Polypharmacy, physical activity, and sedentary time in older adults: A scoping review.

OBJECTIVE: To map out the studies that have investigated the associations of polypharmacy and/or potentially inappropriate medication (PIM) use with physical activity and sedentary time in older adults. METHODS: We conducted a literature search from inception to December 2022 in PubMed, Embase, Web of Science, and Scopus. INCLUSION CRITERIA: observational studies including older adults (≥60 years); English, Portuguese, and Spanish languages; any definition of polypharmacy; implicit and explicit criteria of PIM use; physical activity and/or sedentary time data. RESULTS: Fourteen cross-sectional studies were included; 11 defined polypharmacy as ≥5 medications (prevalence ranging from 9.5 % to 57 %). No study reported information on PIM use. Most studies included participants aged <80 years. Twelve studies included self-reported measures of physical activity, while two studies used accelerometer-measured physical activity. Ten studies included analyses adjusted for confounders, and nine considered polypharmacy as an outcome. All of them demonstrated an inverse association between physical activity and polypharmacy, irrespective of the definition of polypharmacy and the assessment method employed (self-reported or accelerometry). One study reported an inverse association between polypharmacy (as the exposure) and physical activity (as the outcome). None of the studies investigated the association between sedentary time and polypharmacy. CONCLUSIONS: Limited evidence suggests an inverse association between physical activity and polypharmacy in older adults. However, the relationship between PIM use, physical activity, and sedentary time remains unknown. Longitudinal studies utilizing objectively-measured physical activity and sedentary time are needed to better clarify the relationship between these movement behaviors and polypharmacy and/or PIM use in older adults.

High-intensity interval aerobic and resistance training to counteract low relative lean soft tissue mass in middle age: A randomized controlled trial.

BACKGROUND: Age-related loss of skeletal muscle mass and function begins in early middle age, yet research to date has focused on older individuals, limiting our understanding of interventions earlier in the lifespan. To date, no high-intensity interval training studies have been conducted in middle-aged adults with low relative lean soft tissue mass. METHODS: Eighty-two middle-aged adults (40-50 years of age) with low appendicular lean soft tissue mass index confirmed with dual energy x-ray absorptiometry (DXA) were randomly allocated (1:1) to group-based, 20-week, three times a week, high-intensity aerobic and resistance training (HIART) program or 60-min education session (Control). The primary outcome was change in total lean soft tissue mass measured by DXA. Secondary outcomes included cardiorespiratory fitness, physical function (handgrip strength, gait speed, 30-seconds sit-to-stand, quadriceps strength and muscle quality). Measures were obtained at baseline (0 weeks), mid-intervention (10 weeks) and post-intervention (20 weeks). RESULTS: Mean age in HIART was 44.8 (SD 3.2) and 45.4 (SD 2.9) in Control group. The majority of the participants were female with 88 % in HIART and 83 % in Control group. Mean BMI in HIART was 25.8 kg/m2 (SD 3.5) and 26.4 kg/m2 (SD 4.1) Control group. Intention to treat analysis showed that post-intervention, HIART increased significantly more total lean soft tissue mass (0.8 kg, 95%CI 0.15, 1.46), appendicular lean soft tissue mass index (0.2 kg/m2, 95%CI 0.09, 0.33), peak oxygen uptake (5.18 mL/min/kg, 2.97 to 7.39 95%CI), grip strength (2.2 kg, 95%CI 0.09, 4.32), and 30-s sit-to-stand (1.3 times, 95%CI 0.43, 2.12) with significantly greater reductions in body fat percentage (-1.1 %, 95%CI -2.03, -0.10) and maximum gait speed (-0.2 m/s, 95 % CI -0.34, -0.03) compared Control. CONCLUSION: The HIART program is an effective exercise intervention to increase total lean soft tissue mass in middle-aged adults with low relative lean soft tissue mass compared to a waitlist control group.

Consensus guidelines for sarcopenia prevention, diagnosis and management in Australia and New Zealand.

