Biomedical subjects

Chris Jensen

Publications and source records attributed to Chris Jensen.

11 recordsLinked to original sources

PubMed2006

Aliskiren reduces blood pressure and suppresses plasma renin activity in combination with a thiazide diuretic, an angiotensin-converting enzyme inhibitor, or an angiotensin receptor blocker.

Thiazide diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers all cause reactive rises in plasma renin activity. We hypothesized that renin inhibition with aliskiren would prevent this reactive rise and also enhance blood pressure lowering. In 3 open-label studies in which blood pressure was assessed with ambulatory measurement, aliskiren was administered to patients with mild-to-moderate hypertension in combination with hydrochlorothiazide (n=23), ramipril (n=21), or irbesartan (n=23). In the diuretic combination study, the addition of 25 mg of hydrochlorothiazide to 150 mg of aliskiren daily for 3 weeks significantly lowered daytime pressure, compared with aliskiren monotherapy (systolic/diastolic mean change from baseline [SEM]: daytime: -18.4 [2.1]/ -10.6 [1.7] versus -10.4 [1.8]/-5.8 [1.4]; nighttime: -15.6 [2.7]/-8.1 [1.8] versus -8.8 [2.9]/-5.0 [2.2]). In the angiotensin-converting enzyme inhibitor combination study, the addition of 75 or 150 mg of aliskiren to 5 mg of ramipril alone for 3 weeks further lowered both daytime and nighttime pressures compared with ramipril monotherapy (daytime: -10.5 [2.9]/-8.1 [2.1] and -14 [3.7]/-8.7 [2.3] versus -6.1 [2.4]/-5.9 [1.5]; nighttime: -8.1 [2.6]/-5.3 [2.4] and -9.6 [3.4]/-5.3 [2.4] versus -2 [2.3]/-0.7 [2.2]). In the angiotensin receptor blocker combination study, the addition of 75 or 150 mg of aliskiren to 150 mg of irbesartan alone, for 3 weeks, resulted in significantly lower nighttime pressures compared with irbesartan monotherapy (daytime: -14.8 [2]/-8.2 [1.3] and -13.3 [1.6]/-6.8 [0.9] versus -11.4 [1.6]/-6.5 [1.1]; nighttime: -16.1 [2.4]/-8.6 [1.7] and -13.2 [2.7]/-7.2 [1.9] versus -9.0 [2.5]/-4.7 [1.9]). Aliskiren (150 mg) alone significantly inhibited plasma renin activity by 65% (P<0.0001). Ramipril and irbesartan monotherapy caused 90% and 175% increases in plasma renin activity, respectively. By contrast, when aliskiren was coadministered with hydrochlorothiazide, ramipril, or irbesartan, plasma renin activity did not increase but remained similar to baseline levels or was decreased (combination therapy versus untreated; median [interquartile range]; aliskiren and hydrochlorothiazide: 0.4 [0.2 to 1.1] versus 0.7 [0.5 to 1.3]; ramipril and aliskiren: 0.5 [0.3 to 0.9] versus 0.6 [0.5 to 0.8]; irbesartan and aliskiren: 0.4 [0.2 to 0.9] versus 0.6 [0.4 to 0.9]). These results suggest that renin inhibition with aliskiren in these combinations increases renin-angiotensin system suppression, improves 24-hour blood pressure control, and may ultimately provide better end-organ protection in patients with hypertension.

Adult↗

PubMed2006

Psychosocial work environment of hospital workers: validation of a comprehensive assessment scale.

