Biomedical subjects

Michael Kuskowski

Publications and source records attributed to Michael Kuskowski.

16 recordsLinked to original sources

PubMed2007

Activity level in young patients with primary total hip arthroplasty: a 5-year minimum follow-up.

Increased activity level after total hip arthroplasty (THA) is considered a risk factor for early prosthetic failure in young patients. Forty-one primary total hip arthroplasties in 34 patients were evaluated. Walking activity was measured using a pedometer to record gait cycles. Patients completed a University of California, Los Angeles (UCLA) activity questionnaire. Linear wear rates were measured. Mean ages at surgery and final follow-up were 42 and 50.3 years, respectively (mean gait cycles per year, 1.2 million; mean UCLA score, 6; mean linear wear, 0.16 mm/y). Increased body mass index and age correlated with decreased gait cycles per year. Patients with systemic disease were less active than patients with localized hip conditions. Femoral head diameter was a predictor of linear wear. The average gait cycles per year and wear rate for this population do not appear accelerated relative to average values reported in older populations.

Adult↗

PubMed2006

Stability of human methanogenic flora over 35 years and a review of insights obtained from breath methane measurements.

BACKGROUND & AIMS: Breath methane measurements reflect the in situ activity of the methanogenic colonic flora. Thirty-five years ago we found that 34% of healthy adult subjects were methane producers (breath methane level >1 ppm above atmospheric methane levels). The current study presents a new survey of breath methane levels designed to determine if the activity of the methanogenic flora has changed over the past 35 years. In addition, we review insights into the methanogenic flora that have resulted from breath methane measurements. METHODS: The end-alveolar breath methane concentrations of 212 healthy adults living in the Minneapolis area were determined via gas chromatography. The influence of sex, age, and bowel movement frequency on methane production was assessed. RESULTS: The findings that 36.4% of participants were methane producers, with a mean methane concentration in these producers of 16.6 ppm, are strikingly similar to the values of 33.6% and 15.2 ppm observed 35 years ago. Neither sex nor age showed a statistically significant relationship to methane production. There was a negative correlation between frequency of bowel movements and breath methane concentration in methane producers. CONCLUSIONS: The activity of the methanogenic flora of healthy adults remained remarkably stable over the past 35 years despite widespread antibiotic use and dietary changes. A literature review revealed that many associations have been shown between methane production and clinical states, but it remains to be determined if methanogens actively influence human physiology or are simply a marker of colonic function.

Adult↗

PubMed2006

Durability of flexible ureteroscopes: a randomized, prospective study.

PURPOSE: We performed a randomized, prospective, multi-institutional study evaluating the durability of commercially available flexible ureteroscopes. MATERIALS AND METHODS: A total of 192 patients were randomized to the use of 7 less than 9Fr flexible ureteroscopes, including the Storz 11274AA and Flex-X, the ACMI DUR-8 and DUR-8 Elite, Wolf models 7330.170 and 7325.172, and the Olympus URF-P3. Information about total and lower pole use time, the number and method of ureteroscope insertion, and they type and duration of accessory instrumentation was recorded. Surgeons were asked to rate the visibility and maneuverability of the instrument on a scale of 0-poor to 10-excellent. RESULTS: The indication for ureteroscopy was upper tract calculi in 87% of cases. Of ureteroscope insertions 97% were performed through an access sheath. The average of number of cases before repair ranged from 3.25 for the Wolf 7325 to 14.4 for the ACMI DUR-8 Elite. Average ureteroscope operative time was statistically longer for the DUR-8 Elite (494 minutes) than for the Flex-X (p = 0.047), and the Wolf 7325 and 7330 (p = 0.001 and 0.001, respectively). Duration of use before repair for the URF-P3 (373 minutes) was statistically longer than for the Wolf 7325 and 7330 (p = 0.016 and 0.017, respectively). Minutes of use with an instrument in the working channel were significantly more with the DUR-8 Elite and the URF-P3 than the Wolf 7330 (p = 0.017 and 0.008) and 7325 (p = 0.012 and 0.005, respectively). The ureteroscope that experienced the greatest average duration of lower pole use was the URF-P3, while the shortest was the Wolf 7325 (103 vs 20 minutes, p = 0.005). Average minutes of laser use before breakage was significantly longer for the DUR-8 Elite than for the Wolf 7325 (110 vs 21 minutes, p = 0.021) and 7330 (24 minutes, p = 0.025). CONCLUSIONS: Currently available less than 9Fr flexible ureteroscopes remain fragile instruments. The DUR-8 Elite and Olympus URF-P3 proved to be the most durable devices.

