Prevalence and factors associated with fatigue in patients with axial spondyloarthritis: a systematic review and meta-analysis.

Objectives: Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease associated with significant morbidity. Fatigue, a widely recognized disease manifestation, has considerable impacts on patients' work productivity, physical function and mental well-being. However, the reported prevalence of fatigue varies across studies, and pooled data are currently lacking. We aimed to characterize the prevalence of fatigue in patients with axSpA and to identify factors associated with fatigue. Methods: A systematic review and a meta-analysis were conducted to determine the global prevalence of fatigue in patients with axSpA. Databases including CINAHL, Embase, Medline, Cochrane Library, PubMed and Google Scholar were searched from inception until April 2023. Data were extracted, and the quality of studies was assessed. A pooled prevalence of fatigue was determined by using a random-effects model. Meta-analyses were used to determine the observed heterogeneity via subgroup analysis and associations between relevant predictors and the presence of fatigue. Results: Thirty eligible articles were included in the study, including 7893 patients with axSpA. The pooled prevalence of fatigue in patients with axSpA was 0.56 (95% CI: 0.49, 0.63; I2 = 94.6%), with significant levels of heterogeneity. Among the factors of heterogeneity explored, the geographical region of the study (P = 0.0013) was significant for being a possible source. Poorer quality of life was associated with more fatigue (P < 0.05). Conclusion: More than half of patients with axSpA experience fatigue, with poorer quality of life being associated with more fatigue.

The effects of physical exercise in the palliative care phase for people with advanced cancer: a systematic review with meta-analysis.

PURPOSE: The purpose of this systematic review with meta-analysis was to evaluate the safety, feasibility and effectiveness of exercise in the palliative care phase for people with advanced cancer. METHODS: Electronic databases were searched for exercise randomised controlled trials involving individuals with incurable cancer that were published prior to April 14, 2021. Meta-analyses were performed to evaluate the effects of exercise on health outcomes. Subgroup effects for exercise mode, supervision, intervention duration and cancer diagnosis were assessed. RESULTS: Twenty-two trials involving interventions ranging between 2 weeks and 6 months were included. Interventions comprised of aerobic (n = 3), resistance (n = 4), mixed-mode (n = 14) and other exercise (n = 1) modalities. Cancer types consisted of lung (n = 6), breast (n = 3), prostate (n = 2), multiple myeloma (n = 1) and mixed cancer types (n = 10). Meta-analysis of 20 RCTs involving 1840 participants showed no difference in the risk of a grade 2-4 adverse event between exercise and usual care (n = 110 adverse events (exercise: n = 66 events; usual care: n = 44 events), RD = - 0.01 (91% CI = - 0.01, 0.02); p = 0.24). Overall median recruitment, retention and adherence rates were 56%, 80% and 69%, respectively. Meta-analysis of health outcomes showed effects in favour of exercise for quality of life, fatigue, aerobic fitness and lower-body strength (SMD range = 0.27-0.48, all p < 0.05). CONCLUSIONS: Participants who engaged in exercise experienced an increase in quality of life, fitness and strength and a decrease in fatigue. IMPLICATIONS FOR CANCER SURVIVORS: Physical activity programs were found to be safe and feasible for people with advanced cancer in the palliative care phase.

Performance fatigability during isometric vs. concentric quadriceps fatiguing tasks in men and women.