BACKGROUND: Studies have shown that adverse workplace factors can increase the risk of ill-health in hospital workers, but more comprehensive measures of the psychosocial work environment are needed. OBJECTIVES: To test a comprehensive and theory-based psychosocial work environment questionnaire and analyze associations with mental health in a sample of Danish hospital workers. DESIGN AND PARTICIPANTS: Questionnaire-based cross-sectional study with 343 female employees from a large Danish hospital, including patient care workers (nurses, nurse assistants, midwives) and laboratory technicians. METHODS: The psychosocial work environment was measured with 14 scales from the Copenhagen psychosocial questionnaire, version I, covering three main areas: demands at work, work organization and interpersonal relations at work. We further measured self-rated mental health and sociodemographic and employment characteristics of the participants. Cronbach's alphas, analyses of covariance, one-sample t-tests, partial correlations and linear regression models were used to analyze data. RESULTS: Of the 14 work psychosocial workplace scales 12 showed a satisfactory internal consistency (alpha>0.70). Patient care workers had more quantitative, emotional and cognitive demands (all p-values <0.001), higher work pace (p<0.001) and more role conflicts (p=0.01) than laboratory technicians, but also better work organization, including more influence at work, better possibilities for development and a higher meaning of work (all p-values <0.001). Both patient care workers and laboratory technicians had substantially higher scores on the demand scales and lower scores on the influence at work scale than the general Danish working population. Further analyses showed that high levels of demands at work and low levels of work organization and problematic interpersonal relations at work were associated with lower self-rated mental health. CONCLUSION: The Copenhagen psychosocial questionnaire is a suitable instrument to measure the psychosocial work environment of hospital workers. The comprehensive assessment of the psychosocial work environment helps tailoring interventions to the specific needs of different occupational groups.

Adult↗

PubMed2005

Clinical impact and frequency of anatomic pathology errors in cancer diagnoses.

BACKGROUND: To the authors' knowledge, the frequency and clinical impact of errors in the anatomic pathology diagnosis of cancer have been poorly characterized to date. METHODS: The authors examined errors in patients who underwent anatomic pathology tests to determine the presence or absence of cancer or precancerous lesions in four hospitals. They analyzed 1 year of retrospective errors detected through a standardized cytologic-histologic correlation process (in which patient same-site cytologic and histologic specimens were compared). Medical record reviews were performed to determine patient outcomes. The authors also measured the institutional frequency, cause (i.e., pathologist interpretation or sampling), and clinical impact of diagnostic cancer errors. RESULTS: The frequency of errors in cancer diagnosis was found to be dependent on the institution (P < 0.001) and ranged from 1.79-9.42% and from 4.87-11.8% of all correlated gynecologic and nongynecologic cases, respectively. A statistically significant association was found between institution and error cause (P < 0.001); the cause of errors resulting from pathologic misinterpretation ranged from 5.0-50.7% (the remainder were due to clinical sampling). A statistically significant association was found between institution and assignment of the clinical impact of error (P < 0.001); the aggregated data demonstrated that for gynecologic and nongynecologic errors, 45% and 39%, respectively, were associated with harm. The pairwise kappa statistic for interobserver agreement on cause of error ranged from 0.118-0.737. CONCLUSIONS: Errors in cancer diagnosis are reported to occur in up to 11.8% of all reviewed cytologic-histologic specimen pairs. To the authors' knowledge, little agreement exists regarding whether pathology errors are secondary to misinterpretation or poor clinical sampling of tissues and whether pathology errors result in serious harm.

Diagnostic Errors↗

PubMed2005

Anatomic pathology databases and patient safety.

CONTEXT: The utility of anatomic pathology discrepancies has not been rigorously studied. OBJECTIVE: To outline how databases may be used to study anatomic pathology patient safety. DESIGN: The Agency for Healthcare Research and Quality funded the creation of a national anatomic pathology errors database to establish benchmarks for error frequency. The database is used to track more frequent errors and errors that result in more serious harm, in order to design quality improvement interventions intended to reduce these types of errors. In the first year of funding, 4 institutions (University of Pittsburgh, Henry Ford Hospital, University of Iowa, and Western Pennsylvania Hospital) reported cytologic-histologic correlation error data after standardizing correlation methods. Root cause analysis was performed to determine sources of error, and error reduction plans were implemented. PARTICIPANTS: Four institutions self-reported anatomic pathology error data. MAIN OUTCOME MEASURES: Frequency of cytologic-histologic correlation error, case type, cause of error (sampling or interpretation), and effect of error on patient outcome (ie, no harm, near miss, and harm). RESULTS: The institutional gynecologic cytologic-histologic correlation error frequency ranged from 0.17% to 0.63%, using the denominator of all Papanicolaou tests. Based on the nongynecologic cytologic-histologic correlation data, the specimen sites with the highest discrepancy frequency (by project site) were lung (ranging from 16.5% to 62.3% of all errors) and urinary bladder (ranging from 4.4% to 25.0%). Most errors detected by the gynecologic cytologic-histologic correlation process were no-harm events (ranging from 10.7% to 43.2% by project site). Root cause analysis identified sources of error on both the clinical and pathology sides of the process, and error intervention programs are currently being implemented to improve patient safety. CONCLUSIONS: A multi-institutional anatomic pathology error database may be used to benchmark practices and target specific high-frequency errors or errors with high clinical impact. These error reduction programs have national import.

