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Background The management of cervical cancer patients with intraoperative detection of lymph node involvement remains controversial. Since all these patients are referred for (chemo)radiation after the surgery, the key decision is whether radical hysterectomy should be completed as originally planned, taking into account an additional morbidity associated with extensive surgical dissection prior to adjuvant treatment. The ABRAX study investigated whether completing a radical uterine procedure is associated with an improved oncological outcome of such patients. Patients and methods We performed retrospective analyses of 515 cervical cancer patients (51 institutions, 19 countries) who were referred for primary curative surgery between 2005 and 2015 (stage IA–IIB, common tumour types) in whom lymph node involvement was detected intraoperatively. Patients were stratified according to whether the planned uterine surgery was completed (COMPL group, N = 361) or abandoned (ABAND group, N = 154) to compare progression-free survival. Definitive chemoradiation was given to 92.9% patients in the ABAND group and adjuvant (chemo)radiation or chemotherapy to 91.4% of patients in the COMPL group. Results The risks of recurrence (hazard ratio [HR] 1.154, 95% confidence intervals [CI] 0.799–1.666, P = 0.45), pelvic recurrence (HR 0.836, 95% CI 0.458–1.523, P = 0.56), or death (HR 1.064, 95% CI 0.690–1.641, P = 0.78) were not significantly different between the two groups. No subgroup showed a survival benefit from completing radical hysterectomy. Disease-free survival reached 74% (381/515), with a median follow-up of 58 months. Prognostic factors were balanced between the two groups. FIGO stage and number of pelvic lymph nodes involved were significant prognostic factors in the whole study cohort. Conclusion We showed that the completion of radical hysterectomy does not improve survival in patients with intraoperatively detected lymph node involvement, regardless of tumour size or histological type. If lymph node involvement is confirmed intraoperatively, abandoning uterine radical procedure should be considered, and the patient should be referred for definitive chemoradiation. Clinical trials identifier NCT04037124 .

Standard exercise interventions targeting underlying physiologic system impairments have limited success in improving walking. Augmenting standard interventions with timing and coordination training, which incorporates the principles of motor learning and integrates multiple systems, may be more successful.To determine whether a standard strength and endurance program incorporating timing and coordination training (standard-plus) improves gait speed more than strength and endurance training alone.The Program to Improve Mobility in Aging (PRIMA) study was an assessor-blinded, randomized, 2-group intervention trial that included a 12-week intervention and 24-week follow-up period. The trial was conducted at a university research clinic from 2016 to 2020. Participants included 249 community-dwelling older adults (aged ≥65 years) with gait speed between 0.60 and 1.20 m/s. Statistical analysis was performed from December 2020 to March 2021.Participants were randomized to standard strength and endurance (n = 125) or standard-plus, including timing and coordination training (n = 124), 50 to 60 minutes, twice a week for 12 weeks.Primary outcome of gait speed and secondary outcomes representing components of the intervention (leg strength and power, 6-minute walk test, chair sit-and-reach test, and figure of 8 walk test) and activity and participation (Late Life Function and Disability Instrument and daily physical activity measured by accelerometry) were measured at 12, 24, and 36 weeks.Among 249 randomized participants, 163 (65.5%) were female, 22 (8.8%) were Black, 219 (88.0%) were White; mean (SD) age was 77.4 (6.6) years; mean (SD) gait speed was 1.07 (0.16) m/s; and 244 (98.0%) completed the intervention. The 2 groups did not have significantly different improvements in gait speed or secondary outcomes representing the components of the intervention at any time point. For gait speed, individuals in the standard-plus group had a mean (SD) improvement of 0.079 (0.135) m/s over 12 weeks, 0.065 m/s (0.141) over 24 weeks, and 0.059 (0.150) m/s over 36 weeks; individuals in the standard group improved gait speed by 0.081 (0.124) m/s over 12 weeks, 0.051 (0.129) m/s over 24 weeks, and 0.065 (0.148) m/s over 36 weeks.This randomized clinical trial found no difference in gait speed change between the standard and standard-plus intervention groups, and both groups showed sustained improvements in mobility 24 weeks after the intervention.ClinicalTrials.gov Identifier: NCT02663778.

Background Knee osteoarthritis (OA) is prevalent and often associated with meniscal tear. Physical therapy (PT) and exercise regimens are often used to treat OA or meniscal tear, but, to date, few programs have been designed specifically for conservative treatment of meniscal tear with concomitant knee OA. Clinical care and research would be enhanced by a standardized, evidence–based, conservative treatment program and the ability to study the effects of the contextual factors associated with interventions for patients with painful, degenerative meniscal tears in the setting of OA. This paper describes the process of developing both a PT intervention and a home exercise program for a randomized controlled clinical trial that will compare the effectiveness of these interventions for patients with knee pain, meniscal tear and concomitant OA. Methods This paper describes the process utilized by an interdisciplinary team of physical therapists, physicians, and researchers to develop and refine a standardized in-clinic PT intervention, and a standardized home exercise program to be carried out without PT supervision. The process was guided in part by Medical Research Council guidance on intervention development. Results The investigators achieved agreement on an in-clinic PT intervention that included manual therapy, stretching, strengthening, and neuromuscular functional training addressing major impairments in range of motion, musculotendinous length, muscle strength and neuromotor control in the major muscle groups associated with improving knee function. The investigators additionally achieved agreement on a progressive, protocol-based home exercise program (HEP) that addressed the same major muscle groups. The HEP was designed to allow patients to perform and progress the exercises without PT supervision, utilizing minimal equipment and a variety of methods for instruction. Discussion This multi-faceted in-clinic PT program and standardized HEP provide templates for in-clinic and home-based care for patients with symptomatic degenerative meniscal tear and concomitant OA. These interventions will be tested as part of the Treatment of Meniscal Tear in Osteoarthritis (TeMPO) Trial. Trial registration The TeMPO Trial was first registered at clinicaltrials.gov with registration No. NCT03059004 on February 14, 2017. TeMPO was also approved by the Institutional Review Board at Partners HealthCare/Brigham and Women’s Hospital.

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.

Walking difficulty is a common and costly problem in older adults. A potentially important yet unaddressed strategy to enhance walking ability through exercise intervention is to add a timing and coordination component in gait training (i.e. task specific timing and coordination exercise intervention) to the usual strength, endurance, and flexibility training. We describe the methods and rationale of a randomized single-blind, physical therapist supervised, exercise intervention trial to compare the effects of a standard strength, endurance, and flexibility program to a standard plus timing and coordination program in community-dwelling older adults walking slower than the desired gait speed of 1.2 m/s. Exercise sessions are twice weekly for 12 weeks. Participants are assessed at baseline, 12 weeks (post intervention), 24 weeks and 36 weeks. The primary outcome is gait speed, secondary outcomes represent components of the interventions (strength, endurance, flexibility, timing and coordination), and tertiary outcomes are measure of activity and participation (Late Life Function and Disability Instrument and physical activity). The findings of this trial will (1) establish if a standard-plus task specific timing and coordination program is superior to a standard strength and endurance program in improving mobility, activity and participation and (2) determine if the improvements are sustained over time. The information derived from this project will provide valuable insight into the prevention and management of walking difficulty, which is so common in older Americans.

Experimental laboratory study.To characterize the differences in lower extremity gait biomechanics in individuals who have knee osteoarthritis (OA) with and without self-reported knee instability.Individuals with knee OA who experience episodes of knee instability often report gait difficulties that interfere with their daily lives. A better understanding of the alterations in gait biomechanics may help to mitigate symptomatic knee instability in this patient population.Seventeen participants with knee OA and self-reported knee instability and 36 participants with knee OA and no self-reported knee instability underwent instrumented gait analysis on level ground. Knee-specific symptoms and functional limitations were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index.Knee instability was associated with greater odds of reporting moderate to severe gait-related pain (odds ratio = 6.0; 95% confidence interval: 1.2, 28.9) and moderate to severe difficulty when walking on flat surfaces (odds ratio = 10.7; 95% confidence interval: 1.7, 69.2). During early stance, the group with self-reported knee instability walked with a greater knee flexion excursion (P = .02) and a smaller lower extremity support moment (P.01), due to reduced contributions from the hip extensors (P.01) and ankle plantar flexors (P = .04). The group with self-reported knee instability also walked with a greater knee extensor contribution to the lower extremity support moment (P = .04) during the initial knee extension phase of gait compared to their counterparts with good knee stability.These findings suggest that self-reported knee instability is associated with significant alterations in hip, knee, and ankle joint function during the stance phase of gait in individuals with knee OA.

