Guidelines versus evidence: what we can learn from the Australian guideline for low-level laser therapy in knee osteoarthritis? A narrative review.

This narrative review analyses the Australian Guideline (2018) for the treatment of knee osteoarthritis (KOA) developed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The Guideline recommended against the use low-level laser therapy (LLLT). Why this conclusion was reached is discussed in this review in the context of evidence provided in other systematic reviews, the latest of which was published in 2019 and which provided strong support for LLLT for knee OA. We evaluated the reference list cited for the recommendation "against" LLLT and compared this with reference lists of systematic reviews and studies published before and after the publication date of the Guideline. Eight randomised controlled trials (RCTs) of LLLT were cited in the Guideline the latest of which was published in 2012. There were seventeen additional RCTs, five of which together with one systematic review were located in the year of publication, 2018. The most recent systematic review in 2019 included 22 RCTs in its analysis. Discordance with the levels of evidence and recommendations was identified. Although GRADE methodology is said to be robust for systematically evaluating evidence and developing recommendations, many studies were not identified in the Guideline. In contrast, the latest systematic review and meta-analysis provides robust evidence for supporting the use of LLLT in knee OA. The conflict between guidelines based on opinion and evidence based on meta-analysis is highlighted. Given the totality of the evidence, we recommend that the Australian Guideline should be updated immediately to reflect a "for" recommendation.

Ytterbium-doped fibre femtosecond laser offers robust operation with deep and precise microsurgery of C. elegans neurons.

Laser microsurgery is a powerful tool for neurobiology, used to ablate cells and sever neurites in-vivo. We compare a relatively new laser source to two well-established designs. Rare-earth-doped mode-locked fibre lasers that produce high power pulses recently gained popularity for industrial uses. Such systems are manufactured to high standards of robustness and low maintenance requirements typical of solid-state lasers. We demonstrate that an Ytterbium-doped fibre femtosecond laser is comparable in precision to a Ti:Sapphire femtosecond laser (1-2 micrometres), but with added operational reliability. Due to the lower pulse energy required to ablate, it is more precise than a solid-state nanosecond laser. Due to reduced scattering of near infrared light, it can lesion deeper (more than 100 micrometres) in tissue. These advantages are not specific to the model system ablated for our demonstration, namely neurites in the nematode C. elegans, but are applicable to other systems and transparent tissue where a precise micron-resolution dissection is required.

Sperm motility is enhanced by Low Level Laser and Light Emitting Diode photobiomodulation with a dose-dependent response and differential effects in fresh and frozen samples.

BACKGROUND: The effects of Low Level Light Therapy (LLLT) on cellular function arise predominantly from stimulation of ATP production and reduction of oxidative stress. These effects are dose dependent and a function of beam irradiance and irradiation time. Human sperm motility has been shown to increase with LLLT irradiation. The objective of this study was to investigate the effects of laser and Light Emitting Diode (LED) LLLT photobiomodulation on human spermatozoa motility and DNA integrity. METHODS: An in-vitro controlled trial was performed within an IVF clinic laboratory using three human semen specimens, one fresh and two frozen. Sperm were exposed to light from a GaAlAs single laser (810 nm 200 mW) and an LED cluster (660 nm and 850 nm total power 2 W) for various irradiation times. Sperm motility for the test and control aliquots was assessed using a SQA-IIB analyser, but fertilizing ability was not. Sperm chromatin integrity was tested using the Sperm Chromatin Structure Assay. RESULTS: The Sperm Motility Index and Total Functional Sperm Count increased up to four fold compared to controls with inhibitory effects observed at higher doses (longer irradiation times). The maximum effect varied with irradiance and irradiation time and whether the sample was fresh or frozen. DISCUSSION: Human sperm motility is modified by exposure to LLLT and this motility modification is dependent upon beam irradiance and irradiation time as well as the condition of the sample. A higher stimulatory dose provides a rapid increase in motility that is short in duration, while a lower stimulatory dose provides a slower increase in motility. An inhibitory does causes reduced motility. Future research could consider animal models, such as the mouse, to test fertilization capacity and the safety of resulting fetuses.

Selection and Use of Health Services for Infants' Needs by Indigenous Mothers in Canada: Integrative Literature Review.

