Towards more credible shams for physical interventions: A Delphi survey.

BACKGROUND/AIMS: In clinical trials of physical interventions, participant blinding is often poorly addressed and therapist blinding routinely omitted. This situation presents a substantial barrier to moving the field forward. Improving the success of blinding will be a vital step towards determining the true mechanisms of physical interventions. We used a Delphi approach to identify important elements of shams for physical interventions to maximise the likelihood of participant and therapist blinding in clinical trials. METHODS: Two expert groups were recruited: (1) experts in research methodology and (2) experts in deceptive and/or hypnotic techniques including magic. Magicians were included because they were considered a potentially rich source of innovation for developing credible shams due to their unique skills in altering perceptions and beliefs. Three rounds of survey were conducted, commencing with an open-ended question. Responses were converted to single 'items', which participants rated in the following two rounds using a 9-point Likert scale, categorised as 'Not important' (0-3), 'Depends' (4-6) and 'Essential' (7-9). Consensus was pre-defined as ≥80% agreement within a 3-point category. RESULTS: Thirty-eight experts agreed to participate (research methodology: n = 22; deceptive and/or hypnotic techniques: n = 16), and 30 experts responded to at least one round (research methodology: n = 19; deceptive and/or hypnotic techniques: n = 11). Of 79 items, five reached consensus in the 'Essential' category in both groups, which related to beliefs of participants (n = 3 items), interactions with researchers (n = 1 item) and standardisation of clinical assessments (n = 1 item). Thirteen additional items reached consensus in the 'Essential' category in one group. Experts in research methodology had one additional item reach consensus, related to authentic delivery of study information. The remaining 12 additional items that reached consensus in the deceptive and/or hypnotic techniques group related mainly to therapist attitude and behaviour and the clinical interaction. CONCLUSION: Experts agreed that, for shams to be believable, consideration of cognitive influences is essential. Contrary to the focus of previous shams for physical interventions, replicating the tactile sensation of the active treatment was not considered an essential part of sham development. Therefore, when designing sham-controlled clinical trials, researchers should carefully consider the cognitive credibility of the entire intervention experience, and not just the indistinguishability of the sham intervention itself. The findings provide new guidance to researchers on important contributors to blinding in physical intervention trials.

Does walking improve disability status, function, or quality of life in adults with chronic low back pain? A systematic review.

OBJECTIVE: To establish the effectiveness of walking alone and walking compared to other non-pharmacological management methods to improve disability, quality of life, or function in adults with chronic low back pain. DATA SOURCES: A systematic search of the following databases was undertaken: Medline, Embase, CINAHL, Scopus, Pedro, SportDiscus, Cochrane Central Register of Controlled Trials. The following keywords were used: 'back pain' or 'low back pain' or 'chronic low back pain' and 'walk*' or 'ambulation' or 'treadmill*' or 'pedometer*' or 'acceleromet*' or 'recreational' and 'disability' or 'quality of life' or 'function*'. REVIEW METHODS: Primary research studies with an intervention focus that investigated walking as the primary intervention compared to no intervention or any other non-pharmacological method in adults with chronic low back pain (duration >3 months). RESULTS: Seven randomised controlled trials involving 869 participants were included in the review. There was no evidence that walking was more effective than other management methods such as usual care, specific strength exercises, medical exercise therapy, or supervised exercise classes. One study found over-ground walking to be superior to treadmill walking, and another found internet-mediated walking to be more beneficial than non-internet-mediated walking in the short term. CONCLUSION: There is low quality evidence to suggest that walking is as effective as other non-pharmacological management methods at improving disability, function, and quality of life in adults with chronic low back pain.

Allied health: integral to transforming health.

