Development of a prediction model to determine responders to conservative treatment in people with symptomatic hand osteoarthritis: A secondary analysis of a single-centre, randomised feasibility trial.

BACKGROUND: Conservative treatments are beneficial for people with hand osteoarthritis (OA). OBJECTIVE: It was the purpose of this study to develop and internally validate both a basic model and a more complex model that could predict responders to conservative treatments in people with hand OA. DESIGN: This was a secondary analysis of a single-centre, randomised feasibility study. METHODS: Fifty-nine participants (34 responders) with hand osteoarthritis were recruited from the general population. Participants were randomised to receive either advice alone, or advice in combination with blood flow restriction training (BFRT), or traditional high intensity training (HIT). Participants underwent supervised hand exercises three times per week for six weeks. The OMERACT-OARSI criteria were utilised to determine responders vs non responders to treatment at the end of six weeks. A basic logistic regression model (treatment type, expectations, adherence) and a more complex logistic regression model (basic model variables plus pain catastrophising and neuropathic pain features) were created. Discrimination ability, and calibration were assessed. Internal model validation through bootstrapping (200 repetitions) was utilised to calculate the prediction model optimism. RESULTS: The results showed that the basic model presented with acceptable discrimination (optimism corrected c-statistic: 0.72, 95% CI 0.71-0.73) and calibration (slope = 1.41; intercept = 0.68). The more complex model had better discrimination but poorer calibration. CONCLUSION: A prediction tool was created to provide an individualised estimate of treatment response in people with hand OA. Future studies will need to validate this model in other groups of patients. TRIAL REGISTRATION: https://www.anzctr.org.au/- ACTRN12617001270303.

Neglect-like symptoms and their relationships with other clinical features in people with hand osteoarthritis: An exploratory study.

BACKGROUND: Symptomatic hand osteoarthritis (OA) is a debilitating condition. Body schema impairments such as neglect-like symptoms have been previously reported in people with symptomatic hand OA, however, little is known about their clinical importance, or relationships with other clinical features. OBJECTIVES: The aim of this cross-sectional study was to assess the prevalence of neglect-like symptoms in painful hand OA and their association with measures of depression, pain catastrophising, sleep quality, function, pain interference and pain duration whilst controlling for important covariates. DESIGN: Secondary analysis of cross-sectional study. METHODS: Logistic regression with age, sex, and worst pain intensity as covariates were utilised to assess differences between participants with and without neglect-like symptoms. RESULTS: A total of 121 participants were recruited. Sixty-one percent of participants presented with neglect-like symptoms. Participants with longer pain duration had greater odds of presenting with neglect-like symptoms (OR: 1.10 95%CI: 1.01 to 1.19; p = 0.012). No difference was observed for depression, pain catastrophising, sleep quality, function, or pain interference. CONCLUSIONS: A large proportion of participants with symptomatic hand OA reported neglect-like symptoms, the presence of which was associated with longer pain duration.

Antimalarial Activity of Extract and Fractions of Sauropus androgynus (L.) Merr.

Sauropus androgynus (L.) Merr., in the Indonesian local name known as "Katuk," is a tropical shrub plant of the family Euphorbiaceae. Based on genus and chemotaxonomic approaches, as well as in vitro testing of Plasmodium falciparum, leaves of S. androgynus are presumed to have an active compound content as an antimalarial. The current study aims to investigate the antimalarial activity of 96% ethanol extract and fractions of S. androgynus leaves. The ethanolic extract was fractionated using the vacuum liquid chromatography (VLC) method with three solvents of different polarities (n-hexane, chloroform, and 96% ethanol). The fraction obtained was then evaluated for antimalarial activity against P. falciparum 3D7 strain. The ethanolic extract was evaluated for antimalarial suppressive and prophylactic activity against P. berghei-infected mice, as well as inhibitory activity against the heme detoxification process in vitro. Fractionation of ethanolic extract resulted in seven combined fractions, with the most active fraction being FV (50% inhibitory concentration (IC50) = 2.042 µg/mL). The ethanolic extract showed good parasitic suppressive (therapeutic) activity with a median effective dose (ED50) value of 15.35 mg/kg body weight. In a prophylactic test, ethanolic extract showed parasite growth inhibitory activity of 67.74 ± 9.21% after the administration of 400 mg/kg body weight for 4 days before infection, and 65.30 ± 10.44% after the administration of 200 mg/kg body weight for 8 consecutive days (4 days before and after infection). The ethanolic extract also showed an effect in inhibiting the formation of ß-hematin of about 26.87-79.36% at a concentration of 0.1-4 mg/mL and an IC50 value of 0.479 mg/mL. The S. androgynus leaves were shown to have antimalarial activity in vitro and in vivo, where ethanolic extract were more active compared with the fraction obtained. The antimalarial properties of the extract showed a higher suppressive activity than prophylactic activity.

