The mean (± SD) age was 50.5 ±â€…13.0 years, range 29-71 years, entry SBP 142.6 ±â€…23.7 mmHg, entry DBP 89.0 ±â€…17.8 mmHg. The device passed all the requirements listed and the validation protocol. The Riester Big Ben Square Desk aneroid sphygmomanometer slightly underestimated the observer-measured SBP, yet slightly overestimated DBP. The observer-device disagreement was -0.8 ±â€…6.4 mmHg SBP and +0.6 ±â€…4.0 mmHg DBP. CONCLUSION: These data show that the Riester Big Ben Square Desk aneroid sphygmomanometer fulfilled the ESH-IP 2002 requirements for the validation of BP monitors. It was on this basis that the British and Irish Hypertension Society recommended it for clinical use in the adult population.

Screening and management of hypertensive patients with chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. A pilot survey based on questionnaire.

OBJECTIVE: Real-life management of hypertensive patients with chronic kidney disease (CKD) is unclear. METHODS: A survey was conducted in 2023 by the European Society of Hypertension (ESH) to assess management of CKD patients referred to ESH-Hypertension Excellence Centres (ESH-ECs) at first referral visit. The questionnaire contained 64 questions with which ESH-ECs representatives were asked to estimate preexisting CKD management quality. RESULTS: Overall, 88 ESH-ECs from 27 countries participated (fully completed surveys: 66/88 [75.0%]). ESH-ECs reported that 28% (median, interquartile range: 15-50%) had preexisting CKD, with 10% of them (5-30%) previously referred to a nephrologist, while 30% (15-40%) had resistant hypertension. The reported rate of previous recent (<6 months) estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) testing were 80% (50-95%) and 30% (15-50%), respectively. The reported use of renin-angiotensin system blockers was 80% (70-90%). When a nephrologist was part of the ESH-EC teams the reported rates SGLT2 inhibitors (27.5% [20-40%] vs. 15% [10-25], P = 0.003), GLP1-RA (10% [10-20%] vs. 5% [5-10%], P = 0.003) and mineralocorticoid receptor antagonists (20% [10-30%] vs. 15% [10-20%], P = 0.05) use were greater as compared to ESH-ECs without nephrologist participation. The rate of reported resistant hypertension, recent eGFR and UACR results and management of CKD patients prior to referral varied widely across countries. CONCLUSIONS: Our estimation indicates deficits regarding CKD screening, use of nephroprotective drugs and referral to nephrologists before referral to ESH-ECs but results varied widely across countries. This information can be used to build specific programs to improve care in hypertensives with CKD.

The reliability and validity of repeat power ability assessments and measurement indices in loaded vertical jumps.

Background: Repeat power ability (RPA) assessments are a valuable evaluation of an athlete's ability to repeatedly perform high intensity movements. Establishing the most reliable and valid loaded jump RPA assessment and method to quantify RPA has yet to be determined. This study aimed to compare the reliability and validity of an RPA assessment performed with loaded squat jumps (SJ) or countermovement jumps (CMJ) using force-time derived mean and peak power output. Materials and Methods: RPA was quantified using calculations of average power output, a fatigue index and a percent decrement score for all repetitions and with the first and last repetitions removed. Validity was established by comparing to a 30 second Bosco repeated jump test (30BJT). Eleven well-trained male field hockey players performed one set of 20 repetitions of both SJs (20SJ) and CMJs (20CMJ) on separate occasions using a 30% one repetition maximum half squat load. These assessments were repeated 7 days apart to establish inter-test reliability. On a separate occasion, each participant performed the 30BJT. Results: The reliability of average peak power for 20SJ and 20CMJ was acceptable (CV < 5%; ICC > 0.9), while average mean power reliability for 20CMJ (CV < 5%; ICC > 0.9) was better than 20SJ (CV > 5%; ICC > 0.8). Percent decrement of 20CMJ peak power, with the first and final jump removed from the percent decrement calculation (PD%CMJpeak18), was the most reliable measurement of power output decline (CV < 5 %; ICC > 0.8). Average mean and peak power for both RPA protocols had moderate to strong correlations with 30BJT average mean and peak power (r = 0.5-0.8; p< 0.05-0.01). No RPA measurements of power decline were significantly related to BJT measurements of power decline. Conclusions: These findings indicate that PD%CMJpeak18 is the most reliable measure of RPA power decline. The lack of relationship between power decline in the loaded RPA and the 30BJT assessment suggest that each assessment may be measuring a different physical quality. These results provide sport science practitioners with additional methods to assess RPA and provide useful information on the reliability and validity of these outcome measures. Additional research needs to be performed to examine the reliability and validity of the novel RPA assessments in other athletic populations and to determine the sensitivity of these measurements to training and injury.