Objective South Australia is taking an innovative step in transforming the way its healthcare is organised and delivered to better manage current and future demands on the health system. In an environment of transforming health services, there are clear opportunities for allied health to assist in determining solutions to various healthcare challenges. A recent opinion piece proposed 10 clinician-driven strategies to assist in maximising value and sustainability of healthcare in Australia. The present study aimed to seek the perspectives of allied health clinicians, educators, researchers, policy makers and managers on these strategies and their relevance to allied health. Methods A survey of allied health practitioners was undertaken to capture their perspectives on the 10 clinician-driven strategies for maximising value and sustainability of healthcare in Australia. Survey findings were then layered with evidence from the literature. Results Highly relevant across allied health are the strategies of discontinuation of low value practices, targeting clinical interventions to those getting greatest benefit, active involvement of patients in shared decision making and self-management and advocating for integrated systems of care. Conclusions Allied health professionals have been involved in the South Australian healthcare system for a prolonged period, but their services are poorly recognised, often overlooked and not greatly supported in existing traditional practices. The results of the present study highlight ways in which healthcare services can implement strategies not only to improve the quality of patient outcomes, but also to offer innovative solutions for future, sustainable healthcare. The findings call for concerted efforts to increase the utilisation of allied health services to ensure the 'maximum value for spend' of the increasingly scarce health dollar. What is known about the topic? In medicine, clinician-driven strategies have been proposed to minimise inappropriate and costly care and maximise highly appropriate and less expensive care. These strategies were developed based on clinical experiences and with supporting evidence from scientific studies. What does this paper add? Major changes to the health system are required to slow down the growth in healthcare expenditure. This paper describes opportunities in which allied health practitioners can implement similar strategies not only to improve the quality of patient outcomes, but also to offer cost-effective solutions for a sustainable healthcare. What are the implications for practitioners? Allied health practitioners can provide solutions to healthcare challenges and assist in the transformation of healthcare in Australia. However, for this to happen, there should be concerted efforts to increase recognition of and support for the use of allied health services.

Evidence for the use of dry needling and physiotherapy in the management of cervicogenic or tension-type headache: a systematic review.

BACKGROUND: There is good evidence in the literature supporting physiotherapy in the management of some forms of headache. Dry needling of myofascial trigger points is becoming an increasingly common approach despite a paucity of research evidence supporting its use. The purpose of this review was to determine the evidence supporting the use of dry needling in addition to conventional physiotherapy in the management of tension-type and cervicogenic headache. METHODS: Ten databases were searched for evidence of the effect of dry needling on the severity and frequency of tension and cervicogenic headache based ICHD classifications. RESULTS: Three relevant studies were identified and all three showed statistically significant improvements following dry needling, but no significant differences between groups. Only one study reported on headache frequency or intensity, reporting a 45 mm improvement in VAS score following the addition of dry needling to conventional physiotherapy. Two studies showed significant improvements with dry needling over 4-5 weeks of treatment. No adverse events were reported. CONCLUSIONS: The literature suggests that while there is insufficient evidence to strongly advocate for the use of dry needling, it may be a useful addition to conventional physiotherapy in headache management. Further research with a stronger methodological design is required.

Transgender, Gender-Diverse, and Nonbinary Experiences in Physical Therapy: A Descriptive Qualitative Study.

OBJECTIVE: The objective was to explore experiences with and identify barriers and facilitators of utilizing physical therapy for people who identify as transgender, gender diverse, and nonbinary (TGNB). METHODS: A qualitative descriptive design was employed using semistructured interviews conducted in New Zealand. Eligible participants were individuals who were 12 years old or older, who self-identified as TGNB, and who had accessed physical therapy at a community-based clinic that also provides a gender-affirming service. Participants were recruited via email invitation to the clinic database. Interview data were analyzed using reflexive thematic analysis. Demographics are reported descriptively. RESULTS: Seventeen individuals (15-64 years old and identifying as 11 different genders) participated. All participants reported physical therapist experiences relating to 1 or more of the following 4 themes: challenging cisnormativity at policy, environmental, clinic, and therapist levels; safety and trust throughout the clinical experience, including clinic credibility for being a safe provider, clinic displays of TGNB inclusivity, implementation of safe clinic processes, and respectful therapist interactions; inclusive experiences in a clinic that provided affordable care and took active steps to understand and affirm TGNB identities and with physical therapists who had a high level of knowledge of TGNB-specific health issues and took a biopsychosocial approach to care; and sensitivity to body discomfort or dysphoria triggers. Barriers to and facilitators of care were identified at policy, environmental, clinic, and therapist levels. CONCLUSION: People who identify as TGNB face challenges to accessing safe and culturally sensitive physical therapy. However, there are achievable areas for improvement at policy, environmental, clinic, and physical therapist levels to gain trust and engagement in care for the TGNB community. IMPACT: This study provides a detailed exploration of TGNB physical therapist experiences and identifies specific areas of improvement for TGNB physical therapy care to provide clinicians and physical therapy clinics insights into the provision of safe and culturally sensitive physical therapy.

