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The authors of the manuscript 'Complementary and alternative medicine - practice, attitudes, and knowledge among healthcare professionals in New Zealand: an integrative review' [1] disagree with the assertion by McDowell et al. that our manuscript has extrapolation errors., (© 2024. The Author(s).)

Background: Early access to care for carpal tunnel syndrome (CTS) can avoid higher rates of surgery and permanent harm yet is often delayed, particularly for populations more likely to underutilise care., Objective: We sought to explore patient experiences and perspectives of health service access for CTS to inform an equity-focussed co-design of a health service for improving early care access., Methods: In this Normalisation Process Theory (NPT)-informed qualitative study we conducted semistructured in-depth interviews with 19 adults with experience of CTS. Recruitment prioritised New Zealand Māori, Pasifika, low-income, and rural populations. Data were analysed using deductive then inductive thematic analysis., Results: We identified five major themes: (1) the 'Significant Impact of CTS' of the sense-making and relational work to understand the condition, deciding when to get care, compelling clinicians to provide care, and garnering help from others; (2) 'Waiting and Paying for Care'- the enacting, relational, and appraising work to avoid long wait times unless paying privately, particularly where quality of care was low, employment relations poor, or injury compensation processes faltered; (3) circumstances of 'Occupation and CTS Onset' whereby the burden of proof to relate onset of CT symptoms to occupation created excessive relational and enacting work; (4) the 'Information Scarcity' of good information about CTS and the high relational and appraising work associated with using online resources; (5) 'Negotiating Telehealth Perspectives' where telehealth was valued if it meant earlier access for all despite the challenges it held for many., Conclusion: Quality, culturally and linguistically responsive information and communication from clinicians and health services will improve equitable early access to CTS care including realising the potential of telehealth modes of care. Policy changes that reduce individual burden of proof in injury compensation claims processes, enable time off work to attend health appointments, and increase public funding for surgical resources would improve early access to CTS care particularly for Māori and Pacific populations and those in small and rural workplaces. NPT is valuable for understanding where opportunities lie to reduce inequitable delays to accessing care including the impact of racism, particularly for populations more likely to underutilise care., (© 2024. The Author(s).)

Objectives: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of severe and chronic autoimmune diseases. Patients undergo two treatment phases: inducing remission and maintaining remission to prevent organ damage. Immunosuppressants, including glucocorticoids (GCs) are used as first-line treatment, but long-term GC use is associated with toxic effects. Novel treatments reduce or replace the need for long-term GC, and therefore can reduce GC-related toxicity. The evolving treatment landscape has presented new challenges for health technology assessment (HTA) of new treatments in AAV and long-term modelling of costs and outcomes in this disease., Methods: Using the appraisal of avacopan in England (NICE) as a case study, this paper aims to identify the key challenges involved in the economic evaluation of new treatments for AAV, with a particular focus on the long-term modelling of the treatment costs and benefits for the purpose of HTA. The outcome of this study is a set of recommendations for modelling the cost-effectiveness of new treatments for AAV from the HTA perspective., Results: The discussion focuses on the appropriate model structure, approach to modelling end-stage renal disease (ESRD) as a key determinant of costeffectiveness, capturing the impact of GC-related adverse events, and estimation of short and long-term costs of AAV., Conclusions: Economic evaluation of new treatments for AAV needs to capture all relevant downstream effects. ESRD is a key driver of cost-effectiveness but is associated with major uncertainty. Future observational studies need to offer sufficient detail to allow for differentiation in event rates across treatment options.

Purpose: The purpose of this meta-ethnography was to synthesize the research exploring patient/provider perceptions of clinical conversations (CC) centered on chronic musculoskeletal pain (CMP) in vulnerable adult populations., Materials and Methods: A systematic search for qualitative/mixed method studies in CINAHL, PubMed, Scopus, Sociology Database in ProQuest, and Web of Science used PRIMSA-P guidelines. Data synthesis used eMERGe guidelines; findings were presented in nested hierarchal theoretical frameworks., Results: The included studies explored patients' ( n  = 18), providers' ( n  = 2), or patients' and providers' perspectives ( n  = 5) with diversity in patient participants represented ( n  = 415): immigrants, indigenous people, women, and veterans. Themes for each level of the nested hierarchal models revealed greater complexity in patients' perceptions about the CC in CMP relative to clinicians' perceptions. A unique finding was sociopolitical/historical factors can influence CC for vulnerable populations., Conclusion: The combined nested hierarchical models provided insight into the need for clinicians to be aware of the broader array of influences on the CC. Key themes indicated that improving continuity of care and cultural training are needed to improve the CC. Additionally, due to patients' perception of how healthcare systems' policies influence the CC, patients should be consulted to guide the change needed to improve inequitable outcomes.IMPLICATIONS FOR REHABILITATIONHealthcare providers wishing to improve the clinical conversation in chronic musculoskeletal pain can more broadly explore potential factors influencing patients' experiences and perceptions.Screening during the clinical conversation can include assessing for sociopolitical and historical influences on patients' experiences with chronic musculoskeletal pain.Healthcare providers can explore how to minimize disjointed care in an effort to improve the clinical conversation and outcomes in chronic musculoskeletal pain.Healthcare providers and patients can work together to improve inequitable outcomes for vulnerable adults with chronic musculoskeletal pain.This may include cultural training for healthcare providers that is informed by patients.

Background: Chronic kidney disease (CKD) patients with and without heart failure (HF) often present with hyperkalaemia (HK) leading to increased risk of hospitalisations, cardiovascular related events and cardiovascular-related mortality. Renin-angiotensin-aldosterone system inhibitor (RAASi) therapy, the mainstay treatment in CKD management, provides significant cardiovascular and renal protection. Nevertheless, its use in the clinic is often suboptimal and treatment is frequently discontinued due to its association with HK. We evaluated the cost-effectiveness of patiromer, a treatment known to reduce potassium levels and increase cardiorenal protection in patients receiving RAASi, in the UK healthcare setting., Methods: A Markov cohort model was generated to assess the pharmacoeconomic impact of patiromer treatment in regulating HK in patients with advanced CKD with and without HF. The model was generated to predict the natural history of both CKD and HF and quantify the costs and clinical benefits associated with the use of patiromer for HK management from a healthcare payer's perspective in the UK., Results: Economic evaluation of patiromer use compared to standard of care (SoC) resulted in increased discounted life years (8.93 versus 8.67) and increased discounted quality-adjusted life years (QALYs) (6.36 versus 6.16). Furthermore, patiromer use resulted in incremental discounted cost of £2,973 per patient and an incremental cost-effectiveness ratio (ICER) of £14,816 per QALY gained. On average, patients remained on patiromer therapy for 7.7 months, and treatment associated with a decrease in overall clinical event incidence and delayed CKD progression. Compared to SoC, patiromer use resulted in 218 fewer HK events per 1,000 patients, when evaluating potassium levels at the 5.5-6 mmol/l; 165 fewer RAASi discontinuation episodes; and 64 fewer RAASi down-titration episodes. In the UK, patiromer treatment was predicted to have a 94.5% and 100% chance of cost-effectiveness at willingness-to-pay thresholds (WTP) of £20,000/QALY and £30,000/QALY, respectively., Conclusion: This study highlights the value of both HK normalisation and RAASi maintenance in CKD patients with and without HF. Results support the guidelines which recommend HK treatment, e.g., patiromer, as a strategy to enable the continuation of RAASi therapy and improve clinical outcomes in CKD patients with and without HF., (© 2023. The Author(s).)