BACKGROUND: Sarcopenia is an age-associated skeletal muscle condition characterized by low muscle mass, strength, and physical performance. There is no international consensus on a sarcopenia definition and no contemporaneous clinical and research guidelines specific to Australia and New Zealand. The Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force aimed to develop consensus guidelines for sarcopenia prevention, assessment, management and research, informed by evidence, consumer opinion, and expert consensus, for use by health professionals and researchers in Australia and New Zealand. METHODS: A four-phase modified Delphi process involving topic experts and informed by consumers, was undertaken between July 2020 and August 2021. Phase 1 involved a structured meeting of 29 Task Force members and a systematic literature search from which the Phase 2 online survey was developed (Qualtrics). Topic experts responded to 18 statements, using 11-point Likert scales with agreement threshold set a priori at >80%, and five multiple-choice questions. Statements with moderate agreement (70%-80%) were revised and re-introduced in Phase 3, and statements with low agreement (<70%) were rejected. In Phase 3, topic experts responded to six revised statements and three additional questions, incorporating results from a parallel Consumer Expert Delphi study. Phase 4 involved finalization of consensus statements. RESULTS: Topic experts from Australia (n = 62, 92.5%) and New Zealand (n = 5, 7.5%) with a mean ± SD age of 45.7 ± 11.8 years participated in Phase 2; 38 (56.7%) were women, 38 (56.7%) were health professionals and 27 (40.3%) were researchers/academics. In Phase 2, 15 of 18 (83.3%) statements on sarcopenia prevention, screening, assessment, management and future research were accepted with strong agreement. The strongest agreement related to encouraging a healthy lifestyle (100%) and offering tailored resistance training to people with sarcopenia (92.5%). Forty-seven experts participated in Phase 3; 5/6 (83.3%) revised statements on prevention, assessment and management were accepted with strong agreement. A majority of experts (87.9%) preferred the revised European Working Group for Sarcopenia in Older Persons (EWGSOP2) definition. Seventeen statements with strong agreement (>80%) were confirmed by the Task Force in Phase 4. CONCLUSIONS: The ANZSSFR Task Force present 17 sarcopenia management and research recommendations for use by health professionals and researchers which includes the recommendation to adopt the EWGSOP2 sarcopenia definition in Australia and New Zealand. This rigorous Delphi process that combined evidence, consumer expert opinion and topic expert consensus can inform similar initiatives in countries/regions lacking consensus on sarcopenia.

Effectiveness of a complex intervention of group-based nutrition and physical activity to prevent frailty in pre-frail older adults (SUPER): a randomised controlled trial.

BACKGROUND: The increasing prevalence of frailty with age is becoming a public health priority in countries with ageing populations. Pre-frailty presents a window of opportunity to prevent the development of frailty in community-dwelling older adults. This study aimed to examine the effectiveness of a complex intervention that combined a nutrition-based intervention and a physical activity intervention, along with the effectiveness of each intervention individually, to reduce physical frailty in pre-frail older adults over 2 years. METHODS: In this single-blind, 2 x 2 factorial, randomised, controlled trial, we recruited pre-frail community-dwelling older adults in Aotearoa New Zealand via mail through general medical practices. To be eligible, participants had to be pre-frail according to self-reported FRAIL scores of 1 or 2, aged 75 years or older (or 60 years or older for Maori and Pacific Peoples), not terminally ill or with advanced dementia as judged by a general practitioner, able to stand, medically safe to participate in low-intensity exercise, and able to use kitchen utensils safely. Participants were randomly allocated to receive an 8-week Senior Chef programme (SC group), a 10-week Steady As You Go programme (SAYGO group), a 10-week combined SC and SAYGO intervention (combined group), or a 10-week social programme (control group), using computer-generated block randomisation administered through an electronic data capture system by local study coordinators. Assessors were masked to group allocation for all assessments. SC is a group-based nutrition education and cooking class programme (3 h weekly), SAYGO is a group-based strength and balance exercise programme (1 h weekly), and the social control programme was a seated, group socialising activity (once a week). Masked assessors ascertained Fried frailty scores at baseline, end of intervention, and at 6, 12, and 24 months after the programme. The primary outcome was change in Fried frailty score at 2 years. Intention-to-treat analyses were completed for all randomised participants, and all participants who had a high (≥75%) adherence were analysed per protocol. This study is registered at ANZCTR, ACTRN12614000827639. FINDINGS: Between May 12, 2016 and April 9, 2018, we assessed 2678 older adults for eligibility, of whom 468 (17%) consented and completed baseline assessment, with a mean age of 80·3 years (SD 5·1) and a mean Fried score of 1·9 (1·2); 59% were women. We randomly allocated these participants into the four groups: 117 in the SC group, 118 in the SAYGO group, 118 in the combined group, and 115 in the control group; 318 participants attended the 24-month follow-up: 89 in the SC group, 78 in the SAYGO group, 73 in the combined group, and 78 in the control group. At the 24-month follow-up, there were no differences in mean Fried scores between the intervention groups and the control group. No adverse events were reported. INTERPRETATION: The study did not find that the combined SC and SAYGO programme was effective in reducing frailty in pre-frail older adults. Although some short-term benefits were observed in each individual programme, there was no clear evidence of long-term impact. Further research is needed to evaluate combinations of group-based programmes for community-dwelling older adults to optimise their physical function. FUNDING: Health Research Council New Zealand and Ageing Well Challenge (Ministry of Business Innovation and Employment).

