Despite pharmacological treatments for osteoarthritis (OA), more individuals are choosing medical cannabis for OA symptom management and for mitigating opioid prescriptions for OA. This systematic ...review examines the global evidence of medical cannabis use on OA pain and function.OBJECTIVEDespite pharmacological treatments for osteoarthritis (OA), more individuals are choosing medical cannabis for OA symptom management and for mitigating opioid prescriptions for OA. This systematic review examines the global evidence of medical cannabis use on OA pain and function.The search was completed in MEDLINE (PubMed), Embase, and CINAHL within the past 10 years (2012-2022). We limited the search to English language articles. We did not include grey literature or case studies. Participant demographics included all adult individuals with OA who were using medical cannabis for OA. Study quality and risk of bias were evaluated using the Grading of Recommendations, Assessment, Development and Evaluations framework; and the Risk of Bias in Non-randomized Studies of Interventions tool. We used a narrative synthesis approach.METHODSThe search was completed in MEDLINE (PubMed), Embase, and CINAHL within the past 10 years (2012-2022). We limited the search to English language articles. We did not include grey literature or case studies. Participant demographics included all adult individuals with OA who were using medical cannabis for OA. Study quality and risk of bias were evaluated using the Grading of Recommendations, Assessment, Development and Evaluations framework; and the Risk of Bias in Non-randomized Studies of Interventions tool. We used a narrative synthesis approach.Overall, 7 studies were included: 2 randomized controlled trials (RCT) and 5 observational studies. Only 1 of the 2 RCTs reported improvements in pain for cannabis users. All 5 observational studies reported an improvement in pain levels, reduction of opioid use, and/or improvement in overall OA function. Despite high risk of bias ratings and low study quality, the consensus across studies was that medical cannabis use was effective for a subgroup of individuals suffering from OA pain.RESULTSOverall, 7 studies were included: 2 randomized controlled trials (RCT) and 5 observational studies. Only 1 of the 2 RCTs reported improvements in pain for cannabis users. All 5 observational studies reported an improvement in pain levels, reduction of opioid use, and/or improvement in overall OA function. Despite high risk of bias ratings and low study quality, the consensus across studies was that medical cannabis use was effective for a subgroup of individuals suffering from OA pain.There is low quality evidence to support medical cannabis use as a substitute for primary pharmacological treatment of OA. However, this does not negate the observations that medical cannabis may provide therapeutic relief for a subset of patients.CONCLUSIONSThere is low quality evidence to support medical cannabis use as a substitute for primary pharmacological treatment of OA. However, this does not negate the observations that medical cannabis may provide therapeutic relief for a subset of patients.CRD42022354026.SYSTEMATIC REVIEW PROPSERO REGISTRATIONCRD42022354026.
In the last two decades or so, spinning and flow forming have gradually matured as metal forming processes for the production of engineering components in small to medium batch quantities. Combined ...spinning and flow forming techniques are being utilised increasingly due to the great flexibility provided for producing complicated parts nearer to net shape, enabling customers to optimise designs and reduce weight and cost, all of which are vital, especially in automotive industries.
In this paper, process details of spinning and flow forming are introduced. The state of the art is described and developments in terms of research and industrial applications are reviewed. Also, the direction of research and development for future industrial applications are indicated.
The COVID-19 pandemic triggered an unparalleled pursuit of vaccines to induce specific adaptive immunity, based on virus-neutralizing antibodies and T cell responses. Although several vaccines have ...been developed just a year after SARS-CoV-2 emerged in late 2019, global deployment will take months or even years. Meanwhile, the virus continues to take a severe toll on human life and exact substantial economic costs. Innate immunity is fundamental to mammalian host defense capacity to combat infections. Innate immune responses, triggered by a family of pattern recognition receptors, induce interferons and other cytokines and activate both myeloid and lymphoid immune cells to provide protection against a wide range of pathogens. Epidemiological and biological evidence suggests that the live-attenuated vaccines (LAV) targeting tuberculosis, measles, and polio induce protective innate immunity by a newly described form of immunological memory termed "trained immunity." An LAV designed to induce adaptive immunity targeting a particular pathogen may also induce innate immunity that mitigates other infectious diseases, including COVID-19, as well as future pandemic threats. Deployment of existing LAVs early in pandemics could complement the development of specific vaccines, bridging the protection gap until specific vaccines arrive. The broad protection induced by LAVs would not be compromised by potential antigenic drift (immune escape) that can render viruses resistant to specific vaccines. LAVs might offer an essential tool to "bend the pandemic curve," averting the exhaustion of public health resources and preventing needless deaths and may also have therapeutic benefits if used for postexposure prophylaxis of disease.