Equipment Design↗

PubMed2006

Does surgical approach affect total hip arthroplasty dislocation rates?

Dislocation is a common complication of total hip arthroplasty, but exact effect of surgical approach on dislocation rates remains unclear. Because little randomized prospective data exist in this context, we performed a meta-analysis comparing dislocation rates using the posterior approach with and without soft tissue repair. A systematic literature review resulted in five studies which directly compared the posterior approach with and without soft tissue repair. The dislocation rates with and without repair were 0.49% and 4.46%, respectively. The relative risk for dislocation was determined using a fixed effects model with chi square test for interstudy heterogeneity. The posterior approach without soft tissue repair was found to have an 8.21 times greater relative risk of dislocation than with soft tissue repair (95% confidence interval, 4.05-16.67). A separate systematic review of 11 studies revealed comparable dislocation rates associated with the anterolateral, direct lateral, and posterior approaches with soft tissue repair (0.70%, 0.43%, and 1.01%, respectively). These data demonstrate that adequate soft tissue repair greatly reduces the relative risk of dislocation using the posterior approach, and that the dislocation rates for the three most prevalent approaches are similar. Further prospective randomized trials examining dislocation rates and other clinical parameters are needed.

Age Distribution↗

PubMed2006

Outcomes of total and unicompartmental knee arthroplasty for secondary and spontaneous osteonecrosis of the knee.

BACKGROUND: The reported outcomes of patients who underwent total or unicompartmental knee arthroplasty for secondary and spontaneous osteonecrosis of the knee are often from studies that lack the number of subjects necessary to generate meaningful conclusions. We systematically reviewed the available literature in order to define the outcomes of patients after total knee arthroplasty for secondary osteonecrosis and after total or unicompartmental knee arthroplasty for spontaneous osteonecrosis of the knee. METHODS: A literature review yielded twenty cohorts with demographic patient information and outcome scores (global knee scores, radiographic outcomes, and revision rates) for patients who had knee arthroplasty as treatment for either secondary or spontaneous osteonecrosis of the knee. The mean preoperative and postoperative global knee scores, the mean revision rate, and the categorization of the mean "poor" and mean "good" outcomes for the knees with each underlying disease were tabulated and reported. The demographic data and the reported mean global knee scores were weighted by the number of knees in each study. RESULTS: Total knee arthroplasty was performed in 150 knees with secondary osteonecrosis and 148 knees with spontaneous osteonecrosis, and unicompartmental knee arthroplasty was performed in sixty-four knees with spontaneous osteonecrosis. Total knee arthroplasty for spontaneous osteonecrosis of the knee was associated with the best outcomes (higher "good" and postoperative global knee scores and lower revision [3%] and "poor" outcome [6%] rates compared with the other two groups). The outcomes after total knee arthroplasty in knees with secondary osteonecrosis as well as in knees with spontaneous osteonecrosis were better in the cohorts operated on during or after 1985 than in those operated on before 1985. Similarly, the outcomes after unicompartmental knee arthroplasty in knees with spontaneous osteonecrosis of the knee were also better in the cohorts operated on during or after 1985 than in those operated on before 1985. CONCLUSIONS: Total knee arthroplasty performed as treatment for either secondary osteonecrosis or spontaneous osteonecrosis and unicompartmental knee arthroplasty performed as treatment for spontaneous osteonecrosis were associated with improved outcomes in cohorts with more recent operative dates. The evidence suggests that the use of contemporary cemented implants in total knee arthroplasty and the selective use of stems and augments in patients who have development of secondary osteonecrosis after total knee arthroplasty are producing outcomes that are comparable to those seen after total knee arthroplasty for osteoarthritis. Although the outcomes of patients who have total knee arthroplasty for the treatment of spontaneous osteonecrosis of the knee have historically been favorable, such outcomes have also shown particular improvement in the studies from more recent operative periods. Although poor outcomes were seen after unicompartmental knee arthroplasty in earlier studies of patients with spontaneous osteonecrosis of the knee, it is possible that those results were secondary to inappropriate patient selection, as the authors of the most recent and, to our knowledge, the only study to follow established operative indications regarding the use of unicompartmental knee arthroplasty reported excellent results. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions to Authors on jbjs.org for a complete description of levels of evidence.