Background: Many men with Parkinson's Disease (PD) do not meet the recommended levels of physical activity (PA) for health benefits. Tailored, meaningful, and culturally sensitive PA health messages may be a catalyst to shape men's motivations toward participation., Objective: We explored the views of New Zealand (NZ) men with PD about existing PA health messages, and how these could be adapted to be more effective., Methods: This qualitative study recruited six community dwelling, regularly physically active, NZ European men with PD (aged 54-69 years, 2-18 years post-diagnosis) from a community exercise class in Canterbury, NZ. Participants engaged in semi-structured interviews which were audio-recorded, transcribed verbatim, and analyzed inductively for themes., Results: Participants expressed that effective PA health messages should reflect men's motivations for PA which included physical and mental well-being and social connection. Inclusive, positive, and relatable language and imagery were considered crucial PA message communication strategies. Participants viewed health professionals' PA advice as superficial and unhelpful; however, celebrities with PD were considered inspirational messengers. Messages endorsed by trustworthy sources, such as the Parkinson's Society, were perceived to enhance the credibility., Conclusions: Effective PA messages should be gain framed and tailored to the target audience. We recommend health professionals provide comprehensive PA advice or consider onward referral. Future research which uses a co-design participatory methodology to collaborate with men with PD from culturally diverse backgrounds and represent all stages of PA behaviour change is recommended to provide comprehensive insights for meaningful, effective, and culturally sensitive PA health messaging., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Acupoints are considered a dynamic functional area, which can reflect the internal condition of the body. In pathological states, disease-related acupoints are believed to be activated, which is known as acupoint sensitization., Objective: This study aimed to investigate the major manifestations of acupoint sensitization in patients with chronic low back pain (cLBP) to provide better understanding of acupoint sensitization phenomena in the context of cLBP., Methods: This study was a matched-sample cross-sectional study 16 participants diagnosed with cLBP and 16 healthy controls matched in age, sex, and ethnicity were included. The following aspects of sensitization phenomena of targeted points were compared: pressure pain threshold (PPT), skin temperature, surface electrical conductance, receptive field, and morphological change of skin., Results: PPT at points of interest were significantly lower in cLBP participants compared with healthy controls (P< 0.05); in addition, receptive field was found to be larger at left BL 23 in cLBP participants (P< 0.05). There was no statistically significant difference in skin temperature, electrical conductance, or morphology between the two groups., Conclusions: Reduced PPT at all detected points and enlarged receptive field at left BL 23 were found in cLBP participants. These two features appear key in defining acupoint sensitization in cLBP, and provide evidence for selecting and locating acupuncture points in future clinical studies.

Most women who develop cancer have not been screened regularly. One in four women in Scotland, is overdue for cervical screening. Aim was to assess the impact of offering multiple cervical screening options to women whose screening is overdue. A prospective cohort study including all women whose screening was overdue, aged 30-60 years in Dumfries and Galloway in 2012. Potentially eligible women (n = 4146) were identified split into six groups. Women aged 30-55 years were allocated to three different groups. Group 1 (letter, n = 1246), Group 2 (letter and kit, n = 221), Group 3 (letter, n = 2031). Women aged 56-60 years were allocated to: Group 4 (letter, n = 292), Group 5 (letter and kit, n = 292) and Group 6 (control, n = 64). Women who self-collected a vaginal sample were requested to complete a questionnaire. The percentages of women responding were 24 % (21-26), 32 % (25-38), 16 % (14-18), 15 % (11-20) and 12 % (9-17) in groups 1 to 5 respectively, compared with 3 % (0-11) among controls. A significantly higher number of women (n = 383, 10 % of 3815) opted for self-sampling in comparison with undergoing a cervical screening test (CST) at the GP practice (n = 197, 5 %, x 2  = 59.0, p < 0.0001). The Evalyn® Brush was well accepted (218/313 = 70 %) by those who requested self-sampling. Almost all (265/272 = 97 %) women who self-collected a vaginal sample said that if they had the option of self-sampling, they would regularly participate in future cervical screening. Offering more flexible screening options, self-sampling in particular, appears to increase cervical screening participation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: Mentorship is the support model of choice for nursing practice in Ireland and although it follows a similar approach to that provided thus far in the UK, there is little available evidence about the students' lived experience of mentorship and the extent to which it facilitates their development., Aim: To explore undergraduate nursing students' experiences of mentorship in hospital., Method: The study used a qualitative approach. Newell and Burnard's (2011) 6-stage pragmatic approach to qualitative data analysis guided the collection and analysis of data. A purposive sample of six was drawn from fourth-year students who participated in a semi-structured interview., Findings: Six main categories emerged from the data: reality versus expectation of mentorship; student's perception of self; personal feelings and expectations of mentorship; perception of workload; barriers and enablers of mentorship; student perceptions of mentor preparedness. Interpersonal relationships between student and mentor were a pivotal concept in all of the categories. Despite its flaws, participants felt that the concept of mentorship was valuable and worthwhile., Conclusion: This study has shown that the personal and interpersonal aspects of mentorship can have both positive and negative effects on the participants' development as nurses. Although students felt that they achieved their learning outcomes, there were times when this was despite guidance from their mentors. Although this was a small study, the generalisability of the findings and conclusions to similar clinical contexts is likely to be high.

Background: Breast cancer remains a leading cause of death in women and novel imaging biomarkers are urgently required. Here, we demonstrate the diagnostic and treatment-monitoring potential of non-invasive sodium ( 23 Na) MRI in preclinical models of breast cancer., Methods: Female Rag2 -/- Il2rg -/- and Balb/c mice bearing orthotopic breast tumours (MDA-MB-231, EMT6 and 4T1) underwent MRI as part of a randomised, controlled, interventional study. Tumour biology was probed using ex vivo fluorescence microscopy and electrophysiology., Results: 23 Na MRI revealed elevated sodium concentration ([Na + ]) in tumours vs non-tumour regions. Complementary proton-based diffusion-weighted imaging (DWI) linked elevated tumour [Na + ] to increased cellularity. Combining 23 Na MRI and DWI measurements enabled superior classification accuracy of tumour vs non-tumour regions compared with either parameter alone. Ex vivo assessment of isolated tumour slices confirmed elevated intracellular [Na + ] ([Na + ] i ); extracellular [Na + ] ([Na + ] e ) remained unchanged. Treatment with specific inward Na + conductance inhibitors (cariporide, eslicarbazepine acetate) did not affect tumour [Na + ]. Nonetheless, effective treatment with docetaxel reduced tumour [Na + ], whereas DWI measures were unchanged., Conclusions: Orthotopic breast cancer models exhibit elevated tumour [Na + ] that is driven by aberrantly elevated [Na + ] i . Moreover, 23 Na MRI enhances the diagnostic capability of DWI and represents a novel, non-invasive biomarker of treatment response with superior sensitivity compared to DWI alone., (© 2022. The Author(s).)

Background: We evaluated the longitudinal performance of three options: HPV16/18 genotyping (HPV16/18), cytology (LBC), and p16/Ki-67 dual stain cytology (DS) for the triage of high-risk Human Papillomavirus-positive (Hr-HPV+) women within the cervical screening program in Scotland., Methods: Data were derived from a cohort of Hr-HPV+ women (n = 385) who participated in PaVDaG (Papillomavirus Dumfries and Galloway) study. Performance of triage strategies for detecting high-grade disease was assessed at 3 (in women <50 years) or 5 years (in women >50 years). Sensitivity, specificity, PPV, and cNPV of each triage test were calculated for CIN2+ and CIN3+ when used singly or sequentially., Results: The sensitivity of LBC (≥ borderline), DS, and HPV 16/18 genotyping for the detection of CIN2+ was 62.7% (50.7-73.3), 77.7% (63.1-83.7), and 62.7% (50.7-73.3) with corresponding cNPVs of 10.9%, 8.4%, and 11.9%. The option with the highest sensitivity and lowest cNPV was HPV 16/18 genotyping followed by LBC of Hr-HPV other+ and then DS of the LBC negatives. This yielded sensitivity of 94.7% (86.2-98.3) and cNPV 2.7% for CIN2+. Triage performance was similar if women had tested Hr-HPV+ positive by vaginal self-sampling., Conclusions: Two-step triage with HPV 16/18 genotyping before LBC (or DS) for Hr-HPV other+ women was associated with a lower risk of significant disease at follow-up compared with single triage approaches., Impact: This study provides longitudinal performance data on triage strategies in Hr-HPV+ women and will be informative for the evolution of cervical screening programs that increasingly rely on molecular technologies., (©2022 American Association for Cancer Research.)