Reliability of lower limb strength assessment in female team sport athletes.

BACKGROUND: Lower limb injury rates have increased dramatically in line with increased female sport participation levels. Muscle strength is a modifiable lower limb injury risk factor, guiding performance monitoring and rehabilitation. OBJECTIVES: The aim of this study was to investigate the test-retest reliability of isokinetic and isometric lower limb peak torque to body mass of muscles acting on the hip, knee, and ankle in female team sport athletes. It was hypothesised the test-retest reliability would be good (intraclass correlation coefficients (ICC) ≥ 0.75). METHODS: Thirty-eight female athletes (Australian Rules Football = 18, netball = 12, soccer = 8) aged 16-35 years participated in this study. Participants performed isokinetic (60°/s and 120°/s) and isometric testing on a Biodex Isokinetic Dynamometer on three separate days. RESULTS: Poor to good reliability was demonstrated for all joint movements (ICC = 0.38-0.88) with small to moderate effect sizes (0.00-0.43) and typical errors (5.65-24.49). CONCLUSION: Differences in peak torque to body mass were observed between sessions one and two and/or one and three, demonstrating a learning effect. Therefore, three testing sessions, and/or the inclusion of a familiarisation session, is recommended for future assessments in populations unfamiliar with dynamometry.

Does the method of component fixation influence clinical outcomes after total knee replacement? A systematic literature review.

A systematic literature review was conducted to identify the best available evidence describing the differences in clinical outcome associated with the different methods of total knee replacement (TKR) fixation. Randomized trials published between 1980 and January 2011 comparing differences in clinical outcome scores between groups allocated to either cemented or uncemented fixation for TKR were included. Nine of the 11 studies included in the review reported no significant differences in clinical outcomes between groups with either cemented or uncemented prosthesis components. Critical appraisal of methodological bias revealed consistent shortcomings in study design and execution. It is apparent that more rigorous studies with longer follow-up periods are required to verify which method of fixation may be preferable in enhancing clinical outcomes.

Snakes and ladders: the barriers and facilitators of elective hip- and knee-replacement surgery in Australian public hospitals.

OBJECTIVES: Waiting lists for elective surgery are a persistent problem faced by health systems. The progression through elective surgery waiting lists can be likened to a game of snakes and ladders where barriers (snakes) delay access to surgery and facilitators (ladders) expedite access. The aim of the present study was to describe the barriers and facilitators to delivery of total hip- and total knee-replacement surgery in South Australian public-funded hospitals. METHODS: Semistructured interviews with staff, direct observation of administrative processes and documentation analysis were combined under a systems theory framework. RESULTS: System barriers (snakes) were grouped into five categories: resources, workload, hospital engagement, community engagement and system processes. Inadequate resources was the most prominent barrier, patient cancellations resulted in one-third of administrative tasks being repeated and there was a perceived lack of engagement to maximising efficiency. Interestingly, despite a lack of resources being perceived to be the biggest problem, additional resources without system change was not considered an effective long-term strategy. CONCLUSIONS: Given the complexity of the elective surgery system, it is not surprising that single-item reforms have not created lasting reductions in waiting times. Multifaceted, whole-system reforms may be more successful. WHAT IS KNOWN ABOUT THE TOPIC? Waiting lists and waiting times for surgery are controversial, associated with frequent reforms and negative emotive headlines. We know from existing literature and anecdotal reports that individuals frequently experience lengthy delays before receiving elective surgery. Anecdotal reports also suggest that there are inefficiencies within elective surgery systems that contribute to these delays and result in cancellations, patient deterioration and poor overall satisfaction with the public health system in Australia. What isn't clear is whether this perception is accurate and what inefficiencies do exist that could be specifically targeted for reform. WHAT DOES THIS PAPER ADD? This paper adds weight to the argument that some inefficiencies exist within elective surgery systems, and identifies specific barriers to the delivery of total hip- and total knee-replacement surgery in South Australian public hospitals. It also identifies several strategies that could improve system function, some of which have already been implemented at a local level in response to stress on the system, and some of which require broad region- or state-wide change. In contrast to existing research, the level of detail provided in the present paper should allow for targeted reforms with the potential to improve system function and the efficiency with which joint-replacement surgery can be delivered. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? All clinicians aim to provide the best intervention for their patients. Should the findings of this study be used to inform elective surgery system changes, patients and clinicians should experience a more streamlined approach to referral for and receipt of elective surgery in public hospitals. The consistency with which barriers and facilitators were identified across the four hospitals involved in this research supports the generalisability of the results. This further suggests that although specific to hip and knee replacement, many of the same barriers and facilitators could be in place across numerous surgical and non-surgical disciplines.