In Canada, Indigenous infants experience significant health disparities when compared to non-Indigenous infants, including significantly higher rates of birth complications and infant mortality rates. The use of primary health care is one way to improve health outcomes; however, Indigenous children may use health services less often than non-Indigenous children. To improve health outcomes within this growing population, it is essential to understand how caregivers, defined here as mothers, select and use health services in Canada. This integrative review is the first to critique and synthesize what is known of how Indigenous mothers in Canada experience selecting and using health services to meet the health needs of their infants. Themes identified suggest both Indigenous women and infants face significant challenges; colonialism has had, and continues to have, a detrimental impact on Indigenous mothering; and very little is known about how Indigenous mothers select and use health services to meet the health of their infants. This review revealed significant gaps in the literature and a need for future research. Suggestions are made for how health providers can better support Indigenous mothers and infants in their use of health services, based on what has been explored in the literature to date.

Simple and practical screening approach to identify HIV-infected individuals with depression or at risk of developing depression.

OBJECTIVES: Studies have shown that depression and other mental illnesses are under-diagnosed among HIV-infected individuals. The aim of this study was to evaluate the use of mental health history and questionnaire-based screening instruments to identify HIV-infected individuals at risk of depression. METHODS: The Beck Depression Inventory II (BDI-II) was used to assess the prevalence and severity of depressive symptoms among HIV-infected individuals attending two out-patient clinics in Denmark. HIV-infected individuals with a BDI-II score ≥ 20 were offered a clinical evaluation by a consultant psychiatrist. The BDI-II score was compared to the outcome of mental health history review, and to results obtained using the European AIDS Clinical Society (EACS) two-item depression screening tool. RESULTS: A total of 501 HIV-infected individuals were included in the study. Symptoms of moderate/major depression (BDI-II score ≥ 20) were observed in 111 patients (22%); 65 of these patients consulted a psychiatrist, of whom 71% were diagnosed with a co-existing disorder. The BDI-II score was compared to the outcome of a mental health history review, and to results obtained using the European AIDS Clinical Society (EACS) two-item depression screening tool. The two questions showed a sensitivity and specificity of 95% and 68%, respectively, for diagnosis of current depression or risk of depression. A previous psychiatric history and substance abuse were independently associated with an increased risk of depression. CONCLUSIONS: We suggest that the mental health of HIV-infected individuals should be reviewed and a "risk-flag" three-step approach should be used (1) to screen routinely with the two verbal questions suggested by the EACS, (2) to identify whether there is a risk of depression and then screen with the BDI-II, and (3) to identify whether there is still a risk and then perform a full evaluation and obtain an accurate psychiatric diagnosis by a psychiatrist.

Factors associated with risk of depression and relevant predictors of screening for depression in clinical practice: a cross-sectional study among HIV-infected individuals in Denmark.

OBJECTIVES: Depression and psychiatric disorders are frequent among HIV-infected individuals. The aim of this study was to determine the prevalence of depression and describe the psychiatric history of HIV-infected individuals in an out-patient clinic in Denmark and to identify factors of clinical importance that may be used to identify patients at risk of depression. METHODS: In 2013, 212 HIV-infected patients were included in a questionnaire study. We used the Beck Depression Inventory II (BDI-II) to assess the prevalence and severity of depressive symptoms. Patients with a BDI-II score ≥ 20 were offered a clinical evaluation by a consultant psychiatrist. Logistic regression was used to determine predictors associated with risk of depression. RESULTS: Symptoms of depression (BDI-II score ≥ 14) were observed in 75 patients (35%), and symptoms of moderate to major depression (BDI-II score ≥ 20) in 55 patients (26%). There was also a high prevalence of co-occurring mental illness. In a multivariate model, self-reported stress, self-reported perception that HIV infection affects all aspects of life, self-reported poor health, not being satisfied with one's current life situation, previous alcohol abuse, nonadherence to antiretroviral therapy and previously having sought help because of psychological problems were independently associated with risk of depression. CONCLUSIONS: Symptoms of depression and co-occurring mental illness are under-diagnosed and under-treated among HIV-infected individuals. We recommend that screening of depression should be conducted regularly to provide a full psychiatric profile to decrease the risk of depression and improve adherence and quality of life in this population.

The origins of Western mind-body exercise methods.