Benchmarking↗

PubMed2004

Computer users' risk factors for developing shoulder, elbow and back symptoms.

OBJECTIVES: This prospective study concentrated on determining factors of computer work that predict musculoskeletal symptoms in the shoulder, elbow, and low-back regions. METHODS: A questionnaire on ergonomics, work pauses, work techniques, and psychosocial and work factors was delivered to 5033 office workers at baseline in early 1999 (response rate 69%) and to 3361 respondents at the time of the follow-up in late 2000 (response rate 77%). An increased frequency or intensity of symptoms was the outcome variable, including only nonsymptomatic respondents from the baseline questionnaire (symptom frequency below 8 days within the last 12 months or intensity score below 4 within the last 3 months). RESULTS: In the follow-up, 10%, 18%, and 23% had symptoms more often in the elbow, shoulder, and low back, respectively, and 14%, 20%, and 22% had more intense symptoms. Women were more likely to be afflicted than men in all regions. In the full-fit multivariate logistic regression analysis, little influence on the timing of a rest pause and being disturbed by glare or reflection were significant predictors of shoulder symptoms, screen below eye height was a significant predictor for elbow symptoms, and previous symptoms was a significant predictor for symptoms in all regions. Computer worktime and psychosocial dimensions were not significant predictors. CONCLUSIONS: Influence on work pauses, reduction of glare or reflection, and screen height are important factors in the design of future computer workstations. Since previous symptoms was a significant predictor of recurrent symptoms in all three regions under study, it can be concluded that musculoskeletal symptoms are persistent.

Adult↗

PubMed2003

Blood pressure lowering in essential hypertension with an oral renin inhibitor, aliskiren.

Inhibition of the first and rate-limiting step of the renin-angiotensin system has long been an elusive therapeutic goal. Aliskiren, the first known representative of a new class of completely nonpeptide, orally active, renin inhibitors, has been shown to inhibit the production of angiotensin I and II in healthy volunteers and to reduce blood pressure (BP) in sodium-depleted marmosets. The aim of this randomized, double-blind, active comparator trial study was to assess the BP-lowering efficacy and safety of aliskiren. Two hundred twenty-six patients, 21 to 70 years of age, with mild to moderate hypertension, were randomly assigned to receive 37.5 mg, 75 mg, 150 mg, or 300 mg aliskiren or 100 mg losartan daily for 4 weeks. Dose-dependent reductions in daytime ambulatory systolic pressure (mean change, mm Hg [SD of change]; -0.4 [11.7], -5.3 [11.3], -8.0 [11.0], and -11.0 [11.0], P=0.0002) and in plasma renin activity (median change % [interquartile range]; -55 [-64, -11], -60 [-82, -46], -77 [-86, -72], and -83 [-92, -71], P=0.0008) were observed with 37.5, 75, 150, and 300 mg aliskiren. The change in daytime systolic pressure with 100 mg losartan (-10.9 [13.8]) was not significantly different from the changes seen with 75, 150, and 300 mg aliskiren. Aliskiren was well tolerated at all doses studied. This study demonstrates that aliskiren, through inhibition of renin, is an effective and safe orally active BP-lowering agent. Whether renin inhibition results in protection from heart attack, stroke, and nephropathy, similar to angiotensin-converting enzyme inhibition and angiotensin receptor blockade, needs to be researched.

