Causal mechanisms in the clinical course and treatment of back pain

In recent years, there has been increasing interest in studying causal mechanisms in the development and treatment of back pain. The aim of this article is to provide an overview of our current understanding of causal mechanisms in the field. In the first section, we introduce key concepts and terminology. In the second section, we provide a brief synopsis of systematic reviews of mechanism studies relevant to the clinical course and treatment of back pain. In the third section, we reflect on the findings of our review to explain how understanding causal mechanisms can inform clinical practice and the implementation of best practice. In the final sections, we introduce contemporary methodological advances, highlight the key assumptions of these methods, and discuss future directions to advance the quality of mechanism-related studies in the back pain field

Skuteczność leczenia niespecyficznego bólu dolnego odcinka kręgosłupa: metaanaliza randomizowanych badań kontrolowanych placebo

Cel. Wyniki leczenia oceniane w randomizowanych badaniach kontrolowanych placebo są bardziej wiarygodne niż w badaniach o innej konstrukcji. Celem poniższej metaanalizy była ocena skuteczności różnych sposobów leczenia stosowanych w niespecyficznym bólu dolnego odcinka kręgosłupa na podstawie wyników randomizowanych badań kontrolowanych placebo. Metoda. Przeszukano bazy danych Medline, Embase, Cinahl, PsychInfo i Cochrane Central Register of Controlled Trials pod kątem odpowiednio dobranych badań — od najnowszych, do opublikowanych w październiku 2006 roku. Wyniki dotyczące bólu ciągłego przeliczono według wspólnej skali 0–100 i skomasowano z wykorzystaniem modelu losowego (random effects model). Wyniki. Analizą objęto 76 badań oceniających 34 sposoby leczenia. Istotne efekty wykazano w 50% ocenianych sposobów leczenia. W większości przypadków efekty były niewielkie lub umiarkowane: 47% wykazywało estymację punktową efektów leczenia poniżej 10 punktów w skali 100-punktowej, 38% — 10–20 punktów, a 15% — ponad 20 punktów. Tylko w jednym badaniu stwierdzono wyraźne efekty leczenia (> 20 pkt.). Wnioski. W poniższej metaanalizie dowiedziono, że efekt przeciwbólowy wielu sposobów leczenia niespecyficznego bólu dolnego odcinka kręgosłupa jest niewielki i nie różni się w populacjach z objawami ostrymi i przewlekłymi. Polski Przegląd Neurologiczny 2010; 6 (2): 105–11

The analgesic effect of electroencephalographic neurofeedback for people with chronic pain: protocol for a systematic review and meta-analysis

Background: Chronic pain is a global health problem, affecting around 1 in 5 individuals in the general population. The understanding of the key role of functional brain alterations in the generation of chronic pain has led researchers to focus on pain treatments that target brain activity. Electroencephalographic neurofeedback attempts to modulate the power of maladaptive electroencephalography frequency powers to decrease chronic pain. Although several studies have provided promising evidence, the effect of electroencephalographic neurofeedback on chronic pain is uncertain. Objective: This systematic review aims to synthesize the evidence from randomized controlled trials to evaluate the analgesic effect of electroencephalographic neurofeedback. In addition, we will synthesize the findings of nonrandomized studies in a narrative review. Methods: We will apply the search strategy in 5 electronic databases (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycInfo, and CINAHL) for published studies and in clinical trial registries for completed unpublished studies. We will include studies that used electroencephalographic neurofeedback as an intervention for people with chronic pain. Risk-of-bias tools will be used to assess methodological quality of the included studies. We will include randomized controlled trials if they have compared electroencephalographic neurofeedback with any other intervention or placebo control. The data from randomized controlled trials will be aggregated to perform a meta-analysis for quantitative synthesis. The primary outcome measure is pain intensity assessed by self-report scales. Secondary outcome measures include depressive symptoms, anxiety symptoms, and sleep quality measured by self-reported questionnaires. We will investigate the studies for additional outcomes addressing adverse effects and resting-state electroencephalography analysis. Additionally, all types of nonrandomized studies will be included for a narrative synthesis. The intended and unintended effects of nonrandomized studies will be extracted and summarized in a descriptive table. Results: Ethics approval is not required for a systematic review, as there will be no patient involvement. The search for this systematic review commenced in July 2020, and we expect to publish the findings in early 2021. Conclusions: This systematic review will provide recommendations for researchers and health professionals, as well as people with chronic pain, about the evidence for the analgesic effect of electroencephalographic neurofeedback. Trial Registration: International Prospective Register of Systematic Reviews (PROSPERO) CRD42020177608; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=177608 International Registered Report Identifier (IRRID): PRR1-10.2196/2282