Background: Over recent decades, mind-body exercise methods have gained international popularity and importance in the management of musculoskeletal disorders. Objectives: The scope of this paper was to investigate: the origins of Western mind-body methods, their philosophies, exercises, and relationship with mainstream healthcare over the last two centuries. Major findings: Within a few decades of the turn of the 20th century, a cluster of mind-body exercise methods emerged from at least six pioneering founders: Checkley, Müller, Alexander, Randell, Pilates, and Morris. Each was based upon a similar exercise philosophy and similar functional movement-harmonizing exercises. This renaissance of independent mind-body schools occurred in parallel with the demise of the 18th and 19th century gymnasium Physical Culture movement and the concurrent emergence of bodybuilding and strength training. Even though mostly forgotten today, Western mind-body exercise methods enjoyed celebrated success during the first half of the 20th century, were hailed by medical and allied health practitioners and practiced by millions from society's elite to deprived minorities. Conclusions: Rediscovering the Western mind-body exercise movement is hoped to facilitate official healthcare establishment recognition of this kind of training as an integral entity. This may widen research opportunities and consolidate approaches toward: optimal musculoskeletal rehabilitation and injury prevention, promotion of a healthy active lifestyle environment in the modern world, and enhancement of the natural pain-free human athletic look, feel, and performance.

The influence of 'Slacklining' on quadriceps rehabilitation, activation and intensity.

OBJECTIVES: To determine and compare the level of quadriceps activation for knee injured participants during kinetic open-chain, closed-chain and composite-chain (Slackline) clinical exercises. Quadriceps activation is a critical component of lower limb movement and subsequently, rehabilitation. However, selective activation can be difficult due to pain, loss of function and impaired neuro-motor activation. DESIGN: Repeated measures (within-subjects) ANOVA. METHODS: Consecutive physiotherapy outpatients (n=49, 41.8±16.8 years, range 13-72 years, 57% female) with an acute (<2 weeks) knee injury were recruited. Participants were assessed for quadriceps activation using skin mounted electromyography during five separate clinical quadriceps activation exercises: two open-chain, inner range quads and straight leg raise; two closed-chain, step down and step up; and a composite-chain, slacklining step-up. Outcome measures were: median score on electromyography as measured in microvolts (µV); and perceived exertion on an 11-point numerical rating scale. RESULTS: Median scores of the open- and closed-chain exercises showed no statistical difference, while composite-chain Slackline exercise showed significantly (p<0.0001) higher quadriceps activation (F(2.52, 121.00)=21.53, p<0.0001) at significantly lower exertion (F(1.62, 77.70)=26.88, p<0.0001). CONCLUSIONS: The use of Slackline rehabilitation training can provide significant increases in activation and recruitment of the quadriceps for composite-chain exercises in the clinical setting. This activation occurs spontaneously at significantly lower levels of perceived exertion. This spontaneous quadriceps activation in a selective and simple manner is a valuable adjunct exercise for lower limb rehabilitation programmes. This is of particular relevance for the outpatient setting and circumstances where the quadriceps is inhibited and activation is required.

Compliance with and attitudes towards the management of medical emergencies in general dental practice.

Patient safety and risk management are increasing priorities in dental practice today. Ensuring that members of the dental team are prepared and equipped to adequately manage the common medical emergencies that might occur is an expectation of the public and increasingly demanded by the inspecting and regulatory bodies in healthcare.

A modified QuickDASH-9 provides a valid outcome instrument for upper limb function.

BACKGROUND: The 30-item Disabilities Arm Shoulder and Hand (DASH) questionnaire was introduced to facilitate assessment of upper limb functional limitations. To improve practicality and eliminate item redundancy a modified instrument was needed. The 11-item QuickDASH was developed to fulfil these requirements and translated into several languages. However, prospective investigations of psychometric and practical characteristics are limited. No published study investigated readability or used concurrent validation with a standardized upper limb criterion measure. The validity of the QuickDASH has been questioned as the results for factor structure are conflicting, and the English-language version has not yet had factor structure reported. A shortened 9-item version, the QuickDASH-9, that addresses these issues is proposed. METHODS: This two-stage observational study assessed the psychometric and practical characteristics of the QuickDASH and the extracted QuickDASH-9. The Upper Limb Functional Index (ULFI) was the criterion standard in both stages. Stage 1, calibration, reanalyzed extracted QuickDASH and QuickDASH-9 responses from a previous prospective study, by the authors, of the 30-item DASH (n = 137). Stage 2, prospective validation, investigated the QuickDASH through repeated measures in consecutive upper limb musculoskeletal participants' consulting for physical therapy in Australia (n = 67). The QuickDASH and extracted QuickDASH-9 data from both stages was analyzed and compared for psychometric properties, practical characteristics and factor structure. RESULTS: The proposed QuickDASH-9 had a unidimensional structure, high reliability (ICC 2:1, r = 0.92), internal consistency (alpha = 0.93) and responsiveness (ES = 1.05). It correlated highly with both the DASH (r = 0.97), QuickDASH (r = 0.99) and ULFI criterion (r = 0.85). QuickDASH-9 missing responses reduced to 3.5% from 26% in the QuickDASH. Completion and scoring time was 134 +/- 56 seconds and required a computational aid. The QuickDASH demonstrated a bidimensional structure making it invalid. The QuickDASH-9 summary performance was measured on the 'Measurement of Outcome Measures' at 88% and on the 'Bot' clinimetric scale at 75%. CONCLUSIONS: The proposed QuickDASH-9 had a unidimensional structure and similar psychometric precision to the full-length DASH with improved practicality and completion time. The QuickDASH was invalid as its bidimensional structure made a single summated score inappropriate. The QuickDASH-9 offers a future direction for ongoing use of the QuickDASH concept.