Background. Chronic kidney disease (CKD) is a recognized global health problem. While some CKD patients remain stable after initial diagnosis, others can rapidly progress towards end-stage renal disease (ESRD). This makes biomarkers capable of detecting progressive forms of CKD extremely valuable, especially in non-invasive biofluids such as urine. Screening for metabolite markers using non-targeted metabolomic techniques like nuclear magnetic resonance spectroscopy is increasingly applied to CKD research.Methods. A cohort of CKD patients (n = 227) with estimated glomerular filtration rates (eGFRs) ranging from 9.4-130 mL/min/1.73 m(2) was Devaluated and urine metabolite profiles were characterized in relation to declining eGFR. Nested in this cohort, a retrospective subset (n = 57) was investigated for prognostic metabolite markers of CKD progression, independent of baseline eGFR. A transcriptomic analysis of murine models of renal failure was performed to validate selected metabolomic findings.Results. General linear modeling revealed 11 urinary metabolites with significant associations to reduced eGFR. Linear modelling specifically showed that increased urine concentrations of betaine (P < 0.05) and myo-inositol (P < 0.05) are significant prognostic markers of CKD progression.Conclusions. Renal organic osmolytes, betaine and myoinositol play a critical role in protecting renal cells from hyperosmotic stress. Kidney tissue transcriptomics of murine preclinical experimentation identified decreased expression of Slc6a12 and Slc5a11 mRNA in renal tissue consistent with defective tubular transport of these osmolytes. Imbalances in renal osmolyte regulation lead to increased renal cell damage and thus more progressive forms of CKD. Increases in renal osmolytes in urine could provide clinical diagnostic and prognostic information on CKD outcomes.

Key Points Question Can exercise programs delivered at a later stage (>2 months) after total knee replacement improve the functional limitations that persist after surgery? Findings In this randomized clinical trial of 240 individuals at a later stage after knee replacement, all arms (physical therapy, community, and control) improved physical function. There were no differences between arms in the primary outcome of patient-reported physical function, whereas the secondary outcome of performance-based physical function demonstrated greater improvement in the physical therapy arm. Meaning While the primary outcome suggests no benefit of later-stage exercise programs, the secondary outcomes suggest beneficial effects of physical therapy but require confirmation., This randomized clinical trial compares the effectiveness of later-stage exercise programs of clinic-based physical therapy exercise or community-based group exercise vs usual care after total knee replacement and explores heterogeneity of treatment effects., Importance Several functional limitations persist after total knee replacement (TKR). Intensive exercise programs could resolve these limitations but are not well tolerated by many patients until a later stage (>2 months) after surgery. Evidence for exercise at a later stage after TKR is limited. Objectives To compare the effectiveness of later-stage exercise programs after TKR and to explore heterogeneity of treatment effects. Design, Setting, and Participants Three-arm single-blind randomized clinical trial (January 7, 2015, to November 9, 2017) using an intent-to-treat approach with follow-ups at 3 months and 6 months. The setting was Allegheny County, Pennsylvania (an outpatient physical therapy clinic and 4 community centers). Participants had primary TKR performed more than 2 months previously, were 60 years or older, experienced moderate functional limitations, and were medically cleared to exercise. Interventions Clinic-based physical therapy exercise (physical therapy arm), community-based group exercise (community arm), and usual care (control arm). The control arm continued their usual care, whereas the exercise arms participated in supervised exercise programs lasting 12 weeks. Main Outcomes and Measures The primary outcome was arm differences in the Western Ontario and McMaster Universities Osteoarthritis Index–Physical Function (WOMAC-PF) at 3 months. The secondary outcomes included performance-based tests germane to knee replacement and additional surveys of physical function. Data were analyzed by linear mixed models and responder analysis. Results A total of 240 participants (mean [SD] age, 70 [7] years; 61.7% female) were allocated to physical therapy (n = 96), community exercise (n = 96), or control (n = 48). All 3 arms demonstrated clinically important improvement. At 3 months, between-arm analyses for the WOMAC-PF demonstrated no differences between physical therapy and community (−2.2; 98.3% CI, −4.5 to 0.1), physical therapy and control (−2.1; 98.3% CI, −4.9 to 0.7), and community and control (0.1; 98.3% CI, −2.7 to 2.9). Performance-based tests demonstrated greater improvement in the physical therapy arm compared with both the community (0.1 z score units; 98.3% CI, 0.0-0.2) and control (0.3 z score units; 98.3% CI, 0.1-0.4) arms and the community arm compared with the control arm (0.2 z score units; 98.3% CI, 0.0-0.3). The physical therapy arm had more than 17.7% responders than the community arm and more than 19.0% responders than the control arm. There was no difference in responder rates between the community and control arms. Conclusions and Relevance Based on the primary outcome, participation in late-stage exercise programs after TKR offered no benefit over usual care. The benefits of physical therapy identified by the secondary outcomes and responder analysis require confirmation. Trial Registration ClinicalTrials.gov Identifier: NCT02237911

Background The PCSK 9 antibody alirocumab (75 mg every 2 weeks; Q2W) as monotherapy reduced low‐density lipoprotein‐cholesterol ( LDL ‐C) levels by 47%. Because the option of a monthly dosing regimen is convenient, ODYSSEY CHOICE II evaluated alirocumab 150 mg Q4W in patients with inadequately controlled hypercholesterolemia and not on statin (majority with statin‐associated muscle symptoms), receiving treatment with fenofibrate, ezetimibe, or diet alone. Methods and Results Patients were randomly assigned to placebo, alirocumab 150 mg Q4W or 75 mg Q2W (calibrator arm), with dose adjustment to 150 mg Q2W at week (W) 12 if W8 predefined LDL ‐C target levels were not met. The primary efficacy endpoint was LDL ‐C percentage change from baseline to W24. Mean baseline LDL ‐C levels were 163.9 mg/dL (alirocumab 150 mg Q4W, n=59), 154.5 mg/dL (alirocumab 75 mg Q2W, n=116), and 158.5 mg/dL (placebo, n=58). In the alirocumab 150 mg Q4W and 75 mg Q2W groups (49.1% and 36.0% of patients received dose adjustment, respectively), least‐squares mean LDL ‐C changes from baseline to W24 were −51.7% and −53.5%, respectively (placebo [+4.7%]; both groups P LDL ‐C targets at W24. Treatment‐emergent adverse events occurred in 77.6% (alirocumab 150 mg Q4W), 73.0% (alirocumab 75 mg Q2W), and 63.8% (placebo) of patients, with injection‐site reactions among the most common treatment‐emergent adverse events. Conclusions Alirocumab 150 mg Q4W can be considered in patients not on statin with inadequately controlled hypercholesterolemia as a convenient option for lowering LDL ‐C. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 02023879.

Objective To test the feasibility of a comprehensive behavioral intervention (CBI) program that combines intense exercises with an education program, to be implemented at a later stage (3 months) following total knee replacement (TKR), and to get a first impression of the effects of the CBI as compared to a standard of care exercise (SCE) program on the outcomes of physical function and physical activity. Methods A total of 44 subjects participated in a 3-month program of either CBI or SCE, followed by 3 months of a home exercise program. Outcomes of physical function and physical activity were measured at baseline and at 6-month followup. Analysis of variance was used to compare statistical differences between groups, whereas responder analyses were used for clinically important differences. Results The CBI was found to be safe and well tolerated. As compared to the SCE group, the CBI group had less pain (P = 0.035) and better physical function based on the Short Form 36 health survey (P = 0.017) and the single-leg stance test (P = 0.037). The other outcome measures did not demonstrate statistically significant differences between the 2 groups. Results from the responder analysis demonstrated that the CBI group had a 36% higher rate of responders in physical function as compared to the SCE group. Also, the CBI group had 23% more responders in the combined domains of physical function and physical activity. Conclusion The CBI program is feasible and improves physical function and physical activity in patients several months after TKR. Larger pragmatic randomized trials are needed to confirm the results of this study.