Inclusion of Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual, and Other Related Identities Content in Australian Physical Therapy Curricula: Perceived Barriers and Priorities for Inclusive Education.

INTRODUCTION: Providing culturally responsive, patient-centered care is crucial for ensuring safe and positive health care experiences for individuals with diverse gender identities and sexual orientations. Doing so requires adequate training and knowledge of the health professionals involved in those health care experiences. REVIEW OF LITERATURE: Individuals identifying as lesbian, gay, bisexual, transgender, queer, intersex, asexual, and other related identities (LGBTQIA+) experience significant barriers to health and positive health care experiences. In physical therapy, research has identified that individuals who identify as LGBTQIA+ experience discrimination, discomfort, and lack of practitioner knowledge about health needs. The aim of this study was to determine how, and to what extent, content related to LGBTQIA+ individuals is included in Australian physical therapy curricula as well as perceived barriers to inclusion. SUBJECTS: Physical therapy program directors (PDs) as of January 2022 for all Australian universities that deliver physical therapy programs (n = 24). METHODS: A Qualtrics survey was emailed to PDs to collect quantitative and qualitative data regarding the inclusion and mode of delivery of LGBTQIA+ content, as well as the perceived importance, and barriers to inclusion, of LGBTQIA+ curricula. RESULTS: Twenty-four (100%) universities (PD or proxy) responded to the survey. More than 62% (15/24) of PDs reported that their programs included LGBTQIA+ content with 88% (21/24), indicating that LGBTQIA+ content is relevant to the physical therapy curriculum. Time devoted to LGBTQIA+ content ranged from 0 to 6 (median 2-4) hours across any year, delivered primarily in general or foundational courses (37%). Perceived lack of trained faculty (14/22; 64%) and time (13/22; 59%) were barriers to the integration of LGBTQIA+ specific content into the curriculum. DISCUSSION: Our results indicate that the physical therapy curriculum may be contributing to ongoing negative experiences of individuals identifying as LGBTQIA+ with physical therapy encounters. Although most (87%) physical therapy program leaders in Australia believe that LGBTQIA+ specific content is relevant to the training of new graduates, content is included in only 62% of curricula. Perceived barriers to inclusion of LGBTQIA+ specific curriculum were a lack of time and appropriately trained faculty. Externally developed content is available to address limited expertise within programs, but faculty may require guidance on how to overcome perceived lack of time (ie, space in the curriculum). CONCLUSION: Most Australian physical therapy programs include LGBTQIA+ content to a limited extent in their curricula, indicating a lack of perceived importance relative to other topics. In this way, Australian universities are maintaining the pervasive heteronormativity of the physical therapy profession and are complicit in the ongoing health disparities between the LGBTQIA+ and heteronormative communities.

Reliability of the running vertical jump test in female team sport athletes.

Injury rates to the lower limb have increased over the past 40 years, coinciding with increases in female sport participation rates. Sport specific tests such as the running vertical jump (RVJ) are utilised for injury risk profiling, however the test-retest reliability is unknown. OBJECTIVES: The aim of this study was to investigate the test-retest reliability of the thorax, pelvis and lower limb joint angular kinematics and kinetics for the RVJ test in female team sport athletes. DESIGN: Three-dimensional motion capture with force plate integration was utilised as participants performed five trials on each limb on three separate days. SETTING: Testing occurred in a biomechanics laboratory. PARTICIPANTS: Thirty-four females (Australian Rules Football = 15, Netball = 12, Soccer = 7) participated in this study. MAIN OUTCOME MEASURES: Intraclass correlation coefficients (ICC), effect sizes and typical errors (TE) of segment and joint angular kinematics and kinetics were calculated. RESULTS: Poor to excellent reliability (ICC = -0.12 - 0.92), small to large effect sizes (0.00-0.90) and TE (0.02-289.24) were observed across segment and joint angular kinematics and kinetics. CONCLUSIONS: The RVJ test is recommended when analysing ground reaction forces and joint angular kinematics in female team sport athletes.

