Effectiveness of Faster Aspart versus Insulin Aspart in Children with Type 1 Diabetes: A Meta-Analysis.

Background: Intensive insulin regimens are recommended to achieve glycemic goals in children and adolescents with type 1 diabetes. Fast-acting insulin aspart (faster aspart) is a new formulation of insulin aspart (IAsp) in which L-arginine and niacinamide are added to assure formulation stability, early absorption, and ultra-fast action. This meta-analysis compares faster aspart with IAsp for blood sugar control in children with type 1 diabetes. This study suggested treating diabetes with insulin, especially in children with type 1 diabetes. Methods: PubMed, MEDLINE, Embase, Cochrane Library, Web of Science, and Google Scholar were searched from 2000 to 2023 without language restrictions. Blood glucose monitoring, HbA1c, care model, insulin aspart, IAsp, faster aspart, type 1 diabetes, and pediatrics are Mesh keywords. Cochrane Q statistics and index tested heterogeneity. To account for heterogeneity, Q=145.99 (P-value < 0.001) and =97.26%, and the random-effect model was used to aggregate primary study results. The meta-analysis of randomized-controlled trials was conducted in accordance with PRISMA standards. Results: The overall estimate measure i.e. mean difference was found to be 5.44 [0.45, 10.44] and 7.71 [7.16, 8.26] which indicate significant reduction in the HbA1C level in the fast acting insulin aspart group as compared to the IAsp in T1D. However, the mean difference with respect to BMI was found to be -0.06 [-0.60, 0.48] which indicate non-significant reduction. Conclusion: Faster aspart had faster onset and more early exposure than IAsp in children and adolescents with greater and more variable anti-insulin antibody levels than adults did. Hence fast-acting insulin aspart may provide better glucose control than IAsp in T1D.

Islet Autoantibody Standardization Program: interlaboratory comparison of insulin autoantibody assay performance in 2018 and 2020 workshops.

AIMS/HYPOTHESIS: The Islet Autoantibody Standardization Program (IASP) aims to improve the performance of immunoassays measuring autoantibodies in type 1 diabetes and the concordance of results across laboratories. IASP organises international workshops distributing anonymised serum samples to participating laboratories and centralises the collection and analysis of results. In this report, we describe the results of assays measuring IAA submitted to the IASP 2018 and 2020 workshops. METHODS: The IASP distributed uniquely coded sera from individuals with new-onset type 1 diabetes, multiple islet autoantibody-positive individuals, and diabetes-free blood donors in both 2018 and 2020. Serial dilutions of the anti-insulin mouse monoclonal antibody HUI-018 were also included. Sensitivity, specificity, area under the receiver operating characteristic curve (ROC-AUC), partial ROC-AUC at 95% specificity (pAUC95) and concordance of qualitative/quantitative results were compared across assays. RESULTS: Results from 45 IAA assays of seven different formats and from 37 IAA assays of six different formats were submitted to the IASP in 2018 and 2020, respectively. The median ROC-AUC was 0.736 (IQR 0.617-0.803) and 0.790 (IQR 0.730-0.836), while the median pAUC95 was 0.016 (IQR 0.004-0.021) and 0.023 (IQR 0.014-0.026) in the 2018 and 2020 workshops, respectively. Assays largely differed in AUC (IASP 2018 range 0.232-0.874; IASP 2020 range 0.379-0.924) and pAUC95 (IASP 2018 and IASP 2020 range 0-0.032). CONCLUSIONS/INTERPRETATION: Assay formats submitted to this study showed heterogeneous performance. Despite the high variability across laboratories, the in-house radiobinding assay (RBA) remains the gold standard for IAA measurement. However, novel non-radioactive IAA immunoassays showed a good performance and, if further improved, might be considered valid alternatives to RBAs.

Level of attitude, knowledge and practice of nurses toward postoperative pain management, cross-sectional study.