Joint instability has been suggested as a risk factor for knee osteoarthritis and a cause of significant functional decline in those with symptomatic disease. However, the relationship between altered knee joint mechanics and self-reports of instability in individuals with knee osteoarthritis remains unclear.Fourteen subjects with knee osteoarthritis and complaints of joint instability and 12 control volunteers with no history of knee disease were recruited for this study. Dynamic stereo X-ray technology was used to assess the three-dimensional kinematics of the knee joint during the loading response phase of gait.Individuals with concurrent knee osteoarthritis and joint instability demonstrated significantly reduced flexion and internal/external rotation knee motion excursions during the loading response phase of gait (P0.01), while the total abduction/adduction range of motion was increased (P0.05). In addition, the coronal and transverse plane alignment of the knee joint at initial contact was significantly different (P0.05) for individuals with concurrent knee osteoarthritis and joint instability. However, the anteroposterior and mediolateral tibiofemoral joint positions at initial contact and the corresponding total joint translations were similar between groups during the loading phase of gait.The rotational patterns of tibiofemoral joint motion and joint alignments reported for individuals with concurrent knee osteoarthritis and joint instability are consistent with those previously established for individuals with knee osteoarthritis. Furthermore, the findings of similar translatory tibiofemoral motion between groups suggest that self-reports of episodic joint instability in individuals with knee osteoarthritis may not necessarily be associated with adaptive alterations in joint arthrokinematics.

Prospective cohort study.To characterize knee cartilage change in individuals with knee osteoarthritis (KOA) who have completed a therapeutic exercise program.While therapeutic exercise is frequently used successfully to improve pain and function in individuals with KOA, no studies have reported the volume of cartilage change or individual factors that may impact volume of cartilage change in those completing an exercise program for KOA.Thirteen individuals with KOA underwent magnetic resonance imaging to quantify cartilage volume change in the weight-bearing regions of the medial and lateral femoral condyles and the entire surface of the tibial plateaus from baseline to 1-year follow-up. Body structure and function measures were taken for body mass index, knee axis alignment, knee motion, and knee strength. Activity limitations and activity levels were also measured prior to the therapeutic exercise program, using the Western Ontario and McMaster Universities Osteoarthritis Index and the Physical Activity Scale for the Elderly. At 6 months from baseline, follow-up clinical measurements of knee strength and motion were performed. At 1 year from baseline, imaging of the knee cartilage and knee alignment were performed, and participants completed the Western Ontario and McMaster Universities Osteoarthritis Index and Physical Activity Scale for the Elderly.The central region of the medial femoral condyle (cMF) had a median volume of cartilage loss of 3.8%. The other 3 knee tibiofemoral articular surfaces had minimal median cartilage volume change. Individuals were dichotomized into progressors (n = 6) and nonprogressors (n = 7), based on the standard error of measurement of cartilage volume change for the cMF. Progressors were younger, had a larger body mass index, had a higher Kellgren-Lawrence grade in the medial compartment of the knee, and had a greater increase in knee varus alignment from baseline to 1-year follow-up. The progressors also had frontal plane hip and knee kinetics during baseline gait analysis that potentially increased medial knee joint loading.The loss of cMF cartilage volume was highly variable and the median loss of cartilage was within the range previously reported. Seven of the 13 individuals did not have cMF cartilage volume loss greater than the standard error of measurement. Change in cartilage volume of the cMF may be influenced to a greater extent by personal factors than by completion of a therapeutic exercise program. Additional research is needed to decipher the interactions among therapeutic exercise and personal characteristics that impact knee cartilage loss.

Background Impairment-based exercise programs have yielded only small to moderate benefits in reducing pain and improving function in people with knee osteoarthritis (OA). It has previously been proposed that adding agility and perturbation training to exercise programs for people with knee OA may improve treatment effects for pain and function. Objective The purpose of this study was to examine the effectiveness of adding agility and perturbation techniques to standard exercise therapy compared with the standard exercise program alone for people with knee OA. Design This was a single-blinded randomized controlled trial. Setting The study was conducted in the outpatient physical therapy clinic of a large, university-based health center. Participants One hundred eighty-three people with knee OA (122 women, 61 men) participated. Interventions Participants were randomly assigned to either a group that received agility and perturbation training with standard exercise therapy or a group that received only the standard exercise program. Measurements The outcome measures were self-reported knee pain and function, self-reported knee instability, a performance-based measure of function, and global rating of change. Results Although both groups exhibited improvement in self-reported function and in the global rating of change at the 2-, 6-, and 12-month follow-up periods, there were no differences between groups on these outcomes. There was no reduction in knee pain or improvement in performance-based function in either group. Limitations It is possible that more-intense application of the interventions or application of the interventions to participants with knee OA who were at greater risk for falling may have yielded additive effects of the agility and perturbation training approach. Conclusions Both intervention groups exhibited improvement in self-reported function and the global rating of change. Our results, however, did not support an additive effect of agility and perturbation training with standard exercise therapy in our sample of individuals with knee OA. Further study is needed to determine whether there are subgroups of individuals who might achieve an added benefit with this approach.

Background Investigating modifiable factors that contribute to functional limitations in patients with total knee arthroplasty (TKA) may guide changes in rehabilitation protocols and improve functional outcomes. Whereas quadriceps muscle weakness has been demonstrated to contribute to functional limitations in TKA, the role of hip abductor weakness has not received attention. Objective The purpose of this study was to determine whether hip abductor strength (force-generating capacity) contributes to physical function beyond what can be explained by quadriceps muscle strength in patients after a TKA. Design A cross-sectional design was used in the study. Setting The study was conducted in a clinical laboratory at an academic center. Patients Thirty-one people with TKA (74% female; mean age=68 years, SD=8; mean body mass index=31 kg/m2, SD=5) participated in the study. Measurements Strength of quadriceps muscles and hip abductors was measured using an isokinetic dynamometer. Performance-based physical function was assessed with 4 measures: self-selected walking speed, the Figure-of-8 Walk Test, the Stair Ascend/Descend Test, and the 5-Chair Rise Test. Self-reported physical function was assessed with the Western Ontario and McMaster Universities Osteoarthritis Index Physical Function Subscale. Results In hierarchical regression models, after accounting for demographic and anthropometric factors, quadriceps muscle strength was associated with performance on the Stair Ascend/Descend Test. After accounting for demographic, anthropometric, and quadriceps strength, hip abductor strength was associated with performance on the Stair Ascend/Descend Test, the Figure-of-8 Walk Test, and the 5-Chair Rise Test. Limitations The study design precluded ascertainment of causal relationships. Conclusions After TKA, hip abductor strength influenced physical function in participants more than did demographic or anthropometric measures or quadriceps strength. Longitudinal studies with larger samples are warranted. If findings are replicated, they will justify targeting the hip abductors during rehabilitation after TKA.

Summary Background: Co-administration of niacin with statin offers the potential for additional lipid management and cardiovascular risk reduction. However, niacin is underutilised because of the side effects of flushing, mediated primarily by prostaglandin D2 (PGD2). A combination tablet containing extended-release niacin and laropiprant (ERN/LRPT), a PGD2 receptor (DP1) antagonist, offers improved tolerability. This study assessed the efficacy and safety of ERN/LRPT added to statin vs. doubling the dose of statin in patients with primary hypercholesterolaemia or mixed dyslipidaemia who were not at their National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol (LDL-C) goal based on their coronary heart disease risk category (high, moderate or low). Methods: After a 2- to 6-week run-in statin (simvastatin 10 or 20 mg or atorvastatin 10 mg) period, 1216 patients were randomised equally to one of two treatment groups in a double-blind fashion: group 1 received ERN/LRPT (1 g) plus the run-in statin dose and advanced to ERN/LRPT (2 g) after 4 weeks for an additional 8 weeks, with no adjustments to the run-in statin dose; group 2 received simvastatin or atorvastatin at twice their run-in statin dose and remained on this stable dose for 12 weeks. Results: ERN/LRPT added to statin (pooled across statin and statin dose) significantly improved key lipid parameters vs. the doubled statin dose (pooled): the between-treatment group difference in least squares mean per cent change [95% confidence interval (CI)] from baseline to week 12 in LDL-C (primary end-point) was −4.5% (−7.7, −1.3) and in high-density lipoprotein cholesterol (HDL-C) was 15.6% (13.4, 17.9) and in median per cent change for triglyceride (TG) was −15.4% (−19.2, −11.7). Treatment-related adverse experiences (AEs) related to flushing, pruritis, rash, gastrointestinal upset and elevations in liver transaminases and fasting serum glucose occurred more frequently with ERN/LRPT added to statin vs. statin dose doubled. Conclusions: The addition of ERN/LRPT to ongoing statin treatment produced significantly improved lipid-modifying benefits on LDL-C, HDL-C and TG and all other lipid parameters compared with doubling the statin dose in patients with primary hypercholesterolaemia or mixed dyslipidaemia. The types of AEs that occurred at a greater frequency in the ERN/LRPT group were those typically associated with niacin.