Factors associated with persistent opioid use 6-12 months after primary total knee arthroplasty.

Persistent pain following knee arthroplasty occurs in up to 20% of patients and may require ongoing analgesia, including extended opioid administration. A comprehensive secondary analysis was performed from results of a study that considered persistent postoperative pain in 242 patients who underwent unilateral knee arthroplasty using a standardised enhanced recovery programme. Opioid prescribing for 12 months before and 12 months after surgery was evaluated and converted to oral morphine equivalents. Demographic, functional, psychological and pain questionnaires were completed along with quantitative sensory testing and genetic analysis. Forty-nine percent of patients had at least one opioid prescription in the 12 months before surgery. Opioid prescriptions were filled in 93% of patients from discharge to 3 months and in 27% of patients ≥6 months after surgery. Persistent opioid use ≥6 months after surgery was strongly associated with pre-operative opioid use (RR 3.2, p < 0.001 (95%CI 1.9-5.4)). The median (IQR [range]) oral morphine equivalent daily dose was 3.6 (0.9-10.5 [0-100.0]) mg pre-operatively, 35.0 (22.5-52.5 [4.6-180.0]) mg in hospital, 12.8 (5.1-24.8 [0-57.9]) mg from discharge to 3 months and 5.9 (4.5-12.0 [0-44.5]) mg at ≥6 months following surgery. Predictors of increased daily oral morphine equivalent ≥6 months after surgery included increased average daily oral morphine equivalent dose compared with previous values (lag), increased body mass index and three or more comorbid pain sites. Persistent opioid use was not associated with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (RR 1.003, p = 0.655, 95%CI 0.65-1.002) or WOMAC function (RR 1.001, p = 0.99, 95%CI 0.99-1.03) outcomes 6 months after surgery. There was no association between persistent opioid use and pre-operative quantitative sensory testing results or psychological distress. Pre-operatively, patients with a higher body mass index, more comorbid pain sites and those who had filled an opioid prescription in the last 12 months, were at increased risk of persistent opioid use and a higher oral morphine equivalent daily dose ≥ 6 months after surgery. Strategies need to be developed to limit dose and duration of persistent opioid use in patients following knee arthroplasty surgery.

Six weeks of resistance training (plus advice) vs advice only in hand osteoarthritis: A single-blind, randomised, controlled feasibility trial.

BACKGROUND: People with hand osteoarthritis (OA) may benefit from resistance training interventions. To date the feasibility of a such interventions for symptomatic hand OA, as per international guidelines, is unknown. OBJECTIVE: Determine the feasibility of a clinical trial comparing resistance training to an advice only control group in people with symptomatic hand OA. DESIGN: Single-blind, randomised, controlled feasibility study. METHODS: The American College of Rheumatology criteria for hand OA were utilised for inclusion. Participants were randomly allocated (1:1:1) to advice and blood flow restriction training (BFRT), advice and traditional high intensity training (HIT), or advice only (control). Participants receiving BFRT and HIT underwent supervised hand exercises three times a week for six weeks. Feasibility measures included recruitment rate, adherence, exercise induced pain, training acceptability, pain flares, and adverse events. Number of treatment responders, pain, grip strength, and hand function were also recorded. RESULTS: In total, 191 participants were screened, 59 (31%) were included. Retention rate was 89% for BFRT and 79% for HIT. Exercise did not worsen pain following training sessions, and training acceptability was equal between groups. Pain flares occurred in 1.6% (BFRT) and 4% (HIT) out of all the training sessions. There was one adverse event in the HIT group, with the participants withdrawing from the study due to pain. The number of treatment responders, and improvements in pain, were greater with BFRT and HIT. Grip and function did not improve. CONCLUSION: A clinical trial comparing resistance training to advice for people with symptomatic hand OA is feasible.