The journey to total hip or knee replacement.

OBJECTIVES: Despite the incidence of joint replacements in Australia, there is a paucity of information regarding how patients progress from their referral to their surgery. The aim of this study was to describe a patient pathway from referral to receipt of total hip replacement (THR) or total knee replacement (TKR) surgery in South Australian public hospitals. METHODS: Patient perspectives of the pathway to THR and TKR surgery were obtained via a postal survey (n=450) and hospital employee perspectives were attained via semi-structured interviews (n=19). Survey data were analysed using descriptive statistics and interview data were analysed thematically. RESULTS: A typical patient pathway to THR and TKR surgery can be divided into two distinct phases; referral-to-initial appointment (9-24 months), and initial appointment-to-surgery (12-15 months). This gives an overall waiting period between 2 and 3 years for THR or TKR surgery. CONCLUSIONS: Waiting times for THR and TKR surgery reported in this study were longer than other reports in the literature. Current Australian health policy does not consider the first (and longest) phase of the patient pathway. Excluding this initial phase could be generating an erroneous perception of the patient pathway to THR or TKR surgery, possibly leading to poorly considered health reforms.

Health sciences librarians' research on medical students' use of information for their studies at the medical school, University of Queensland, Australia.

This study reports the findings of research undertaken by health sciences librarians at the University of Queensland Library into how medical students use information for their studies, particularly resources and services provided by the Library. The methods utilized were an online survey and focus groups. Results indicated that students favor print resources over electronic, value accessing resources on a one-stop basis, and prefer training to be delivered flexibly. The implication of these results for future resource selection, service provision, and instructional design and delivery is discussed.

A novel blinding protocol to test participant and therapist blinding during dry needling: a randomised controlled experiment.

OBJECTIVES: Dry needling is widely used in physiotherapy. Lack of blinding in clinical trials means that dry needling effects and mechanisms remain unclear, with blinding issues accepted as an unavoidable barrier to better evidence. The authors aimed to overcome this barrier by designing a protocol to double-blind dry needling trials. DESIGN: A prospectively registered randomised experiment tested a novel blinding protocol for blinding effectiveness. SETTING: University physiotherapy clinic. PARTICIPANTS: Therapists (n=15) and asymptomatic volunteers ('recipients') (n=45) were randomly allocated to real and/or sham interventions. INTERVENTIONS: The protocol involved custom-made needles and cognitive and multisensory blinding techniques. MAIN OUTCOME MEASURES: The primary outcome was guesses about allocation. The a priori criterion for successful blinding was ≤50% correct guesses (random chance). Secondary analyses explored blinding patterns using blinding indices. RESULTS: Correct guesses were not different from 50% for therapists [41% (95%CI 30 to 50), n=120 guesses] or recipients [49% (95%CI 38 to 60), n=90 guesses]. Blinding indices supported the primary result but revealed that recipients were better at detecting real dry needling than sham. CONCLUSION: Both therapists and recipients were successfully blinded, which contrasts with the widely held assumption that double-blinding is impossible for needling interventions. The authors recommend that any future trials can, and therefore should, blind therapists. However, secondary analyses revealed that recipients receiving real dry needling were less blinded than sham recipients, which may still create bias in clinical trials and suggests further work is needed to improve recipient blinding. Nonetheless, the current findings offer an opportunity to gain better evidence concerning the effects and mechanisms of dry needling. STUDY REGISTRATION: https://osf.io/rkzeb/.

A collaborative experiential problem-solving approach to develop shams for complex physical interventions: a case study of dry needling.

