Characterizing Acupuncture Stimuli Using Brain Imaging with fMRI - A Systematic Review and Meta-Analysis of the Literature

Background The mechanisms of action underlying acupuncture, including acupuncture point specificity, are not well understood. In the previous decade, an increasing number of studies have applied fMRI to investigate brain response to acupuncture stimulation. Our aim was to provide a systematic overview of acupuncture fMRI research considering the following aspects: 1) differences between verum and sham acupuncture, 2) differences due to various methods of acupuncture manipulation, 3) differences between patients and healthy volunteers, 4) differences between different acupuncture points. Methodology/Principal Findings We systematically searched English, Chinese, Korean and Japanese databases for literature published from the earliest available up until September 2009, without any language restrictions. We included all studies using fMRI to investigate the effect of acupuncture on the human brain (at least one group that received needle-based acupuncture). 779 papers were identified, 149 met the inclusion criteria for the descriptive analysis, and 34 were eligible for the meta-analyses. From a descriptive perspective, multiple studies reported that acupuncture modulates activity within specific brain areas, including somatosensory cortices, limbic system, basal ganglia, brain stem, and cerebellum. Meta-analyses for verum acupuncture stimuli confirmed brain activity within many of the regions mentioned above. Differences between verum and sham acupuncture were noted in brain response in middle cingulate, while some heterogeneity was noted for other regions depending on how such meta-analyses were performed, such as sensorimotor cortices, limbic regions, and cerebellum. Conclusions Brain response to acupuncture stimuli encompasses a broad network of regions consistent with not just somatosensory, but also affective and cognitive processing. While the results were heterogeneous, from a descriptive perspective most studies suggest that acupuncture can modulate the activity within specific brain areas, and the evidence based on meta-analyses confirmed some of these results. More high quality studies with more transparent methodology are needed to improve the consistency amongst different studies

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions

Assessments of early patellofemoral joint osteoarthritis features after anterior cruciate ligament reconstruction: a cross-sectional study

Abstract Background Persistent anterior knee pain and subsequent patellofemoral joint (PFJ) osteoarthritis (OA) are common symptoms after anterior cruciate ligament reconstruction (ACLR). Quadriceps weakness and atrophy is also common after ACLR. This can be contributed by arthrogenic muscle inhibition and disuse, caused by joint swelling, pain, and inflammation after surgery. With quadriceps atrophy and weakness are associated with PFJ pain, this can cause further disuse exacerbating muscle atrophy. Herein, this study aims to identify early changes in musculoskeletal, functional and quality of health parameters for knee OA after 5 years of ACLR. Methods Patients treated with arthroscopically assisted single-bundle ACLR using hamstrings graft for more than 5 years were identified and recruited from our clinic registry. Those with persistent anterior knee pain were invited back for our follow-up study. For all participants, basic clinical demography and standard knee X-ray were taken. Likewise, clinical history, symptomatology, and physical examination were performed to confirm isolated PFJ pain. Outcome measures including leg quadriceps quality using ultrasound, functional performance using pressure mat and pain using self-reported questionnaires (KOOS, Kujala and IKDC) were assessed. Interobserver reproducibility was assessed by two reviewers. Results A total of 19 patients with unilateral injury who had undergone ACLR 5-years ago with persistent anterior knee pain participated in this present study. Toward the muscle quality, thinner vastus medialis and more stiffness in vastus lateralis were found in post-ACLR knees (p < 0.05). Functionally, patients with more anterior knee pain tended to shift more of their body weight towards the non-injured limb with increasing knee flexion. In accordance, rectus femoris muscle stiffness in the ACLR knee was significantly correlated with pain (p < 0.05). Conclusion In this study, it was found that patients having higher degree of anterior knee pain were associated with higher vastus medialis muscle stiffness and thinner vastus lateralis muscle thickness. Similarly, patients with more anterior knee pain tended to shift more of their body weight towards the non-injured limb leading to an abnormal PFJ loading. Taken together, this current study helped to indicate that persistent quadriceps muscle weakness is potential contributing factor to the early development of PFJ pain

Comparison of the in vivo kinematics between Robotic-Assisted Bi-Cruciate Retaining (BCR) and Bi-Cruciate Stabilized (BCS) total knee arthroplasty

Background Up to 20% of patients remain unsatisfied after total knee arthroplasty (TKA), prompting the development of new implants. Bi-Cruciate Retaining (BCR) TKA preserves both the ACL and PCL, with the ACL beneficial for its proprioceptive qualities1. The Bi-Cruciate Stabilized (BCS) TKA substitutes the ACL and PCL with a unique dual cam-post mechanism. Robotics improve accuracy and facilitate technically demanding TKA2. Methods This was a retrospective case-control study recruited from two centres. Measured outcomes include kinematics analysis, proprioception, and functional outcomes. Results There was a significantly larger maximum flexion angle and range of flexion to extension in sit-to-stand and stairs in BCR when compared to BCS. Further analysis revealed more similarities between BCR and normal native knees. Proprioception and functional scores didn’t have any statistical difference. Conclusion BCR TKA demonstrated better knee flexion in weight-bearing active range of motion and shows similarities with normal knee kinematics.</p

The effects of pulsed electromagnetic field therapy on muscle strength and pain in patients with end-stage knee osteoarthritis: A randomized controlled trial

Background: Osteoarthritis (OA) of the knee is one of the most common chronic degenerative joint conditions affecting aging population. Aim: To investigate the effectiveness of a combination of home-based exercise and pulsed electromagnetic field (PEMF) therapy to improve muscle strength, physical function, and pain. Methods: Sixty patients were randomly assigned to either home-based exercise alone (control group; n = 30) or combined with PEMF therapy (treatment group; n = 30) twice a week for eight weeks. Knee extension, flexion muscle strength, gait speed (GS), 5 time sit-to-stand test (5STS), Visual Analogue Scale (VAS) pain and Knee Injury and Osteoarthritis Outcome Score (KOOS) were recorded at baseline and 4 and 8 weeks. Results: Significant improvements in symptomatic knee extension muscle strength (SKE, p = 0.001), flexion strength (SKF, p = 0.011), contralateral knee extension muscle strength (CKE, p = 0.002), and flexion strength (CKF, p = 0.009) were observed for the PEMF treatment group at 8 weeks. Significant reductions in VAS pain scores were observed in both the treatment (p p p = 0.010, partial η2 = 0.111) and 8 (p = 0.046, partial η2 = 0.068) week assessment in VAS pain. A significant time difference was found in GS and 5STS between baseline and week 8 (GS: difference 0.051, p = 0.026; 5STS: difference 2.327, p p = 0.013) in female patients while pain in male patients (p = 0.026). Patients aged over 70 years have a significantly superior improvement in SKE, SKF, and CKF after 8 weeks of PEMF therapy. Conclusion: The combination of PEMF therapy and home-based exercise superiorly improved knee muscle strength and reduced pain in end-stage knee OA subjects and showed a promising tendency to improve performance-based physical function. PEMF therapy was shown to preferentially benefit knee muscle strength in female patients and patients aged over 70 years, whereas male patients were more responsive to PEMF therapy in the form of pain relief. Clinical trial registration: clinicalTrials.gov, NCT05550428.</p