Administration, Oral↗

PubMed2003

Structure-based design of aliskiren, a novel orally effective renin inhibitor.

Hypertension is a major risk factor for cardiovascular diseases such as stroke, myocardial infarction, and heart failure, the leading causes of death in the Western world. Inhibitors of the renin-angiotensin system (RAS) have proven to be successful treatments for hypertension. As renin specifically catalyses the rate-limiting step of the RAS, it represents the optimal target for RAS inhibition. Several peptide-like renin inhibitors have been synthesized previously, but poor pharmacokinetic properties meant that these compounds were not clinically useful. We employed a combination of molecular modelling and crystallographic structure analysis to design renin inhibitors lacking the extended peptide-like backbone of earlier inhibitors, for improved pharmacokinetic properties. This led to the discovery of aliskiren, a highly potent and selective inhibitor of human renin in vitro, and in vivo; once-daily oral doses of aliskiren inhibit renin and lower blood pressure in sodium-depleted marmosets and hypertensive human patients. Aliskiren represents the first in a novel class of renin inhibitors with the potential for treatment of hypertension and related cardiovascular diseases.

Administration, Oral↗

PubMed2003

Muscle activity during computer-based office work in relation to self-reported job demands and gender.

The aim was to investigate whether quantitative job demands influence muscle activity among women, and whether there are gender differences in duration of computer, mouse, and keyboard use and muscle activity of shoulder and forearm muscles during work. The study was carried out in an occupational setting, and 24 women and 11 men from a municipal administration participated. The duration of computer, mouse, and keyboard use was measured by a commercial software package. Quantitative job demands were registered by questionnaire. Electromyography (EMG) was measured bilaterally from the upper trapezius and the extensor digitorum communis muscles. No association was found between self-reported quantitative job demands and muscle activity among the women ( n=24). The women used the keyboard more frequently ( p=0.020) and tended to perform fewer mouse clicks compared to men ( p=0.057), but no difference was seen in EMG activity between men ( n=11) and women ( n=11) from the same department. However, office assistants (six women) showed significantly higher static EMG activity levels ( p=0.042) and almost significantly shorter EMG gap times ( p=0.060) than the rest of the subjects (5 women and 11 men). This indicated that shorter muscular resting periods among female office assistants as compared to the other subjects were due to differences in job content rather than gender differences.

Activities of Daily Living↗

PubMed2003

Development of neck and hand-wrist symptoms in relation to duration of computer use at work.

OBJECTIVES: This study attempted to identify risk factors for musculoskeletal symptoms in the neck and hand-wrist regions among employees using computers at work. METHODS: Computer users (N=5033) first received a questionnaire in the beginning of 1999 (69% response rate, N=3475), and a follow-up questionnaire was mailed in December of 2000 to the 3361 respondents to the baseline survey (77% response rate, N=2576). Health outcome was defined as musculoskeletal symptoms for >7 days within the last year of follow-up among the nonsymptomatic respondents at baseline. RESULTS: Men's and women's previous symptoms, women's low influence at work and high-placed computer screen, and men's short time in the same job and good computer skills were associated with neck symptoms. Hand-wrist symptoms were predicted by previous symptoms and low influence at work for both the men and women and sensorial demands for the women only. The duration of computer use predicted hand-wrist symptoms [eg, odds ratio (OR) of 2.3, 95% confidence interval (95% CI) 1.2-4.3, for almost continual computer use], but not neck symptoms. For those with almost continual computer use, hand-wrist symptoms were associated with mouse use for at least half of the worktime (OR 4.0, 95% CI 1.0-15.5) and not using the mouse at all (OR 4.0, 95% CI 1.1-14.4), as compared with mouse use for one-fourth of the worktime. CONCLUSIONS: Limiting computer use to less than three-fourths of the worktime would help to prevent hand-wrist symptoms. Furthermore, low influence at work predicts both neck and hand-wrist symptoms.

Adolescent↗

PubMed2002

Risk factors for neck-shoulder and wrist-hand symptoms in a 5-year follow-up study of 3,990 employees in Denmark.