We consider the effect of a nonvanishing fraction of initially infected nodes (seeds) on the susceptible-infected-recovered epidemic model on random networks. This is relevant when the number of arriving infected individuals is large, or to the spread of ideas with publicity campaigns. This model is frequently studied by mapping to a bond percolation problem, in which edges are occupied with the probability p of eventual infection along an edge. This gives accurate measures of the final size of the infection and epidemic threshold in the limit of a vanishingly small seed fraction. We show, however, that when the initial infection occupies a nonvanishing fraction, f, of the network, this method yields ambiguous results, as the correspondence between edge occupation and contagion transmission no longer holds. We propose instead to measure the giant component of recovered individuals within the original contact network. We derive exact equations for the size of the epidemic and the epidemic threshold in the infinite size limit in heterogeneous sparse random networks, and we confirm them with numerical results. We observe that the epidemic threshold correctly depends on f, decreasing as f increases. When the seed fraction tends to zero, we recover the standard results.

Background: Pain affects the majority of patients with inflammatory bowel disease (IBD), where pain experiences may be influenced by multiple patient factors and changes within central pain processing pathways, termed central sensitization. The current study aimed to investigate pain processing pathways in patients with IBD through somatosensory testing and associations with multiple patient factors., Methods: A cross-sectional study of adults with IBD. Assessments included: somatosensory tests [i.e. pressure pain thresholds (PPT), temporal summation (TS), conditioned pain modulation (CPM)], and patient factors (i.e. demographics, comorbidity, sleep quality, psychological, pain severity and interference, and IBD features). Multiple regression analyses explored associations between somatosensory tests and multiple patient factors., Results: Decreased CPM in participants (N = 51) was associated with worse abdominal pain severity and use of biologic therapies (R2 = 0.30, F(5,44) = 5.18, P = 0.001). Increased TS was associated with biologic use (R2 = 0.11, F(1,49) = 6.13, P = 0.017). Decreased PPT at the low back (R2 = 0.29, F(2,48) = 11.21, P < 0.001) and Tibialis anterior (R2 = 0.41, F(2,48) = 18.26, P < 0.001) were associated with female sex and the absence of a stoma., Conclusion: Study results demonstrated associations between multiple patient factors and somatosensory tests in patients with IBD. The absence of a stoma and female sex was associated with greater sensitivity to pressure in two remote body regions, suggestive of widespread hyperalgesia. Worse abdominal pain severity and biologic use were associated with decreased pain inhibition, and biologic use was also associated with increased pain facilitation. These findings suggest the presence of altered pain processing and mechanisms of central sensitization in patients with IBD., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Self-sampling provides a powerful means to engage women in cervical screening. In the original Papillomavirus Dumfries and Galloway study (PaVDaG), we demonstrated cross-sectional similarity of high-risk human papillomavirus (Hr-HPV) testing on self-taken vaginal vs clinician-taken samples for the detection of cervical intraepithelial neoplasia 2 or worse (CIN2+). Few data exist on the longitudinal performance of self-sampling; we present longitudinal outcomes of PaVDaG. Routinely screened women provided a self-taken and a clinician-collected sample. Ninety-one percent of 5136 women from the original cohort completed a further screening round. Sensitivity, specificity, positive predictive value and complement of the negative predictive value of the Hr-HPV test on self-samples for detection of CIN2+ and CIN3+ up-to 5 years after testing were determined. Additionally, clinical accuracy of Hr-HPV testing on vaginal and clinician-collected samples was assessed. A total of 183 CIN2+ and 102 CIN3+ lesions were diagnosed during follow-up. Risk of CIN2+ and CIN3+ following an Hr-HPV negative self-sample was 0.6% and 0.2%, respectively, for up to 5 years after testing. The relative sensitivity for CIN3+ and specificity for ≤CIN1 of Hr-HPV testing on self-taken specimens was slightly lower vs clinician-collected samples: 0.95 (95% CI: 0.90-0.99; P McN = .0625) and 0.98 (95% CI: 0.95-1.00; P McN  = <.0000), respectively. The low risk of CIN2+ in women with Hr-HPV-self-sample(s) suggests, that the 3 to 5-year recall interval implemented in several cervical screening settings, based on clinician-taken samples, may be safe for self-samples. Future assessment will show if "universal" 5-year screening is appropriate for programs based on self-sampling., (© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Objective: Chronic musculoskeletal pain (CMP) outcomes are affected by numerous variables, including the clinical conversation. When good therapeutic/working alliances are formed, congruent clinical conversations can lead to improved CMP outcomes. Identifying patient/provider attitudes, beliefs, and biases in CMP that can influence the clinical conversation, and thus clinical management decisions, is foundationally important., Design: The aims of this systematic review were to 1) summarize the evidence of the attitudes and beliefs of patients and health care providers (HCPs) involved in the clinical conversation about CMP, and 2) examine whether and how these perceptions impacted the process of care., Methods: A systematic search of CINAHL, PubMed, Scopus, Sociology Database in ProQuest, and Web of Science used the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Included studies were those investigating vulnerable adult populations with chronic pain. Study bias was examined with the Downs and Black tool., Results: Seven retrospective studies were included. When making pharmaceutical management decisions, HCPs demonstrated negative implicit biases toward minorities and women. When making referrals to multidisciplinary care, HCPs demonstrated negative implicit biases toward women with lower educational attainment. Unmet patient expectations resulted in higher dropout rates at multidisciplinary pain management programs. Patients' trust was influenced by the health care setting, and patients often had limited options secondary to health insurance type/status., Conclusion: These findings suggest that patients with CMP may experience a marginalized process of care due to HCPs' negative implicit biases, unmet patient expectations, and the health care setting. Results suggest several factors may contribute to inequitable care and the recalcitrant nature of CMP, particularly in vulnerable populations with limited health care choices., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Weak multiplex percolation generalizes percolation to multi-layer networks, represented as networks with a common set of nodes linked by multiple types (colors) of edges. We report a novel discontinuous phase transition in this problem. This anomalous transition occurs in networks of three or more layers without unconnected nodes, [Formula: see text]. Above a critical value of a control parameter, the removal of a tiny fraction [Formula: see text] of nodes or edges triggers a failure cascade which ends either with the total collapse of the network, or a return to stability with the system essentially intact. The discontinuity is not accompanied by any singularity of the giant component, in contrast to the discontinuous hybrid transition which usually appears in such problems. The control parameter is the fraction of nodes in each layer with a single connection, [Formula: see text]. We obtain asymptotic expressions for the collapse time and relaxation time, above and below the critical point [Formula: see text], respectively. In the limit [Formula: see text] the total collapse for [Formula: see text] takes a time [Formula: see text], while there is an exponential relaxation below [Formula: see text] with a relaxation time [Formula: see text]., (© 2022. The Author(s).)

The promise of machine learning methods to act as decision support systems for pathologists continues to grow. However, central to their successful adoption must be interpretable implementations so that people can trust and learn from them effectively. Generative modeling, most notable in the form of adversarial generative models, is a naturally interpretable technique because the quality of the model is explicit from the quality of images it generates. Such a model can be further assessed by exploring its latent space, using human-meaningful concepts by defining concept vectors. Motivated by these ideas, we apply for the first time generative methods to histological images of basal cell carcinoma (BCC). By simultaneously learning to generate and encode realistic image patches, we extract feature rich latent vectors that correspond to various tissue morphologies, namely BCC, epidermis, keratin, papillary dermis and inflammation. We show that a logistic regression model trained on these latent vectors can achieve high classification accuracies across 6 binary tasks (86-98%). Further, by projecting the latent vectors onto learned concept vectors we can generate a score for the absence or degree of presence for a given concept, providing semantically accurate "conceptual summaries" of the various tissues types within a patch. This can be extended to generate multi-dimensional heat maps for whole-image specimens, which characterizes the tissue in a similar way to a pathologist. We additionally find that accurate concept vectors can be defined using a small labeled dataset., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Hyperpolarized 13 C-MRI is an emerging tool for probing tissue metabolism by measuring 13 C-label exchange between intravenously injected hyperpolarized [1- 13 C]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyperpolarized 13 C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric 1 H-MRI and hyperpolarized 13 C-MRI before and 7-11 days after commencing treatment. An increase in the lactate-to-pyruvate ratio of approximately 20% identified three patients who, following 5-6 cycles of treatment, showed pathological complete response. This ratio correlated with gene expression of the pyruvate transporter MCT1 and lactate dehydrogenase A ( LDHA ), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of LDHA and the hypoxia marker CAIX was associated with reduced relapse-free and overall survival. Hyperpolarized 13 C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential. SIGNIFICANCE: Hyperpolarized carbon-13 MRI allows response assessment in patients with breast cancer after 7-11 days of neoadjuvant chemotherapy and outperformed state-of-the-art and research quantitative proton MRI techniques., (©2021 The Authors; Published by the American Association for Cancer Research.)

