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Background: The intervertebral disc has been implicated as a major cause of chronic lumbar spinal pain based on clinical, basic science, and epidemiological research. There is, however, a lack of consensus regarding the diagnosis and treatment of intervertebral disc disorders. Based on controlled evaluations, lumbar intervertebral discs have been shown to be the source of chronic back pain without disc herniation in 26% to 39% of patients. Lumbar provocation discography, which includes disc stimulation and morphological evaluation, is often used to distinguish a painful disc from other potential sources of pain. Despite the extensive literature, intense debate continues about lumbar discography as a diagnostic tool. Study Design: A systematic review of the diagnostic accuracy of lumbar provocation and analgesic discography literature. Objective: To systematically assess and re-evaluate the diagnostic accuracy of lumbar discography. Methods: The available literature on lumbar discography was reviewed. A methodological quality assessment of included studies was performed using the Quality Appraisal of Reliability Studies (QAREL) checklist. Only diagnostic accuracy studies meeting at least 50% of the designated inclusion criteria were included in the analysis. However, studies scoring less than 50% are presented descriptively and critically analyzed. The level of evidence was classified as good, fair, and limited or poor based on the quality of evidence developed by the U.S. Preventive Services Task Force (USPSTF). Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to September 2012, and manual searches of the bibliographies of known primary and review articles. Results: Over 160 studies were considered for inclusion. Of these, 33 studies compared discography with other diagnostic tests, 30 studies assessed the diagnostic accuracy of discography, 22 studies assessed surgical outcomes for discogenic pain, and 3 studies assessed the prevalence of lumbar discogenic pain. The quality of the overall evidence supporting provocation discography based on the above studies appears to be fair. The prevalence of internal disc disruption is estimated to be 39% to 42%, whereas the prevalence of discogenic pain without assessing internal disc disruption is 26%. Conclusion: This systematic review illustrates that lumbar provocation discography performed according to the International Association for the Study of Pain (IASP) criteria may be a useful tool for evaluating chronic lumbar discogenic pain. Key words: Lumbar intervertebral disc, lumbar discography, provocation discography, analgesic discography, diagnostic accuracy

In 2011, the Institute of Medicine (IOM) re-engineered its definition of clinical guidelines as follows: “clinical practice guidelines are statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefit and harms of alternative care options.” This new definition departs from a 2-decade old definition from a 1990 IOM report that defined guidelines as “systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances.” The revised definition clearly distinguishes between the term “clinical practice guideline” and other forms of clinical guidance derived from widely disparate development processes, such as consensus statements, expert advice, and appropriate use criteria. The IOM committee acknowledged that for many clinical domains, high quality evidence was lacking or even nonexistent. Even though the guidelines are important decisionmaking tools, along with expert clinical judgment and patient preference, their value and impact remains variable due to numerous factors. Some of the many factors that impede the development of clinical practice guidelines include bias due to a variety of conflicts of interest, inappropriate and poor methodological quality, poor writing and ambiguous presentation, projecting a view that these are not applicable to individual patients or too restrictive with elimination of clinician autonomy, and overzealous and inappropriate recommendations, either positive, negative, or non-committal. Consequently, a knowledgeable, multidisciplinary panel of experts must develop guidelines based on a systematic review of the existing evidence, as recently recommended by the IOM. Chronic pain is a complex and multifactorial phenomenon associated with significant economic, social, and health outcomes. Interventional pain management is an emerging specialty facing a disproportionate number of challenges compared to established medical specialties, including the inappropriate utilization of ineffective and unsafe techniques. In 2000, the American Society of Interventional Pain Physicians (ASIPP) created treatment guidelines to help practitioners. There have been 5 subsequent updates. These guidelines address the issues of systematic evaluation and ongoing care of chronic or persistent pain, and provide information about the scientific basis of recommended procedures. These guidelines are expected to increase patient compliance; dispel misconceptions among providers and patients, manage patient expectations reasonably; and form the basis of a therapeutic partnership between the patient, the provider, and payers. Key words: Evidence-based medicine (EBM), comparative effectiveness research (CER), clinical practice guidelines, systematic reviews, meta-analysis, interventional pain management, evidence synthesis, methodological quality assessment, clinical relevance, recommendations.