Background: Patients still experience unnecessary pain in many hospitals, especially after surgery, despite increasing awareness of pain management in many healthcare settings. Unrelieved postoperative pain has been shown to increase the incidence of postoperative complications (such as atelectasis, pneumonia, thromboembolism, and impaired immune function. Little known and not known, evidence to understand gaps in nurses' attitudes and practices regarding postoperative pain management in our hospital. Methods: A descriptive cross-sectional study was performed with 144 nurses A systematic random sampling technique was used to select study participants. Data were collected using a self-administered and verified structured questionnaire; Data were entered and analyzed using SPSS software version 24. Descriptive results are presented by frequency, percentage, mean, bar graph, and pie chart. Results: Overall results from 144 study participants showed that nurses had good knowledge 78 (54.2%), favorable attitudes 67 (60.4%), and practice 81 (56). %) on pain management after surgery. In terms of nurse training, 60 (41.7%) have a bachelor's degree holders and only 34 (23.6%) nurses are trained in postoperative pain management. Conclusions: In this study, the nurses' overall knowledge of postoperative management was good, with favorable attitudes and good practices. But the level of knowledge, attitude, and practice according to the research are only average; therefore, it will make it possible to recommends to the responsible authorities of universities, hospitals, and nurses to organize continuing education.

Iran's National Suicide Prevention Program.

Background and Aims: Iran is one of the few countries in the Eastern Mediterranean Region (EMR) to have developed a national suicide prevention program (NSPP). This report introduces Iran's NSPP to policy planners and researchers working in suicide prevention, and is intended to encourage other low- and middle-income countries to develop, implement, and evaluate their own NSPPs. Method: This was a case study of a NSPP in one country, integrating quantitative and qualitative data. Bibliographic searches were conducted using both international and national databases, supplemented by other documents. The study benefited from the experiential evidence provided by the senior author. Results: While the national incidence of suicide is low, there are higher rates among young adults, particularly women, in western regions. In 2010, Iran's NSPP was integrated into primary health care. A rigorous evaluation of Iran's suicide prevention program concluded that Iran has the potential to take a leadership role in suicide prevention within the EMR, although several challenges were identified. Limitation: The findings of this case study cannot be generalized to other contexts. Conclusion: Given Iran's unstable situation, the NSPP needs to be monitored, evaluated, and adjusted according to evidence and ongoing changing national and local needs.

Principles of the activin receptor signaling pathway and its inhibition.

This review captures the anabolic and stimulatory effects observed with inhibition of the transforming growth factor ß superfamily in muscle, blood, and bone. New medicinal substances that rectify activin, myostatin, and growth differentiation factor 11 signaling give hope to the many whose lives are affected by deterioration of these tissues. The review first covers the origin, structure, and common pathway of activins, myostatin, and growth differentiation factor 11 along with the pharmacodynamics of the new class of molecules designed to oppose the activin receptor signaling pathway. Current terminology surrounding this new class of molecules is inconsistent and does not infer functionality. Adopting inhibitors of the activin receptor signaling pathway (IASPs) as a generic term is proposed because it encapsulates the molecular mechanisms along the pathway trajectory. To conclude, a pragmatic classification of IASPs is presented that integrates functionality and side effects based on the data available from animals and humans. This provides researchers and clinicians with a tool to tailor IASPs therapy according to the need of projects or patients and with respect to side effects.

Chronic pain after breast surgery: incidence, associated factors, and impact on quality of life, an observational prospective study.

BACKGROUND: Chronic pain after breast surgery (CPBS) has a disabling impact on postoperative health status. Mainly because of the lack of a clear definition, inconsistency does exist in the literature concerning both the actual incidence and the risk factors associated to CPBS. The aim of this prospective, observational study is to describe the incidence of and risk factors for CPBS, according to the definition provided by the IASP taskforce. The impact of CPBS on patients' function and quality of life is also described. METHODS: Women aged 18+ undergoing oncological or reconstructive breast surgery from Jan until Apr 2018 at the Breast Unit of Careggi Hospital (Florence, Italy) were prospectively observed. Postoperative pain was measured at 0 h, 3 h, 6 h, 12 h, 24 h, 48 h, and 3 months (CPBS) after surgery. Preoperative, intraoperative, and postoperative factors were compared in CPBS and No-CPBS groups through multivariate logistic regression analysis. RESULTS: Among the 307 patients considered in this study, the incidence of CPBS was 28% [95% CI 23.1-33.4%]. Results from the logistic regression analysis suggest that axillary surgery (OR [95% CI], 2.99 [1.13-7.87], p = 0.03), preoperative use of pain medications (OR [95% CI], 2.04 [1.20-3.46], p = 0.01), and higher dynamic NRS values at 6 h postoperatively (OR [95% CI], 1.28 [1.05-1.55], p = 0.01) were all independent predictors for CPBS. CONCLUSIONS: Chronic pain after breast surgery is a frequent complication. In our cohort, long-term use of analgesics for pre-existing chronic pain, axillary surgery, and higher dynamic NRS values at 6 h postoperatively were all factors associated with increased risk of developing CPBS. The possibility to early detect persistent pain, particularly in those patients at high risk for CPBS, might help physicians to more effectively prevent pain chronicisation. TRIAL REGISTRATION: ClinicalTrials.gov registration NCT04309929 .