Densely labelled segmentation data for digital pathology images is costly to produce but is invaluable to training effective machine learning models. We make available 290 hand-annotated histopathology tissue sections of the 3 most common skin cancers; basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and intraepidermal carcinoma (IEC). These non-melanoma skin cancers constitute over 90% of all skin cancer diagnoses and hence this dataset gives an opportunity to the scientific community to benchmark analytic methodologies on a significant portion of the dermatopathology workflow. The data represents typical cases of the three cancer types (not requiring a differential diagnosis) across shave, punch and excision biopsy contexts. Each image is accompanied with a segmentation mask which characterizes the section into 12 tissue types, specifically: keratin, epidermis, papillary dermis, reticular dermis, hypodermis, inflammation, glands, hair follicles and background, as well as BCC, SCC and IEC. Included also are cancer margin measurements to work towards automated assessment of surgical margin clearance and tumour invasion. This leaves open many opportunities for researchers to utilize or extend the dataset, building upon recent work on image analysis problems in skin cancer (Thomas et al., 2021)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2021 Published by Elsevier Inc.)

Objective: Real-world secukinumab gastrointestinal-related adverse events (GIRAE) data during treatment for AS and PsA are lacking. We aimed to obtain this through baseline evaluation of pre-existing IBD rates and predictors of GIRAE., Methods: Patient electronic and paper records commencing secukinumab from 10 UK hospitals between 2016 and 2019 were reviewed. GIRAE after initiation were defined as: definite [objective evidence of IBD (biopsy proven), clear temporal association, resolution of symptoms on drug withdrawal, no alternative explanation felt more likely], probable (as per definite, but without biopsy confirmation) or possible (gastrointestinal symptoms not fulfilling definite or probable criteria)., Results: Data for all 306 patients started on secukinumab were analysed: 124 (40.5%) AS and 182 (59.5%) PsA. Twenty-four of 306 (7.8%) experienced GIRAE after starting secukinumab. Amongst patients who developed GIRAE, four (1.3%) had definite, seven (2.3%) probable and 13 (4.2%) possible IBD. All definite cases were patients with AS and stopped secukinumab; two had pre-existing IBD and two (0.7%) were de novo cases of which one required surgical intervention. Seven patients (2.3%) had pre-existing diagnoses of IBD prior to initiation, of which five patients experienced GIRAE., Conclusion: Absolute rates of new IBD in patients starting secukinumab are low. The majority of patients developing new GIRAE did not develop objective evidence of IBD or stop therapy. For patients with pre-existing IBD and AS the risk of GIRAE is much higher, and prescribing alternatives should be considered., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In the UK, women between 50-70 years are invited for 3-yearly mammography screening irrespective of their likelihood of developing breast cancer. The only risk adaption is for women with >30% lifetime risk who are offered annual magnetic resonance imaging (MRI) and mammography, and annual mammography for some moderate-risk women. Using questionnaires, breast density, and polygenic risk scores, it is possible to stratify the population into the lowest 20% risk, who will develop <4% of cancers and the top 4%, who will develop 18% of cancers. Mammography is a good screening test but has low sensitivity of 60% in the 9% of women with the highest category of breast density (BIRADS D) who have a 2.5- to fourfold breast cancer risk. There is evidence that adding ultrasound to the screening mammogram can increase the cancer detection rate and reduce advanced stage interval and next round cancers. Similarly, alternative tests such as contrast-enhanced mammography (CESM) or abbreviated MRI (ABB-MRI) are much more effective in detecting cancer in women with dense breasts. Scintimammography has been shown to be a viable alternative for dense breasts or for follow-up in those with a personal history of breast cancer and scarring as result of treatment. For supplemental screening to be worthwhile in these women, new technologies need to reduce the number of stage II cancers and be cost effective when tested in large scale trials. This article reviews the evidence for supplemental imaging and examines whether a risk-stratified approach is feasible., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

To fully exploit the benefits of additive manufacturing (AM), an understanding of its processing, microstructural, and mechanical aspects, and their interdependent characteristics, is necessary. In certain instances, AM materials may be desired for applications where impact toughness is a key property, such as in gas turbine fan blades, where foreign or direct object damage may occur. In this research, the impact energy of a series of Ti-6Al-4V specimens produced via electron beam powder bed fusion (EBPBF) was established via Charpy impact testing. Specimens were produced with five different processing parameter sets, in both the vertical and horizontal build orientation, with microstructural characteristics of prior β grain area, prior β grain width, and α lath width determined in the build direction. The results reveal that horizontally oriented specimens have a lower impact energy compared to those built in the vertical orientation, due to the influence of epitaxial grain growth in the build direction. Relationships between process parameters, microstructural characteristics, and impact energy results were evaluated, with beam velocity displaying the strongest trend in terms of impact energy results, and normalised energy density exhibiting the most significant influence across all microstructural measurements.

Introduction: In patients with inflammatory bowel disease (IBD), iron deficiency anaemia (IDA) can impair quality of life and increase healthcare costs. Treatment options for IDA-associated IBD include oral iron and intravenous iron formulations (such as ferric carboxymaltose [FCM], ferric derisomaltose [FD, previously known as iron isomaltoside 1000], and iron sucrose [IS]). The present analysis compared the cost-effectiveness of FCM versus FD, IS, and oral iron sulfate in terms of additional cost per additional responder in the UK setting., Methods: Cost-effectiveness was calculated for FCM versus FD, IS, and oral iron individually in terms of the additional cost per additional responder, defined as haemoglobin normalisation or an increase of ≥2 g/dL in haemoglobin levels, in a model developed in Microsoft Excel. Relative efficacy inputs were taken from a previously published network meta-analysis, since there is currently no single head-to-head trial evidence comparing all therapy options. Costs were calculated in 2020 pounds sterling (GBP) capturing the costs of iron preparations, healthcare professional time, and consumables., Results: The analysis suggested that FCM may be the most effective intervention, with 81% of patients achieving a response. Response rates with FD, IS, and oral iron were 74%, 75%, and 69%, respectively. Total costs with FCM, FD, IS, and oral iron were GBP 296, GBP 312, GBP 503, and GBP 56, respectively. FCM was found to be more effective and less costly than both FD and IS, and therefore was considered dominant. Compared with oral iron, FCM was associated with an incremental cost-effectiveness ratio of GBP 2045 per additional responder., Conclusions: FCM is likely to be the least costly and most effective IV iron therapy in the UK setting. Compared with oral iron, healthcare payers must decide whether the superior treatment efficacy of FCM is worth the additional cost., Competing Interests: Aysegül Aksan has received consulting or speaker fees from the following Immundiagnostik and Vifor Pharma, and research funding from Immundiagnostik. Ian LP Beales has received fees for consulting and advisory boards from Vifor Pharma Group, Pharmacosmos UK Limited and Norgine Limited. Garth Baxter, Antonio Ramirez de Arellano and Simona Gavata are employees of Vifor Pharma Group. William J Valentine and Barnaby Hunt are employees of Ossian Health Economics and Communications, which received consulting fees from Vifor Pharma Group to support the preparation of the analysis. The authors report no other conflicts of interest in this work., (© 2021 Aksan et al.)

