Incremental Clinical Effectiveness and Cost Effectiveness of Providing Supervised Physiotherapy in Addition to Usual Medical Care in Patients with Osteoarthritis of The Hip or Knee: 2-Year Results of The MOA Randomised Controlled Trial

Objective To investigate the clinical- and cost-effectiveness at 2-year follow-up of providing individual, supervised exercise physiotherapy and/or manual physiotherapy in addition to usual medical care. Method People with hip or knee osteoarthritis meeting the American College of Rheumatology clinical diagnostic criteria were randomised (1:1, concealed, assessor-blinded) to four groups: usual medical care; supervised exercise physiotherapy; manual physiotherapy; or combined exercise and manual physiotherapy. Physiotherapy group participants were provided 10 50-min treatment sessions including booster sessions at 4 and 13 months, in addition to usual care. The primary outcome at 2-year follow-up was incremental cost-utility ratio (ICUR) of each physiotherapy intervention in addition to usual care, compared with usual care alone, from the health system and societal perspectives. To allow interpretation of negative ICURs, we report incremental net benefit (INB). The primary clinical outcome was the Western Ontario and McMaster Osteoarthritis Index (WOMAC). Results Of 206 patients, 186 (90·3%) were retained at 2-year follow-up. Exercise physiotherapy and manual physiotherapy dominated usual care, demonstrating cost savings; combined therapy did not. Exercise therapy had the highest incremental net benefits (INBs), statistically significant at all willingness-to-pay (base-case: societal New Zealand (NZ)$6,312, 95$8,065, 95%CI 136 to 15,994). Clinical improvements were superior to usual care only in the exercise physiotherapy group (−28.2 WOMAC points, 95%CI -49.2 to −7.1). No serious adverse events were recorded. Conclusion Individually supervised exercise therapy is cost-effective and clinically effective in addition to usual medical care at 2-year follow-up, and leads to cost savings for the health system and society

Phylogeography of the Endangered Otago Skink, Oligosoma otagense: Population Structure, Hybridisation and Genetic Diversity in Captive Populations

Climatic cooling and substantial tectonic activity since the late Miocene have had a pronounced influence on the evolutionary history of the fauna of New Zealand's South Island. However, many species have recently experienced dramatic range reductions due to habitat fragmentation and the introduction of mammalian predators and competitors. These anthropogenic impacts have been particularly severe in the tussock grasslands of the Otago region. The Otago skink (Oligosoma otagense), endemic to the region, is one of the most critically endangered vertebrates in New Zealand. We use mitochondrial DNA sequence data to investigate the evolutionary history of the Otago skink, examine its population genetic structure, and assess the level of genetic diversity in the individuals in the captive breeding program. Our data indicate that the Otago skink diverged from its closest relatives in the Miocene, consistent with the commencement of tectonic uplift of the Southern Alps. However, there is evidence for past introgression with the scree skink (O. waimatense) in the northern Otago-southern Canterbury region. The remnant populations in eastern Otago and western Otago are estimated to have diverged in the mid-Pliocene, with no haplotypes shared between these two regions. This divergence accounts for 95% of the genetic diversity in the species. Within both regions there is strong genetic structure among populations, although shared haplotypes are generally evident between adjacent localities. Although substantial genetic diversity is present in the captive population, all individuals originate from the eastern region and the majority had haplotypes that were not evident in the intensively managed populations at Macraes Flat. Our data indicate that eastern and western populations should continue to be regarded as separate management units. Knowledge of the genetic diversity of the breeding stock will act to inform the captive management of the Otago skink and contribute to a key recovery action for the species

Why Should ACT Work When CBT Has Failed? a Study Assessing Acceptability and Feasibility of Acceptance and Commitment Therapy (ACT) for Paediatric Patients With Chronic Fatigue Syndrome/myalgic Encephalomyelitis (CFS/ME)

AIMS: Paediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) effects 0.5–3.28% of children. NICE guidance recommends Activity Management, Graded Exercise Therapy or Cognitive Behavioural Therapy for fatigue (CBT-f). Approximately 15% of patients do not achieve full recovery within one year with current treatments. Acceptance and Commitment Therapy (ACT) is an effective treatment in many chronic illnesses. There are no studies investigating ACT for paediatric CFS/ME. This feasability study aimed to assess if ACT is a feasible and acceptable alternative treatment when current treatment has not led to recovery. METHODS: This feasability cohort study aimed to enrol a minimum of 12 participants aged 11–18 yearswith CFS/ME attending the Royal United Hospitals Bath NHS Foundation Trust Specialist Paediatric CFS/ME Service, who were still symptomatic after 12 months or 12 sessions of standard treatment and were offered six to 12 sessions of ACT. Retention and recruitment data were analysed. Participants were asked to complete questionnaires before, during and after treatment. A selection of participants and their parents were interviewed about their experience of the study. Interviews were analysed using thematic analysis. RESULTS: 19 participants (95% of those approached) were recruited. Only 4 participants of this hard-to-reach group did not complete treatment. In almost all sessions participants reported that they felt ‘totally’ listened to in post session questionnaires (31/33 sessions). Preliminary interviews (n = 12) indicate acceptability of ACT, with all young people and their parents stating that they thought ACT should be offered to this population. Participants particularly commented that the absence of thought challenging (used in CBT-f) was a positive element of ACT. Participant's openness to try new approaches and altruistic desire to be in a study was noted. CONCLUSION: Recruitment data indicate that it is feasible to recruit and retain 11–18-year-olds with CFS/ME to a study offering ACT. Interviews with participants and parents were broadly positive suggesting ACT is an acceptable treatment in this population. Results indicated that it is both feasible and acceptable to offer ACT to 11–18-year-olds with CFS/ME using this protocol, supporting the prospect of an RCT in this area