Revisions to the IASP definition of pain-What does this mean for children?

The complexity of the phenomenon of pain defies a simple and straightforward definition. Acute, chronic, nociplastic and neuropathic pain account for multiple pathologic mechanisms and forms of expression. Pain varies widely in intensity, duration and nature, often complicating description for those who are experiencing the pain and/ or those who are observing it. Assessment of pain in children can be challenging, especially in those who may be incapable of self-report report due to development immaturity or disability. In these children the responsibility of assessing pain often falls to the professional or lay care provider, whose knowledge, expertise and beliefs influence their judgements. The experience of pain includes not only the physiologic and behavioural indicators most frequently included in pain assessment measures but also encompasses the social and cognitive components that often go unrecognized. The 1979 IASP definition of pain has been praised for its brevity, simplicity and attention to the multidimensional nature of the phenomenon. It has also been criticized for ignoring mind-body interactions, disempowering and neglecting vulnerable populations, paying little attention to ethical dimensions, and excluding cognitive and social factors that are integral to the experience of pain. After four decades, the 1979 definition of pain and the accompanying notes were evaluated and revised by a 14-member IASP presidential task force with representation from basic and clinical research, geographical location and populations served (Pain, 2020, 161, 1976). These revisions resulted in decreasing the emphasis of pain associated with tissue damage in the definition, and, by removing the word 'described', allowing those who were nonverbal to be assessed using other validated pain indicators. Important revisions were also made to the Notes. The revisions that are most relevant for pain in children are discussed.

Activin type IIA decoy receptor and intermittent parathyroid hormone in combination overturns the bone loss in disuse-osteopenic mice.

Damage of the lower motor neuron cell bodies or their axons results in reduced or abolished voluntary movement accompanied by a substantial loss of bone and muscle mass. Intermittent parathyroid hormone 1-34 (PTH) (teriparatide) is one of the most potent bone-anabolic treatment regimens. ActRIIA-mFc is an activin type IIA decoy receptor that increases bone mass mediated by inhibition of the activin receptor signaling pathway. We investigated whether PTH or ActRIIA-mFc alone or in combination could prevent loss of bone and muscle mass induced by injecting botulinum toxin A (BTX) into the right hind limb in mice. Seventy-two 16-week-old female C57BL/6 mice were allocated to the following groups: Baseline, Control, BTX, BTX + ActRIIA-mFc (10 mg/kg), BTX + PTH (100 µg/kg), and BTX + ActRIIA-mFc + PTH. The mice were sacrificed after three weeks of disuse and treatment. In contrast to monotherapy with PTH, ActRIIA-mFc alone or in combination with PTH was able partly or completely to prevent disuse-induced loss of whole femoral bone mass, trabecular thickness, and bone strength. Moreover, an additive effect of ActRIIA-mFc and PTH on areal bone mineral density and trabecular bone volume was found. In summary, ActRIIA-mFc and PTH in combination were more effective in preventing disuse-induced bone loss and deterioration of trabecular micro-architecture than either treatment alone.

The International Collaboration on ADHD and Substance Abuse (ICASA): Mission, Results, and Future Activities.