Objectives: Increased symptoms related to central sensitization have previously been reported in inflammatory bowel disease (IBD) patients, identified by the original central sensitization inventory (CSI-25). However, the recently developed CSI short form (CSI-9) may be more clinically useful. The aim of the present study was to evaluate the performance of CSI-9 compared to the original CSI-25 in individuals with IBD. Study objectives were to investigate the criterion validity of the CSI-9 to the CSI-25, assess individual association of the CSI measures with clinical features of IBD and pain presentations, and to establish disease-specific CSI-9 and CSI-25 cut-off scores for discriminating the presence of self-reported pain in individuals with IBD., Methods: Cross-sectional online survey was performed on adults with IBD exploring self-reported demographics, comorbidity, and clinical IBD and pain features. Criterion validity of the CSI-9 was investigated using intraclass correlation coefficient (ICC) 3,1 . Area under the receiver operating characteristic curve (AUC-ROC) analysis was conducted to investigate the discriminative ability of both versions of CSI., Results: Of the 320 participants, 260 reported the presence of abdominal and/or musculoskeletal pain. CSI-9 and CSI-25 demonstrated substantial agreement (ICC 3,1 =0.64, 95% CI [0.58, 0.69]). AUC (95% CI) indicated that CSI-9 (0.788 (0.725, 0.851), p<0.001) and CSI-25 (0.808 (0.750, 0.867), p<0.001) were able to adequately discriminate the presence of pain using cut-offs scores of ≥17 (CSI-9) and ≥40 (CSI-25). Abdominal pain severity was the only feature to differ in significant association to CSI-25 (p=0.002) compared to CSI-9 (p=0.236). All other features demonstrated significant associations to both CSI versions, except age (p=0.291 and 0.643) and IBD subtype (p=0.115 and 0.675)., Conclusions: This is the first study to explore and validate the use of CSI-9 in IBD patients. Results demonstrated concurrent validity of the CSI-9 to CSI-25, with similar significant association to multiple patient features, and a suggested cut-off value of 17 on CSI-9 to screen for individuals with pain experiences. Study findings suggest that CSI-9 is suitable to use as a brief tool in IBD patients., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: First carpometacarpal (CMC1) joint osteoarthritis (OA) is typically understood as part of the disease entity of hand OA. However, CMC1 joint OA often occurs in isolation or is a primary source of symptoms. The aim of the current study was to explore the experiences of New Zealanders with CMC1 joint OA to better understand the unique impact of this condition, ascertain outcomes of importance, and identify treatment targets., Methods: In this pragmatic qualitative study, patients who either reported a history suggestive of CMC1 joint OA or had been diagnosed by a physician were recruited from health and community settings in 2 centers on the South Island of New Zealand. Thirty participants (11 men and 19 women, mean ± SD age 65.4 ± 11.36 years) took part in individual face-to-face interviews and kept diaries. The interviews were audio recorded, and along with the diaries, transcribed. Data were analyzed by thematic analysis using a primarily inductive approach. The Health Impact Model was employed to help with interpretation of the results., Results: Five interrelated levels of health impact were identified: symptom status, functional limitations, restrictions in social activities and roles, negative thoughts and feelings, and an altered sense of self. Constant pain and pain at night were key symptoms that were associated with impact at the other levels., Conclusion: Constant pain, pain at night, functional capacity, medication burden, emotional impact, and sense of self are important outcomes and treatment targets in people with CMC1 joint OA., (© 2019, American College of Rheumatology.)

Background: Walking is an easily prescribed physical activity for people with low back pain (LBP). However, the evidence for its effectiveness to improve pain and disability levels for people with chronic low back pain (CLBP) within a community setting has not been evaluated. This study evaluates the effectiveness of a clinician guided, pedometer-driven, walking intervention for increasing physical activity and improving clinical outcomes compared to education and advice., Methods: Randomized controlled trial recruiting N = 174 adults with CLBP. Participants were randomly allocated into either a standardized care group (SG) or pedometer based walking group (WG) using minimization allocation with a 2:1 ratio to the WG. Prior to randomization all participants were given a standard package of education and advice regarding self-management and the benefits of staying active. Following randomization the WG undertook a physiotherapist guided pedometer-driven walking program for 12 weeks. This was individually tailored by weekly negotiation of daily step targets. Main outcome was the Oswestry Disability Index (ODI) recorded at baseline, 12 weeks, 6 and 12 months. Other outcomes included, numeric pain rating, International Physical Activity Questionnaire (IPAQ), Fear-Avoidance Beliefs Questionnaire (FABQ), Back Beliefs questionnaire (BBQ), Physical Activity Self-efficacy Scale, and EQ-5D-5L quality of life estimate., Results: N = 138 (79%) participants completed all outcome measures at 12 weeks reducing to N = 96 (55%) at 12 months. Both observed and intention to treat analysis did not show any statistically significant difference in ODI change score between the WG and the SG at all post-intervention time points. There were also no significant between group differences for change scores in all secondary outcome measures. Post hoc sensitivity analyses revealed moderately disabled participants (baseline ODI ≥ 21.0) demonstrated a greater reduction in mean ODI scores at 12 months in the WG compared to SG, while WG participants with a daily baseline step count < 7500 steps demonstrated a greater reduction in mean ODI scores at 12 weeks., Conclusions: Overall, we found no significant difference in change of levels of (ODI) disability between the SG and WG following the walking intervention. However, ODI responses to a walking program for those with moderate levels of baseline disability and those with low baseline step count offer a potential future focus for continued research into the benefit of walking as a management strategy for chronic LBP., Trial Registration: United States National Institutes of Health Clinical Trails registry (http://ClinicalTrials.gov/) No. NCT02284958 (27/10/2014).

Background: The prevalence of CAM use is increasing. This integrative review investigated New Zealand healthcare professionals' practice of, attitudes toward, and knowledge about complementary and alternative medicine (CAM)., Methods: Literature search was conducted in four databases from inception to April 2020. Studies were included if they reported results from primary data collection on practice of, attitudes toward, or knowledge about CAM amongst New Zealand healthcare professionals., Results: Eleven studies (two of 'high-quality', seven of 'moderate-quality', and two of 'low-quality') were identified with 2060 healthcare professionals including general practitioners (GPs), nurses, midwives, pharmacists, physiotherapists, and medical specialists. New Zealand healthcare professionals were generally positive regarding CAM use, but have concerns on the scientific evidence, regulation, safety, financial costs of CAM, and encourage an evidence-based CAM practice and stronger CAM regulation. Findings indicated that around 25% of GPs practise CAM, and 82.3% refer patients to CAM practitioners. When treating pregnant women, 48.4% of physiotherapists practise acupuncture, and 37.3% of midwives recommend CAM. GPs believe that acupuncture is the most helpful CAM modality, and most commonly practiced and referred patients to acupuncture. Up to 58% of GPs and Plunket nurses wanted to receive further education on CAM, and up to 66.7% GPs favour the idea CAM should be included in medical curriculums., Conclusions: Nine of the 11 included studies were of moderate to high quality, thus enhancing the reliability of the review findings. In order to better manage CAM in New Zealand New Zealand clinical settings, there is a need to invest in CAM research and education, and enhance CAM regulation. This review is a first step in developing an evidence base to offer insights for further development of effective CAM policies regarding safety, efficacy, regulation and integration in New Zealand.