The effect of intra-operative hypotension on acute kidney injury, postoperative mortality and length of stay following emergency hip fracture surgery.

The association between intra-operative hypotension and postoperative acute kidney injury, mortality and length of stay has not been comprehensively evaluated in a large single-centre hip fracture population. We analysed electronic anaesthesia records of 1063 patients undergoing unilateral hip fracture surgery, collected from 2015 to 2018. Acute kidney injury, 3-, 30- and 365-day mortality and length of stay were evaluated to assess the relationship between intra-operative hypotension absolute values (≤ 55, 60, 65, 70 and 75 mmHg) and duration of hypotension. The rate of acute kidney injury was 23.7%, mortality at 3-, 30- and 365 days was 3.7%, 8.0% and 25.3%, respectively, and median (IQR [range]) length of stay 8 (6-12 [0-99]) days. Median (IQR [range]) time ≤ MAP 55, 60, 65, 70 and 75 mmHg was 0 (0-0.5[0-72.1]); 0 (0-4.4 [0-104.9]); 2.2 (0-8.7 [0-144.2]); 6.6 (2.2-19.7 [0-198.8]); 17.5 (6.6-37.1 [0-216.3]) minutes, and percentage of surgery time below these thresholds was 1%, 2.5%, 7.9%, 12% and 21% respectively. There were some univariate associations between hypotension and mortality; however, these were no longer evident in multivariable analysis. Multivariable analysis found no association between hypotension and acute kidney injury. Acute kidney injury was associated with male sex, antihypertensive medications and cardiac/renal comorbidities. Three-day mortality was associated with delay to surgery ? 48 hours, whilst 30-day and 365-day mortality was associated with delay to surgery ≥ 48 hours, impaired cognition and cardiac/renal comorbidities. While the rate of acute kidney injury was similar to other studies, use of vasopressors and fluids to reduce the time spent at hypotensive levels failed to reduce this complication. Intra-operative hypotension at the levels observed in this cohort may not be an important determinant of acute kidney injury, postoperative mortality and length of stay.

The feasibility of home monitoring of young people with cystic fibrosis: Results from CLIMB-CF.

BACKGROUND: CF is traditionally assessed in clinic. It is unclear if home monitoring of young people with CF is feasible or acceptable. The COVID-19 pandemic has made home monitoring more of a necessity. We report the results of CLIMB-CF, exploring home monitoring's feasibility and potential obstacles. METHODS: We designed a mobile app and enrolled participants with CF aged 2-17 years and their parents for six months. They were asked to complete a variety of measures either daily or twice a week. During the study, participants and their parents completed questionnaires exploring depression, anxiety and quality of life. At the end of the study parents and participants completed acceptability questionnaires. RESULTS: 148 participants were recruited, 4 withdrew prior to starting the study. 82 participants were female with median (IQR) age 7.9 (5.2-12 years). Median data completeness was 40.1% (13.6-69.9%) for the whole cohort; when assessed by age participants aged ≥ 12 years contributed significantly less (15.6% [9.8-30%]). Data completeness decreased over time. There was no significant difference between parental depression and anxiety scores at the start and the end of the study nor in CFQ-R respiratory domain scores for participants ≥ 14 years. The majority of participants did not feel the introduction of home monitoring impacted their daily lives. CONCLUSIONS: Most participants felt home monitoring did not negatively impact their lives and it did not increase depression, anxiety or decrease quality of life. However, uptake was variable, and not well sustained. The teenage years pose a particular challenge and further work is required.