Adult↗

PubMed2005

Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain.

Cancer colonization of bone leads to the activation of osteoclasts, thereby producing local tissue acidosis and bone resorption. This process may contribute to the generation of both ongoing and movement-evoked pain, resulting from the activation of sensory neurons that detect noxious stimuli (nociceptors). The capsaicin receptor TRPV1 (transient receptor potential vanilloid subtype 1) is a cation channel expressed by nociceptors that detects multiple pain-producing stimuli, including noxious heat and extracellular protons, raising the possibility that it is an important mediator of bone cancer pain via its capacity to detect osteoclast- and tumor-mediated tissue acidosis. Here, we show that TRPV1 is present on sensory neuron fibers that innervate the mouse femur and that, in an in vivo model of bone cancer pain, acute or chronic administration of a TRPV1 antagonist or disruption of the TRPV1 gene results in a significant attenuation of both ongoing and movement-evoked nocifensive behaviors. Administration of the antagonist had similar efficacy in reducing early, moderate, and severe pain-related responses, suggesting that TRPV1 may be a novel target for pharmacological treatment of chronic pain states associated with bone cancer metastasis.

Activating Transcription Factor 3↗

PubMed2005

Randomized evaluation of Ureteral Stents using validated Symptom Questionnaire.

BACKGROUND AND PURPOSE: Ureteral stents are associated with significant pain and urinary symptoms. Manufacturers have altered stent designs and materials in an attempt to minimize this morbidity. This study evaluated the impact of these modifications. PATIENTS AND METHODS: Stent manufacturers were asked to provide the 6F ureteral stent they believed would be associated with the least patient discomfort. Patients undergoing uncomplicated ureteroscopy were randomized to the Bard Inlay, Cook Endo-Sof, Microvasive Contour, Applied Medical Vertex, or Surgitek Classic Double-Pigtail stent. The Ureteric Stent Symptom Questionnaire (USSQ) was administered on days 1, 3, and 5, and the patients maintained a narcotic diary. The data were analyzed using ANOVA and nonparametric methods. RESULTS: A total of 44 patients (73%) completed all USSQ questionnaires. Urinary symptom scores were significantly lower for the Inlay stent on day 3 than for the Vertex (P = 0.01), Contour (P = 0.05), Endo-Sof (P = 0.03), and Classic (P = 0.02) stents. No significant differences were noted in pain and general symptom scores or narcotic use. CONCLUSIONS: The Bard Inlay stent is associated with less-severe urinary symptoms than other ureteral stents. The USSQ is a sensitive tool to measure differences between stents.

Adult↗

PubMed2005

Driving habits and patterns in older men with glaucoma.

Glaucoma, an eye disorder that gradually decreases peripheral vision, affects millions of older adults. Consequences of glaucoma can mean changes in the ability to perform familiar tasks, including driving an automobile. We surveyed older drivers with glaucoma and a control comparison group in order to learn more about their driving habits and expectations about driving cessation. Findings indicate that compared to the control group, drivers with glaucoma are significantly more likely to change their driving habits with regard to driving at night (p=0.003), on freeways (p=0.05), and in unfamiliar areas (p=0.01). Drivers with glaucoma were also significantly more likely to report family concern about their driving (p=0.01). However, the drivers with glaucoma did not anticipate that their disease would force them to discontinue driving. Social workers play a pivotal role in coordinating the complex care needs of visually impaired elders. When driving skills are affected, social workers must address transportation, housing as well as quality of life concerns.

Adaptation, Psychological↗

PubMed2005

Advanced age does not exclude lobectomy for non-small cell lung carcinoma.