BACKGROUND: The International Collaboration on ADHD and Substance Abuse (ICASA) is a network of 28 centers from 16 countries initiated to investigate the link between attention deficit-hyperactivity disorder (ADHD) and substance use disorder (SUD). In this article, we present the mission, the results of finished studies, and the current and future research projects of ICASA. METHODS: During the past 10 years, 3 cross-sectional studies were conducted: two International ADHD in Substance use disorders Prevalence (IASP-1 and IASP-2) studies, directed at the screening, diagnosis, and the prevalence of adult ADHD in treatment-seeking patients with SUD, and the Continuous performance test for ADHD in SUD Patients (CASP) study, testing a novel continuous performance test in SUD patients with and without adult ADHD. Recently, the prospective International Naturalistic Cohort Study of ADHD and Substance Use Disorders (INCAS) was initiated, directed at treatment provision and treatment outcome in SUD patients with adult ADHD. RESULTS: The IASP studies have shown that approximately 1 in 6 adult treatment-seeking SUD patients also have ADHD. In addition, those SUD patients with adult ADHD compared to SUD patients without ADHD report more childhood trauma exposure, slower infant development, greater problems controlling their temperament, and lower educational attainment. Comorbid patients also reported more risk-taking behavior, and a higher rate of other psychiatric disorders compared to SUD patients without ADHD. Screening, diagnosis, and treatment of this patient group are possible even before abstinence has been achieved. The results of the CASP study are reported separately in this special issue. CONCLUSIONS: The ICASA research to date has demonstrated a high prevalence of comorbid ADHD and SUD, associated with elevated rates of additional comorbidities and risk factors for adverse outcomes. More research is needed to find the best way to treat these patients, which is the main topic of the ongoing INCAS study.

Does the IASP definition of pain need updating?

The current IASP definition of pain has come under renewed criticisms recently. There is a new momentum for its revision as reflected by the fact that IASP has now a Presidential Task Force dedicated to look into whether there is enough warrant to update the definition. I critically review all the major criticisms of the current definition in detail, and raise new difficulties rarely discussed before. I show that none of the major criticisms has enough warrant to force us to substantially revise the current definition. Combined with the discussion of the new difficulties, there is nonetheless a need to restate the definition using slightly different terminology that will make the original intent of the current definition clearer and more precise. A restatement of the definition is proposed and its potential is discussed in light of some empirical questions that remain.

A follistatin-based molecule increases muscle and bone mass without affecting the red blood cell count in mice.

Inhibitors of the activin receptor signaling pathway (IASPs) have become candidate therapeutics for sarcopenia and bone remodeling disorders because of their ability to increase muscle and bone mass. However, IASPs utilizing activin type IIA and IIB receptors are also potent stimulators of erythropoiesis, a feature that may restrict their usage to anemic patients because of increased risk of venous thromboembolism. Based on the endogenous TGF-ß superfamily antagonist follistatin (FST), a molecule in the IASP class, FSTΔHBS-mFc, was generated and tested in both ovariectomized and naive BALB/c and C57BL/6 mice. In ovariectomized mice, FSTΔHBS-mFc therapy dose-dependently increased cancellous bone mass up to 42% and improved bone microstructural indices. For the highest dosage of FSTΔHBS-mFc (30 mg/kg, 2 times/wk), the increase in cancellous bone mass was similar to that observed with parathyroid hormone therapy (1-34, 80 µg/kg, 5 times/wk). Musculus quadriceps femoris mass dose-dependently increased up to 21% in ovariectomized mice. In both ovariectomized and naive mice, FSTΔHBS-mFc therapy did not influence red blood cell count or hematocrit or hemoglobin levels. If the results are reproduced, a human FSTΔHBS-mFc version could be applicable in patients with musculoskeletal conditions irrespective of hematocrit status.-Lodberg, A., van der Eerden, B. C. J., Boers-Sijmons, B., Thomsen, J. S., Brüel, A., van Leeuwen, J. P. T. M., Eijken, M. A follistatin-based molecule increases muscle and bone mass without affecting the red blood cell count in mice.

Deconstructing chronicity of musculoskeletal pain: intensity-duration relations, minimal dimensions and clusters of chronicity.