Tuberculosis can be treated, prevented, and cured. Rapid, sustained declines in tuberculosis deaths in many countries during the past 50 years provide compelling evidence that ending the pandemic is ...feasible. Yet this disease—which has plagued humanity since before recorded history and has killed hundreds of millions of people over the past two centuries—remains a relentless scourge. In 2017, 1·6 million people died from tuberculosis, including 300 000 people with HIV, representing more deaths than any other infectious disease. Moreover, in many parts of the world, drugresistant forms of tuberculosis threaten struggling control efforts. The world can no longer ignore the enormous pall cast by the tuberculosis epidemic. Going forward, the global tuberculosis response must be an inclusive, comprehensive response within the broader sustainable development agenda. No one-size-fits-all approach can succeed.
Objective
Countries have adopted different approaches, at different times, to reduce the transmission of coronavirus disease 2019 (COVID‐19). Cross‐country comparison could indicate the relative ...efficacy of these approaches. We assess various nonpharmaceutical interventions (NPIs), comparing the effects of voluntary behavior change and of changes enforced via official regulations, by examining their impacts on subsequent death rates.
Data Sources
Secondary data on COVID‐19 deaths from 13 European countries, over March–May 2020.
Study Design
We examine two types of NPI: the introduction of government‐enforced closure policies and self‐imposed alteration of individual behaviors in the period prior to regulations. Our proxy for the latter is Google mobility data, which captures voluntary behavior change when disease salience is sufficiently high. The primary outcome variable is the rate of change in COVID‐19 fatalities per day, 16–20 days after interventions take place. Linear multivariate regression analysis is used to evaluate impacts.
Data collection/extraction methods: publicly available.
Principal Findings
Voluntarily reduced mobility, occurring prior to government policies, decreases the percent change in deaths per day by 9.2 percentage points (pp) (95% confidence interval CI 4.5–14.0 pp). Government closure policies decrease the percent change in deaths per day by 14.0 pp (95% CI 10.8–17.2 pp). Disaggregating government policies, the most beneficial for reducing fatality, are intercity travel restrictions, canceling public events, requiring face masks in some situations, and closing nonessential workplaces. Other sub‐components, such as closing schools and imposing stay‐at‐home rules, show smaller and statistically insignificant impacts.
Conclusions
NPIs have substantially reduced fatalities arising from COVID‐19. Importantly, the effect of voluntary behavior change is of the same order of magnitude as government‐mandated regulations. These findings, including the substantial variation across dimensions of closure, have implications for the optimal targeted mix of government policies as the pandemic waxes and wanes, especially given the economic and human welfare consequences of strict regulations.
To examine the intersection between location of residence along the rural-urban continuum (metropolitan, urban, and rural) and sulfonylurea dispensation records for the management of type 2 diabetes.
...This retrospective cohort study used administrative health records of adult new metformin users between April 2008 and March 2019 in Alberta, Canada. Multivariable logistic regression was performed to examine the association between sulfonylurea-based treatment intensification and location of residence.
Treatment was intensified in 66,084 (38%) of 171,759 new metformin users after a mean of 1.5 years. At treatment intensification, mean age was 55 years, 62% of users were male, and 27% were rural residents. The most common antihyperglycemic drug, given to 30,297 people (46%) for treatment intensification, was a sulfonylurea. At the beginning of our observation period, the proportion of people dispensed a sulfonylurea at first treatment intensification was highest in rural (57%), compared with urban (54%) and metropolitan (52%) areas (P = 0.009). Although proportions decreased over time across the province, rural residents continued to constitute the highest proportion of sulfonylurea users (45%), compared with urban (35%) and metropolitan (37%) residents (P < 0.001), and the trend away from sulfonylurea use was delayed by ∼4 years for rural residents. Adjusting for potential sources of confounding, rural residence was associated with a significantly higher likelihood of using a sulfonylurea compared with metropolitan residence (adjusted odds ratio 1.34; 95% CI 1.29-1.39).
