IMPORTANCE: Parkinson disease is a progressive neurologic disorder. Limited evidence suggests endurance exercise modifies disease severity, particularly high-intensity exercise. OBJECTIVES: To ...examine the feasibility and safety of high-intensity treadmill exercise in patients with de novo Parkinson disease who are not taking medication and whether the effect on motor symptoms warrants a phase 3 trial. DESIGN, SETTING, AND PARTICIPANTS: The Study in Parkinson Disease of Exercise (SPARX) was a phase 2, multicenter randomized clinical trial with 3 groups and masked assessors. Individuals from outpatient and community-based clinics were enrolled from May 1, 2012, through November 30, 2015, with the primary end point at 6 months. Individuals with idiopathic Parkinson disease (Hoehn and Yahr stages 1 or 2) aged 40 to 80 years within 5 years of diagnosis who were not exercising at moderate intensity greater than 3 times per week and not expected to need dopaminergic medication within 6 months participated in this study. A total of 384 volunteers were screened by telephone; 128 were randomly assigned to 1 of 3 groups (high-intensity exercise, moderate-intensity exercise, or control). INTERVENTIONS: High-intensity treadmill exercise (4 days per week, 80%-85% maximum heart rate n = 43), moderate-intensity treadmill exercise (4 days per week, 60%-65% maximum heart rate n = 45), or wait-list control (n = 40) for 6 months. MAIN OUTCOMES AND MEASURES: Feasibility measures were adherence to prescribed heart rate and exercise frequency of 3 days per week and safety. The clinical outcome was 6-month change in Unified Parkinson’s Disease Rating Scale motor score. RESULTS: A total of 128 patients were included in the study (mean SD age, 64 9 years; age range, 40-80 years; 73 57.0% male; and 108 84.4% non-Hispanic white). Exercise rates were 2.8 (95% CI, 2.4-3.2) days per week at 80.2% (95% CI, 78.8%-81.7%) maximum heart rate in the high-intensity group and 3.2 (95% CI, 2.8-3.6; P = .13) days per week at 65.9% (95% CI, 64.2%-67.7%) maximum heart rate in the moderate-intensity group (P < .001). The mean change in Unified Parkinson’s Disease Rating Scale motor score in the high-intensity group was 0.3 (95% CI, −1.7 to 2.3) compared with 3.2 (95% CI, 1.4 to 5.1) in the usual care group (P = .03). The high-intensity group, but not the moderate-intensity group, reached the predefined nonfutility threshold compared with the control group. Anticipated adverse musculoskeletal events were not severe. CONCLUSIONS AND RELEVANCE: High-intensity treadmill exercise may be feasible and prescribed safely for patients with Parkinson disease. An efficacy trial is warranted to determine whether high-intensity treadmill exercise produces meaningful clinical benefits in de novo Parkinson disease. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01506479.
Background
Tinnitus affects 10% to 15% of the adult population, with about 20% of these experiencing symptoms that negatively affect quality of life. In England alone there are an estimated ¾ million ...general practice consultations every year where the primary complaint is tinnitus, equating to a major burden on healthcare services. Clinical management strategies include education and advice, relaxation therapy, tinnitus retraining therapy (TRT), cognitive behavioural therapy (CBT), sound enrichment using ear‐level sound generators or hearing aids, and drug therapies to manage co‐morbid symptoms such as insomnia, anxiety or depression. Hearing aids, sound generators and combination devices (amplification and sound generation within one device) are a component of many tinnitus management programmes and together with information and advice are a first line of management in audiology departments for someone who has tinnitus.
Objectives
To assess the effects of sound therapy (using amplification devices and/or sound generators) for tinnitus in adults.
Search methods
The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL, via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 23 July 2018.
Selection criteria
Randomised controlled trials (RCTs) recruiting adults with acute or chronic subjective idiopathic tinnitus. We included studies where the intervention involved hearing aids, sound generators or combination hearing aids and compared them to waiting list control, placebo or education/information only with no device. We also included studies comparing hearing aids to sound generators, combination hearing aids to hearing aids, and combination hearing aids to sound generators.