Ethnic variations in lipid-lowering in response to a statin (EVIREST): a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).

BACKGROUND: Statins improve lipid profiles and reduce cardiovascular morbidity and mortality but there are few data on their relative effects in different ethnic groups. METHODS: We used data from the randomised, placebo-controlled Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA) to conduct a prespecified comparison of the lipid-lowering efficacy of statin therapy among hypertensive participants from different ethnic groups in the UK and Ireland. The effects of atorvastatin (10 mg daily) and placebo on fasting plasma lipid profiles were compared in matched groups of Whites and Blacks (of African-Caribbean or African origin) and Whites and South Asians (from the Indian subcontinent), adjusting for placebo effect. RESULTS: In the active treatment group, 156 Blacks and 72 South Asians were compared with 419 and 198 Whites, respectively. In multivariable analyses adjusted for baseline lipid levels and other potential confounders, atorvastatin reduced total cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides from baseline in all ethnic groups. There were no clinically or statistically significant differences in the effect between Whites and Blacks or between Whites and South Asians after adjusting for placebo effect; similar proportions in each group achieved lipid targets. There was no significant effect of atorvastatin on high-density lipoprotein (HDL)-cholesterol in any group. CONCLUSIONS: A standard dose of atorvastatin improved lipid profiles to a similar extent in Whites, Blacks and South Asians. Given the proven benefits of statins, these results suggest that, when used in standard doses, they are likely to be similarly effective for cardiovascular disease prevention in all ethnic groups.

Maximal and submaximal isometric torque is elevated immediately following highly controlled active stretches of the hamstrings.

Hamstring strain rehabilitation programs with an eccentric bias are effective but have a low adherence rate. Post-stretch isometric (PS-ISO) contractions which incorporate a highly controlled eccentric contraction followed by an isometric contraction resulting in elevated torque during following stretch, compared with isometric contractions at the same joint angle. This study measured torque, activation and musculotendinous unit behaviour of the hamstrings during PS-ISO contractions of maximal and submaximal levels using two stretch amplitudes. Ten male participants (24.6 years ± 2.22 years) completed maximal and submaximal baseline isometric contractions at 90°, 120° and 150° knee flexion and PS-ISO contractions of maximal and submaximal intensity initiated at 90° and 120° incorporating active stretch of 30° and 60° at 60°·s-1. Torque and muscle activation of the knee flexors were simultaneously recorded. Musculotendinous unit behaviour of the biceps femoris long head was recorded via ultrasound during all PS-ISO contractions. Compared with baseline, torque was 8% and 39% greater in the maximal and submaximal PS-ISO conditions respectively with no change in muscle activation. The biceps femoris long head muscle lengthened during all PS-ISO contractions. PS-ISO contractions may be beneficial where the effects of highly controlled eccentric contractions and elevated isometric torque are desired, such as hamstring rehabilitation.

Residual Force Enhancement Is Present in Consecutive Post-Stretch Isometric Contractions of the Hamstrings during a Training Simulation.

Residual force enhancement (rFE) is observed when isometric force following an active stretch is elevated compared to an isometric contraction at corresponding muscle lengths. Acute rFE has been confirmed in vivo in upper and lower limb muscles. However, it is uncertain whether rFE persists using multiple, consecutive contractions as per a training simulation. Using the knee flexors, 10 recreationally active participants (seven males, three females; age 31.00 years ± 8.43 years) performed baseline isometric contractions at 150° knee flexion (180° representing terminal knee extension) of 50% maximal voluntary activation of semitendinosus. Participants performed post-stretch isometric (PS-ISO) contractions (three sets of 10 repetitions) starting at 90° knee extension with a joint rotation of 60° at 60°·s-1 at 50% maximal voluntary activation of semitendinosus. Baseline isometric torque and muscle activation were compared to PS-ISO torque and muscle activation across all 30 repetitions. Significant rFE was noted in all repetitions (37.8-77.74%), with no difference in torque between repetitions or sets. There was no difference in activation of semitendinosus or biceps femoris long-head between baseline and PS-ISO contractions in all repetitions (ST; baseline ISO = 0.095-1.000 ± 0.036-0.039 Mv, PS-ISO = 0.094-0.098 ± 0.033-0.038 and BFlh; baseline ISO = 0.068-0.075 ± 0.031-0.038 Mv). This is the first investigation to observe rFE during multiple, consecutive submaximal PS-ISO contractions. PS-ISO contractions have the potential to be used as a training stimulus.