Studies report neonatal outreach helps to reduce mother-baby separation and length of hospital stay.1 2 As neonatal units face increasing pressure due to rising preterm birth rates and improving survival rates,3 the role of neonatal outreach has become increasingly vital in ensuring effective inpatient care pathways.4 There is currently no national guidance on the delivery of outreach care. Table 1 The number of neonatal units with dedicated neonatal outreach services within each neonatal network Operational delivery network or neonatal network Total number of neonatal units Number of units with outreach services (%) West Midlands 14 14 (100) East Midlands 11 11 (100) Wales 9 9 (100) Isle of Man 1 1 (100) North Central and North East London 10 9 (90.0) Scotland 15 13 (86.7) Kent, Surrey and Sussex 13 11 (84.6) North West London 6 5 (83.3) East of England 17 14 (82.4) Yorkshire and Humber 17 11 (64.7) North West 20 12 (60.0) South West 12 7 (58.3) Thames Valley and Wessex 14 7 (50.0) South London 10 3 (30.0) Northern 10 2 (20.0) Total 179 129 (72.1) The NHS Scotland National Neonatal Discharge Planning and Follow-up Framework highlights the potential for earlier baby discharges with comprehensive 7-day neonatal community support. Table 2 Services provided by NCOTs Type of outreach services provided by NCOTs responses n=94 N (%) Home oxygen 88 (93.6) Nasogastric tube feeds 82 (87.2) Basic life support training 78 (83.0) Sleep studies 70 (74.5) Palivizumab administration 60 (63.8) Parent support service, for example, parentcraft, coffee and chat 49 (52.1) Neonatal abstinence syndrome 35 (37.2) Outreach clinic 27 (28.7) Retinopathy of prematurity screening 18 (19.1) Phototherapy 16 (17.0) Intravenous antibiotics 4 (4.3) NCOTs, neonatal community outreach teams.

Since the Covid-19 pandemic, a surgical backlog for total hip replacement (THR) and total knee replacement (TKR) surgery remains in the United Kingdom. Multimodal prehabilitation pathways (encompassing exercise, nutritional support and psychological wellbeing) can be utilised to 'optimise\" physical and mental resilience prior to the challenge of surgical intervention. BoneFit is an open-label, non-randomised feasibility trial to determine the recruitment and attendance/adherence rates, delivery and implementation challenges, fidelity, acceptability, and safety of a student-led multimodal prehabilitation intervention in people listed for THR/TKR surgery. We will also determine participant and clinician views of the intervention, and identify any challenges and enablers of inter-institutional partnership working. Individuals listed for THR/TKR surgery aged between 18 to 75 years will be assigned to an intervention (n = 25) or usual-care control group (n = 25). The primary outcome measures will be feasibility of delivering the BoneFit intervention. Physical, psychological, quality of life and clinical outcomes will be assessed at three major time-points; T1 (baseline; 2 months from surgery), T2 (2-10 days from surgery), and T3 (3 months following surgery). We aim to show that the trial is feasible and that we can identify a signal of efficacy based on clinical outcomes collected compared to controls. The study was ethically approved by the Health Research Authority (London Bridge Research Ethics Committee: REC reference: 24/PR/0092) in March 2024. The development of a multimodal prehabilitation pathway could improve the physical and mental resilience of individuals awaiting orthopaedic surgery. We aim to determine if this translates to faster discharge and reduced complication rates, thus helping boost surgical throughput and potentially easing surgical backlog. It is likely that the concept of 'waiting' lists for surgery should be challenged, rather, individuals should be encouraged to use the time available to 'prepare' for surgery. Registration details ClinicalTrials.gov registration number: NCT06341920.

The relationship between repeated exposure to blast overpressure and neurological function was examined in the context of breacher training at the U.S. Marine Corps Weapons Training Battalion Dynamic Entry School. During this training, Students are taught to apply explosive charges to achieve rapid ingress into secured buildings. For this study, both Students and Instructors participated in neurobehavioral testing, blood toxin screening, vestibular/auditory testing, and neuroimaging. Volunteers wore instrumentation during training to allow correlation of human response measurements and blast overpressure exposure. The key findings of this study were from high-memory demand tasks and were limited to the Instructors. Specific tests showing blast-related mean differences were California Verbal Learning Test II, Automated Neuropsychological Assessment Metrics subtests (Match-to-Sample, Code Substitution Delayed), and Delayed Matching-to-Sample 10-second delay condition. Importantly, apparent deficits were paralleled with functional magnetic resonance imaging using the n-back task. The findings of this study are suggestive, but not conclusive, owing to small sample size and effect. The observed changes yield descriptive evidence for potential neurological alterations in the subset of individuals with occupational history of repetitive blast exposure. This is the first study to integrate subject instrumentation for measurement of individual blast pressure exposure, neurocognitive testing, and neuroimaging.