OBJECTIVES: A prospective follow-up study of employees in Denmark was analyzed in order to investigate the association between physical and psychosocial exposures and musculoskeletal symptoms in the neck-shoulder and wrist-hand regions. METHODS: Data were derived from a 5-year follow-up questionnaire study of a sample of employees in Denmark, aged between 18 and 59 years. Occupational and individual background factors were assessed in 1990, and the associations with symptoms in 1995 were analyzed using logistic regression. The analysis was restricted to comprise employees free of symptoms in 1990. The neck-shoulder and wrist-hand analyses included 1,895 and 3,179 employees, respectively. RESULTS: Among men, neck-shoulder symptoms were predicted by twisting or bending (odds ratio (OR) 1.5, 95% confidence interval (CI) 1.01-2.26) and social support at work (OR 1.8, CI 1.24-2.50 for low versus rather high social support, OR 1.4, CI 1.00-2.09 for high versus rather high social support). Furthermore, an interacting effect of heavy lifting and sedentary work was indicated. Symptoms in the wrist-hand region were predicted by stress symptoms (OR 1.7, CI 1.12-2.71) and twisting or bending (OR 1.7, CI 1.18-2.57). For women, smoking habits predicted neck-shoulder symptoms (OR 1.8, CI 1.14-2.82, former versus never smokers). Symptoms in the wrist-hand region were predicted by stress symptoms (OR 1.7, CI 1.16-2.41) and twisting or bending (OR 1.9, CI 1.34-2.80). CONCLUSION: The results confirm that physical exposures at work influence the development of musculoskeletal symptoms in the neck-shoulder and wrist-hand regions. However, the results also suggest that a psychosocial exposure (social support) and perceived stress symptoms influence musculoskeletal symptoms.

Adolescent↗

PubMed2002

Angiotensin II suppression in humans by the orally active renin inhibitor Aliskiren (SPP100): comparison with enalapril.

Renin is the main determinant of angiotensin (Ang) II levels. It, therefore, always appeared desirable to reduce Ang II levels by direct inhibition of renin. So far, specific renin inhibitors lacked potency and/or oral availability. We tested the new orally active nonpeptidic renin inhibitor SPP100 (Aliskiren, an octanamide with a 50% inhibitory concentration [IC50] in the low nanomolar range) in 18 healthy volunteers on a constant 100 mmol/d sodium diet using a double-blind, 3-way crossover protocol. In 3 periods of 8 days, separated by wash-outs of 6 days, each volunteer received 2 dosage levels of Aliskiren (low before high; 40 and 80 or 160 and 640 mg/d) and randomized placebo or 20 mg enalapril. Aliskiren was well tolerated. Not surprisingly, blood pressure and heart rate remained unchanged in these normotensive subjects. There was a dose-dependent decrease in plasma renin activity, Ang I, and Ang II following single doses of Aliskiren starting with 40 mg. Inhibition was still marked and significant after repeated dosing with maximal decreases in Ang II levels by 89% and 75% on Days 1 and 8, respectively, when the highest dose of Aliskiren was compared with placebo. At the same time, mean plasma active renin was increased 16- and 34-fold at the highest dose of Aliskiren. Plasma drug levels of Aliskiren were dose-dependent with maximal concentrations reached between 3 to 6 hours after administration; steady state was reached between 5 and 8 days after multiple dosing. Less than 1% of dose was excreted in the urine. Plasma and urinary aldosterone levels were decreased after doses of Aliskiren > or =80 mg and after enalapril. Aliskiren at 160 and 640 mg enhanced natriuresis on Day 1 by +45% and +62%, respectively, compared with placebo (100%, ie, 87+/-11 mmol/24h) and enalapril (+54%); kaliuresis remained unchanged. In conclusion, the renin inhibitor Aliskiren dose-dependently decreases Ang II levels in humans following oral administration. The effect is long-lasting and, at a dose of 160 mg, is equivalent to that of 20 mg enalapril. Aliskiren has the potential to become the first orally active renin inhibitor that provides a true alternative to ACE-inhibitors and Ang II receptor antagonists in therapy for hypertension and other cardiovascular and renal diseases.

Administration, Oral↗