STUDY OBJECTIVES: Localized non-small cell lung carcinoma (NSCLC) is best treated by complete surgical resection, commonly requiring lobectomy. The impact of lobectomy on the health status of the elderly patient is not well-characterized. The aim of this study was to compare the effect of lobectomy in elderly patients (> or = 70 years of age) and younger patients (< 70 years of age) on their pulmonary function and functional status 1 year following surgery. DESIGN: One hundred forty patients underwent lobectomy for NSCLC at the Minneapolis Veterans Affairs Medical Center from January 1999 to December 2003. All patients underwent pulmonary function tests (PFTs) and functional status assessment using Karnofsky scores (KS) that were assessed preoperatively. Sixty-three of 140 lobectomy patients were available 1 year postoperatively for reevaluation by PFTs and KS. RESULTS: There was no statistical difference between groups in either the pulmonary function or functional status testing results at 1 year after undergoing lobectomy. FVC decreased by 14% in the elderly patient and by 9% in the younger patient group. FEV1 decreased by 19% in elderly patients and by 13% in younger patients. Functional status declined for two older patients (8%), who dropped their KS from 80 to 100% (normal activity without limitation) to 40 to 70% (unable to work, but able to care of self at home). Nine of the younger patients (24%) had KS drop from 80 to 100% to 40 to 70%. There was one perioperative death (30-day mortality rate for the study groups, 1.5%). CONCLUSIONS: Elderly patients > or = 70 years of age undergoing lobectomy for NSCLC had similar PFT results and functional status as younger patients < 70 years of age 1 year after undergoing surgery. Curative resection should not be denied based on age alone.

Age Factors↗

PubMed2004

Comparison of nitinol tipless stone baskets in an in vitro caliceal model.

PURPOSE: Tipless stone baskets facilitate caliceal calculi extraction during flexible ureteroscopy. We evaluated the stone capture rate of 9 commercially available tipless stone baskets in an in vitro model using novice and expert operators. MATERIALS AND METHODS: The Microvasive Zerotip (2.4Fr, 3.0Fr), Cook N-Circle (2.2Fr, 3.0Fr, 3.2Fr), Bard Dimension (3.0Fr, Sacred Heart Medical Halo (1.9Fr), Vantage (1.9Fr) and Circon-ACMI Sur-Catch-NT (3.0Fr) were tested by 3 novice and 3 experienced basket operators. Each operator performed stone extraction of 2, 5 and 8 mm calculi (size determined by digital caliper with 3 repetitions of each basket. The time to extraction of the calculus from a convex based test tube caliceal model was recorded. Statistical analysis was performed using repeated measures ANOVA and Fisher's pairwise comparisons. RESULTS: After a learning curve of 27 basket retrievals, there was no significant difference in stone capture times between novice (38 +/- 54 seconds) and expert operators (32 +/- 49 seconds, p = 0.174). For total stone capture (all sizes) the Sacred Heart Halo resulted in the most rapid stone extraction (17 +/- 14 seconds) by novices and experts, while the Sur-Catch NT resulted in the slowest stone extraction (78 +/- 90, seconds, p = 0.001). The Halo (14 +/- 9 seconds) and Vantage (19 +/- 12 seconds) baskets were significantly faster for 2 mm calculi than the N-Circle (73 +/- 60 seconds, p = 0.006), Sur-Catch (169 +/- 85 seconds, p = 0.0005) and Dimension (73 +/- 70 seconds, p = 0.017). The Zerotip functioned well for 2 mm calculi in the hands of expert operators (15 +/- 9 seconds) but not novice operators (94 +/- 95 seconds). The Sur-Catch NT was significantly slower for 2 mm calculi than the N-Circle (p = 0.01), Dimension (p =.03), Halo (p =.0005), Vantage (p =.001) and Zerotip (p =.002). For 5 mm calculi the Halo was superior (12 +/- 8 seconds), while the Zerotip were superior for 8 mm calculi (8 +/- 3 seconds) compared to the N-Circle (23 +/- 28 seconds, p = 0.026), Halo (26 +/- 18 seconds, p = 0.021) and Vantage (23 +/- 15 seconds, p = 0.006). CONCLUSIONS: The Sacred Heart Halo and Vantage baskets resulted in the most expeditious stone extraction, especially for 2 to 5 mm calculi while the Microvasive Zerotip was optimal for 8 mm calculi. The Sur-Catch NT had the slowest stone capture rate for all stone sizes. Caliceal models of stone basketing may be useful to train novice urology residents and nursing assistants.

Alloys↗

PubMed2004

The Lapidus procedure as salvage after failed surgical treatment of hallux valgus. Surgical technique.