OBJECTIVE: Complex physical interventions are widely used in physiotherapy, despite doubts over the validity of clinical trial results due to lack of credible shams. Credible shams are critically needed, so too, therefore, is a process by which they can be developed. The authors used a novel methodology to develop and test blinding protocols for dry needling, a complex physical intervention for which blinding is particularly difficult. DESIGN: The research design was a practical three-day workshop influenced by Participatory Action Research, which uses iteration and reflection to solve a problem. PARTICIPANTS: Five multidisciplinary experts (researchers, clinicians, technician, magician) were invited. Healthy volunteers ('recipients', n=17) and accredited physiotherapists (n=6) were recruited to enable testing of blinding strategies. MAIN OUTCOME MEASURES: Primary outcomes were expert opinion on the potential to blind recipients/therapists for (1) individual blinding strategies, and (2) entire blinding protocols. Secondary outcomes included recipient/therapist blinding effectiveness and acceptability. RESULTS: Experts iteratively developed 11 blinding protocols involving 22 blinding strategies. Experts rated 18 of the blinding strategies to 'definitely have potential' and identified four categories: knowledge of the sham, clinical interaction, disinformation, and sensation. Recipient and therapist blinding became more successful as the protocols evolved. CONCLUSIONS: Credible shams capable of simultaneous recipient and therapist blinding have been regarded to be impossible in dry needling. The preliminary success of the devised protocols suggest that our novel approach may be a crucial step in sham development. Improvements in expert rankings and blinding effectiveness as the protocols progressed support the value of this workshop approach.

Towards more homogenous and rigorous methods in sham-controlled dry needling trials: two Delphi surveys.

OBJECTIVES: Sham-controlled trials of dry needling, a popular treatment for pain, use a range of methods and theoretical frameworks and most have high risk of bias. Critically, patient blinding is often unsuccessful and therapist blinding has not been attempted. The specific effects of dry needling on pain therefore remain unclear. Our objectives were to identify (1) important elements of active dry needling; (2) important elements of shams for dry needling. DESIGN AND PARTICIPANTS: Two Delphi surveys (to quantify levels of consensus) were undertaken with three expert groups: experts in (1) dry needling, (2) research methodology, and (3) deceptive/hypnotic techniques including magic. Experts in dry needling participated in Delphi 1 and all three groups participated in Delphi 2. Each survey commenced with an open-ended question. Responses were converted to single 'items' suitable for rating on 9-point Likert scales [categorised as 'Not important' (0-3), Depends (4-6), and Essential (7-9)], which participants rated in the following two rounds. Consensus was pre-defined as ≥80% agreement within a 3-point category. RESULTS: In Delphi 1 (n=20 experts), of 80 items, 35 reached consensus in the 'Essential' category, which related to explanations, therapist knowledge/skills, intervention rationale, the setting, and safety. In Delphi 2 (n=53 experts), of 97 items, 15 items reached consensus in the 'Essential' category in all three groups, which related to standardisation/indistinguishability, therapist attributes, expectations/beliefs, vision, protocol, and environment. CONCLUSIONS: Experts placed high importance on the entire intervention experience for active and sham protocols. Cognitive influences that extend beyond mimicking of tactile sensations should be used to create a believable simulation of active dry needling.

Calreticulin requires an ancillary adjuvant for the induction of efficient cytotoxic T cell responses.

Molecular chaperones stimulate the immune system to induce both protective immune responses and therapeutic tumor rejection. However, the underlying basis for this immunogenic activity is not well understood. A variety of chaperones, including calreticulin, hsp70 and grp94, function as vehicles to efficiently traffic associated peptides into professional antigen presenting cells. Importantly, these chaperones have also been proposed to function as adjuvants by stimulating the dendritic cell activation and co-stimulatory responses required to elicit peptide-specific CD8(+) T cell cytolytic activity. The efficacy of chaperone-mediated tumor rejection has been attributed to the ability of chaperones to function in both of these capacities. However, purified calreticulin has not previously been assessed for its ability to elicit DC maturation and, moreover, recent data indicates that it is not efficient at inducing Nf-kappaB activity which often accompanies or stimulates DC maturation. Here we use two complementary methods to produce endotoxin-free calreticulin and demonstrate that it does not measurably mature or activate dendritic cells both in vitro and in vivo. Additionally, a calreticulin/peptide complex required the addition of an exogenous adjuvant to elicit in vivo cytotoxic CD8(+) T cell responses. These data are discussed with respect to current models for chaperone-derived immune responses and in regard to rational vaccine design.

Scavenger receptor-A-targeted leukocyte depletion inhibits peritoneal ovarian tumor progression.