We apply for the first-time interpretable deep learning methods simultaneously to the most common skin cancers (basal cell carcinoma, squamous cell carcinoma and intraepidermal carcinoma) in a histological setting. As these three cancer types constitute more than 90% of diagnoses, we demonstrate that the majority of dermatopathology work is amenable to automatic machine analysis. A major feature of this work is characterising the tissue by classifying it into 12 meaningful dermatological classes, including hair follicles, sweat glands as well as identifying the well-defined stratified layers of the skin. These provide highly interpretable outputs as the network is trained to represent the problem domain in the same way a pathologist would. While this enables a high accuracy of whole image classification (93.6-97.9%), by characterising the full context of the tissue we can also work towards performing routine pathologist tasks, for instance, orientating sections and automatically assessing and measuring surgical margins. This work seeks to inform ways in which future computer aided diagnosis systems could be applied usefully in a clinical setting with human interpretable outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Aim: To undertake a meta-analysis of the diagnostic performance of abbreviated (ABB) magnetic resonance imaging (MRI) and full diagnostic protocol MRI (FDP-MRI) in breast cancer., Materials and Methods: This meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy (PRISMA-DTA) guidelines. The PubMed and EMBASE databases were searched through August 2019 for studies comparing the diagnostic performance of ABB-MRI and FDP-MRI in the breast. Studies were reviewed by two authors independently according to eligibility and exclusion criteria and split into two subgroups (screening population studies and studies using cohorts enriched with known cancers) to avoid bias. Quality assessment and bias for diagnostic accuracy was determined with Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The diagnostic accuracy for each subgroup was pooled using a bivariate random effects model and summary receiver operating characteristic (sROC) curves produced. Sensitivities and specificities were compared using a paired t-test., Results: Five screening (62/2,588 cancers/patients) and eight enriched cohort (540/1,432 cancers/patients) studies were included in the meta-analysis. QUADAS-2 assessment showed a low risk of bias in most studies. The pooled sensitivity/specificity/area under the receiver operating characteristic curve (AUC) for screening studies was 0.90/0.92/0.94 for ABB-MRI and 0.92/0.95/0.97 for FDP-MRI. The pooled sensitivity/specificity/AUC for enriched cohort studies was 0.93/0.83/0.94 for ABB-MRI and 0.93/0.84/0.95 for FDP-MRI. There was no significant difference in sensitivity or specificity using ABB-MRI or FDP-MRI (p=0.18 and 0.27, p=0.18 and 0.93, respectively)., Conclusion: The diagnostic performances of the ABB-MRI and FDP-MRI protocols used in either screening or enriched cohorts were comparable. There was a large variation in patient population, study methodology, and abbreviated protocols reported., (Copyright © 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objectives: Musculoskeletal (MSK) pain is a common complaint in patients with inflammatory bowel diseases (IBD). MSK pain in IBD has previously demonstrated association with symptoms of central sensitization; however it is uncertain whether these symptoms are influenced simply by the presence of MSK pain and/or IBD. Primary aim of this study was to investigate whether symptoms of central sensitization differed across three groups: IBD patients with and without MSK pain and healthy controls. Secondary aim was to investigate between-group differences for measures of somatosensory functioning., Methods: Cross-sectional study was performed on adults with IBD. Assessments included: central sensitization inventory (CSI), pressure pain threshold, temporal summation, conditioned pain modulation, perceived stress, affect style, anxiety, depression, and pain catastrophizing. One-way analyses of variance and covariance were used to investigate between-group differences for measures of central sensitization and potential confounding by psychological factors., Results: Study participants (n = 66) were age/gender matched across three study groups. Between-group differences were solely demonstrated for CSI scores [ F (2,63)=19.835, p<0.001, r=0.62], with IBD patients with MSK pain demonstrating the highest CSI scores and healthy controls the lowest. After controlling for individual psychological features, post hoc comparisons indicated that CSI scores were significantly different between-groups (p≤0.025) after controlling for most psychological variables, with the exception of perceived stress (p=0.063) and pain catastrophizing (p=0.593)., Conclusions: IBD patients as a whole demonstrated significantly greater symptoms of central sensitization compared to healthy controls. However, IBD patients with persistent MSK pain demonstrated the greatest symptoms of central sensitization compared to patients without MSK pain and healthy controls. Between-group differences for CSI in IBD patients with MSK were not confounded by psychological features., Implications: Study results indicate that persistent MSK pain in IBD represents patients with greater central sensitization symptomology. This increased symptomology is suggestive of underlying mechanisms related to central sensitization, highlighting patient potentially at risk for worse pain experiences., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Compression, filtering, and cryptography, as well as the sampling of complex systems, can be seen as processing information. A large initial configuration or input space is nontrivially mapped to a smaller set of output or final states. We explored the statistics of filtering of simple patterns on a number of deterministic and random graphs as a tractable example of such information processing in complex systems. In this problem, multiple inputs map to the same output, and the statistics of filtering is represented by the distribution of this degeneracy. For a few simple filter patterns on a ring, we obtained an exact solution of the problem and numerically described more difficult filter setups. For each of the filter patterns and networks, we found three key numbers that essentially describe the statistics of filtering and compared them for different networks. Our results for networks with diverse architectures are essentially determined by two factors: whether the graphs structure is deterministic or random and the vertex degree. We find that filtering in random graphs produces much richer statistics than in deterministic graphs, reflecting the greater complexity of such graphs. Increasing the graph's degree reduces this statistical richness, while being at its maximum at the smallest degree not equal to two. A filter pattern with a strong dependence on the neighbourhood of a node is much more sensitive to these effects.

We describe the critical behavior of weak multiplex percolation, a generalization of percolation to multiplex or interdependent networks. A node can determine its active or inactive status simply by referencing neighboring nodes. This is not the case for the more commonly studied generalization of percolation to multiplex networks, the mutually connected clusters, which requires an interconnecting path within each layer between any two vertices in the giant mutually connected component. We study the emergence of a giant connected component of active nodes under the weak percolation rule, finding several nontypical phenomena. In two layers, the giant component emerges with a continuous phase transition, but with quadratic growth above the critical threshold. In three or more layers, a discontinuous hybrid transition occurs, similar to that found in the giant mutually connected component. In networks with asymptotically powerlaw degree distributions, defined by the decay exponent γ, the discontinuity vanishes but at γ=1.5 in three layers, more generally at γ=1+1/(M-1) in M layers.

Low back pain (LBP) is the leading contributor to years lived with disability, and imposes an enormous burden on individuals and on health-care systems. General practitioners and physiotherapists are generally the front-line health professionals dealing with patients with LBP, and have a key role in minimising its effect. Here we review six key issues associated with LBP including its effects, diagnosis and management in primary care, and highlight the importance of the biopsychosocial model and matched care for patients with LBP.

Introduction: A systematic review and meta-analysis were performed to determine the diagnostic performance of dynamic contrast-enhanced computed tomography (DCE-CT) for the differentiation between malignant and benign pulmonary nodules., Methods: Ovid MEDLINE and EMBASE were searched for studies published up to October 2018 on the diagnostic accuracy of DCE-CT for the characterisation of pulmonary nodules. For the index test, studies with a minimum of a pre- and post-contrast computed tomography scan were evaluated. Studies with a reference standard of biopsy for malignancy, and biopsy or 2-year follow-up for benign disease were included. Study bias was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies). The sensitivities, specificities, and diagnostic odds ratios were determined along with 95% confidence intervals (CIs) using a bivariate random effects model., Results: Twenty-three studies were included, including 2397 study participants with 2514 nodules of which 55.3% were malignant (1389/2514). The pooled accuracy results were sensitivity 94.8% (95% CI 91.5; 96.9), specificity 75.5% (69.4; 80.6), and diagnostic odds ratio 56.6 (24.2-88.9). QUADAS 2 assessment showed intermediate/high risk of bias in a large proportion of the studies (52-78% across the domains). No difference was present in sensitivity or specificity between subgroups when studies were split based on CT technique, sample size, nodule size, or publication date., Conclusion: DCE-CT has a high diagnostic accuracy for the diagnosis of pulmonary nodules although study quality was indeterminate in a large number of cases., Key Points: • The pooled accuracy results were sensitivity 95.1% and specificity 73.8% although individual studies showed wide ranges of values. • This is comparable to the results of previous meta-analyses of PET/CT (positron emission tomography/computed tomography) diagnostic accuracy for the diagnosis of solitary pulmonary nodules. • Robust direct comparative accuracy and cost-effectiveness studies are warranted to determine the optimal use of DCE-CT and PET/CT in the diagnosis of SPNs.