Knee osteoarthritis (OA) is a common chronic condition affecting more than 4.3 million older adults in the United States (1). It is a major cause of pain and functional impairment including difficulty with several activities of daily living (1–3). Weakness of the quadriceps muscle is well documented in subjects with knee OA(4–6), is strongly associated with pain, and is an important determinant of disability(4;7). Quadriceps strength is an important factor to target because weakened quadriceps muscles may increase joint stresses from decreased ability to attenuate loads across the joint(8). Additionally, quadriceps weakness may play a role in the etiology and progression of OA(6;8;9). Multiple factors play a role in the etiology of muscle weakness. In addition to pain and disuse atrophy, reduced quadriceps activation (QA) has been suggested to contribute (4;8;10). The presence of reduced QA (failure to fully activate the muscle) is well established in subjects with knee joint effusions (11;12) and traumatic injuries(10;13–17), and also can be present in knee OA even in the absence of pain and effusion (4;5;7;18). The proposed mechanism for the etiology of reduced QA in knee OA is a damaging cycle. Degenerative changes in the joint may damage articular mechanoreceptors which lead to abnormal processing of sensory information and inhibition of muscle activation. This, in turn, predisposes the quadriceps to weaken which increases risk for more joint damage (4;8). Recently, it has been suggested that reduced QA may have an impact on physical function in subjects with knee OA by moderating the relationship of quadriceps strength to function (19). Subjects with low strength and reduced QA had lower function than those with similar strength but high QA (19). While exercise leads to increased quadriceps strength along with improved pain and function (20;21), strength deficits remain and overall effect sizes have been variable (10;22). It is possible that the presence of reduced QA could contribute to this lack of robust response. A few studies have suggested some improvement in QA with exercise alone, but results have been inconclusive, and there has not been an attempt to examine how pre-therapy level of QA might affect or predict the degree of response to therapeutic exercise (10;23;24). It may be possible that reduced QA might not allow an individual the capacity to produce enough tension in the muscle during exercise to achieve an exercise training effect, which in turn may limit their responsiveness to an exercise program. We are specifically interested in looking at how pre-therapy QA levels may affect response to therapeutic exercise in terms of quadriceps strength, which is a key determinant of function in subjects with knee OA. Therefore, the study aim was to examine whether pretreatment magnitude of QA helps predict changes in quadriceps strength after exercise therapy in subjects with knee OA. We hypothesized that subjects with lower magnitudes of QA (greater failure of muscle activation) would have smaller gains in strength compared to those with higher magnitudes of QA following exercise therapy.

Objective: To assess internal and external responsiveness of the Activity of Daily Living Scale of the Knee Outcome Sur­ vey and Numeric Pain Rating Scale on patients with patello­ femoral pain. Design: One group pre­post design. Subjects: A total of 60 individuals with patellofemoral pain (33 women; mean age 29.9 (standard deviation 9.6) years). Methods: The Activity of Daily Living Scale and the Numeric Pain Rating Scale were assessed before and after 8 weeks of physical therapy program. Patients completed a global rat­ ing of change scale at the end of therapy. The standardized effect size, Guyatt responsiveness index, and the minimum clinical important difference were calculated. Results: Standardized effect size of the Activity of Daily Liv­ ing Scale was 0.63, Guyatt responsiveness index was 1.4, area under the curve was 0.83 (95% confidence interval: 0.72, 0.94), and the minimum clinical important difference corre­ sponded to an increase of 7.1 percentile points. Standardized effect size of the Numeric Pain Rating Scale was 0.72, Guy­ att responsiveness index was 2.2, area under the curve was 0.80 (95% confidence interval: 0.70, 0.92), and the minimum clinical important difference corresponded to a decrease of 1.16 points. Conclusion: Information from this study may be helpful to therapists when evaluating the effectiveness of rehabilitation intervention on physical function and pain, and to power fu­ ture clinical trials on patients with patellofemoral pain.

Background Current guidelines for post-mastectomy radiotherapy (PMRT) derive largely from extrapolating information from multicentre trials. The aim of this study was to describe outcomes of patients who underwent mastectomy without radiotherapy in a single institution. Patients and methods 650 patients had total mastectomy and axillary dissection without PMRT between 1997 and 2001. Median follow-up was 65 months. Results 5-year cumulative incidence of loco-regional recurrence (LRR) was 6.8% (3.0, 8.1, 9.9% in node negative, 1–3, ≥4 positive nodes, respectively). At the multivariate analysis, positive lymph nodes and endocrine non-responsive tumours were found to shorten LRR disease-free survival. In patients with positive hormone receptors, 5-year cumulative incidence of LRR disease-free survival were 2.3%, 7.6% and 7.6% for node negative, 1–3 and ≥4 positive lymph nodes, respectively. The same figures were 5.9%, 10.3% and 20.0% in patients with endocrine non-responsive tumours. Conclusions patients with endocrine-responsive tumours treated by mastectomy and complete (level III) axillary dissection have a low risk of LRR even if four or more positive lymph nodes are involved, thus giving rise to doubts on the use of PMRT in this subset of patients. On the other hand, PMRT might play a role for patients with negative hormone receptors and four or more positive nodes.

Despite the importance of hypertension in adults, its effects on child health are poorly understood. This cross-sectional epidemiological study was designed to look for a relationship between elevated blood pressure (BP) in children and 24-h urinary excretion of sodium (Na) and potassium (K), and between BP and dietary salt intake. The study population was all 59 856 schoolchildren aged 6 to 14 years in the province of Almeria in southern Spain, among whom 613 participants were chosen randomly for study. We measured 24-h urinary Na and K concentrations, systolic and diastolic BP, body weight and height. There was a weak correlation between Na excretion and systolic BP (r = 0.18, 95% confidence interval 0.10-0.26), and between K excretion and systolic BP (r = 0.49, 95% CI = 0.04-0.20). Body weight was the variable that best correlated with systolic (r = 0.49, 95% CI = 0.43-0.55) and diastolic BP, and with Na excretion (r = 0.48, 95% CI = 0.42-0.55). Multiple regression analysis also showed that body weight was the variable that best correlated with systolic BP (b = 0.58), although the variables in the equation explained little of the total variability in BP (26%). These correlations were significant at P < 0.05. In conclusion urinary electrolytes correlated poorly with BP in a sample of Spanish schoolchildren. Body weight was the only variable that showed a weak relationship with BP and Na excretion.