Urinary drug metabolite testing in chronic heart failure patients indicates high levels of adherence with life-prolonging therapies.

AIMS: Despite medical therapy for heart failure (HF) having proven benefits of improving quality of life and survival, many patients remain under-treated. This may be due to a combination of under-prescription by medical professionals and poor adherence from patients. In HF, as with many other chronic diseases, adherence to medication can deteriorate over time particularly when symptoms are well controlled. Therefore, detecting and addressing non-adherence has a crucial role in the management of HF. Significant flaws and inaccuracies exist in the methods currently used to assess adherence such as patient reporting, pill counts, and pharmacy fill records. We aim to use high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) to detect metabolites of HF medications in the urine samples of chronic HF patients. METHODS AND RESULTS: Urine samples were collected from 35 patients in a specialist HF clinic. Patients were included if they had an ejection fraction <45% and were taking at least two disease-modifying HF medications. They were excluded if they had been admitted to hospital for HF in the 3 months preceding clinic attendance. These samples were sent for HPLC-MS and tested for all HF medications prescribed for that patient. A high rate of complete adherence of 89% was detected in these patients, with 94% being partially adherent (at least one HF medication detected) to therapy (at least one HF medication detected). This analysis also highlighted that mineralocorticoid antagonists represent both the most under-prescribed (67%) and poorly adhered (75%) medication class. CONCLUSIONS: This analysis revealed a surprisingly high level of adherence to disease-modifying therapy in chronic HF patients and highlights that most of our 'total' under-treatment is likely to be from a failure to prescribe rather than a failure to adhere. Testing for metabolites of disease-modifying HF drugs in urine using HPLC-MS is feasible and is a useful adjunct to a specialist HF service. At present, the distinction between treatment failure and failure to take treatment is not always clear, which is important because the investigation and potential solutions are different. The former needs initiation of additional therapies and consideration of additional diagnoses, whereas the latter requires strategies to understand reasons underlying poor adherence and collaborative working to improve this: the wrong strategy will be ineffective.

Effect of doxazosin gastrointestinal therapeutic system as third-line antihypertensive therapy on blood pressure and lipids in the Anglo-Scandinavian Cardiac Outcomes Trial.

BACKGROUND: The role of doxazosin in treatment of hypertension remains controversial. METHODS AND RESULTS: We evaluated the effects on blood pressure (BP) and biochemical parameters of doxazosin GITS (gastrointestinal therapeutic system) as a third-line antihypertensive agent among 10,069 participants in the Anglo-Scandinavian Cardiac Outcomes Trial--Blood Pressure Lowering Arm (ASCOT-BPLA) whose BP remained above 140/90 mm Hg (130/80 mm Hg in those with diabetes mellitus). Among those who received doxazosin, mean age was 63 years (SD 9 years), 79% were male, and 32% had diabetes. Doxazosin was initiated a median of 8 months (interquartile range 3 to 24 months) after randomization and was added to a mean of 2.0 (SD 0.3) other antihypertensive drugs; the mean starting and final doses were 4.1 (SD 0.6) and 7.0 (SD 3.1) mg, respectively. During a median of 12 months (interquartile range 4 to 31 months) of uninterrupted doxazosin treatment, during which other antihypertensive treatments remained unchanged, mean BP fell 11.7/6.9 mm Hg (SD 18.8/9.6 mm Hg, P<0.0001) from 158.7/89.2 mm Hg (SD 18.3/10.6 mm Hg). After the addition of doxazosin, 29.7% of participants achieved target BP. There was no apparent excess of heart failure among doxazosin users. There were associated modest favorable effects on plasma lipid profiles, but a small rise in fasting plasma glucose was observed. Doxazosin was generally well tolerated, with 7.5% of participants discontinuing the drug because of adverse events, most frequently dizziness, fatigue, headache, and edema. CONCLUSIONS: alpha-Blockers are no longer recommended as add-on therapy in some hypertension guidelines. However, although they are nonrandomized and were not placebo-controlled, the present findings suggest that doxazosin is a safe and effective third-line antihypertensive agent.