Background and aims Evaluating the degree to which pain has become chronic beyond mere duration poses several problems. The IASP Pain Taxonomy Axis IV employs intensity and duration combined to nine ordered categories. The Chronic Pain Grade links intensity and disability, but only the latter contributes to higher grades. The Mainz Pain Staging System includes temporal and spatial aspects, medication and health care utilization. Their interrelations, scale properties and construct validity are not always known or debatable. The study challenges the generality and homogeneity of the chronicity construct of musculoskeletal pain aiming at necessary and sufficient sub-constructs identified by separable marker clusters. We show chronicity to vary in content and structure with severity and duration and between different populations. This raises the question of validity conditions of general chronicity indices and requires further work on adequate chronicity measures. Methods Diagnostic entrance data of 185 patients with chronic regional vs. widespread musculoskeletal pain (unspecific back pain, fibromyalgia) from regional pain clinics and 170 active employees in a nationwide prevention program were included in a retrospective cross-sectional analysis of the combined marker sets of the three chronicity indices above. The samples of patients and employees provided intensity, duration and disability degrees over the whole range of the assumed chronicity. Intensity-duration relations were quantified by correlations and frequency distributions of successive duration classes. The dimensional structure of pain and chronicity variables was assessed by factor and cluster analyses. Results Pain intensity distributions showed inhomogeneous courses from short to long durations - lowest intensities predominating at longer durations in patients and at shorter in employees. Moreover, pain intensity and duration related nonlinearly to Chronic Pain Grade and Mainz Pain Stage and differently in patients compared to employees, and these indices correlated only moderately to each other. Factor and cluster analyses revealed different dimensions and clusters of chronicity markers for patients and employees. In the former, three dimensions with four clusters were identified with clinical characteristics (intensity, temporal and spatial aspects) separated from direct consequences (disability/interference with activities, medication usage) and chronic development (duration, healthcare utilization). In employees, only two dimensions with three clusters were obtained and clinical pain characteristics clustered with direct consequences both separated from chronic development. Similar differences were shown between unspecific back pain and fibromyalgia but were less well defined. Conclusions There appears to be no coherent "chronicity" entity over the entire range of severity and duration for all pain populations with different clinical pictures and social contexts. Statements about chronicity must be differentiated with respect to those aspects relative to patient career. Implications General indices do not capture the complex and changing composition of chronicity. There is evidence for at least three weakly coupled core domains of chronicity, i.e. the primary clinical characteristics, the direct consequences of current interference with activities, and aspects of the patient history. Hence, multivariate assessment is recommended. The particular syndrome, the diagnostic context and the population under investigation should likewise be considered.

Socioeconomic value of intervention for chronic pain.

PURPOSE: The purpose of this study was to examine the cost-effectiveness of pain treatments in two pain centers in Japan. METHODS: The study population comprised 91 patients receiving various treatments for chronic pain, which were divided into three categories: (1) medication, (2) medication + nerve block, and (3) other modalities (exercise and/or pain education). Pain was assessed using the Pain Disability Assessment Scale (PDAS) score, Hospital Anxiety and Depression Scale (HADS) score, Pain Catastrophizing Scale (PCS) score, and EQ-5D score. First, the reliability of the EQ-5D score first assessed by evaluating the correlation this score with those of the other pain-related evaluation instruments, and then the cost effectiveness of the pain treatments was evaluated. Evaluation of medical costs was based on data provided from the Management Services of the hospital, which in turn were based on national health scheme medical treatment fees. The quality-adjusted life year (QALY) value was calculated from the EQ-5D score, converted to 12 months, and then used for cost-benefit analysis along with medical treatment fees. RESULTS: According to the recent IASP classification, more patients had chronic neuropathic pain (41) than chronic primary pain (37 patients) or chronic musculoskeletal pain (27 patients). There was a significant correlation between the EQ-5D score and the PDAS, HADS, and PCS scores, which demonstrated the reliability of the EQ-5D score. Significant improvement in the HADS, PCS, and EQ-5D scores was noted after 3 months of pain treatment. Calculation of the cost-effectiveness based on the estimated annual medical treatment cost and QALY revealed a mean value of US $45,879 ± 103,155 per QALY (median US $16,903), indicating adequate socioeconomic utility. CONCLUSION: Based on our results, the EQ-5D is reliable for evaluating chronic pain in patients. The medico-economic balance was appropriate for all treatments provided in two comprehensive pain centers in Japan.

Deep brain stimulation of the dorsal anterior cingulate cortex for the treatment of chronic neuropathic pain.