Analysis of trimodal and bimodal therapy in a selective-surgery paradigm for locally advanced oesophageal squamous cell carcinoma.

BACKGROUND: Long-term survival outcomes of trimodal therapy (TMT; chemoradiation plus surgery) and bimodal therapy (BMT; chemoradiation) have seldom been analysed. In a selective-surgery paradigm, the benefit of TMT in patients with a complete clinical response is controversial. Factors associated with survival in patients with a clinical complete response to chemoradiation were evaluated. METHODS: Patients with stage II-III oesophageal squamous cell carcinoma treated with TMT or BMT from 2002 to 2017 were evaluated. The BMT group consisted of patients who were otherwise eligible for surgery but underwent chemoradiation alone followed by observation. This group included patients who later had salvage oesophagectomy. Survival was evaluated and compared between TMT and BMT groups. Elastic net regularization was performed to select co-variables for Cox multivariable survival analysis in patients with a clinical complete response. RESULTS: Of 143 patients, 60 (41.9 per cent) underwent TMT and 83 (58.0 per cent) BMT. Patients who underwent TMT had longer median overall survival than those who had BMT (77 versus 33 months; P = 0.019). For patients with a clinical complete response, TMT achieved longer median overall survival than BMT (123 versus 55 months; P = 0.04). BMT had a high locoregional recurrence rate (48 versus 6 per cent; P < 0.001); 26 of 29 patients with locoregional recurrence in the BMT groupunderwent salvage resection. Cox multivariable analysis demonstrated that upper-mid oesophageal tumour location (hazard ratio (HR) 2.04; P = 0.024) and tumour length (HR 1.18; P = 0.046) were associated with worse survival. Although TMT was not associated with survival, it was a predictor of reduced recurrence (HR 0.28; P = 0.028). The maximum standardized uptake value after chemoradiation also predicted recurrence (HR 1.33; P < 0.001). CONCLUSION: In patients who achieve a clinical complete response, TMT reduces locoregional recurrence but may not prolong survival. The differences in survival outcomes may be due to patient selection; therefore, a selective-surgery strategy in oesophageal squamous cell carcinoma is a reasonable approach.

Steroids to reduce the impact on delirium (STRIDE): a double-blind, randomised, placebo-controlled feasibility trial of pre-operative dexamethasone in people with hip fracture.

Neuro-inflammation may be important in the pathogenesis of postoperative delirium following hip fracture surgery. Studies have suggested a potential role for steroids in reducing postoperative delirium; however, the potential efficacy and safety of pre-operative high-dose dexamethasone in this specific population is largely unknown. Conducting such a study could be challenging, considering the multidisciplinary team involvement and the emergency nature of the surgery. The aim of this study was to assess feasibility and effectiveness of dexamethasone given as early as possible following hospital admission for hip fracture, to inform whether a full-scale trial is warranted. This single-centre, randomised, double-blind, placebo-controlled study randomly allocated 79 participants undergoing hip fracture surgery to dexamethasone 20 mg or placebo pre-operatively. Eligibility and recruitment rates, timing of the intervention and adverse events were recorded. Incidence and severity of postoperative delirium were assessed using the 4AT delirium screening tool and the Memorial Delirium Assessment Scale. Postoperative pain, length of stay and mortality were also assessed. The eligibility rate for inclusion was 178/527 (34%), and 57/178 (32%) of eligible patients presented to hospital when no researcher was available (e.g. after-hours, weekends, public holidays). Recruitment was limited mainly by ethical limitations (not including patients with impaired cognition) and lack of weekend staffing. Median (IQR [range]) time from emergency department admission to drug administration was 13.3 (5.9-17.6 [1.8-139.6]) hours. There was a significant difference in delirium severity scores, favouring the dexamethasone group: median (IQR [range]) 5 (3-6 [3-7]) vs. 9 (6-13 [5-14]) in the placebo group, with the probability of superiority effect size being 0.89, p = 0.010. Delirium incidence did not differ between groups: 6/40 (15%) in the dexamethasone group vs. 9/39 (23%) in the placebo group, relative risk (95%CI) 0.65 (0.22-1.65), p = 0.360). A larger randomised controlled trial is feasible and ideally this should include people with existing cognitive impairment, seven days-a-week cover and a multicentre design.