Background and Purpose: Tai chi has been suggested as a potential effective intervention for improving function and wellbeing in breast cancer patients. This systematic review evaluated the current evidence for the effectiveness of tai chi in patients with breast cancer., Methods: Randomized Controlled Trials (RCTs) evaluating the effects of tai chi in breast cancer patients were identified through searches in OVID MEDLINE, AMED, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, CNKI, VIP, and Wanfang Data, up to June 2019. Meta-analyses were performed for results syntheses., Results: Sixteen RCTs involving 1268 participants were included in this review. It was demonstrated that tai chi is no different from conventional supportive care interventions in improving fatigue, sleeping quality, depression or body mass index at either 3 months or 6 months; however it significantly improves overall quality of life (QoL) at 3 months. Moreover, tai chi, when offered as an adjunct to conventional therapy, is more effective in improving fatigue at 3 months, and QoL at 3 months and 6 months compared to conventional therapy alone., Conclusion: Tai chi shows no improvement in fatigue compared with conventional supportive interventions, but it significantly relieves fatigue symptom for breast cancer patients when used with conventional supportive care interventions. Tai chi versus conventional supportive care interventions, and as an adjunct to conventional therapy is effective in improving QoL for breast cancer patients., Competing Interests: Declaration of competing interest LL is supported as the Breast Cancer Foundation New Zealand Belinda Scott Clinical Fellowship 2017., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

As part of traditional Chinese medicine, acupoints are considered a dynamic functional area, which can reflect the internal condition of the body. When the body is suffering from disease or injury, corresponding acupoints are believed to be activated and manifest in several sensitized forms, including expansion of the receptive field, pain sensitization, and heat sensitization. Such phenomena are believed to gradually disappear concomitantly with recovery from the disease. Acupoint states are therefore changeable according to health status, a phenomenon known as acupoint sensitization. This review aims to provide an overview of acupoint sensitization based on existing research results and determine priorities for future research. Systematic literature retrieval was conducted in Medline, Embase, Cochrane Library, CINAHL, and AMED from inception to 18 July 2018. Current evidence from research findings to date indicate that acupoint sensitization is based on neurogenic inflammation and that stimulation of sensitized acupoints presents a potential trend of generating a better clinical effect when compared with stimulation of unsensitized points., Competing Interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and publication of this article.

Pain is reported to affect over 70% of individuals with inflammatory bowel diseases (IBD), with abdominal and musculoskeletal (MSK) pain representing the most common complaints. MSK pain is typically considered within the narrow framework of inflammatory extraintestinal manifestations of IBD, resulting in a limited scope for the nature and underlying mechanisms participating in MSK pain experiences in this population. Symptoms related to central sensitization have recently demonstrated association with active IBD and worse MSK pain experiences, suggesting a potential roll for central mechanisms in MSK-related pain. Current literature exploring persistent pain in chronic inflammatory and MSK populations propose complex pain models comprised of dynamic nervous system relationships influenced by primary disease features and concomitant pain states, as well as affective and cognitive components. Nervous system contributions in the development and maintenance of persistent pain are postulated to include mechanisms of peripheral and central sensitization, changes in descending central modulation, as well as structural brain changes. These models go beyond current MSK pain models described in IBD literature, highlighting the need for new frameworks for considering MSK-related pain in IBD. Consequently, this paper proposes a broader theoretical model whereby central mechanisms, such as central sensitization and grey matter changes, as well as psychological and disease factors are suggested to modulate pain experiences in this population. Exploration of relationships within the proposed framework may provide not only a deeper understanding of the generation and maintenance of persistent MSK pain in IBD, but also highlight the need for new targeted management pathways in this population. This paper hypothesizes that exploration of central sensitization in IBD patients will demonstrate altered somatosensory functioning in patients with MSK pain, and that IBD activity and psychological factors will be associated with altered somatosensory functioning and worse pain experiences., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background : Many footwear characteristics are argued as risk factors for running related injuries (RRI). Several footwear assessment tools are available; however, their use in studies of RRI is unknown. Objective : This systematic review evaluated the characteristics and methods of assessing footwear in studies of RRI. Design : Five online databases were searched for studies on adult runners, in running style footwear, who experienced running-related pain or injury. The methodological quality of included articles was independently assessed by two raters using a modified Downs and Black checklist. Study and participant characteristics, footwear assessment tools used, and footwear characteristics reported were extracted for qualitative synthesis. Results : Twenty-four articles were included in the review. Low risk of bias was determined for 11 (44%) of the included studies. Twenty-eight different footwear characteristics were grouped into four categories: nomenclature, measurements, qualitative features, and subjective features. Fifteen different methods for assessing the 28 footwear characteristics were reported among the included studies. Only three methods were described previously, as valid and reliable. Conclusion : Differences in assessing footwear may mask the link between footwear characteristics and injury risk. Systematic footwear assessments and nomenclature are needed to evaluate the effects of footwear characteristics on RRI.

Introduction: This study compared adverse outcomes and resource use for patients with a diagnosis of pain treated with tapentadol prolonged-release (PR) versus those treated with morphine controlled-release (CR) and oxycodone CR., Methods: Data were sourced from the Clinical Practice Research Datalink (CPRD), a database derived from UK primary care. Patients prescribed tapentadol PR between May 2011 and December 2016 were selected and matched to two groups of controls treated with either morphine CR or oxycodone CR on gender, age, pain duration, pain site, pain aetiology, Charlson index and prior analgesia. Times to first adverse event (constipation or nausea/vomiting) were compared within a Cox proportional hazards model. Rates of primary care contacts, accident and emergency contacts and, for a subset of patients linked to Hospital Episode Statistics (HES), inpatient admissions and outpatient contacts were compared using incidence rate ratios (IRRs) derived from Poisson regression., Results: A total of 1907 patients prescribed tapentadol PR were identified and 1791 (93.9%) had a pain diagnosis. Of these 1246 (65.3%) were matched to morphine controls and 829 (43.4%) to oxycodone controls. Compared to controls, gastrointestinal adverse events with tapentadol PR treatment were reduced; aHR = 0.532 (0.402-0.703; p < 0.001) versus morphine CR and 0.517 (0.363-0.735; p < 0.001) versus oxycodone CR. Compared with morphine CR, primary care contacts [IRR = 0.831 (0.802-0.861)], accident and emergency attendance [0.739 (0.572-0.951)], outpatient contacts [0.917 (0.851-0.989)] and inpatients contacts [0.789 (0.664-0.938)] were reduced. For oxycodone, the respective figures were 0.735 (0.703-0.768), 0.971 (0.699-1.352), 0.877 (0.799-0.962) and 0.748 (0.601-0.932)., Conclusion: Tapentadol PR was associated with significantly fewer adverse gastrointestinal events than morphine CR and oxycodone CR in patients with a diagnosis of pain. There was also significantly reduced primary and secondary care resource use. As with all observational studies, potential bias due to residual confounding and confounding by indication should be considered., Funding: Grünenthal Ltd.

Objective: To evaluate the effectiveness of a treadmill-based aerobic exercise intervention on pain and associated symptoms of primary dysmenorrhea., Methods: Seventy women with primary dysmenorrhea were included in the study. The experimental group underwent supervised aerobic training for 4 weeks followed by unsupervised home exercise for the next 6 months. The control group continued usual care. The primary outcome was pain. Secondary outcomes included quality of life (QoL), daily functioning, and sleep., Results: After the 4-week training, compared to the control group exercise significantly improved primary outcomes pain quality (mean difference (MD) -1.9, 95% CI 3.8 to -0.04, p < .05), and intensity (MD -4.7, 95% CI -9.3 to -0.09, p < .05), but not present pain. Significant effects were also reported for pain interference (MD -1.7, 95% CI -3.4 to -0.02, p < .05) at 4 weeks; the other outcomes did not significantly differ between groups at this time. During the follow-up period of 7-months, the effect on pain improved to 22 mm (95% CI 18 to 25). Significant benefits of exercise were maintained up to 7-months for present pain, QoL and daily functioning., Conclusion: Exercise has significant effects on primary dysmenorrhea-related pain, QoL and function., Trial Registration: ACTRN12613001195741., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Additive Layer Manufacturing (ALM) is an innovative net shape manufacturing technology that offers the ability to produce highly intricate components not possible through traditional wrought and cast procedures. Consequently, the aerospace industry is becoming ever more attentive in exploiting such technology for the fabrication of nickel-based superalloys in an attempt to drive further advancements within the holistic gas turbine. Given this, the requirement for the mechanical characterisation of such material is rising in parallel, with limitations in the availability of material processed restricting conventional mechanical testing; particularly with the abundance of process parameters to evaluate. As such, the Small Punch Creep (SPC) test method has been deemed an effective tool to rank the elevated temperature performance of alloys processed through ALM, credited to the small volumes of material utilised in each test and the ability to sample material from discrete locations. In this research, the SPC test will be used to assess the influence of a number of key process variables on the mechanical performance of Laser Powder Bed Fused (LPBF) Ni-based superalloy CM247LC. This will also include an investigation into the influence of build orientation and post-build treatment on creep performance, whilst considering the structural integrity of the different experimental builds.