Variation in sulfonylurea dispensation across the rural-urban continuum provides a basis for continued research in the differences in process of care by location.
Purpose of Review
This systematic review aims to inform the current state of evidence about the efficacy and effectiveness of medical cannabis use for the treatment of LBP, specifically on pain ...levels and overall opioid use for LBP. Searches were conducted in MEDLINE (PubMed), Embase, and CINAHL. The search was limited to the past 10 years (2011-2021). Study inclusion was determined by the critical appraisal process using the Joanna Briggs Institute framework. Only English language articles were included. Participant demographics included all adult individuals with LBP who were prescribed medical cannabis for LBP and may be concurrently using opioids for their LBP. Study quality and the risk of bias were both evaluated. A narrative synthesis approach was used.
Recent Findings
A total of twelve studies were included in the synthesis: one randomized controlled trial (RCT), six observational studies (one prospective, four retrospective, and one cross-over), and five case studies. All study results, except for the RCT, indicated a decrease in LBP levels or opioid use over time after medical cannabis use. The RCT reported no statistically significant difference in LBP between cannabis and placebo groups.
Summary
Low back pain (LBP) affects 568 million people worldwide. In the United States, LBP treatment represents more than half of regular opioid users. With the opioid epidemic, alternative methods, particularly medical cannabis, is now increasingly sought by practicing physicians and patients. Due to its infancy, there is minimal high-quality evidence to support medical cannabis use as a first line treatment for LBP.
Abstract
STUDY QUESTION
Does developmental exposure to the combination of hyperandrogenemia and western-style diet (WSD) worsen adult metabolic function compared to either treatment alone?
SUMMARY ...ANSWER
Young female rhesus macaques treated for 3 years, beginning at menarche, with combined testosterone (T) and WSD have increased weight gain and insulin resistance compared to controls and animals treated with either T or WSD alone.
WHAT IS KNOWN ALREADY
Hyperandrogenemia is a well-established component of polycystic ovary syndrome (PCOS) and can be observed in peripubertal girls, indicating a potential pubertal onset of the disease. Obesity is often associated with hyperandrogenemia in peripubertal girls, and overweight girls appear to be at higher risk for the development of PCOS later in life.
STUDY DESIGN, SIZE, DURATION
Juvenile (2.5- year old) female rhesus macaques were divided into four groups (n = 10/group): control animals receiving cholesterol implants and a control diet with 15% of calories derived from fat (C), animals receiving T implants (mean serum levels: 1.35 ± 0.01 ng/ml) and a control diet (T), animals receiving a cholesterol implant and a WSD with 36% of calories derived from fat (WSD) and animals receiving a T implant and a WSD (T + WSD). Animals were maintained on the treatments for 36 months and were 5.5 years old at study completion.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Metabolic testing consisted of body measurements including weight, dual-energy X-ray absorptiometry scans, activity monitoring, and glucose tolerance testing at zero months and at least once every 12 months for the remainder of the study. Indirect calorimetry and serum hormone assays were performed following 36 months of treatment.
MAIN RESULTS AND THE ROLE OF CHANCE
Body weight and fat mass gain were significantly increased in T + WSD at 24 and 36 months of treatment compared to the other three groups. Log transformed fasting insulin and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were significantly increased in T + WSD animals at 3 years of treatment compared to all other groups. T-treatment caused a greater rate of decline in activity after 18 months, while food intake and metabolic rate were largely unaffected by treatments.
LIMITATIONS REASONS FOR CAUTION
Variability was present in the metabolic parameters measured; however, this is similar to the heterogeneity observed in human populations.
WIDER IMPLICATIONS OF THE FINDINGS
Chronic hyperandrogenemia beginning at puberty may exacerbate metabolic dysfunction in women consuming a WSD and account for the increased rates of obesity and insulin resistance observed in PCOS patients. Counseling of female patient populations with elevated androgens about the potential benefit of consuming a lower fat diet could improve long-term metabolic health outcomes.
STUDY FUNDING/COMPETING INTEREST(S)
Eunice Kennedy Shriver National Institute of Child Health & Human Development P50HD071836 and Oregon National Primate Center Grant P51 OD011092. The authors have no competing conflict of interests to disclose.
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