An evaluation of DistillerSR's machine learning-based prioritization tool for title/abstract screening - impact on reviewer-relevant outcomes.

BACKGROUND: Systematic reviews often require substantial resources, partially due to the large number of records identified during searching. Although artificial intelligence may not be ready to fully replace human reviewers, it may accelerate and reduce the screening burden. Using DistillerSR (May 2020 release), we evaluated the performance of the prioritization simulation tool to determine the reduction in screening burden and time savings. METHODS: Using a true recall @ 95%, response sets from 10 completed systematic reviews were used to evaluate: (i) the reduction of screening burden; (ii) the accuracy of the prioritization algorithm; and (iii) the hours saved when a modified screening approach was implemented. To account for variation in the simulations, and to introduce randomness (through shuffling the references), 10 simulations were run for each review. Means, standard deviations, medians and interquartile ranges (IQR) are presented. RESULTS: Among the 10 systematic reviews, using true recall @ 95% there was a median reduction in screening burden of 47.1% (IQR: 37.5 to 58.0%). A median of 41.2% (IQR: 33.4 to 46.9%) of the excluded records needed to be screened to achieve true recall @ 95%. The median title/abstract screening hours saved using a modified screening approach at a true recall @ 95% was 29.8 h (IQR: 28.1 to 74.7 h). This was increased to a median of 36 h (IQR: 32.2 to 79.7 h) when considering the time saved not retrieving and screening full texts of the remaining 5% of records not yet identified as included at title/abstract. Among the 100 simulations (10 simulations per review), none of these 5% of records were a final included study in the systematic review. The reduction in screening burden to achieve true recall @ 95% compared to @ 100% resulted in a reduced screening burden median of 40.6% (IQR: 38.3 to 54.2%). CONCLUSIONS: The prioritization tool in DistillerSR can reduce screening burden. A modified or stop screening approach once a true recall @ 95% is achieved appears to be a valid method for rapid reviews, and perhaps systematic reviews. This needs to be further evaluated in prospective reviews using the estimated recall.

Psychosocial and pharmacologic interventions for methamphetamine addiction: protocol for a scoping review of the literature.

BACKGROUND: Methamphetamine use and harms are rising rapidly. Management of patients with methamphetamine use disorder (MUD) and problematic methamphetamine use (PMU) is challenging, with no clearly established best approach; both psychosocial and pharmacologic interventions have been described. Furthermore, given the diversity of individuals that use methamphetamines, there is a need to assess evidence for treatments for subgroups including youths; gay, bisexual, and other men who have sex with men; individuals with mental health comorbidities; and individuals in correction services. Establishing awareness of the messages regarding treatment from recent clinical practice guidelines (CPG) in the field is also of value. The first study objective will be to establish a greater understanding of the methods, populations, and findings of controlled studies for psychosocial and pharmacologic treatments for MUD and PMU. Investigation of this information can help establish the potential for advanced syntheses of the evidence (such as network meta-analysis) to compare therapies for this condition and to identify gaps related to key populations where more primary research is needed. Summarizing the recommendations regarding treatment of MUD/PMU from recent CPGs and systematic reviews will be an important secondary objective. METHODS: A scoping review will be performed. Using the OVID platform, MEDLINE, Embase, PsycINFO, and relevant Cochrane databases from EBM Reviews will be searched (from databases' inception onwards). Eligibility criteria will include individuals described as having MUD or PMU, with designs of interest including randomized trials, non-randomized trials, and controlled cohort studies with three or more months of follow-up; systematic reviews and CPGs will also be sought. Two reviewers (with support from automation tools) will independently screen all citations, full-text articles, and chart data. Different approaches to handling and summarizing the data will be implemented for each type of study design. Tables and graphics will be used to map evidence sources and identify evidence gaps. DISCUSSION: This research will enhance awareness of evidence addressing the effects of psychosocial and pharmacologic interventions for MUD/PMU overall and in sub-populations, both in terms of recent CPGs/reviews and primary studies; inspection of the latter will also help establish the feasibility of future syntheses to compare treatments, such as network meta-analysis. SYSTEMATIC REVIEW PROTOCOL REGISTRATION: Open Science Framework ( https://osf.io/9wy8p ).