Background In the Determining the Efficacy and Tolerability of cholesteryl ester transfer protein (CETP) INhibition with AnacEtrapib (DEFINE) trial, anacetrapib added to statin produced robust low-density lipoprotein cholesterol (LDL-C)-lowering and high-density lipoprotein cholesterol (HDL-C)-raising vs placebo in patients with coronary heart disease (CHD). Predictors of the degree of LDL-C and HDL-C responses to anacetrapib, however, are poorly understood. Objective Lipid effects of anacetrapib in patient subgroups within the DEFINE trial (clinicaltrials.gov: NCT00685776) are reported. Methods The percent of placebo-corrected changes from baseline for LDL-C (estimated by Friedewald calculation [Fc-LDL-C]) and HDL-C after 24 weeks of anacetrapib 100 mg/day were compared among patients by age, gender, race, diabetes status, type of concomitant statin with or without other lipid therapies, and baseline HDL-C, Fc-LDL-C, and triglyceride (TG) levels. Results Percent decreases in Fc-LDL-C and increases in HDL-C with anacetrapib were similar (magnitude of difference generally

To assess the incidence of postoperative complications, blood transfusions and survival at one month, in the old patients operated for hip fracture undergoing chronic treatment with antiplatelet drugs.Two hundred twenty three patients operated for hip fracture were studied retrospectively, separated into 3 groups: patients who received acetylsalicylic acid (group I), patients who were given 100mg/day of acetylsalicylic acid or 300mg/day of triflusal (group II) and patients receiving100mg/day of acetylsalicylic acid, or300mg/day of triflusal or thienopyridines (group III). Surgery was delayed for 4 days in patients in group III. Demographic, biological, clinical and treatment characteristics, postoperative complications and survival at one month were recorded.Patients in group III were older and sustain worse general health status. Patients with a higher transfusion requirement were those of group II (73.8%) (P=0.192), who also showed a higher percentage of anaemia on admission. Severe cardiovascular complications were experienced by 5.4% of group III patients, 4.8% of group II patients and 2.1% of group I patients. Patients from group III presented a significant amount of respiratory complications (P=0.007).Our results suggest that delaying surgery for 4 days in patients treated with clopidogrel can be associated to an increase in postoperative respiratory complications and severe adverse cardiovascular events, without increasing the tranfusional index, hospital stay, mortality, and without complications related to neuraxial anaesthesia.

Background and purpose Drug-induced parkinsonism usually resolves after discontinuation of the causative agent. However, it persists in some patients, who actually have subclinical neurodegenerative parkinsonism. Identification of this condition is important because these patients could benefit from therapeutic measures. The objective of this study was to prove whether transcranial sonography, a technique used in the diagnosis of neurodegenerative parkinsonism, can be used for the said identification. Methods In this prospective study, patients with drug-induced parkinsonism were followed for at least 6 months after discontinuation of the causative drug and performance of blinded transcranial sonography. Patients were categorized as having iatrogenic parkinsonism if the clinical presentation had resolved or subclinical drug-exacerbated parkinsonism if it persisted. Once the patient was classified into one of the two groups, an expert assessed the transcranial sonography findings and their agreement with the clinical diagnosis. Results Twenty patients composed the group for analysis of results. Assessing hyperechogenicity in the substantia nigra >20 mm2 and/or hyperechogenic lentiform nucleus, differences were detected between the iatrogenic parkinsonism and the subclinical drug-exacerbated parkinsonism groups, although they did not reach statistical significance (Fisher's exact test 0.09). Joint assessment of sonographic alterations in both structures had a negative predictive value of 85.7% for diagnosis of drug-induced parkinsonism, with a negative likelihood ratio of 0.3. Conclusions Although in our study statistically significant differences were not found between the transcranial sonography characteristics of subclinical drug-exacerbated parkinsonism and iatrogenic parkinsonism patients, we believe that transcranial sonography is a valid technique for diagnosis of drug-induced parkinsonism.

Objective To evaluate the association between severity of coexisting patellofemoral (PF) disease with lower extremity impairments and functional limitations in patients with tibiofemoral (TF) osteoarthritis (OA). Methods Radiographic views of the TF and PF compartments, knee extension strength, and knee range of motion were obtained for 167 patients with knee OA. Additionally, knee-specific symptoms and functional limitations were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Activities of Daily Living Scale (ADLS). Results Moderate/severe PFOA was associated with lower knee extension strength (mean ± SD 1.4 ± 0.5 Nm/body weight [BW]) compared to no PFOA (mean ± SD 1.8 ± 0.5 Nm/BW). Additionally, total knee range of motion was significantly lower for patients with moderate/severe PFOA (mean ± SD 120.8° ± 14.4°) compared to no PFOA (mean ± SD 133.5° ± 10.7°) and mild PFOA (mean ± SD 125.8° ± 13.0°). Moderate/severe PFOA and mild PFOA were also associated with less pain while standing (odds ratio [OR] 0.2, 95% confidence interval [95% CI] 0.1–0.7 and OR 0.2, 95% CI 0.1–0.6, respectively) on the WOMAC, and moderate/severe PFOA was associated with greater difficulty with going downstairs (OR 2.9, 95% CI 1.0–8.1) on the ADLS. Conclusion It appears that knees with more severe coexisting PF disease demonstrate features distinct from those observed in TFOA in isolation or in combination with mild PF disease. Treatment strategies targeting the PF joint may be warranted to mitigate the specific lower extremity impairments and functional problems present in this patient population.

Relatives play an important role in the disease process of patients admitted to Intensive Care Units (ICU). It is therefore important to know the needs of people close to the patient in order to try to improve their adaption to a situation as difficult as an ICU admission. The aim of this study was the adaptation and validation of the short version of the Critical Care Family Needs Inventory (CCFNI) for a Spanish sample. The inventory was applied to 55 relatives of patients admitted to the ICU of the Hospital General de Castellón. After the removal of three items for different reasons, we performed an Exploratory Factor Analysis with the 11 remaining items to determine the factor structure of the questionnaire. We also made a descriptive analysis of the items, and internal consistency and construct validity were calculated through Cronbach's α and Pearson correlation coefficient respectively. The results of the principal components factor analysis using varimax rotation indicated a four-factor solution. These four factors corresponded to: medical attention to the patient, personal attention to the relatives, communication between the family and the doctor, and perceived improvements in the Unit. The short version of CCFNI showed good internal consistency for both the total scale and factors. The results suggest that the CCFNI is a suitable measure for assessing the different needs presented by the relatives of patients admitted to an Intensive Care Unit, showing adequate psychometric properties.

OBJECTIVE To assess if very elderly people with hypertension obtain early benefit from antihypertensive treatment. DESIGN One year open label active treatment extension of randomised controlled trial (Hypertension in the Very Elderly Trial (HYVET)). SETTING Hospital and general practice based centres mainly in eastern and western Europe, China, and Tunisia. PARTICIPANTS People on double blind treatment at the end of HYVET were eligible to enter the extension. INTERVENTIONS Participants on active blood pressure lowering treatment continued taking active drug; those on placebo were given active blood pressure lowering treatment. The treatment regimen was as used in the main trial-indapamide SR 1.5 mg (plus perindopril 2-4 mg if required)-with the same target blood pressure of less than 150/80 mm Hg. MAIN OUTCOME MEASURES The primary outcome was all stroke; other outcomes included total mortality, cardiovascular mortality, and cardiovascular events. RESULTS Of 1882 people eligible for entry to the extension, 1712 (91%) agreed to participate. During the extension period, 1682 patient years were accrued. By six months, the difference in blood pressure between the two groups was 1.2/0.7 mm Hg. Comparing people previously treated with active drug and those previously on placebo, no significant differences were seen for stroke (n = 13; hazard ratio 1.92, 95% confidence interval 0.59 to 6.22) or cardiovascular events (n = 25; 0.78, 0.36 to 1.72). Differences were seen for total mortality (47 deaths; hazard ratio 0.48, 0.26 to 0.87; P = 0.02) and cardiovascular mortality (11 deaths; 0.19, 0.04 to 0.87; P = 0.03). CONCLUSION Very elderly patients with hypertension may gain immediate benefit from treatment. Sustained differences in reductions of total mortality and cardiovascular mortality reinforce the benefits and support the need for early and long term treatment. Trial registration Clinical trials NCT00122811.

BackgroundPatients with total knee arthroplasty (TKA) have impaired balance and movement control. Exercise interventions have not targeted these impairments in this population.ObjectivesThe purposes of this study were: (1) to determine the feasibility of applying a balance exercise program in patients with TKA, (2) to investigate whether a functional training (FT) program supplemented with a balance exercise program (FT+B program) could improve physical function compared with an FT program alone in a small group of individuals with TKA, and (3) to test the methods and calculate sample size for a future randomized trial with a larger study sample.DesignThis study was a double-blind, pilot randomized clinical trial.SettingThe study was conducted in the clinical laboratory of an academic center.ParticipantsThe participants were 43 individuals (30 female, 13 male; mean age=68 years, SD=8) who underwent TKA 2 to 6 months prior to the study.InterventionsThe interventions were 6 weeks (12 sessions) of a supervised FT or FT+B program, followed by a 4-month home exercise program.MeasurementsFeasibility measures included pain, stiffness, adherence, and attrition. The primary outcome measure was a battery of physical performance tests: self-selected gait speed, chair rise test, and single-leg stance time. Secondary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index and the Lower Extremity Functional Scale.ResultsFeasibility of the balance training in people with TKA was supported by high exercise adherence, a relatively low dropout rate, and no adverse events. Both groups demonstrated clinically important improvements in lower-extremity functional status. The degree of improvement seemed higher for gait speed, single-leg stance time, and stiffness in the FT+B group compared with the FT group.LimitationsDue to the pilot nature of the study, differences between groups did not have adequate power to show statistical significance.ConclusionsThere is a need for conducting a larger randomized controlled trial to test the effectiveness of an FT+B program after TKA.