Periodate oxidized ATP (oATP) reduces hyperalgesia in mice: involvement of P2X7 receptors and implications for therapy.

Some inflammatory mediators play an important role not only in the pathogenesis of the inflammatory pain, but also in that of neuropathic and visceral pain. We previously showed the antihyperalgesic effect of oATP, the inhibitor of the P2X7 receptors for the pro-nociceptive ATP, in experimental inflammation. Here we show the antihyperalgesic effect of oATP in mouse models of neuropathic and visceral pain, other than in a model of arthritic pain mimicking rheumatoid arthritis in humans. We also show that mice lacking P2X7 receptors (KO) are resistant to hyperalgesic thermal stimuli following the induction of arthritic, neuropathic and visceral pain. Local (injection into the right hind paw) pre-treatment with oATP is able to prevent the successive induction of ATP-dependent hyperalgesia in wild type mice. In addition, KO mice are not insensitive to intraplantar treatment with ATP. Our data suggest that, even if oATP is able to inhibit purinoceptors different from P2X7, the latter are the more important involved in pain transmission.

The Upper Limb Functional Index: development and determination of reliability, validity, and responsiveness.

PURPOSE: Current upper limb regional self-report outcome measures are criticized for poor clinical utility, including length, ease, and time to complete and score, missing responses, and poor psychometric properties. To address these concerns a new measure, the Upper Limb Functional Index (ULFI), was developed with reliability, validity, and responsiveness being determined in a prospective study. METHODS: Patients from nine Australian outpatient settings completed the ULFI and two established scales, the Disabilities of the Arm, Shoulder, and Hand (DASH) (n=214) and the Upper Extremity Functional Scale (UEFS) (n=64) concurrently to enable construct and criterion validity to be assessed. Two subgroups were used to assess test-retest reliability at 48-hour intervals (n=46) and responsiveness through distribution-based methods (n=29). Internal consistency, change scores, and missing responses were calculated. Practical characteristics of the scale were assessed. RESULTS: The ULFI correlated with the DASH (r=0.85; 95% CI) and UEFS (r=0.78; 95% confidence interval [CI]), demonstrated test-retest reliability (intraclass correlation coefficient=0.96; 95% CI) and internal consistency (Cronbach alpha=0.89). The change scores of the ULFI with standard error of the measurement was 4.5% or 1.13 ULFI-points and minimal detectable change at the 90% CI was 10.4% or 2.6 ULFI-points. Responsiveness indices were standardized response mean at 1.87 and effect size at 1.28. The ULFI demonstrated an impairment range of 0-100%, with no missing responses and a combined patient completion and therapist scoring time of less than 3 minutes. CONCLUSIONS: The ULFI demonstrated sound psychometric properties, practical characteristics, and clinical utility thereby making it a viable clinical outcome tool for the determination of upper limb status and impairment. The ULFI is suggested as the preferred upper limb regional tool due to its superior practical characteristics and clinical utility, and comparable psychometric properties without a tendency toward item redundancy.

Identification and characterization of a novel class of interleukin-1 post-translational processing inhibitors.