A Digital Health Solution for Child Growth Monitoring at Home: Testing the Accuracy of a Novel “GrowthMonitor” Smartphone Application to Detect Abnormal Height and Body Mass Indices

Objective To develop and evaluate a smartphone application that accurately measures height and provides notifications when abnormalities are detected. Patients and Methods A total of 145 (75 boys) participants with a mean age ± SD of 8.7±4.5 years (range, 1.0-17.0 years), from the Children’s Hospital at Barts Health Trust, London, United Kingdom, were enrolled in the study. “GrowthMonitor” (UCL Creatives) iPhone application (GMA) measures height using augmented reality. Using population-based (UK-WHO) references, algorithms calculated height SD score (HSDS), distance from target height (THSDSDEV), and HSDS change over time (ΔHSDS). Pre-established thresholds discriminated normal/abnormal growth. The GMA and a stadiometer (Harpenden; gold standard) measured standing heights of children at routine clinic visits. A subset of parents used GMA to measure their child’s height at home. Outcome targets were 95% of GMA measurements within ±0.5 SDS of the stadiometer and the correct identification of abnormal HSDS, THSDSDEV, and ΔHSDS. Results Bland-Altman plots revealed no appreciable bias in differences between paired study team GMA and stadiometer height measurements, with a mean of the differences of 0.11 cm with 95% limits of agreement of −2.21 to 2.42 cm. There was no evidence of greater bias occurring for either shorter/younger children or taller/older children. The 2 methods of measurements were highly correlated (R=0.999). GrowthMonitor iPhone application measurements performed by parents in clinic and at home were slightly less accurate. The κ coefficient indicated reliable and consistent agreement of flag alerts for HSDS (κ=0.74) and THSDSDEV (κ=0.88) between 83 paired GMA and stadiometer measurements. GrowthMonitor iPhone application yielded a detection rate of 96% and 97% for HSDS-based and THSDSDEV-based red flags, respectively. Forty-two (18 boys) participants had GMA calculated ΔHSDS using an additional height measurement 6-16 months later, and no abnormal flag alerts were triggered for ΔHSDS values. Conclusion GrowthMonitor iPhone application provides the potential for parents/carers and health care professionals to capture serial height measurements at home and without specialized equipment. Reliable interpretation and flagging of abnormal measurements indicate the potential of this technology to transform childhood growth monitoring

Treatment decision-making among men with lower urinary tract symptoms:A qualitative study of men’s experiences with recommendations for patient-centred practice

Aims: To inform and guide patient-centred care for men with lower urinary tract symptoms (LUTS), by providing in-depth qualitative evidence regarding men’s perspectives on treatment decision-making for LUTS.Methods: Interview study of men recruited from 26 English urology departments. Purposive sampling captured, surgical/non-surgical treatment decisions, and diversity in demographics and symptom burden, in men who had urodynamics and those who did not. After diagnostic assessments, men were interviewed either pre-treatment, or after LUTS surgery. Thematic analysis was conducted. Participants’ descriptions of how LUTS treatment decisions were made were categorised as patient-led, doctor-led, or shared.Results: 41 men participated (25 pre-treatment, 16 post-surgery), ages 52-89. 20/41 described the treatment decision as shared with their consultant, 14 as doctor-led, and 7 as patient-led. There was no obvious association between treatment decision-making style and patients’ satisfaction with either clinicians’ role in their decision or their treatment decision. Incomplete or rushed discussions and misperceptions of LUTS and its treatment were reported, indicating a risk of suboptimal decision-making support by clinicians. As well as clinician opinion, men’s treatment decision-making was influenced by the results of urological assessments, comparing current symptoms with possible side-effects of surgery, and others’ experiences and opinions. Conclusions: Men with LUTS report and prefer different kinds of decision-making support from their clinicians, who must tailor their input to patients’ preferences and needs. Patients’ treatment decision-making involves multiple factors and can be challenging, and areas of inadequate clinician support were identified. Recommendations for patient-centred consultations about LUTS treatment are presented. <br/

Sulforaphane restores cellular glutathione levels and reduces chronic periodontitis neutrophil hyperactivity in vitro

The production of high levels of reactive oxygen species by neutrophils is associated with the local and systemic destructive phenotype found in the chronic inflammatory disease periodontitis. In the present study, we investigated the ability of sulforaphane (SFN) to restore cellular glutathione levels and reduce the hyperactivity of circulating neutrophils associated with chronic periodontitis. Using differentiated HL60 cells as a neutrophil model, here we show that generation of extracellular O2 . - by the nicotinamide adenine dinucleotide (NADPH) oxidase complex is increased by intracellular glutathione depletion. This may be attributed to the upregulation of thiol regulated acid sphingomyelinase driven lipid raft formation. Intracellular glutathione was also lower in primary neutrophils from periodontitis patients and, consistent with our previous findings, patients neutrophils were hyper-reactive to stimuli. The activity of nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of the antioxidant response, is impaired in circulating neutrophils from chronic periodontitis patients. Although patients' neutrophils exhibit a low reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio and a higher total Nrf2 level, the DNA-binding activity of nuclear Nrf2 remained unchanged relative to healthy controls and had reduced expression of glutamate cysteine ligase catalytic (GCLC), and modifier (GCLM) subunit mRNAs, compared to periodontally healthy subjects neutrophils. Pre-treatment with SFN increased expression of GCLC and GCM, improved intracellular GSH/GSSG ratios and reduced agonist-activated extracellular O2 . - production in both dHL60 and primary neutrophils from patients with periodontitis and controls. These findings suggest that a deficiency in Nrf2-dependent pathways may underpin susceptibility to hyper-reactivity in circulating primary neutrophils during chronic periodontitis. © 2013 Dias et al