Almeida GJ, Schroeder CA, Gil AB, Fitzgerald GK, Piva SR. Interrater reliability and validity of the stair ascend/descend test in subjects with total knee arthroplasty. Objective (1) To determine the interrater reliability and measurement error of an 11-step stair ascend/descend test (STTotal-11) and stair up (ascend) test (STUp-11); (2) to seek evidence for the STTotal-11 and STUp-11 as valid measures of physical function by determining if they relate to measures of physical function and do not relate to measures not of physical function; and (3) to explore if the STTotal-11 and STUp-11 scores relate to lower-extremity muscle weakness and knee range of motion (ROM) in subjects with total knee arthroplasty (TKA). Design Cross-sectional study. Setting Academic center. Participants Subjects (N=43, 30 women; mean age, 68±8y) with unilateral TKA. Interventions Not applicable. Main Outcome Measures STTotal-11 and STUp-11 were performed twice, and scores were compared with scores on 4 lower extremity performance-based tasks, 2 patient-reported questionnaires of physical function, 3 psychologic factors, knee ROM, and strength of quadriceps, hip extensors, and abductors. Results Intraclass correlation coefficient was .94 for both the STTotal-11 and STUp-11, standard error of measurements were 1.14 seconds and .82 seconds, and minimum detectable change associated with 90% confidence interval was 2.6 seconds and 1.9 seconds, respectively. Correlations between stair tests and performance-based measures and knee and hip muscle strength ranged from Pearson correlation coefficient ( r )=.40 to .78. STTotal-11 and STUp-11 had a small correlation with one of the patient-reported measures of physical function. Stair tests were not associated with psychologic factors and knee extension ROM and were associated with knee flexion ROM. Conclusions STTotal-11 and STUp-11 have good interrater reliability and minimum detectable changes adequate for clinical use. The pattern of associations supports the validity of the stair tests in TKA.

Diabetic patients commonly have increased urinary excretion of zinc, although blood concentrations may be normal, lowered, or raised. We analyzed zinc levels in plasma and urine after an intravenous overload of zinc sulphate (8 mg) in 22 patients with insulin-dependent diabetes mellitus (IDDM) and 22 healthy individuals. No significant differences were found in basal levels of serum zinc in either group (111 +/- 29 micrograms/dl in IDDM vs 119 +/- 19 micrograms/dl in controls), although urinary excretion of zinc was significantly raised in diabetics (1396 +/- 622 micrograms/24 h) versus controls (611 +/- 235 micrograms/24 h). After zinc overload, both serum and urinary levels of this element varied between the two groups. Serum zinc in IDDM patients initially increased more markedly, and subsequently showed a more significant decline, than in controls. Urinary zinc levels in IDDM patients, in contrast to control values, showed no increase after overload. These alterations in serum and urinary zinc concentrations suggest that our diabetic patients may be zinc-deficient.

Perinatal asphyxia is a potential cause of brain injury that can produce some alterations on the neurologic development of the newborn. On the last years most part of the investigation have been focused on the physiopathology of the perinatal asphyxia, but correlation between asphyxia and brain damage is not well defined.A retrospective study was made of the patients with the diagnosis of perinatal asphyxia born at the General Hospital of Segovia during a period of ten years (1992-2001). We took data about gestation, birth, neonatal period and follow-up period from their clinical histories.Over this period of ten years 703 cases of perinatal asphyxia have been diagnosed, supposing this an incidence of 7,2 cases of each 100 newborns. 116 of these newborns present risk factors of brain damage and were followed at least two years. 53 of the 116 newborns (45%) present evidence of hypoxic-ischemic encephalopathy on neonatal period. During the period of two years, 42 of the asphyxiated infants follow up (36%) present neurologic sequelae, being psychomotor retardation the most common.For a correct interpretation of the relationship between perinatal asphyxia and neurologic sequelae we have to analyze all of the perinatal data and discard any other possible aetiology or pathogenic mechanism.

Objective. To determine whether subgroups of rheumatoid arthritis (RA) patients classified according to their synovial vascular pattern have a different expression of angiogenic mediators or exhibit distinct clinical or biological characteristics. Methods. Arthroscopies were performed in 27 patients with RA and synovial samples were obtained. Vascular morphology was classified in three patterns: straight (S), tortuous (T) and mixed (M). Immunostaining was performed with antivascular endothelial growth factor (anti-VEGF), anti-vascular endothelial growth factor receptor (VEGFR)-1, anti-VEGFR-2, anti-IL-8 and anti-TGF-b, and measured by digital image analysis. Serum levels of VEGF, TGF-b and IL-8, and clinical, radiographic and serological data were also analysed. Results. Eleven (41%) patients had the S pattern, nine (33%) the M pattern and seven (26%) the T pattern. The S and M groups had a higher prevalence of rheumatoid factor positivity and erosive disease, and higher levels of markers of systemic inflammation compared with the T group. Synovial expression of VEGF was higher in the S and T groups compared with the M group, whereas TGF-b was higher in the T compared with the S and M groups. Distinct synovial distribution of VEGF and TGF-b between groups was also observed. Conclusions. This preliminary study suggests that RA patients with the S and M patterns share different clinical, biological and serological characteristics compared with those with the T pattern, which may constitute a group with less severe disease. Differences in the intensity and distribution of synovial expression of VEGF and TGF-b observed between groups could have pathophysiological relevance. However, larger, prospective multicentre studies would be need to determine the clinical relevance of vascular patterns in RA.

Diabetics frequently suffer diffuse coronary disease with difficulties for coronary artery bypass graft, which means that they require multiple medical treatment. Trimetazidine is an anti-ischemic agent that improves the myocardial metabolism and that can be especially useful in the ischemic myocardium of diabetic patients. The objective of this study is to evaluate in diabetic patients the anti-ischemic effectiveness of trimetazidine associated with regular medical treatment.In the DIETRIC study 580 patients with diabetes type 2 and coronary disease have been included for the assessment of antianginous effect of trimetazidine (20 mg/8 h). Basal clinical record, physical examination, laboratory evaluation, ECG and exercise test were carried out, with 6-month follow-up. In this article the clinical and exercise test response to the treatment is analyzed.A reduction of angina episodes was observed (2.8 vs 0,9; p0.001), in addition to a reduction of the number of weekly nitroglycerin tablets (2.5 vs 0,7; p0.001). In the exercise test carried out at 6-month follow-up an increase in its length was observed (441 vs 391 s; p0.001); also an increase of the time up to the decline of ST segment (214 vs 209 s; p = 0.02); at the same time a smaller decline of ST segment occurred (1.7 vs 1,2; p0.001). Tolerance was excellent.In this group of patients with diabetes mellitus type 2 and coronary artery disease, trimetazidine associated with regular medical treatment decreased the incidence of angina episodes and the ischemic response in the exercise test with an excellent tolerance.

Diabetes is a disease with high prevalence that involves high mortality. The control of risk factors reduces the cardiovascular complications. The objective of this study is to define the control degree of cardiovascular risk factors in patients with diabetes and coronary artery disease.In DIETRIC study 628 patients with diabetes type 2 and coronary artery disease have been included with the aim to study the antianginous effect of trimetazidine. Patients were studied basally with clinical history, physical exploration, laboratory testing, ECG and exercise test, with 6-month follow-up. In this article the profile of cardiovascular risk and the level of control of the risk factors in the basal study are analyzed.More than 80% of patients showed excess weight or obesity, 73% dyslipemia and 59% hypertension. More than 60% of patients showed 3 or more related risk factors. Only 15% had adequate control of blood pressure, and the control of diastolic pressure (55%) was most frequent than that of systolic (17%). Only 7.5% had adequate control of plasma lipids. Many patients did not take drugs to reduce mortality, as aspirin and statins.Most of these diabetic patients with coronary artery disease do not have adequate control of risk factors. A limited use of drugs that have proven to reduce cardiovascular mortality in these patients is observed.