In the present study, we aimed to provide a robust comparison of the fatigability of the knee extensors following isometric (ISO) and concentric (CON) tasks. Twenty young adults (25 ± 4 yr, 10 women) randomly performed the ISO and CON quadriceps intermittent fatigue test, consisting of ten (5 s on/5-s off, ISO) or one-hundred (0.5-s on/0.5-s off, CON) contractions with 10 % increments per stage until exhaustion. Performance fatigability was quantified as maximal isometric (MVIC) and concentric (MVCC) torque loss. Voluntary activation and contractile function (peak-twitch) were investigated using peripheral nerve stimulation. Number of stages (6.2 ± 0.7 vs. 4.9 ± 0.8; P < 0.001) and torque-time integral (20,166 ± 7,821 vs. 11,285 ± 4,933 Nm.s; P < 0.001) were greater for ISO than CON. MVIC, MVCC and voluntary activation decreased similarly between sessions (P > 0.05) whereas peak-twitch amplitude decreased more for CON (P < 0.001). The number of contractions was similar across sexes (ISO: men = 62 ± 8, women = 61 ± 5; CON: men = 521 ± 67, women = 458 ± 76, P > 0.05). MVCC was more reduced in women for both sessions (all P < 0.05), while MVIC loss was similar between sexes. We concluded that, despite greater torque-time integral and duration for ISO, both sessions induced a similar performance fatigability at exhaustion. Contractile function was more altered in CON. Finally, sex-related difference in fatigability depends on the contraction mode used during testing.

Exercise Adherence in Men with Prostate Cancer Undergoing Androgen Deprivation Therapy: A Systematic Review and Meta-Analysis.

Androgen deprivation therapy (ADT) for prostate cancer treatment is associated with adverse physiological changes; however, exercise can improve outcomes. This systematic review and meta-analysis aimed to determine exercise intervention adherence and its effects on physiological outcomes in men diagnosed with prostate cancer undergoing ADT. Uniquely, this review incorporated a meta-aggregation of qualitative data, providing perspectives from the men's experiences. A systematic review and meta-analysis were completed following PRISMA guidelines. Databases (CINAHL, Cochrane, PubMed) were searched for studies using "prostate cancer", "exercise intervention", and "androgen deprivation therapy". Quantitative randomised controlled trials describing adherence to exercise interventions were selected, with qualitative articles selected based on descriptions of experiences around participation. Subgroup meta-analyses of adherence, exercise mode, and intervention duration were completed for quality of life, aerobic fitness, fatigue, and strength. In total, 644 articles were identified, with 29 (n = 23 quantitative; n = 6 qualitative) articles from 25 studies included. Exercise had no effects (p < 0.05) on quality of life and fatigue. Significant effects (all p < 0.05) were observed for aerobic fitness, and upper- and lower-body strength. Adherence to exercise-based interventions was 80.38%, with improvements observed in aerobic fitness and strength. Subgroup analysis revealed exercise adherence impacted fatigue and strength, with greater improvements observed in programs >12-weeks.

Pulmonary tuberculosis and COVID-19 coinfection: Hickam's Dictum revisited.

COVID-19 and pulmonary tuberculosis (PTB) coinfection is associated with increased mortality and presents a unique diagnostic challenge to the clinician. We describe three cases of newly diagnosed PTB in COVID-19 patients treated at our centre and their clinical and radiological features. The challenges associated with diagnosis and management are also explored. Patient 1 was a case of smear positive, endobronchial tuberculosis incidentally diagnosed due to CT changes, and eventually made good recovery. Patient 2 was a case of COVID-19 who succumbed but was diagnosed posthumously due to a positive sputum culture for tuberculosis. Patient 3 showed radiographic features of PTB and was treated empirically for TB. In conclusion, COVID-19 and PTB coinfection should be suspected in the presence of constitutional symptoms, prior immunocompromised states, prolonged respiratory symptoms or fever, or unresolved radiological abnormalities, more so in regions where TB is endemic.

A Randomised, Comparative, Effectiveness Trial Evaluating Low- versus High-Level Supervision of an Exercise Intervention for Women with Breast Cancer: The SAFE Trial.