Immunosuppressive leukocytes are emerging as a critical factor in facilitating tumor progression. These leukocytes are converted by the tumor microenvironment to become tolerogenic, facilitate metastasis, and to aid in neovascularization. The predominant variety of suppressive leukocytes found in human and murine ovarian cancer are called vascular leukocytes (VLC), due to sharing functions and cell surface markers of both dendritic cells and endothelial cells. Using the ID8 murine model of ovarian cancer, the aim of this study was to test the efficacy of VLC elimination as an ovarian tumor therapy. We show that carrageenan-mediated depletion of peritoneal tumor-associated leukocytes inhibits ovarian tumor progression. We then identified scavenger receptor-A (SR-A) as a cell surface receptor that is robustly and specifically expressed within human and murine ovarian tumor ascites upon VLCs. Administration of anti-SR-A immunotoxin to mice challenged with peritoneal ID8 tumors eliminated tumor-associated VLCs and, importantly, substantially inhibited peritoneal tumor burden and ascites accumulation. Moreover, the toxin required targeting to SR-A because mice that received untargeted toxin did not exhibit inhibition of tumor progression. We conclude that SR-A constitutes a novel and specific target for efficacious immunotherapeutic treatment of peritoneal ovarian cancer.

Blinding Strategies in Dry Needling Trials: Systematic Review and Meta-Analysis.

BACKGROUND: Blinding of participants and therapists in trials of physical interventions is a significant and ongoing challenge. There is no widely accepted sham protocol for dry needling. PURPOSE: The purpose of this review was to summarize the effectiveness and limitations of blinding strategies and types of shams that have been used in dry needling trials. DATA SOURCES: Twelve databases were searched from inception to February 2016. STUDY SELECTION: Trials that compared active dry needling with a sham that simulated dry needling were included. DATA EXTRACTION: The main domains of data extraction were participant/therapist details, intervention details, blinding strategies, blinding assessment outcomes, and key conclusions of authors. Reported blinding strategies and sham types were synthesized descriptively, with available blinding effectiveness data synthesized using a chance-corrected measurement of blinding (blinding index). DATA SYNTHESIS: The search identified 4894 individual publications with 27 trials eligible for inclusion. In 22 trials, risk of methodological bias was high or unclear. Across trials, blinding strategies and sham types were heterogeneous. Notably, no trials attempted therapist blinding. Sham protocols have focused on participant blinding using strategies related to group standardization and simulation of tactile sensations. There has been little attention given to the other senses or cognitive strategies to enhance intervention credibility. Nonpenetrating sham types may provide effective participant blinding. LIMITATIONS: Trials were clinically and methodologically diverse, which limited the comparability of blinding effectiveness across trials. Reported blinding evaluations had a high risk of chance findings with power clearly achieved in only 1 trial. CONCLUSIONS: Evidence-based consensus on a sham protocol for dry needling is required. Recommendations provided in this review may be used to develop sham protocols so that future protocols are more consistent and potentially more effective.

Redundancy renders the glycoprotein 96 receptor scavenger receptor A dispensable for cross priming in vivo.

CD8(+) T cells (T(CD8+)) differentiate into effector cells following recognition of specific peptide-major histocompatibility complex (MHC) class I complexes (pMHC-I) on the surface of professional APCs (pAPCs), such as dendritic cells. Antigenic pMHC-I can be generated from two spatially distinct sources. The direct presentation pathway involves generation of peptide from protein substrate synthesized within the cell that is presenting the pMHC-I. Alternatively, the cross presentation pathway involves presentation of antigen that is not synthesized within the presenting cell, but is derived from exogenous proteins synthesized within other donor cells. The mechanisms by which cross presentation of exogenous antigens occur in vivo remain controversial. The C-type lectin scavenger receptor A (SR-A) has been implicated in a number of potential cross presentation pathways, including the presentation of peptide bound to heat shock proteins, such as glycoprotein 96 (gp96), and the transfer of pMHC-I from a donor cell to the pAPC. We demonstrate here that initiation of T(CD8+) responses is normal in mice lacking SR-A, and that the redundancy of ligand binding exhibited by the SR family is likely to be an important mechanism that ensures cross presentation in vivo. These observations emphasize the requirement to target multiple receptors and antigen-processing pathways during the rational design of vaccines aimed at eliciting protective T(CD8+).