Chronic neuropathic pain is estimated to affect 3%-4.5% of the worldwide population. It is associated with significant loss of productive time, withdrawal from the workforce, development of mood disorders such as depression and anxiety, and disruption of family and social life. Current medical therapeutics often fail to adequately treat chronic neuropathic pain. Deep brain stimulation (DBS) targeting subcortical structures such as the periaqueductal gray, the ventral posterior lateral and medial thalamic nuclei, and the internal capsule has been investigated for the relief of refractory neuropathic pain over the past 3 decades. Recent work has identified the dorsal anterior cingulate cortex (dACC) as a new potential neuromodulation target given its central role in cognitive and affective processing. In this review, the authors briefly discuss the history of DBS for chronic neuropathic pain in the United States and present evidence supporting dACC DBS for this indication. They review existent literature on dACC DBS and summarize important findings from imaging and neurophysiological studies supporting a central role for the dACC in the processing of chronic neuropathic pain. The available neurophysiological and empirical clinical evidence suggests that dACC DBS is a viable therapeutic option for the treatment of chronic neuropathic pain and warrants further investigation.

Sensory abnormalities and masticatory function after microvascular decompression or balloon compression for trigeminal neuralgia compared with carbamazepine and healthy controls.

OBJECT: Idiopathic trigeminal neuralgia (iTN) is a neurological condition treated with pharmacotherapy or neurosurgery. There is a lack of comparative papers regarding the outcomes of neurosurgery in patients with iTN. The objective of this study was to investigate sensory thresholds and masticatory function in 78 patients with iTN who underwent microvascular decompression (MVD) or balloon compression (BC), and compare these treatments with carbamazepine and 30 untreated healthy controls. METHODS: The authors conducted a case-controlled longitudinal study. Patients were referred to 1 of 3 groups: MVD, BC, or carbamazepine. All patients were evaluated before and after treatment with a systematic protocol composed of a clinical orofacial questionnaire, Research Diagnostic Criteria for temporomandibular disorders, Helkimo indices, and a quantitative sensory-testing protocol (gustative, olfactory, cold, warm, touch, vibration, superficial, and deep pain thresholds). RESULTS: Both MVD and BC were effective at reducing pain intensity (p = 0.012) and carbamazepine doses (p < 0.001). Myofascial and articular complaints decreased in both groups (p < 0.001), but only the patients in the MVD group showed improvement in Helkimo indices (p < 0.003). Patients who underwent MVD also showed an increase in sweet (p = 0.014) and salty (p = 0.003) thresholds. The sour threshold decreased (p = 0.003) and cold and warm thresholds increased (p < 0.001) in patients after MVD and BC, but only the patients who underwent BC had an increase in touch threshold (p < 0.001). CONCLUSIONS: Microvascular decompression and BC resulted in a reduction in myofascial and jaw articular complaints, and the impact on masticatory function according to Helkimo indices was greater after BC than MVD. MVD resulted in more gustative alterations, and both procedures caused impairment in thermal thresholds (warm and cold). However, only BC also affected touch perception. The sensorial and motor deficits after BC need to be included as targets directly associated with the success of the surgery and need to be assessed and relieved as goals in the treatment of iTN.

Prevalence of neuropathic pain according to the IASP grading system in patients with chronic non-malignant pain.

OBJECTIVE: The primary objective was to determine the prevalence of neuropathic pain according to the new International Association for the Study of Pain (IASP) grading system. The secondary objective was to compare the system classification of neuropathic pain with the classification of neuropathic pain according to a patient-administered screening questionnaire. SETTING: A Multidisciplinary Pain Center. SUBJECTS: One hundred twenty patients with a variety of chronic pain conditions referred to a multidisciplinary pain center. METHODS: Consecutively referred patients filled out the PainDETECT Questionnaire before the first consultation. During the first consultation, patients had pain history taken and bedside examination performed by a pain specialist. Patients were classified according to the score on the PainDETECT Questionnaire and graded according to the IASP grading system about the certainty of neuropathic pain. RESULTS: According to the IASP grading system, 22 patients (18.3%) classified as probable or definite neuropathic pain and 90 patients (75%) as unlikely neuropathic pain. According to the PainDETECT Questionnaire, 55 patients (45%) were classified as likely neuropathic pain and 13 patients (10.8%) as unlikely neuropathic pain. Eleven patients (20%) who were classified as neuropathic pain according to PainDETECT were also classified as probable or definite neuropathic pain by the new IASP grading system. CONCLUSIONS: According to the new IASP grading system, less than 20% of the patients referred to a multidisciplinary pain center fulfilled the criteria for neuropathic pain. The classification of neuropathic pain with the IASP system varies from the classification of neuropathic pain with the use of a self-administered screening questionnaire.