BACKGROUND: Recurrent hallux valgus is a relatively common, yet challenging, condition for both the patient and the surgeon. The literature on the treatment of recurrent hallux valgus is sparse. The purpose of this study was to evaluate prospectively the functional outcome and patient satisfaction following the Lapidus procedure for the treatment of recurrent hallux valgus deformity. METHODS: Twenty-four patients with a total of twenty-six symptomatic recurrences of hallux valgus after previous procedures for treatment of the deformity were included in the study. Exclusion criteria included prior fusion procedures on the foot or ankle, a previous Keller or Mayo procedure, insulin dependent diabetes, peripheral vascular disease, or peripheral neuropathy. A visual analog pain scale and the American Orthopaedic Foot and Ankle Society Hallux Metatarsophalangeal-Interphalangeal Scale were administered preoperatively, at six months postoperatively, and yearly thereafter. Weight-bearing radiographs were also made preoperatively; at six weeks, three months, six months, and one year postoperatively; and yearly thereafter. Patient satisfaction was assessed at the latest follow-up evaluation. RESULTS: At twenty-four months, the mean score according to the American Orthopaedic Foot and Ankle Society (AOFAS) Hallux Metatarsophalangeal-Interphalangeal Scale had increased from 47.6 to 87.9 points, the mean score according to the visual analog pain scale had improved from 6.2 to 1.4, the mean hallux valgus angle had improved from 37.1 degrees to 17.1 degrees, and the mean intermetatarsal angle had improved from 18 degrees to 8.6 degrees. The patients were very satisfied after 77% of the twenty-six procedures, satisfied after 4%, and somewhat satisfied after 19%; no patient was dissatisfied. There were no cases of hallux varus. Complications included three nonunions, all of which occurred in smokers, and two superficial wound infections. CONCLUSIONS: In appropriately selected patients, the Lapidus procedure is a reliable and effective operation after failed surgical treatment of hallux valgus.

Hallux Valgus↗

PubMed2003

The Lapidus procedure as salvage after failed surgical treatment of hallux valgus: a prospective cohort study.

BACKGROUND: Recurrent hallux valgus is a relatively common, yet challenging, condition for both the patient and the surgeon. The literature on the treatment of recurrent hallux valgus is sparse. The purpose of this study was to evaluate prospectively the functional outcome and patient satisfaction following the Lapidus procedure for the treatment of recurrent hallux valgus deformity. METHODS: Twenty-four patients with a total of twenty-six symptomatic recurrences of hallux valgus after previous procedures for treatment of the deformity were included in the study. Exclusion criteria included prior fusion procedures on the foot or ankle, a previous Keller or Mayo procedure, insulin-dependent diabetes, peripheral vascular disease, or peripheral neuropathy. A visual analog pain scale and the American Orthopaedic Foot and Ankle Society Hallux Metatarsophalangeal-Interphalangeal Scale were administered preoperatively, at six months postoperatively, and yearly thereafter. Weight-bearing radiographs were also made preoperatively; at six weeks, three months, six months, and one year postoperatively; and yearly thereafter. Patient satisfaction was assessed at the latest follow-up evaluation. RESULTS: At twenty-four months, the mean score according to the American Orthopaedic Foot and Ankle Society (AOFAS) Hallux Metatarsophalangeal-Interphalangeal Scale had increased from 47.6 to 87.9 points, the mean score according to the visual analog pain scale had improved from 6.2 to 1.4, the mean hallux valgus angle had improved from 37.1 degrees to 17.1 degrees, and the mean intermetatarsal angle had improved from 18 degrees to 8.6 degrees. The patients were very satisfied after 77% of the twenty-six procedures, satisfied after 4%, and somewhat satisfied after 19%; no patient was dissatisfied. There were no cases of hallux varus. Complications included three nonunions, all of which occurred in smokers, and two superficial wound infections. CONCLUSION: In appropriately selected patients, the Lapidus procedure is a reliable and effective operation after failed surgical treatment of hallux valgus. LEVEL OF EVIDENCE: Therapeutic study, Level IV (case series [no, or historical, control group]). See p. 2 for complete description of levels of evidence.

Adult↗

PubMed2002

Global molecular epidemiology of the O15:K52:H1 extraintestinal pathogenic Escherichia coli clonal group: evidence of distribution beyond Europe.