The aim of this comparative, effectiveness trial was to evaluate the safety, feasibility and effect of an exercise intervention delivered via low-level versus high-level supervision. The target population were women who were diagnosed with ≥stage II breast cancer, had ≥ one comorbidity and/or persistent treatment-related side-effects, and were insufficiently physically active. Sixty women (50 ± 9 years) were randomized to the low-supervision group (n = 30) or high-supervision group (n = 30). The low-supervision group participated in a 12-week, individually-tailored exercise intervention supported by five supervised sessions with an exercise professional. The high-supervision group participated in the same exercise intervention but received 20 supervised sessions across the 12-week period. The target weekly dosage of 600 metabolic equivalent minutes of exercise per week (MET-mins/wk) and the session content, such as safety and behaviour change topics, were standardized between the groups. The primary outcomes were intervention safety, defined as the number, type, and severity of exercise-related adverse events (e.g., musculoskeletal injury or exacerbated treatment-related side effects), and feasibility, which was defined as compliance to target exercise dosage. The effect of the intervention on quality of life, physical activity, self-efficacy, fitness, and strength was also assessed (pre- and post-intervention, and at 12-week follow-up). The intervention was safe, with no exercise-related adverse events of grade 3 or above in either group. Both groups reported high compliance to the target exercise dosage (median MET-mins/wk: High = 817; Low = 663), suggesting the exercise intervention was feasible, irrespective of supervision level. Improvements in quality of life, physical activity and fitness were observed post-intervention and maintained at follow-up for both groups (p < 0.05). Only the high-supervision group showed clinically-relevant improvements in strength and self-efficacy at post-intervention (p < 0.05). Individually-targeted exercise delivered under high- or low-levels of supervision is safe, feasible and beneficial for women with stage II+ breast cancer. Future research needs to assess whether the greater gains observed in the group who received higher supervision may contribute to longer term maintenance of physical activity levels and overall health benefits. Australian and New Zealand Clinical Trials Registry: ACTRN12616000547448.

The effect of exercise for improving bone health in cancer survivors - A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of exercise for improving bone-related outcomes among cancer survivors. DESIGN: Systematic review and meta-analysis. METHODS: An electronic search using the following databases: SPORTDiscus, Science Direct, CINAHL, MEDLINE, Cochrane, Pubmed, Ebscohost, ProQuest Nursing and Allied Health Source. Randomised, controlled, exercise trials involving cancer survivors were eligible. Effect data on bone mineral content (BMC) and density (BMD) outcomes were extracted. Risk of bias was assessed using the Physiotherapy Evidence Database tool. Standardised mean differences (SMD) were calculated to compare differences between exercise and usual care. Subgroup analyses were conducted to assess whether effect differed by exercise mode, intervention length, supervision, treatment, cancer type and risk of bias. RESULTS: Twenty-six trials were included, with intervention durations ranging between 12 weeks and 2 years. Most trials involved breast cancer (n = 13, 50%), and most interventions were supervised (n = 18, 69%) and evaluated mixed-mode (i.e., combined aerobic and resistance) exercise (n = 13, 50%). Significant effects in favour of exercise (aerobic, resistance, mixed-mode and other exercise) were observed for whole body BMD, hip BMD, trochanter BMD and femoral neck BMD (SMD range: 0.19-0.39, all p < 0.05) compared to usual care. CONCLUSION: Participation in various modes (aerobic, resistance, mixed-mode and other) of supervised and unsupervised exercise is associated with improvements in BMD. The present results provide evidence for clinicians and other health care professionals (e.g., exercise physiologists and physiotherapists) to recommend exercise for cancer survivors to prevent bone loss during and following treatment.

Effect and feasibility of wearable physical activity trackers and pedometers for increasing physical activity and improving health outcomes in cancer survivors: A systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the effect of wearable devices for improving physical activity and health-related outcomes in cancer survivors. METHODS: CINAHL, Cochrane, Ebscohost, MEDLINE, Pubmed, ProQuest Health and Medical Complete, ProQuest Nursing and Allied Health Source, ScienceDirect, and SPORTDiscus databases were searched for randomized controlled trials published before September 1, 2020, that evaluated interventions involving wearable devices in cancer survivors. Standardized mean differences (SMDs) were calculated to assess effects on physical activity and health-related outcomes. Subgroup analyses were conducted to assess whether the effects differed by interventions and cancer characteristics. Risk of bias was assessed using the Cochrane risk of bias tool. RESULTS: Thirty-five trials were included (breast cancer, n = 15, 43%). Intervention durations ranged between 4 weeks and 1 year. Most trials (n = 25, 71%) involved pedometer-based physical activity interventions. Seven (20%) involved Fitbit-based interventions, and 3 (9%) involved other wearable physical activity trackers (e.g., Polar, Garmin). Compared to usual care, wearable devices had moderate-to-large effects (SMD range 0.54-0.87, p < 0.001) on moderate-intensity physical activity, moderate-to-vigorous-intensity physical activity, total physical activity, and daily steps. Compared to usual care, those in the intervention had higher quality of life, aerobic fitness, physical function, and reduced fatigue (SMD range = 0.18-0.66, all p < 0.05). CONCLUSION: Wearable physical activity trackers and pedometers are effective tools that increase physical activity and improve health-related outcomes in individuals with cancer. Identifying how these devices can be implemented for longer-term use with other intervention components remains an area for future research.