Lipopolysaccharide (LPS)-activated monocytes and macrophages produce large quantities of pro-interleukin (IL)-1beta but externalize little mature cytokine. Efficient post-translational processing of the procytokine occurs in vitro when these cells encounter a secretion stimulus such as ATP, cytolytic T cells, or hypotonic stress. Each of these stimuli promotes rapid conversion of 31-kDa pro-IL-1beta to its mature 17-kDa species and release of the 17-kDa cytokine. In this study, two novel pharmacological agents, CP-424,174 and CP-412,245, are identified as potent inhibitors of stimulus-coupled IL-1beta post-translational processing. These agents, both diarylsulfonylureas, block formation of mature IL-1beta without increasing the amount of procytokine that is released extracellularly, and they inhibit independently of the secretion stimulus used. Conditioned medium derived from LPS-activated/ATP-treated human monocytes maintained in the absence and presence of CP-424,174 contained comparable quantities of IL-6, tumor necrosis factor-alpha (TNFalpha), and IL-1RA, but 30-fold less IL-1beta was generated in the test agent's presence. As a result of this decrease, monocyte conditioned medium prepared in the presence of CP-424,174 demonstrated a greatly diminished capacity to promote an IL-1-dependent response (induction of serum amyloid A synthesis by Hep3B cells). Oral administration of CP-424,174 to mice resulted in inhibition of IL-1 in the absence of an effect on IL-6 and TNFalpha. These novel agents, therefore, act as selective cytokine release inhibitors and define a new therapeutic approach for controlling IL-1 production in inflammatory diseases.

Case-crossover studies of occupational trauma: methodological caveats.

OBJECTIVES: The case-crossover study design was developed to examine triggers for the onset of myocardial infarction. This paper seeks to examine selected methodological issues when applying the case-crossover method to the study of traumatic injuries in the work environment. METHODS: Researchers known to be working on occupational case-crossover studies were invited to present at a workshop held at the National Occupational Injury Research Symposium in October 2000. Data from ongoing studies were used to illustrate various methodological issues involved in case-crossover studies of occupational injury. KEY FINDINGS AND ISSUES IDENTIFIED: To utilize the case-crossover design, investigators must clearly define the time during which a worker is at risk of injury, the period of time during which a particular transient exposure could cause an injury and carefully select control time periods that estimate the expected frequency of exposure. Other issues of concern are changing work tasks over time, correlated exposures over time and information bias. CONCLUSIONS AND FUTURE RESEARCH NEEDS: More case-crossover studies of occupational injury are needed to compare results from multiple studies. The validation of the timing of transient exposures relative to injury onset, whether done in a laboratory or field setting, should be conducted. Nested case-crossover designs in other epidemiological studies (case-control or cohort) can examine both transient and fixed risk factors for occupational injury, and should be attempted.

LL-Z1271alpha: an interleukin-1beta production inhibitor.

LL-Z1271alpha, a fungal metabolite, dose-dependently inhibited interleukin-1beta (IL-1beta) production in lipopolysaccharide (LPS)-stimulated human whole blood. Oral administration of LL-Z1271alpha to LPS-challenged mice caused significant lowering in the IL-1beta levels in peritoneal cavity. Data presented suggest that LL-Z1271alpha inhibits IL-1beta production by a novel mechanism as the inhibitory activity was not due to effects on caspase-1 (IL-1beta converting enzyme), the ATP-induced release mechanism or a lysosomotrophic effect.

Altered cytokine production in mice lacking P2X(7) receptors.

The P2X(7) receptor (P2X(7)R) is an ATP-gated ion channel expressed by monocytes and macrophages. To directly address the role of this receptor in interleukin (IL)-1 beta post-translational processing, we have generated a P2X(7)R-deficient mouse line. P2X(7)R(-/-) macrophages respond to lipopolysaccharide and produce levels of cyclooxygenase-2 and pro-IL-1 beta comparable with those generated by wild-type cells. In response to ATP, however, pro-IL-1 beta produced by the P2X(7)R(-/-) cells is not externalized or activated by caspase-1. Nigericin, an alternate secretion stimulus, promotes release of 17-kDa IL-1 beta from P2X(7)R(-/-) macrophages. In response to in vivo lipopolysaccharide injection, both wild-type and P2X(7)R(-/-) animals display increases in peritoneal lavage IL-6 levels but no detectable IL-1. Subsequent ATP injection to wild-type animals promotes an increase in IL-1, which in turn leads to additional IL-6 production; similar increases did not occur in ATP-treated, LPS-primed P2X(7)R(-/-) animals. Absence of the P2X(7)R thus leads to an inability of peritoneal macrophages to release IL-1 in response to ATP. As a result of the IL-1 deficiency, in vivo cytokine signaling cascades are impaired in P2X(7)R-deficient animals. Together these results demonstrate that P2X(7)R activation can provide a signal that leads to maturation and release of IL-1 beta and initiation of a cytokine cascade.