Escherichia coli O15:K52:H1 is a significant extraintestinal pathogen in Europe (G. Prats et al., J. Clin. Microbiol. 38:201-209, 2000). To search for evidence of this clonal group outside of Europe, 75 non-European E. coli isolates of serogroup O15 were compared with five members of the O15:K52:H1 clonal group from Barcelona, Spain, according to genomic background, virulence genotypes, and antimicrobial resistance profiles. Amplification phylotyping showed that 16 (21%) of the 75 non-European O15 isolates corresponded with the O15:K52:H1 clonal group. The 16 non-European O15:K52:H1 clonal group members represented diverse geographic locales. They were isolated almost exclusively from humans with extraintestinal infections and accounted for 50% of all O15 isolates from five human clinical collections studied. Most non-European clonal group members exhibited a consensus virulence factor profile that included the F16 or F7-2 papA alleles (P fimbrial structural subunit), papG allele II (P fimbrial adhesin), iha (putative adhesin siderophore), and iutA (aerobactin receptor). This resembles the virulence profiles of (i) European representatives of the O15:K52:H1 clonal group and (ii) phylogenetically related "clonal group A," a recently recognized significant contributor to trimethoprim-sulfamethoxazole resistance in the United States (A. R. Manges et al., N. Engl. J. Med. 345:1007-1013, 2001). Antimicrobial resistance profiles were variable, and resistance was inconsistently transferred by conjugation. These findings indicate that the O15:K52:H1 clonal group is broadly distributed beyond Europe, exhibits previously unrecognized phenotypic and genotypic diversity, and contributes significantly to extraintestinal infections in humans.

Animals↗

PubMedDate not supplied

Retrospective review of treatment retention in pathological gambling.

Although research on pathological gambling is increasing, there are few studies examining correlates of treatment retention. In the current study, 50 outpatients with a primary DSM-IV diagnosis of pathological gambling treated in a clinical practice were assessed by chart review. Standard scales were used to rate subjects at baseline and at 2-month intervals. Subjects who dropped out of treatment were contacted by telephone to determine reasons for discontinuation of treatment. The mean duration of follow-up was 360.4 +/- 352.2 days. Twenty-four (48%) of the subjects discontinued treatment, including 14 (36.8%) of those subjects who were responders (defined as Clinical Global Impression [CGI] scale of "very much" or "much" improved) during at least one assessment point. Of those who discontinued treatment, 41.7% reported missing the thrill of gambling and 20.8% reported feeling certain that they could win and relieve financial burdens. Predictors of treatment continuation were responding to treatment within 8 weeks (odds ratio [OR], 6.00; 95% confidence interval [CI], 1.13 to 32.00; P =.04) and having a supportive environment (OR, 22.99; 95% CI, 5.04 to 104.76; P <.001). We conclude that a large percentage of patients with pathological gambling discontinue treatment. Predictors of treatment continuation may have clinical importance. Prospective longitudinal studies are needed to further elucidate the course of pathological gambling.

Adult↗

PubMedDate not supplied

Driving cessation in older men with dementia.

The process of driving cessation was studied in a group of older men with dementia. During the initial phase of the project, 53 drivers with dementia provided information about their driving history, driving habits, and expectations about driving cessation. A collateral for each patient completed a similar questionnaire providing corroborating information about the patient's driving. Collaterals were contacted 25-39 months later to gather information about patients' current driving habits. Twenty patients (46.5%) continued to drive almost 5 days per week. Twenty-three subjects (53.5%) were no longer driving at follow-up. The decision to stop driving was frequently abrupt and often made in response to a physician recommendation. Using logistic regression analyses, lower Mini-Mental State Examination scores (p = 0.02) and increased age (p = 0.02) at baseline were shown to be significant predictors of driving cessation. Findings indicate that an unexpected number of men with dementia continue to drive for several years after disease onset.

Aged↗

PubMedDate not supplied

Ondansetron in the treatment of cognitive decline in Alzheimer dementia.

The authors performed a multicenter, double-blind, placebo-controlled clinical trial to assess the efficacy and safety of ondansetron (20 microg/day and 100 microg/ day) in treating cognitive decline in 185 patients with Alzheimer disease. Although ondansetron was well tolerated without any serious drug-related side effects, the study failed to demonstrate any significant cognitive improvement.

Aged↗