Toxic Effects of High-dose Meloxicam and Carprofen on Female CD1 Mice.

The nonsteroidal anti-inflammatory drugs meloxicam and carprofen are commonly used as analgesics in mice. The current recommended doses of meloxicam at 0.2-1.0 mg/kg once daily and carprofen at 5-10 mg/kg twice daily may not be adequate to provide analgesia in mice. Several studies have suggested that doses up to 20 mg/kg of meloxicam and carprofen are needed to provide analgesic efficacy. This study investigated the clinical safety of these higher doses of meloxicam and carprofen by evaluating their potential for renal and gastrointestinal toxicity. Female CD-1 mice were given 20 mg/kg of either meloxicam, carprofen, or an equivalent volume of saline subcutaneously once daily for 3 or 7 d. On day 4, mice treated for 3 d were euthanized, and on days 8 and 15, mice treated for 7 d were euthanized. Blood was collected by cardiocentesis for serum chemistry analysis. Feces was collected from the colon for fecal occult blood testing, and tissues were collected for histopathology. No clinically significant changes in serum chemistry profiles were found in the drug-treated mice at any time point as compared with the saline controls. Fecal occult blood and histologic evidence of gastritis was associated with meloxicam administration in mice evaluated at days 4 and 8. By day 15, there was no association with meloxicam treatment and the presence of fecal occult blood or gastritis. There was no association between fecal occult blood and gastritis in the carprofen or saline-treated mice regardless of the treatment durations. These findings suggest that 20 mg/kg of meloxicam in mice causes gastric toxicity when given for 3 or 7 d and should be used cautiously; however, carprofen at 20 mg/kg appears to have minimal toxic effects with regard to the parameters measured.

Effect of race distance on performance fatigability in male trail and ultra-trail runners.

The etiology of changes in lower-limb neuromuscular function, especially to the central nervous system, may be affected by exercise duration. Direct evidence is lacking as few studies have directly compared different race distances. This study aimed to investigate the etiology of deficits in neuromuscular function following short versus long trail-running races. Thirty-two male trail runners completed one of five trail-running races as LONG (>100 km) or SHORT (<60 km). Pre- and post-race, maximal voluntary contraction (MVC) torque and evoked responses to electrical nerve stimulation during MVCs and at rest were used to assess voluntary activation and muscle contractile properties of knee-extensor (KE) and plantar-flexor (PF) muscles. Transcranial magnetic stimulation (TMS) was used to assess evoked responses and corticospinal excitability in maximal and submaximal KE contractions. Race distance correlated with KE MVC (ρ = -0.556) and twitch (ρ = -0.521) torque decreases (p ≤ .003). KE twitch torque decreased more in LONG (-28 ± 14%) than SHORT (-14 ± 10%, p = .005); however, KE MVC time × distance interaction was not significant (p = .073). No differences between LONG and SHORT for PF MVC or twitch torque were observed. Maximal voluntary activation decreased similarly in LONG and SHORT in both muscle groups (p ≥ .637). TMS-elicited silent period decreased in LONG (p = .021) but not SHORT (p = .912). Greater muscle contractile property impairment in longer races, not central perturbations, contributed to the correlation between KE MVC loss and race distance. Conversely, PF fatigability was unaffected by race distance.