Data collection and analysis
We used the standard methodological procedures expected by Cochrane. Our primary outcomes were tinnitus symptom severity as measured as a global score on multi‐item tinnitus questionnaire and significant adverse effects as indicated by an increase in self‐reported tinnitus loudness. Our secondary outcomes were depressive symptoms, symptoms of generalised anxiety, health‐related quality of life and adverse effects associated with wearing the device such as pain, discomfort, tenderness or skin irritation, or ear infections. We used GRADE to assess the quality of evidence for each outcome; this is indicated in italics.
Main results
This review included eight studies (with a total of 590 participants). Seven studies investigated the effects of hearing aids, four combination hearing aids and three sound generators. Seven studies were parallel‐group RCTs and one had a cross‐over design. In general, risk of bias was unclear due to lack of detail about sequence generation and allocation concealment. There was also little or no use of blinding.
No data for our outcomes were available for any of our three main comparisons (comparing hearing aids, sound generators and combination devices with a waiting list control group, placebo or education/information only). Data for our additional comparisons (comparing these devices with each other) were also few, with limited potential for data pooling.
Hearing aid only versus sound generator device only
One study compared patients fitted with sound generators versus those fitted with hearing aids and found no difference between them in their effects on our primary outcome, tinnitus symptom severity measured with the Tinnitus Handicap Inventory (THI) at 3, 6 or 12 months (low‐quality evidence). The use of both types of device was associated with a clinically significant reduction in tinnitus symptom severity.
Combination hearing aid versus hearing aid only
Three studies compared combination hearing aids with hearing aids and measured tinnitus symptom severity using the THI or Tinnitus Functional Index. When we pooled the data we found no difference between them (standardised mean difference ‐0.15, 95% confidence interval ‐0.52 to 0.22; three studies; 114 participants) (low‐quality evidence). The use of both types of device was again associated with a clinically significant reduction in tinnitus symptom severity.
Adverse effects were not assessed in any of the included studies.
None of the studies measured the secondary outcomes of depressive symptoms or depression, anxiety symptoms or generalised anxiety, or health‐related quality of life as measured by a validated instrument, nor the newly developed core outcomes tinnitus intrusiveness, ability to ignore, concentration, quality of sleep and sense of control.
Authors' conclusions
There is no evidence to support the superiority of sound therapy for tinnitus over waiting list control, placebo or education/information with no device. There is insufficient evidence to support the superiority or inferiority of any of the sound therapy options (hearing aid, sound generator or combination hearing aid) over each other. The quality of evidence for the reported outcomes, assessed using GRADE, was low. Using a combination device, hearing aid or sound generator might result in little or no difference in tinnitus symptom severity.
Future research into the effectiveness of sound therapy in patients with tinnitus should use rigorous methodology. Randomisation and blinding should be of the highest quality, given the subjective nature of tinnitus and the strong likelihood of a placebo response. The CONSORT statement should be used in the design and reporting of future studies. We also recommend the use of validated, patient‐centred outcome measures for research in the field of tinnitus.
It is challenging to reliably assess the motor features of Parkinson's disease in real‐time. This has motivated the search for new digital outcomes that can objectively and remotely measure the ...severity of parkinsonian motor impairments over an extended period of time. The United States Food and Drug Administration (FDA) has recently granted a 510(k) clearance to the Rune Labs Kinematics System, an ambulatory, smartwatch‐based monitoring system to remotely track tremor and dyskinesias in persons with Parkinson's disease. The FDA clearance means that this new digital approach can be regarded as being safe for use in daily practice, with acceptable correlations to clinically based measures. However, the immediate implications for clinicians are limited, because it remains to be demonstrated whether the digital signals correlate well to clinically meaningful outcomes at patient level. The impact on research is also restricted for now, as more validation studies are needed before this new digital approach can be used as primary or secondary endpoint in clinical trials. ANN NEUROL 2023;93:681–685
Questionnaires are essential for measuring tinnitus severity and intervention-related change but there is no standard instrument used routinely in research settings. Most tinnitus questionnaires are ...optimised for measuring severity but not change. However, the Tinnitus Functional Index (TFI) claims to be optimised for both. It has not however been fully validated for research purposes. Here we evaluate the relevant psychometric properties of the TFI, specifically the questionnaire factor structure, reproducibility, validity and responsiveness guided by quality criteria for the measurement properties of health-related questionnaires.