Chemotherapy Agents Alter Plasma Lipids in Breast Cancer Patients and Show Differential Effects on Lipid Metabolism Genes in Liver Cells.

Cardiovascular complications have emerged as a major concern for cancer patients. Many chemotherapy agents are cardiotoxic and some appear to also alter lipid profiles, although the mechanism for this is unknown. We studied plasma lipid levels in 12 breast cancer patients throughout their chemotherapy. Patients received either four cycles of doxorubicin and cyclophosphamide followed by weekly paclitaxel or three cycles of epirubicin, cyclophosphamide and 5'-fluorouracil followed by three cycles of docetaxel. Patients demonstrated a significant reduction (0.32 mmol/L) in high density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA1) levels (0.18 g/L) and an elevation in apolipoprotein B (apoB) levels (0.15 g/L) after treatment. Investigation of the individual chemotherapy agents for their effect on genes involved in lipoprotein metabolism in liver cells showed that doxorubicin decreased ATP binding cassette transporter A1 (ABCA1) via a downregulation of the peroxisomal proliferator activated receptor γ (PPARγ) and liver X receptor α (LXRα) transcription factors. In contrast, ABCA1 levels were not affected by cyclophosphamide or paclitaxel. Likewise, apoA1 levels were reduced by doxorubicin and remained unaffected by cyclophosphamide and paclitaxel. Doxorubicin and paclitaxel both increased apoB protein levels and paclitaxel also decreased low density lipoprotein receptor (LDLR) protein levels. These findings correlate with the observed reduction in HDL-C and apoA1 and increase in apoB levels seen in these patients. The unfavourable lipid profiles produced by some chemotherapy agents may be detrimental in the longer term to cancer patients, especially those already at risk of cardiovascular disease (CVD). This knowledge may be useful in tailoring effective follow-up care plans for cancer survivors.

Testosterone and Adipokines are Determinants of Physical Performance, Strength, and Aerobic Fitness in Frail, Obese, Older Adults.

In this study, we evaluated the independent and combined effects of baseline circulating gonadal, anabolic hormones and adipokines on physical function in 107 frail, obese (BMI ≥ 30 kg/m(2)), and older (≥65 yr) subjects. Our results showed significant positive correlations between circulating testosterone and insulin growth factor-1 (IGF-1) with knee flexion, knee extension, one-repetition maximum (1-RM), and peak oxygen consumption (VO2 peak), while no correlation was observed with estradiol. Among the adipokines, high sensitivity C-reactive protein (Hs-CRP) and leptin negatively correlated with the modified physical performance testing (PPT), knee flexion, knee extension, 1-RM, and VO2 peak. Interleukin-6 ( Il-6) negatively correlated with knee flexion and VO2 peak and soluble tumor necrosis factors receptor-1 (sTNFr1) correlated with PPT, 1-RM, and VO2 peak. Adiponectin correlated negatively with 1-RM. Multiple regression analysis revealed that, for PPT, sTNFr1 was the only independent predictor. Independent predictors included adiponectin, leptin, and testosterone for knee flexion; leptin and testosterone for knee extension; adiponectin, leptin, and testosterone for 1-RM; and IGF-1, IL-6, leptin, and testosterone for VO2 peak. In conclusion, in frail obese older adults, circulating levels of testosterone, adiponectin, and leptin appear to be important predictors of physical strength and fitness, while inflammation appears to be a major determinant of physical frailty.

Evolution of a health navigator model of care within a primary care setting: a case study.