Sex Differences in Neuromuscular Fatigue and Changes in Cost of Running after Mountain Trail Races of Various Distances.

INTRODUCTION: Women have been shown to experience less neuromuscular fatigue than men in knee extensors (KE) and less peripheral fatigue in plantar flexors (PF) after ultratrail running, but it is unknown if these differences exist for shorter trail running races and whether this may impact running economy. The purpose of this study was to characterize sex differences in fatigability over a range of running distances and to examine possible differences in the postrace alteration of the cost of running (Cr). METHODS: Eighteen pairs of men and women were matched by performance after completing different races ranging from 40 to 171 km, divided into SHORT versus LONG races (<60 and >100 km, respectively). Neuromuscular function and Cr were tested before and after each race. Neuromuscular function was evaluated on both KE and PF with voluntary and evoked contractions using electrical nerve (KE and PF) and transcranial magnetic (KE) stimulation. Oxygen uptake, respiratory exchange ratio, and ventilation were measured on a treadmill and used to calculate Cr. RESULTS: Compared with men, women displayed a smaller decrease in maximal strength in KE (-36% vs -27%, respectively, P < 0.01), independent of race distance. In SHORT only, women displayed less peripheral fatigue in PF compared with men (Δ peak twitch: -10% vs -24%, respectively, P < 0.05). Cr increased similarly in men and women. CONCLUSIONS: Women experience less neuromuscular fatigue than men after both "classic" and "extreme" prolonged running exercises but this does not impact the degradation of the energy Cr.

French Translation and Validation of the Rating-of-Fatigue Scale.

BACKGROUND: The Rating of Fatigue (ROF) scale can measure changes in perceived fatigue in a variety of contexts. OBJECTIVE: The aim of the present study was to translate and subsequently validate the ROF scale in the French language. METHODS: The study was composed of three phases. Phase 1 involved a comprehensive translation, back-translation, and consolidation process in order to produce the French ROF scale. During phase 2, the face validity of the French ROF scale was assessed. A cohort of 60 native French speaking participants responded to a range of Likert scale items which probed the purposes of the ROF scale and what it is intended to measure. During phase 3, the convergent and divergent validity of the ROF scale was assessed during ramped cycling to exhaustion and 10 min of resting recovery. RESULTS: The results from phase 1 demonstrated comparability and interpretability between the original and back-translated ROF scale. In phase 2, participants reported a high face validity, with a score of 3.48 ± 0.70 out of 4 when given the item probing whether the scale "measures fatigue". This score further improved (3.67 ± 0.57, P = 0.01) after participants read the accompanying instructions. Participants were able to distinguish the purposes of the scale for measuring fatigue rather than exertion. In phase 3, strong correlations were found between ROF and heart rate (HR) both during exercise (r = 0.91, P < 0.01) and recovery (r = 0.92, P < 0.01), while discriminant validity between ROF and rating of perceived exertion (RPE) was found during recovery. CONCLUSION: The present study permits the applications of the ROF scale in the French language.

Arthritis as an initial presentation of malignancy: two case reports.

BACKGROUND: Arthritis is rarely reported as a paraneoplastic manifestation of occult malignancy. We report herein two cases of paraneoplastic arthritis due to occult malignancy. CASE 1: The patient was a 65-year-old woman of asian descent who was a former smoker with a history of spine surgery performed for L4/L5 degenerative disc disease. She presented with a 1-month history of oligoarthritis affecting both ankle joints and early morning stiffness of about 3 hours. Laboratory tests were positive for antinuclear antibody at a titer of 1:320 (speckled) but negative for rheumatoid factor. She was treated for seronegative spondyloarthritis and started on prednisolone without much improvement. A routine chest radiograph incidentally revealed a right lung mass which was found to be adenocarcinoma of the lung. She was treated with gefitinib and her arthritis resolved. CASE 2: The patient was a 64-year-old woman of asian descent, nonsmoker, who presented with a chief complaint of asymmetrical polyarthritis involving her right wrist, second and third metacarpophalangeal joints, and first to fifth proximal interphalangeal joints. She was treated for seronegative rheumatoid arthritis (RA) and started on sulfasalazine, with poor clinical response. Six months later, she developed abdominal pain which was diagnosed as ovarian carcinoma by laparotomy. Her arthritis resolved following treatment of her malignancy with chemotherapy. CONCLUSION: In summary, paraneoplastic arthritis usually presents in an atypical manner and responds poorly to disease-modifying antirheumatic drugs. Accordingly, we recommend screening for occult malignancy in patients presenting with atypical arthritis.