Morbidity following salvage esophagectomy for squamous cell carcinoma: the MD Anderson experience.

The survival advantage associated with the addition of surgical therapy in esophageal squamous cell carcinoma (ESCC) patients who demonstrate a complete clinical response to chemoradiotherapy is unclear, and many institutions have adopted an organ-preserving strategy of selective surgery in this population. We sought to characterize our institutional experience of salvage esophagectomy (for failure of definitive bimodality therapy) and planned esophagectomy (as a component of trimodality therapy) by retrospectively analyzing patients with ESCC of the thoracic esophagus and GEJ who underwent esophagectomy following chemoradiotherapy between 2004 and 2016. Of 76 patients who met inclusion criteria, 46.1% (35) underwent salvage esophagectomy. Major postoperative complications (major cardiovascular and pulmonary events, anastomotic leak [grade ≥ 2], and 90-day mortality) were frequent and occurred in 52.6% of the cohort (planned resection: 36.6% [15/41]; salvage esophagectomy: 71.4% [25/35]). Observed rates of 30- and 90-day mortality for the entire cohort were 7.9% (planned: 7.3% [3/41]; salvage: 8.6% [3/35]) and 13.2% (planned: 9.8% [4/41]; salvage: 17.1% [6/35]), respectively. In summary, esophagectomy following chemoradiotherapy for ESCC at our institution has been associated with frequent postoperative morbidity and considerable rates of mortality in both planned and salvage settings. Although a selective approach to surgery may permit organ preservation in many patients with ESCC, these results highlight that salvage esophagectomy for failure of definitive-intent treatment of ESCC may also constitute a difficult clinical undertaking in some cases.

Screening questionnaires for substance abuse post brain injury: a review.

OBJECTIVE: To assess the psychometric properties of the available assessment questionnaires for substance abuse studied within a brain injury population. METHODS: A literature search was conducted on MEDLINE, PsycINFO, CINAHL, and Embase databases. Articles published in English from inception through March 2018 on the screening questionnaires used to identify substance abuse post brain injury were reviewed. Eligible primary studies had to include: adults (participants ≥18 years old) post brain injury; and report measures of diagnostic accuracy (e.g., sensitivity, specificity, and diagnostic odds ratio). RESULTS: Six screening questionnaires were included: Alcohol Use Disorders Identification Test, Brief Michigan Alcohol Screening Test, CAGE, Drug Abuse Screening Test, Substance Abuse Screening Inventory and the Short Michigan Alcohol Screening Test (SMAST). All questionnaires, except the SMAST, used the Diagnostic and Statistical Manual of Mental Disorders as the criterion measure. While report measures of diagnostic accuracy were reported and summarized, none of the studies provided reliability information or subgroup analysis among those with brain injury. CONCLUSIONS: Concerns of social desirability, population demographics, responsiveness to treatment effects, and administrative burden are important when selecting a questionnaire. Research examining the reliability of substance abuse screening questionnaires in the brain injury population is lacking and future research is warranted.

Persistent postoperative pain after total knee arthroplasty: a prospective cohort study of potential risk factors.