The study involved a retrospective analysis of data collected for 294 members of the general public who participated in a randomised controlled trial of a novel tinnitus device (ClinicalTrials.gov Identifier: NCT01541969). Participants completed up to eight commonly used assessment questionnaires including the TFI, Tinnitus Handicap Inventory (THI), Tinnitus Handicap Questionnaire (THQ), a Visual Analogue Scale of loudness (VAS-Loudness), Percentage Annoyance question, the Beck's Depression Inventory (BDI), Beck's Anxiety Inventory (BAI), and the World Health Organisation Quality of Life-Bref (WHOQOL-BREF). A series of analyses assessed the study objectives. Forty four participants completed the TFI at a second visit (within 7–21 days and before receiving any intervention) providing data for reproducibility assessments.
The 8-factor structure was not fully confirmed for this general (non-clinical) population. Whilst it was acceptable standalone subscale, the ‘auditory’ factor showed poor loading with the higher order factor ‘functional impact of tinnitus’. Reproducibility assessments for the overall TFI indicate high internal consistency (α = 0.80) and extremely high reliability (ICC: 0.91), whilst agreement was borderline acceptable (93%). Construct validity was demonstrated by high correlations between scores on the TFI and THI (r = 0.82) and THQ (r = 0.82), moderate correlations with VAS-L (r = 0.46), PR-A (r = 0.58), BDI (r = 0.57), BAI (r = 0.39) and WHOQOL (r = −0.48). Floor effects were observed for more than 50% of the items. A smallest detectable change score of 22.4 is proposed for the TFI global score.
Even though the proposed 8-factor structure was not fully confirmed for this population, the TFI appears to cover multiple symptom domains, and to measure the construct of tinnitus with an excellent reliability in distinguishing between patients. While the TFI may discriminate those whose tinnitus is not a problem, floor effects in many items means it is less appropriate as a measure of change in this subgroup. Further investigation is needed to determine whether these effects are relevant in other populations.
Display omitted
•The TFI provides a composite measures of the functional impact of tinnitus.•The TFI has good convergent and discriminant validity and test-retest reliability.•Not all TFI subscales contribute equally to this composite measure of tinnitus.•The TFI Quality of life subscale does not assess generic quality of life.•TFI scores may be poorly responsive to change in a research population.
Daily step counts is an intuitive metric that has demonstrated success in motivating physical activity in adults and may hold potential for future public health physical activity recommendations. ...This review seeks to clarify the pattern of the associations between daily steps and subsequent all-cause mortality, cardiovascular disease (CVD) morbidity and mortality, and dysglycemia, as well as the number of daily steps needed for health outcomes.
A systematic review was conducted to identify prospective studies assessing daily step count measured by pedometer or accelerometer and their associations with all-cause mortality, CVD morbidity or mortality, and dysglycemia (dysglycemia or diabetes incidence, insulin sensitivity, fasting glucose, HbA1c). The search was performed across the Medline, Embase, CINAHL, and the Cochrane Library databases from inception to August 1, 2019. Eligibility criteria included longitudinal design with health outcomes assessed at baseline and subsequent timepoints; defining steps per day as the exposure; reporting all-cause mortality, CVD morbidity or mortality, and/or dysglycemia outcomes; adults ≥18 years old; and non-patient populations.
Seventeen prospective studies involving over 30,000 adults were identified. Five studies reported on all-cause mortality (follow-up time 4-10 years), four on cardiovascular risk or events (6 months to 6 years), and eight on dysglycemia outcomes (3 months to 5 years). For each 1000 daily step count increase at baseline, risk reductions in all-cause mortality (6-36%) and CVD (5-21%) at follow-up were estimated across a subsample of included studies. There was no evidence of significant interaction by age, sex, health conditions or behaviors (e.g., alcohol use, smoking status, diet) among studies that tested for interactions. Studies examining dysglycemia outcomes report inconsistent findings, partially due to heterogeneity across studies of glycemia-related biomarker outcomes, analytic approaches, and sample characteristics.
Evidence from longitudinal data consistently demonstrated that walking an additional 1000 steps per day can help lower the risk of all-cause mortality, and CVD morbidity and mortality in adults, and that health benefits are present below 10,000 steps per day. However, the shape of the dose-response relation is not yet clear. Data are currently lacking to identify a specific minimum threshold of daily step counts needed to obtain overall health benefit.