Reliability and agreement of a dynamic quadriceps incremental test for the assessment of neuromuscular function.

The quadriceps-intermittent-fatigue (QIF) test assesses knee extensors strength, endurance and performance fatigability in isometric condition. We aimed to assess reliability and agreement for this test in dynamic conditions and with the use of transcranial magnetic stimulation. On two separate sessions, 20 young adults (25 ± 4 yr, 10 women) performed stages of 100 knee extensors concentric contractions at 120°/s (60° range-of-motion) with 10% increments of the initial maximal concentric torque until exhaustion. Performance fatigability across the test was quantified as maximal isometric and concentric torque loss, and its mechanisms were investigated through the responses to transcranial magnetic and electrical stimulations. Reliability and agreement were assessed using ANOVAs, coefficients of variation (CVs) and intra-class correlation coefficients (ICCs) with 95% CI. Good inter-session reliability and high agreement were found for number of contractions [489 ± 75 vs. 503 ± 95; P = 0.20; ICC = 0.85 (0.66; 0.94); CV = 5% (3; 7)] and total work [11,285 ± 4,932 vs. 11,792 ± 5838 Nm.s; P = 0.20; ICC = 0.95 (0.87; 0.98); CV = 8% (5; 11)]. Poor reliability but high agreement were observed for isometric [-33 ± 6 vs. -31 ± 7%; P = 0.13; ICC = 0.47 (0.05; 0.75); CV = 6% (4;8)] and concentric [-20 ± 11% vs. -19 ± 9%; P = 0.82; ICC = 0.26 (-0.22; 0.63); CV = 9% (6; 12)] torque loss. The dynamic QIF test represents a promising tool for neuromuscular evaluation in isokinetic mode.

Pharmacokinetics and Efficacy of a Long-lasting, Highly Concentrated Buprenorphine Solution in Mice.

Buprenorphine is a commonly used opioid for mitigating pain in laboratory mice after surgical procedures; however, the dosing interval necessary for standard buprenorphine may require treatment every 4 to 6 h to maintain an adequate plane of analgesia. An alternative formulation that provides prolonged plasma concentration with long-lasting effects would be beneficial in achieving steady-state analgesia. We evaluated a long-lasting and highly concentrated formulation of buprenorphine (Bup-LHC) in mice. Pharmacokinetic analysis was performed to assess plasma concentrations in male C57BL/6J (B6) and female CD1 mice after subcutaneous injection of 0.9 mg/kg. The Bup-LHC formulation provided plasma drug levels that exceeded the therapeutic level for at least 12 h in male B6 mice and was below therapeutic levels by 8 h in female CD1 mice. An experimental laparotomy model was used to assess analgesic efficacy. Female CD1 mice were treated with either Bup-LHC (0.9 mg/kg) or saline at 1 h before undergoing an ovariectomy via a ventral laparotomy. At 3, 6, 12, 24, and 48 h after surgery, pain was assessed based on the following behaviors: orbital tightness, grooming, wound licking, rearing, arched posture, ataxia, piloerection, nest building, and general activity. At 3 and 6 h after surgery, Bup-LHC-treated mice had significantly less wound licking and orbital tightness and considerably higher activity levels than did saline-treated mice. At 12 h, wound licking, orbital tightness and activity in Bup-LHC-treated mice were no longer significantly different from those of saline-treated mice. The results of this study suggest that Bup-LHC at 0.9 mg/kg provides sufficient plasma concentrations for analgesia in mice for 6 to 12 h after administration, as demonstrated behaviorally for at least 6 h after surgery.