BACKGROUND: Persistent postoperative pain (PPP) is common after total knee arthroplasty (TKA). The primary aim of this prospective cohort study was to identify important predictors of moderate to severe PPP 6 and 12 months after TKA. METHODS: Consenting patients (n=300) undergoing primary unilateral TKA attended a preoperative session to collect clinical information (age, gender, BMI, preoperative knee pain, comorbid pain, likely neuropathic pain) and psychological variables (depression, anxiety, catastrophising, expected pain). Quantitative sensory testing (pressure pain thresholds, temporal summation, conditioned pain modulation) was performed, and blood samples were obtained for subsequent genotyping of OPRM1 and COMT. Acute postoperative pain was measured at rest and during movement. Surgical factors (surgery time, patella resurfacing, anaesthetic type) were collected after operation. Follow-up questionnaires were sent 6 and 12 months after surgery. Multivariate logistic regression was used to identify predictors of PPP. RESULTS: The prevalence of moderate to severe PPP was 21% (n=60) and 16% (n=45) 6 and 12 months after surgery, with 55% (n=33) and 60% (n=31) of PPP likely neuropathic in nature. At 6 months, a combination of preoperative pain intensity, expected pain, trait anxiety, and temporal summation (Akaike information criterion, 309.9; area under receiver operating characteristic (ROC) curve, 0.70) was able to correctly classify 66% of patients into moderate to severe PPP and no to mild PPP groups. At 12 months, preoperative pain intensity, expected pain, and trait anxiety (Akaike information criterion, 286.8; area under ROC curve, 0.66) correctly classified 66% of patients. CONCLUSIONS: Findings from this study highlight several factors that may be targeted in future intervention studies to reduce the development of PPP. TRIAL REGISTRY NUMBER: ACTRN12612001089820.

Label-free multimodal coherent anti-Stokes Raman scattering analysis of microparticles in unconstrained microfluidics.

Fast, label-free optical identification and quantification of biomolecules and other relevant biological materials in microfluidic devices and the vascular system will play a major role in liquid biopsy and related diagnoses. An optical microscope probing simultaneously non-linear coherent anti-Stokes Raman scattering (CARS) and linear scattering (LS) was used to probe microparticles in aqueous solutions flowed unconstrained in microfluidic channels. Despite the optical complexity of these systems, where out-of-focus microparticles randomly impede CARS and LS, and where water CARS generates a substantial background, we demonstrate that in-focus microparticles can be individually and unambiguously detected when CARS and LS are co-analyzed. The ability to chemically discriminate microscale features in optically realistic flows supports the relevance of multimodal CARS platforms for liquid biopsy.

Twelve-year follow-up of chronic pain in twins: Changes in environmental and genetic influence over time.

BACKGROUND: While genetic influences on chronic pain have been repeatedly demonstrated, we do not know whether these effects are stable or dynamic over time. AIMS: To determine the temporal pattern of genetic and environmental effects to individual differences in chronic pain over 12 years, we use a sample of n = 961 female twins. METHODS: Data on chronic pain were collected in 2004 (T1) and 2016 (T2) using the same comprehensive body map which divides the body into 31 distinct anatomical areas. Multivariate twin analyses for repeated measures were conducted to track changes in genetic and environmental influences. RESULTS: Heritability for chronic pain was 63% at baseline and 55% at follow-up. The best-fitting AE Cholesky model revealed one genetic factor explaining 62% of variance in chronic pain at T1 and 11% at T2. No additional genetic factors explaining the variance in chronic pain at T2 could be detected. Furthermore, a unique environmental factor (E1) explaining 37% of the variance in chronic pain at T1 and 12% at T2 and an additional environmental factor (E2) explaining 77% of the variance at T2 were found. CONCLUSION: We demonstrate for the first time that the same genetic influences are operative over time and that novel environmental factors are important in pain maintenance. The findings highlight the value of more in depth exploration of these non-shared environmental influences that could provide clues to the mechanisms behind remittance and/or maintenance of chronic pain. The identification of important environmental influences could point to novel therapeutic interventions in future. SIGNIFICANCE: The variability in chronic pain is mainly explained by new environmental factors influencing incidence, aggravation and/or chronic pain remission. Integration of these findings may provide a useful conceptual framework for the treatment and prevention of pain and pain chronification.

Transcranial direct current stimulation for upper limb neuropathic pain: A double-blind randomized controlled trial.