BACKGROUND: Opioid prescribing in the United States is decreasing, however, the opioid epidemic is continuing at an uncontrollable rate. Available data show a significant number of opioid deaths, primarily associated with illicit fentanyl use. It is interesting to also note that the data show no clear correlation between opioid prescribing (either number of prescriptions or morphine milligram equivalent [MME] per capita), opioid hospitalizations, and deaths. Furthermore, the data suggest that the 2016 guidelines from the Centers for Disease Control and Prevention (CDC) have resulted in notable problems including increased hospitalizations and mental health disorders due to the lack of appropriate opioid prescribing as well as inaptly rapid tapering or weaning processes. Consequently, when examined in light of other policies and complications caused by COVID-19, a fourth wave of the opioid epidemic has been emerging. OBJECTIVES: In light of this, we herein seek to provide guidance for the prescription of opioids for the management of chronic non-cancer pain. These clinical practice guidelines are based upon a systematic review of both clinical and epidemiological evidence and have been developed by a panel of multidisciplinary experts assessing the quality of the evidence and the strength of recommendations and offer a clear explanation of logical relationships between various care options and health outcomes. METHODS: The methods utilized included the development of objectives and key questions for the various facets of opioid prescribing practice. Also utilized were employment of trustworthy standards, and appropriate disclosures of conflicts of interest(s). The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed. The recommendations were developed after the appropriate review of text and questions by a panel of multidisciplinary subject matter experts, who tabulated comments, incorporated changes, and developed focal responses to questions posed. The multidisciplinary panel finalized 20 guideline recommendations for prescription of opioids for chronic non-cancer pain. Summary of the results showed over 90% agreement for the final 20 recommendations with strong consensus. The consensus guidelines included 4 sections specific to opioid therapy with 1) ten recommendations particular to initial steps of opioid therapy; 2) five recommendations for assessment of effectiveness of opioid therapy; 3) three recommendations regarding monitoring adherence and side effects; and 4) two general, final phase recommendations. LIMITATIONS: There is a continued paucity of literature of long-term opioid therapy addressing chronic non-cancer pain. Further, significant biases exist in the preparation of guidelines, which has led to highly variable rules and regulations across various states. CONCLUSION: These guidelines were developed based upon a comprehensive review of the literature, consensus among expert panelists, and in alignment with patient preferences, and shared decision-making so as to improve the long-term pain relief and function in patients with chronic non-cancer pain. Consequently, it was concluded – and herein recommended – that chronic opioid therapy should be provided in low doses with appropriate adherence monitoring and understanding of adverse events only to those patients with a proven medical necessity, and who exhibit stable improvement in both pain relief and activities of daily function, either independently or in conjunction with other modalities of treatments. KEY WORDS: Chronic pain, persistent pain, non-cancer pain, controlled substances, substance abuse, prescription drug abuse, dependency, opioids, prescription monitoring, drug testing, adherence monitoring, diversion DISCLAIMER: The guidelines presented are based upon the best available evidence, and do not constitute or represent inflexible treatment recommendations. This document is not intended to be regarded and/or used as a “standard of care.”

The interpretation of quantitative trait locus (QTL) studies is limited by the lack of information on metabolic pathways leading to most economic traits. Inferences about the roles of the underlying genes with a pathway or the nature of their interaction with other loci are generally not possible. An exception is resistance to the corn earworm Helicoverpa zea (Boddie) in maize (Zea mays L.) because of maysin, a C-glycosyl flavone synthesized in silks via a branch of the well characterized flavonoid pathway. Our results using flavone synthesis as a model QTL system indicate: (i) the importance of regulatory loci as QTLs, (ii) the importance of interconnecting biochemical pathways on product levels, (iii) evidence for \"channeling\" of intermediates, allowing independent synthesis of related compounds, (iv) the utility of QTL analysis in clarifying the role of specific genes in a biochemical pathway, and (v) identification of a previously unknown locus on chromosome 9S affecting flavone level. A greater understanding of the genetic basis of maysin synthesis and associated corn earworm resistance should lead to improved breeding strategies. More broadly, the insights gained in relating a defined genetic and biochemical pathway affecting a quantitative trait should enhance interpretation of the biological basis of variation for other quantitative traits