Telmisartan, an angiotensin II receptor blocker, is an effective once-daily antihypertensive agent available either alone or in fixed-dose combination with hydrochlorothiazide (HCTZ). This multicentre, prospective, randomised, open-label, blinded-endpoint (PROBE) study assessed the efficacy and safety of six weeks' treatment with telmisartan 40 mg/HCTZ 12.5 mg (n = 199) and telmisartan 80 mg/HCTZ 12.5 mg (n = 200) versus losartan 50 mg/HCTZ 12.5 mg (n = 198) in patients with mild to moderate essential hypertension. During the last six hours of the dosing interval, telmisartan 40 mg/HCTZ 12.5 mg and telmisartan 80 mg/HCTZ 12.5 mg reduced mean ambulatory diastolic blood pressure (DBP) to a greater extent than losartan 50 mg/HCTZ 12.5 mg (treatment differences 1.8 mmHg [p0.05] and 2.5 mmHg [p0.001], respectively). Telmisartan 80 mg/HCTZ 12.5 mg also lowered mean 24-hour DBP by 2.3 mmHg more than losartan 50 mg/HCTZ 12.5 mg (p0.001). Telmisartan 40 mg/HCTZ 12.5 mg and telmisartan 80 mg/HCTZ 12.5 mg produced greater reductions in ambulatory systolic blood pressure versus losartan 50 mg/HCTZ 12.5 mg of 2.5 mmHg and 3.4 mmHg, respectively, during the last six hours of the dosing interval (p0.05), and of 2.1 mmHg and 3.4 mmHg, respectively, over the entire 24-hour dosing interval (p0.05). All treatments were well tolerated.

There is a pediatric consensus that maternal milk is the best food for the new born, but when this is impossible, one turns to artificial nutrition. The main objective of infant formulae is to achieve a gastrointestinal tolerance that is similar to maternal milk. With this in mind, we carried out an observational, prospective, and multicentric study with the objective of evaluating the gastrointestinal tolerance of Similac, taking maternal milk and other formulae on the market as reference. The study included 2 pediatric visits, a diary in which the parents recorded the gastrointestinal parameters, and a final questionnaire to evaluate the degree of satisfaction. Information was obtained from 6,617 evaluable cases, 82.2% fed with Similac (S), 8.8% with maternal milk (MM) and 9% with other formulae (OF). The analysis of the data showed that the percentage of children with signs of gastrointestinal intolerance, was reduced to more than half when using S compared to OF (5.6% S, 5% LM, and 14.1% OF). The color and consistency of the feces was significantly associated with the formula group, and in both cases S showed a greater similarity to the pattern obtained with MM compared to the OF group. 18.6% of the children with OF presented hard feces, and this percentage was reduced to at least half with S (6.2%). The S group showed a greater percentage of lack of regurgitations and no aerophagia and the lowest percentage for three or more regurgitations and severe aerophagia. Those questioned considered that S was easier to reconstitute up, is liked better, and is better tolerated than the OF used. Similac achieved a greater similarity in gastrointestinal tolerance to that of maternal milk than other formulae did.

Blood pressure (BP) has a circadian rhythm. Most of the people presents a BP fall between 10-20% during nighttime hours (dipper condition). Measurement of these circadian variations is performed by continuous blood pressure ambulatory monitoring. We have studied the possible relation between blood pressure nocturnal fall and cardiovascular risk factors in hypertensive patients.We selected 100 hypertensive patients from the Hypertension and Lipids Unit of San Cecilio University Hospital of Granada, Spain. They were divided into two groups: dippers group and non-dippers, depending of whether or not the fall of nocturnal systolic and diastolic BP was10%. All patients included in the study underwent complete clinical history, exhaustive physical examination, complementary examinations, urine and hematology tests, and continuous blood pressure ambulatory monitoring by the Space Labs system.The heart rate was found to be significantly higher (p = 0.0253) in the hypertensive dippers group than in the non-dippers. The latter showed higher plasma creatinine values (p = 0.0343) and lower potassemia values (p = 0.0140) than the dippers group. The dippers group presented concentrations of HDL-cholesterol significantly higher (p = 0.008) and diurnal diastolic BP values (p = 0.0211) also higher than the other group.Non dippers hypertensive patients present a higher number of cardiovascular risk factors as well as a higher tendency to renal lesions, and worse prognosis than the dippers group.

It has been studied the effect of the growth hormone (GH) in the atherogenic indexes, during the postoperative period in 28 patients, operated for digestive surgery.Patients were divided in: I) control group, patients without treatment, and II) treatment group, patients treated with 8 U.I. of GH during five days after the intervention.Results show that, while in the control group the atherogenic values increased to pathologic levels, in the treatment group, these values stabilized in the physiological limits.Thus, these results let conclude to the beneficial antiatherogenic effect of growth hormone in the postoperative disease.

Great interindividual variability in the pharmacokinetics of mycophenolate mofetil (MMF) exists among kidney transplanted patients. The within-patient variability in stable transplanted patients is not well established. We performed 258 determinations of trough MMF levels in 86 stable transplant patients without hematological or gastrointestinal toxicity after at least year of a functioning kidney and a fixed dose of MMF. We examined the within-patient variability of levels related with clinical factors (age, gender, underlying cause of kidney failure, time since transplant, associated immunosuppression, and MMF dose) and analytical factors (serum creatinine, proteinuria, hemoglobin). Trough MMF levels were 3.6 mg/L, percentile (Pc) 25 1.6 mg/L, Pc 75 4.4 mg/L with intraindividual variability median of 65% (Pc 25 14%, Pc 75 79%). For the data analysis a variation of 14% was chosen, which corresponded to the 25th percentile. We did not observed differences between patients with variation below or above the Pc 25 in age, gender, underling cause of kidney failure, basal MMF levels, and MMF dose. Patients with greater variations showed significantly higher serum creatinine and proteinuria values than the others (1.84 +/- 0.54 vs 1.46 +/- 0.44 mg/dL and 0.45 +/- 0.42 vs 0.19 +/- 0.14 g/L; P.05). Therefore, great within-patient variability in trough MMF levels was associated with poor kidney function and proteinuria.

The objective of this study was to evaluate the effect of nucleotide supplements on the incidence, duration and severity of diarrhea in healthy infants.A total of 3,243 cases were studied. This was an observational cohort study with a 1:1 ratio between infants receiving a nucleotide supplemented/unsupplemented diet. From the start of the study until the infant reached 6 months of age, the infant's mother recorded the duration and severity of each episode of diarrhea. The infant's height and weight were measured at the beginning and at the end of the follow-up period and the nutritional index (NI) was calculated [NI = (actual weight/actual height)/(ideal weight/ideal height)/100]. Data collection was performed during the months of June through December 1996 at 340 pediatric clinics distributed throughout Spain.The study groups were found to be homogeneous and there were no significant differences in age, gender, duration of follow-up, referring pediatric offices, number of siblings, usual residence, habitat or nursery attendance. The incidence of diarrhea was significantly lower (p0.001) in the nucleotide supplemented group (11.1%) versus the unsupplemented group (17.4%). Similarly, both the maximum duration of diarrhea (p0.05) and the severity of episodes of diarrhea (p0.001) were significantly lower in the nucleotide supplemented group. No significant differences were found between the initial and final nutritional indexes within a group nor when comparing the two groups.Nucleotide supplemented starter formulas reduce the incidence, duration and severity of diarrhea in healthy infants, but weight and height were not affected.