...while there are multiple ways of perceiving tinnitus, it is also associated with multiple causal risk factors—hearing loss, temporomandibular joint disorder, and aging being among the most common ...ones. Within this topic, current knowledge is reviewed and new theories of tinnitus generation are proposed, animal models are used to understand the neural correlates better, audiological, and psychological aspects are explored, neuroimaging techniques investigate the involved brain networks, new questionnaire instruments are developed and others adapted to new languages, genome-wide associations are pioneered, mobile applications are used to explore tinnitus on new time-scales, and, finally, multiple therapeutic approaches are tested. ...the fifth chapter refers to advances on tinnitus therapies. Age-related hearing loss and tinnitus can go hand in hand and one of the most well-established theories considers tinnitus as the perceptual consequence of neuronal hyperactivity in the central auditory system; emerging after loss of normal input from the ear.
People with tinnitus report anecdotal difficulties in mental concentration and psychological treatments for tinnitus advise on concentration difficulties and how to manage them. Yet the literature ...lacks any coherent discussion about what precise theoretical cognitive constructs might be mediating reported concentration problems. This review addresses this gap by describing and critically appraising the behavioural evidence for the effects of tinnitus on cognitive performance (namely working memory and attention). Empirical evidence is somewhat limited, but there is some support that tinnitus interferes with executive attention, and mixed support that it impairs working memory and selective attention. We highlight a number of methodological considerations to help drive the field forward and we propose a putative model of the complex inter-relationships between tinnitus, cognition and confounding factors. This model provides a basis for hypothesis testing.
•Our review shows mixed support that tinnitus impairs working memory, executive attention and selective attention.•We found no support for the claim that tinnitus interferes with sustained or alerting attention.•The suggestion that the severity of tinnitus symptoms affects cognitive performance also lacks strong support.•We propose a testable model describing how tinnitus, working memory and attention may be interconnected.
Although Parkinson's disease (PD) is a progressive neurodegenerative disease, the disease does not progress or persist in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model, the most ...common animal model of PD. Recently, we have described that supplementation of regulated on activation, normal T cell expressed and secreted (RANTES), a chemokine known to drive infiltration of T cells, induces persistent nigrostriatal pathology in MPTP mouse model. However, which particular T cell subsets are recruited to the substantia nigra (SN) by RANTES is not known. Here, by adoptive transfer of different subset of T cells from tomato red transgenic mice to MPTP-intoxicated immunodeficient Rag1−/− mice, we describe that invasion of Th17 cells into the SN is stimulated by exogenous RANTES administration. On the other hand, RANTES supplementation remained unable to influence the infiltration of Th1 and Tregs into the SN of MPTP-insulted Rag1−/− mice. Accordingly, RANTES supplementation increased MPTP-induced TH cell loss in Rag1−/−mice receiving Th17, but neither Th1 nor Tregs. RANTES-mediated aggravation of nigral TH neurons also paralleled with significant DA loss in striatum and locomotor deficits in MPTP-intoxicated Rag1−/− mice receiving Th17 cells. Finally, we demonstrate that levels of IL-17 (a Th17-specific cytokine) and RANTES are higher in serum of PD patients than age-matched controls and that RANTES positively correlated with IL-17 in serum of PD patients. Together, these results highlight the importance of RANTES-Th17 pathway in progressive dopaminergic neuronal loss and associated PD pathology.
Objectives: The lived experience of tinnitus has biopsychosocial characteristics which are influenced by sociocultural factors. The main purpose of this study is to investigate how tinnitus affects ...people in their everyday life in China. A deductive qualitative analysis examined whether an a priori Western-centric conceptual framework could extend to an Asian context.
Design: A large-scale prospective survey collected patient-reported problems associated with tinnitus in 485 adults attending four major ENT clinics in Eastern and Southern mainland China.
Results: The evidence suggests that patients in China express a narrower range of problem domains associated with the lived experience of tinnitus. While 13 tinnitus-related problem domains were confirmed, culture-specific adaptations included the addition uncomfortable (a novel concept not previously reported), and the potential exclusion of concepts such as intrusiveness, loss of control, loss of peace and loss of sense of self.
Conclusions: The sociocultural context of patients across China plays an important role in defining the vocabulary used to describe the patient-centred impacts of tinnitus. Possible explanatory factors include cultural differences in the meaning and relevance of certain concepts relating to self and in help-seeking behaviour, low health literacy and a different lexicon in Chinese compared to English to describe tinnitus-related problems.
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