This paper demonstrates that the influence of mesoscale landscape spatial variability on the atmosphere must be parameterized (or explicitly modeled) in larger-scale atmospheric model simulations including general circulation models. The mesoscale fluxes of heat that result from this variability are shown to be of the same order of magnitude but with a different vertical structure than found for the turbulent fluxes. These conclusions are based on experiments in which no phase changes of water were permitted. When, for example, cumulus clouds organized in response to the landscape pattern develop, the mesoscale influence on larger-scale climate is likely to be even more important. To parameterize surface thermal inhomogeneities, the influence of landscape must be evaluated using spectral analysis or an equivalent procedure. For horizontal scales much less than the local Rossby radius, based on the results of Dalu and Pielke, the surface heat fluxes over the different land surfaces can be proportionately summed and an average grid-area value used as proposed by Avissar and Pielke. Moisture fluxes can probably be represented in the same fashion as for heat fluxes. For larger-scale spatial variability, however, the mesoscale fluxes must also be included as shown in this paper. While the linear effect could be parameterized using a procedure such as presented in Dalu and Pielke, where the spectral analysis is used to fractionally weight the contributions of the different spatial scales, the complete vertical mesoscale heat flux requires the incorporation of nonlinear advective effects. To include the nonlinear contribution of each scale, numerical model simulations for the range of observed surface and overlying atmospheric conditions must be performed.

Objectives: To determine relative effects of diets high in synthetic sources of myristic (14:0), palmitic (16:0) or stearic (18:0) acid on concentrations and metabolism of serum lipoproteins. Design: Eighteen healthy women participated in a three-way cross-over study for five week periods separated by seven week washout periods, diets were assigned in random order. Subjects: Premenopausal women, not on medication, were from three races (Caucasian, African-American, Asian) and four apolipoprotein E phenotype groups (3/3, 3/2, 4/3, and 4/2). Intervention: During the first week the subjects consumed a baseline diet providing 11 energy (en)% saturated fat, 10 en% polyunsaturated fat and 14 en% monounsaturated fat. Followed by test diets with 19 en% saturated fat (including 14 en% test saturated fatty acid), 3 en% polyunsaturated fat, and 14 en% monounsaturated fat for four weeks. Synthetic fats (trimyristin, tripalmitin, and tristearin) were used in blends with natural fats and oils. Results: Mean concentrations of serum total, esterified and LDL cholesterol were significantly lower after 18:0 than after 16:0 (n = 16-18, P < 0.01 for treatment effect). Myristic acid (14:0) had an intermediate effect. Receptor-mediated degradation of (125)I-LDL in mononuclear cells obtained from the subjects was lower after 16:0 than after 14:0 and 18:0 (n = 16-18, P = 0.05 for treatment effect). Differences in the digestibilities of the fats were not a major factor in the results. Strong cholesterolemic responses to the 16:0 diet were partly explained by apoE phenotype. Conclusions: As noted previously, stearic acid was neutral compared to 14:0 and 16:0. In contrast to studies involving natural fats, 14:0, fed as a synthetic triglyceride was less cholesterolemic than 16:0 in a majority of subjects. ApoE phenotype influenced the cholesterolemic response particularly when diets high in 16:0 were eaten.

BACKGROUND: Genetic predisposition and gliadin exposure are known to be crucial factors in the development of coeliac disease. Circumstantial evidence suggests that other unidentified environmental factors may also be of pathogenetic importance. AIM: To define the relation between cigarette smoking and the risk of development of symptomatic adult onset coeliac disease. SUBJECTS: Eighty six recently diagnosed adult coeliac disease patients and 172 controls matched for age and sex. METHOD: Matched case control study, using a simple questionnaire to determine smoking history, and in particular smoking status at the time of diagnosis of coeliac disease. RESULTS: At the time of diagnosis, the proportion of current smokers was 7% in the coeliac group, and 32.6% in the control group, giving a matched odds ratio of 0.15 (95% confidence intervals 0.06, 0.38). The difference could not be accounted for by social class, nor by coeliac patients giving up smoking after the onset of symptoms as most non-smokers in the coeliac group had never smoked. CONCLUSION: Cigarette smoking, or a factor closely linked to it, seems to exert a major protective effect against the development of symptomatic adult onset coeliac disease. The implication is that gliadin exposure is not the only important environmental factor involved in the pathogenesis of this condition.