Objective: To examine the effectiveness of splinting for reducing pain and improving function and health-related quality of life (HR-QoL) in people with thumb carpometacarpal osteoarthritis (CMC OA)., Design: The Cochrane Library, MEDLINE, Embase, CINAHL, ISI Web of Science, Scopus and Google Scholar, 3 trial registries and 4 conference proceedings were systematically searched for randomised and non-randomised controlled trials up to March 17th, 2018. Two reviewers independently applied the inclusion criteria to select potential studies and assess risk of methodologic bias using the Cochrane Collaboration's Risk of Bias Tool. Studies were pooled using the inverse variance method to calculate standardised mean difference (SMD). Sensitivity analyses were conducted and the quality of evidence for each outcome was judged following the Grades of Recommendation Assessment, Development and Evaluation (GRADE) approach., Results: Twelve studies were retrieved (n = 1353), 4 comparing a splint to control and 8 to another splint. In the medium-term (3-12 months), low quality evidence showed that splints cause a moderate to large reduction in pain (SMD 0.7 [95% confidence interval (CI) 1.04, 0.35], P < 0.0001) and small to moderate improvement in function (SMD 0.42 [95% CI 0.77, 0.08], P = 0.02). No significant effect was found at short-term or for different types of splints. No studies reported HR-QoL., Conclusions: Splinting demonstrated a moderate to large effect for pain and small to moderate effect for function in the medium-term but not in the short term. Quality of the evidence is low. Major challenges are the lack of diagnostic criteria and of a gold-standard outcome measure for thumb CMC OA., (Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Walking ability is one of the primary components of human motor function, and interventions aimed at improving walking ability are common in physical therapy, particularly in children. One element encountered in a participatory, or natural, environment is unpredictability, defined as the presence of an unexpected obstacle, stimulus, or alteration of the environmental conditions. Little research has assessed the influence of unpredictability on biomechanical adaptations to walking in children who are developing typically or children with motor disabilities. A variety of impairments may result in an inadequate response to unpredictability, and we propose that there may be a relationship between response to an unpredictable visual cue and mobility-based participation.

Background: Breast cancer patients experience various side effects during cancer therapy, often resulting in reduced quality of life and poor adherence to treatment. A limited range of proven interventions has been developed to target such side effects. While Tai Chi offers benefits for the health and well-being of breast cancer survivors, the effectiveness of Tai Chi across the treatment continuum has not been evaluated. Improved patient education and support has been suggested as a priority for breast cancer care. This pilot study assesses the feasibility of a randomized controlled trial (RCT) to evaluate the effectiveness of "an integrative Tai Chi" (ANITA) program for breast cancer patients undergoing cancer therapy., Methods/design: This is a single-centre, two-arm feasibility RCT. Twenty-four patients with breast cancer who have undergone surgical treatment will be recruited from the Dunedin Hospital (New Zealand) over a 12-month period (from August 2017 to July 2018). Subject to informed consent, patients will be randomized to receive standard cancer treatment alone or standard cancer treatment plus the ANITA program, consisting of peer support, health education, and Tai Chi Ruler exercise. The program runs alongside the patient's adjuvant cancer therapy, which may include chemotherapy, radiation therapy, antibody treatment, and/or antihormonal therapy. Analysis in this study will focus on process evaluation of participant recruitment, retention, treatment fidelity, acceptability of the program, and occurrence of adverse events. Clinical outcomes (i.e., fatigue, sleep quality, anxiety and depression and quality of life) will be assessed at baseline, and at 12 weeks and 24 weeks post-randomization., Discussion: Outcomes from this study will inform the feasibility and methodology for a future fully-powered RCT., Trial Registration: Australian New Zealand Clinical Trials Registry with the identifier ACTRN12617000975392., (Copyright © 2018 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.)

Objective: The aim of the present study was to determine the feasibility of a relaxation-based yoga intervention for rheumatoid arthritis, designed and reported in accordance with Delphi recommendations for yoga interventions for musculoskeletal conditions., Methods: Participants were recruited from a hospital database, and randomized to either eight weekly 75-min yoga classes or a usual care control. Feasibility was determined by recruitment rates, retention, protocol adherence, participant satisfaction and adverse events. Secondary physical and psychosocial outcomes were assessed using self-reported questionnaires at baseline (week 0), week 9 (primary time point) and week 12 (follow-up)., Results: Over a 3-month period, 26 participants with mild pain, mild to moderate functional disability and moderate disease activity were recruited into the study (25% recruitment rate). Retention rates were 100% for yoga participants and 92% for usual care participants at both weeks 9 and 12. Protocol adherence and participant satisfaction were high. Yoga participants attended a median of seven classes; additionally, seven of the yoga participants (54%) reported continuing yoga at home during the follow-up period. No serious adverse events were related to the study. Secondary outcomes showed no group effects of yoga compared with usual care., Conclusions: A relaxation-based yoga programme was found to be feasible and safe for participants with rheumatoid arthritis-related pain and functional disability. Adverse events were minor, and not unexpected from an intervention including physical components. This pilot provides a framework for larger intervention studies, and supports further exploration of yoga as a complex intervention to assist with the management of rheumatoid arthritis., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: Breast cancer related lymphedema (BCRL) is a prevalent complication secondary to cancer treatments which significantly impacts the physical and psychological health of breast cancer survivors. Previous research shows increasing use of low level laser therapy (LLLT), now commonly referred to as photobiomodulation (PBM) therapy, for BCRL. This systematic review evaluated the effectiveness of LLLT (PBM) in the management of BCRL., Methods: Clinical trials were searched in PubMed, AMED, Web of Science, and China National Knowledge Infrastructure up to November 2016. Two reviewers independently assessed the methodological quality and adequacy of LLLT (PBM) in these clinical trials. Primary outcome measures were limb circumference/volume, and secondary outcomes included pain intensity and range of motion. Because data were clinically heterogeneous, best evidence synthesis was performed., Results: Eleven clinical trials were identified, of which seven randomized controlled trials (RCTs) were chosen for analysis. Overall, the methodological quality of included RCTs was high, whereas the reporting of treatment parameters was poor. Results indicated that there is strong evidence (three high quality trials) showing LLLT (PBM) was more effective than sham treatment for limb circumference/volume reduction at a short-term follow-up. There is moderate evidence (one high quality trial) indicating that LLLT (PBM) was more effective than sham laser for short-term pain relief, and limited evidence (one low quality trial) that LLLT (PBM) was more effective than no treatment for decreasing limb swelling at short-term follow-up., Conclusions: Based upon the current systematic review, LLLT (PBM) may be considered an effective treatment approach for women with BCRL. Due to the limited numbers of published trials available, there is a clear need for well-designed high-quality trials in this area. The optimal treatment parameters for clinical application have yet to be elucidated.

Objective: To evaluate the feasibility of a randomized controlled trial investigating the optimal number of treatment sessions of acupuncture, used as an adjunct to usual care, for managing chronic low back pain., Methods: In total, 45 participants with chronic low back pain were recruited and randomly allocated to receive usual care plus 4, 7, or 10 sessions of acupuncture (15/group). Primary outcomes were recruitment rate, randomization rate, treatment compliance, completion of the outcome measures, and retention rates. Secondary outcomes included back function, pain intensity and bothersomeness, generic health status, activity disability, and participant satisfaction. Data were collected at baseline and discharge, and at 6 and 12 weeks post randomization., Results: The recruitment method was demonstrated to be successful: recruitment rate was 43.7%, and randomization rate was 100%. Compliance with treatment was high among participants (86.7%, 86.7%, and 100% for the 4-, 7-, and 10-session group, respectively). Outcome questionnaires used in this study were found to be appropriate for a future randomized controlled trial. Participant retention rates were 88.9% at discharge and at 6 weeks post randomization and 84.4% at 12 weeks post randomization. Secondary outcomes (except for pain intensity) favored the 10-session acupuncture group at 12 weeks post randomization. Over 90% of participants indicated that they were "very satisfied" and/or "extremely satisfied" with the acupuncture treatment., Conclusion: This study demonstrated that a full-scale randomized controlled trial using the methodology described above is feasible, and such a trial is essential to test the dose dependence of acupuncture.