BACKGROUND: While promising, there are mixed findings for the efficacy of transcranial direct current stimulation (tDCS) for the management of chronic pain. The goal of this study was to evaluate the effect of anodal tDCS on pain and function in people with upper limb neuropathic pain. METHODS: The study was a double-blinded, randomized controlled trial. Thirty participants were randomly allocated into active and sham tDCS groups. Baseline assessments of pain and function, as well as quantitative sensory testing (QST) to probe the function of the nociceptive system, were undertaken prior to participants receiving 5 days of active or sham anodal tDCS (1 mA) over the primary motor cortex. The outcome measures were re-assessed 1, 3 and 8 weeks following the intervention. RESULTS: Group analyses revealed no significant improvement in pain, function, or QST measures over time in either group. However, there were significantly more individual responders (≥30% change in pain) in the active compared to the sham tDCS group at the final follow-up. In the active group, there was a significant correlation indicating those with higher baseline pain had greater pain relief. CONCLUSIONS: On group analyses, no evidence was provided that 1 mA tDCS is beneficial for people with upper limb neuropathic pain, although it may provide lasting pain relief for some individuals. SIGNIFICANCE: At the group level, we found no evidence that 5 days of active 1 mA tDCS is effective for people with upper limb neuropathic pain. However, there were more individual responders in the active tDCS group compared to sham, and those who responded early after treatment experienced sustained pain relief.

Long-term effects of Class II orthodontic treatment on oral health.

AIM: To investigate the long-term (≥15 years) benefit of orthodontic Class II treatment (Tx) on oral health (OH). SUBJECTS AND METHODS: All patients (Department of Orthodontics, University of Giessen, Giessen, Germany) who underwent Class II correction (Herbst-multibracket Tx, end of active Tx ≥ 15 years ago) and agreed to participate in a recall (clinical examination, interview, impressions, and photographs) were included. Records after active Tx were used to assess the long-term OH effects. Data were compared to corresponding population-representative age-cohorts as well as to untreated Class I controls without orthodontic Tx need during adolescence. RESULTS: Of 152 treated Class II patients, 75 could be located and agreed to participate at 33.7 ± 3.0 years of age (pre-Tx age: 14.0 ± 2.7 years). The majority (70.8%) were fully satisfied with their teeth and with their masticatory system. The Decayed, Missing, Filled Teeth Index (DMFT) was 7.1 ± 4.8 and, thus, almost identical to that of the untreated Class I controls (7.9 ± 3.6). In contrast, the DMFT in the population-representative age-cohort was 56% higher. The determined mean Community Periodontal Index (CPI) maximum score (1.6 ± 0.6) was also comparable to the untreated Class I controls (1.7 ± 0.9) but in the corresponding population-representative age-cohort it was 19-44% higher. The extent of lower incisor gingival recessions did not differ significantly between the treated Class II participants and the untreated Class I controls (0.1 ± 0.2 vs. 0.0 ± 0.1 mm). CONCLUSION: Patients with orthodontically treated severe Class II malocclusions had a lower risk for oral health impairment than the general population. The risk corresponded to that of untreated Class I controls (without orthodontic Tx need during adolescence).

TENS Alleviates Muscle Weakness Attributable to Attenuation of Ia Afferents.

Quadriceps weakness is a notable problem following knee damage. Research has shown effectiveness of TENS in improving Quadriceps weakness associated with arthrogenic muscle inhibition. However, these studies were not focused upon short term delivery of TENS, nor did they examine the potential mechanism(s). The present study examined the effect of 25-30 s of TENS upon weakness induced temporarily by a prolonged vibration. Subjects performed eccentric MVCs under 2 conditions (TENS and no-TENS). First, MVC was measured at baseline. For the TENS condition, TENS was applied to each subject's knee joint during a second MVC measurement after vibration. For no-TENS condition, TENS was not applied during the 2nd MVC measurement. MVC between pre-and post-vibration stimulation were compared across the 2 conditions. The results showed that MVC and EMG of TENS-condition was larger than that of no-TENS condition. Our results suggest that TENS could partially restore α-motoneuron activation, despite the induced dysfunctional γ-loop. These results suggest that mechanisms independent of the γ-loop such as a direct facilitation of the QF α-motoneuron pool by a long latency spinal-reflex and/or supraspinal mechanisms appear more likely to be responsible. The findings provide further support for utilizing TENS, even when γ-loop dysfunction is present following joint damage.