For a substantial number of patients with acute pancreatitis, no recognizable causes can be identified and such cases are called "idiopathic". With the introduction of duodenal bile collection for microscopic examination, it became possible to detect minor constituents of the bile, such as cholesterol and/or calcium bilirrubinate crystals. The mechanism by which crystals produce pancreatitis seems to be related to migration of aggregate crystals through the papilla, inducing papillary trauma or temporary impaction which can cause a biliopancreatic reflux. We now report a series of 45 patients with acute pancreatitis idiopathic, 120 with gallstones and 22 alcoholic. Of the patients with idiopathic pancreatitis whom we studied by biliary drainages, 22 were found to have abnormal drainages (MC+) (20 cholesterol crystals and 2 calcium bilirrubinate), 9 patients had more than 10 crystals per slide. The microcrystals positive (MC+) group had significantly higher values for AST (69.8 +/- 1.7) (mean +/- SEM), ALT (123.3 +/- 28.1), FA (252 +/- 28.1), G-GT (144.6 +/- 26.7) and BT (1.83 +/- 0.37) than the microcrystals negative group: AST (19.6 +/- 2.5), ALT (28.3 +/- 5.8), FA (170.5 +/- 15.1), G-GT (54.3 +/- 10.7) and BT (0.76 +/- 0.09). The more 10 crystals group had higher values (AST: 82.0 +/- 29.1, ALT: 143.1 +/- 43.5, FA: 294.8 +/- 57.2, G-GT: 171.8 +/- 38.4, BT: 2.61 +/- 0.82) than in the microcrystals negative group. We concluded that in the absence of other overt causes, the presence of crystals in bile of patients with pancreatitis justifies etiology. The number is not important.

The objective of this paper was to determine wether the clinical and sociological factors are implicated on the social rejection against the death. This is an inmutable phenomenon it is also changing and it has historicity. On the western countries it has become a peculiar phenomenon the dying patients and the death has shifted from home to hospital. Death on the hospital has been deshumaniced. Also, the physical and social death are differentiated and social and historical factors and social attitude changer are analyzed.

Growing old is a process of natural diminish with decrease of biological answer to extrinsic and intrinsic factors and a bigger risk of presenting cardiovascular and metabolic processes. The aim of this study has been to analyse the incidence of cardiovascular factors in an aged population from Almería.The group is by 172 patients (29 gave up); average global age 72.6 +/- 6.1 (85 women and 58 men). In all cases history and a whole clinic exam have been undertaken; general analytical study (glucose, creatinine, hepatic function cholesterol, HDL-c, LDL-c, trigliceride fibrinogen, microalbuminuria, etc.); blood pressure.T Students, varianza analysis, Kolmogorov-Smirnov test.With regard to overweight, this was bigger in women (32.1 +/- 4.8 Kg/m2) in relation to men (27.9 +/- 4 Kg/m2). The most frequent risk factor has been hypertension (50.3%) followed by over weight-obesity (46.8%) and hypercholesterolemia (45.4%), only 11.2% did not present any risk factor; shile three factors appeared in 29.5%. Hypertension patients have more risk factors (increase of cholesterol and triglicerids, obesity, diabetes) than normotensive old patients; also diabetic patients have a bigger cardiovascular and lipid risk than non diabetic patients. The ingestion of estatinas or fibrates improves the lipid profile of old patients. In summarizing, conventional therapy can improve the cardiologic and metabolic situation, decreasing so the morbidity and mortality of old patients.

Rationale Deterioration of ventricular fibrillation (VF) into asystole or severe bradycardia (electrical failure) heralds a fatal outcome of cardiac arrest. The role of metabolism in the timing of electrical failure remains unknown. Objective To determine metabolic factors of early electrical failure in an Ex-vivo canine model of cardiac arrest (VF+global ischemia). Methods and Results Metabolomic screening was performed in left ventricular biopsies collected before and after 0.3, 2, 5, 10 and 20 min of VF and global ischemia. Electrical activity was monitored via plunge needle electrodes and pseudo-ECG. Four out of nine hearts exhibited electrical failure at 10.1±0.9 min (early-asys), while 5/9 hearts maintained VF for at least 19.7 min (late-asys). As compared to late-asys, early-asys hearts had more ADP, less phosphocreatine, and higher levels of lactate at some time points during VF/ischemia (all comparisons p

Gastric emptying of a solid meal and of 10 indigestible radiopaque solids was measured with scintigraphic and radiological techniques in 50 healthy volunteers (controls), 41 patients with insulin-dependent diabetes mellitus, and 50 patients with functional dyspepsia. Gastroparesis was found in 51% of our diabetic patients and 74% of our patients with dyspepsia. The values ofTlag,T1/2 and the percentage of isotope remaining in the stomach at 105 min were 14.9 min, 59.4 min and 25.3% in control subjects; 21.4 min, 88.1 min, and 46.9% in diabetic patients (P

Dermatomyositis is an inflammatory disease of unknown etiology whose association to pregnancy is uncommon. The impact of dermatomyositis with uncomplicated pregnancy while active is very high for the fetus without major maternal consequences. The monitoring of cases with pregnancy associated hypertension and dermatomyositis, must be performed independently for the mother and the fetus, since fetal prognosis is usually bad and does not modify with treatment. The case presented herein is to our knowledge the first with eclampsia and dermatomyositis which ended in a normal product delivered and the mother decreased.

Hepatitis C virus (HCV) is an RNA virus that replicates in both the liver and lymphoid cells. Interferon-alpha (IFN-alpha) is a useful treatment of chronic hepatitis C (CHC) although resistance to this drug occurs frequently. The mechanisms underlying resistance to IFN remain unknown. In this work, we have measured the levels of glutathione in plasma and peripheral lymphoid cells from 15 healthy controls and 24 CHC patients, 10 of whom were without treatment and 14 showed high serum alanine aminotransferase (ALT) values despite therapy with lymphoblastoid IFN for more than 4 months. In all patients, glutathione levels in plasma and in mononuclear cells were depressed in comparison to controls. In IFN-unresponsive patients, the addition of 600 mg tid of oral N-acetyl cysteine (NAC), a glutathione precursor, resulted in a steady decrease of ALT values in all patients, with complete normalization in 41% of cases after 5-6 months of combined therapy. Administration of NAC alone for 1 month was without effect in the 10 patients that were not receiving IFN. Supplementation of IFN with NAC induced a near normalization of intralymphocytic glutathione, but plasma levels were only moderately increased. HCV replication was markedly inhibited in lymphocytes and viremia was cleared in one of the 8 patients tested. In conclusion, NAC enhances the response to IFN in CHC. Controlled studies are needed to ascertain whether antioxidant therapy might act in synergy with IFN in chronic viral hepatitis.

The existence of a cellular immune deficit in alcoholic cirrhosis, and the alterations described in cytokine synthesis in this disease, led us to compare serum concentrations of tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6 in a group of 33 patients with alcoholic cirrhosis (classified according to the Child-Pugh grade of severity of liver disease) and 43 healthy volunteers. Serum concentrations of tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6 were significantly raised in alcoholic cirrhosis patients, with no significant differences between patients with liver disease of different grades of severity. The results suggest that cirrhosis involves the activation of the monocyte-macrophage system, which may contribute to the progression of the disease and its clinical manifestations.

Quality of life has been one of the main goals of medicine during the past years. With the increase of chronic degenerative diseases and the stability of the life expectancy at birth, we are beginning to think that it is not only important the number of years that we live, but as well the number of years that we live free of discapacities. On the other hand, the increase in the survival rate due to the advance of the biotechnology, as it happens with cancer, lead us to consider several psychosocial aspects neglected a few years ago.

The existence of cellular immune deficit in alcoholic cirrhosis, together with the role of alpha- and gamma-interferon and interleukin-2 in the immune system, led us to compare serum levels of these immune system mediators in a group of 40 patients with alcoholic cirrhosis classified according to Child-Pugh's grade of severity of liver disease and 23 healthy volunteers. Serum levels of alpha-IFN, gamma-IFN, and IL-2 were significantly depressed in alcoholic cirrhotics, with no significant differences between the different degrees of hepatic damage. The results suggest a profound alteration in the immune system of alcoholic cirrhotics, which may contribute to the development of the disease and the accompanying immune system deficit.

Alterations in nervous transmission might be an early feature of diabetic peripheral polyneuropathy, even in the subclinical stage. We performed a study on 100 diabetic patients. Those with possible endogenous or exogenous causes of neuropathy were not included. We studied the motor distal latency of right peroneal and cubital nerve and the sensory distal latency of median nerve by the use of electromyogram. The neuropathy incidence was 34.3%. One of the results was that conduction in males was slower than in the female control group; this disappeared in diabetic patients.