OBJECTIVE: Patient navigation originated as an approach for reducing disparities in cancer care and consequent health outcomes. Over time navigator models have evolved and been used to address various health issues in differing contexts. This case study outlines the evolution, purpose and effects of a lay-led health navigator model in a deprived, sparsely populated, New Zealand rural setting, where primary care services are frequently understaffed and routinely overstretched. METHODS: Routinely collected service utilisation data, survey results and health navigator interview data were utilised to illustrate the client group the service works with, why primary care refer to the service, as well as lessons learned from implementation to ongoing service provision. RESULTS: Those referred to the navigator service generally represented the most vulnerable in the community. Survey respondents, overall, were highly satisfied with the service. Navigators identified barriers and facilitators to implementation, as well as ongoing obstacles and enablers to service provision. CONCLUSIONS: This lay-led navigator service provided support to a group of unwell individuals, with few resources and multiple barriers to negotiate, and has effectively engaged with health and social care services, while overcoming various barriers and obstacles to its establishment and ongoing operation.

Using accelerometers and GPS units to identify the proportion of daily physical activity located in parks with playgrounds in New Zealand children.

OBJECTIVE: To identify the proportion of children's physical activity occurring in public parks with playgrounds. METHODS: Children (n=184) aged 5 to 10 years were recruited from schools located in two low socio-economic status communities in Dunedin, New Zealand. Accelerometers (Actigraph GT1M) and global positioning system units (Globalsat DG-100) were used to quantify and identify where physical activity had occurred over a 7-day period. Cross-sectional data were collected October to December 2007 (southern hemisphere spring) and the child's height and weight were measured at school. RESULTS: At least 84% of participants had accelerometer and global positioning system data available for five or more hourly periods per day, for at least 4 days. Overall, 1.9% of recorded activity took place at city parks (95% confidence interval: 1.4, 2.4), although this was 2.7% (95% confidence intervals: 0.7, 4.6) among obese children. CONCLUSIONS: Accelerometers and GPS data was able to be successfully recorded and matched among this age group. The proportion of children's activity taking place in parks with playgrounds was low, although this may still be important for some subgroups.

Estradiol effects on the growth hormone/insulin-like growth factor-1 axis in amenorrheic athletes.

Disruption of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis has been reported and studied in menopause, hypothalamic amenorrhea, and anorexia nervosa, but not in weight-stable amenorrheic athletes. We investigated the effects of short-term transdermal estradiol on basal and exercise-stimulated serum GH, IGF-1, and associated binding proteins (IGFBP-1 and IGFBP-3) in seven weight-stable female amenorrheic athletes with percentage body fats greater that 12%. Each subject received a 72 h placebo patch followed by 144 h of transdermal estradiol. Serum samples for GH, IGF-1, IGFBP-1, and IGFBP-3 were obtained at baseline (t1), 72 hr (t2), 144 hr (t3), and during three 90-minute trials of aerobic exercise. Basal, and exercise GH, IGF-1, and IGFBP-1 were not different between trials. Baseline IGFBP-3 decreased from t1 to t2 (p = 0.04) and serum free fatty acids increased from t1 to t2, and t1 to t3 (p = 0.04, and 0.02 respectively). These findings differ from postmenopausal women, and women having weightloss-associated amenorrhea, suggesting that estrogen, exercise, and nutritional deficiencies may have independent effects on the GH/IGF-1 axis.

Skeletal muscle mitochondrial function and lean body mass in healthy exercising elderly.

BACKGROUND: The decline in muscle mass (sarcopenia) with aging may be related to a decline in mitochondrial function. However, investigators have yet to reach a consensus as to whether a decline in mitochondrial function can be attenuated by physical activity has yet to reach a consensus. METHODS: Using dynamic 31PMRS to measure mitochondrial function, we measured baseline Phosphocreatine (PCr), inorganic phosphate (Pi), phosphodiester (PDE), [ADP], pH and recovery times (t(1/2)) for PCr and [ADP] following exercise, in 45 older (73+/-4 years, SD), and 20 younger subjects (25+/-4 years, SD) who were matched for body mass across high and low activity levels and within age and sex groupings. RESULTS: Baseline PCr, and Pi, were lower, and PDE higher in the older subjects compared to younger subjects (all P<0.01). The t(1/2)(ADP) was longer in older subjects (P<0.001) controlling for age and sex in the low activity group (P=0.02). In the older low activity groups, t(1/2)(PCr) was longer than high activity groups. Higher PDE levels were positively correlated with longer t(1/2)(PCr) in the older low activity females (both P<0.05). CONCLUSIONS: Our data suggests that mitochondrial function declines with age in healthy, exercising elderly adults and that the decline appears to be influenced by the level of physical activity.