Do sensorimotor cortex activity, an individual's capacity for neuroplasticity, and psychological features during an episode of acute low back pain predict outcome at 6 months: a protocol for an Australian, multisite prospective, longitudinal cohort study

INTRODUCTION:Low back pain (LBP) is the leading cause of disability worldwide, with prevalence doubling in the past 14 years. To date, prognostic screening tools display poor discrimination and offer no net benefit of screening over and above a 'treat all' approach. Characteristics of the primary sensory (S1) and motor (M1) cortices may predict the development of chronic LBP, yet the prognostic potential of these variables remains unknown. The Understanding persistent Pain Where it ResiDes (UPWaRD) study aims to determine whether sensorimotor cortex activity, an individual's capacity for plasticity and psychosocial factors in the acute stage of pain, predict LBP outcome at 6 months. This paper describes the methods and analysis plan for the development of the prediction model. METHODS AND ANALYSIS:The study uses a multicentre prospective longitudinal cohort design with 6-month follow-up. 120 participants, aged 18 years or older, experiencing an acute episode of LBP (less than 6 weeks duration) will be included. Primary outcomes are pain and disability. ETHICS AND DISSEMINATION:Ethical approval has been obtained from Western Sydney University Human Research Ethics Committee (H10465) and from Neuroscience Research Australia (SSA: 16/002). Dissemination will occur through presentations at national and international conferences and publications in international peer-reviewed journals. TRIAL REGISTRATION NUMBER:ACTRN12619000002189; Pre-results.Luke C Jenkins, Wei-Ju Chang, Valentina Buscemi, Matthew Liston, Barbara Toson, Michael Nicholas, Thomas Graven-Nielsen, Michael Ridding, Paul W Hodges, James H McAuley, Siobhan M Schabru

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure : an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013

Long-term changes in parenting and child behavior after the Home-Start family support program

Background: The intervention Home-Start is a wide spread program in a number of countries, among which the Netherlands. In Home-Start, trained volunteers visit families with young children in need of support once or twice a week to help them to deal with problems in family life and parenting. Little is known, however, about the effects of Home-Start. This study describes short-term and long term changes in families that participated in Home-Start. Methods: Three groups of families with young children (at the start mean age 1 1/2 years) were followed over a period of four years. One of the groups of families participated in the Home-Start family support program in the first 6.6 months of this period. The two other groups were (1) a randomly selected community sample and (2) a group of families with elevated parenting stress and a need for support. Data were collected at the beginning of the study, (after median 1.4 months), directly after the intervention (median 6.6 months) and at two follow-up occasions (respectively, median 12.5 and 49.2 months after the first measurement). At the last measurement, data were available for 33, 45 and 34 families respectively. Results: Multilevel analysis showed more positive changes in parental wellbeing, competence and behavior (more consistent behavior and less rejection) during the intervention period in the Home-Start group than in the two other groups. At the three year follow up, the Home-Start group showed, compared to the other groups, more improvements in parenting (more responsiveness), but also diminished child externalizing and internalizing behavior problems (less oppositional defiant behavior, affective problems and anxiety problems). Conclusions: Home-Start seems a promising family support intervention that deserves to be studied more extensively

Women’s beliefs about medicines and adherence to pharmacotherapy in pregnancy: Opportunities for community pharmacists?

Background During pregnancy women might weigh benefits of treatment against potential risks to the unborn child. However, non-adherence to necessary treatment can adversely affect both mother and child. To optimize pregnant women’s beliefs and medication adherence, community pharmacists are ideally positioned to play an important role in primary care. Objective This narrative review aimed to summarize the evidence on 1) pregnant women’s beliefs, 2) medication adherence in pregnancy, and 3) community pharmacists’ counselling during pregnancy. Method Three search strategies were used in Medline and Embase to find original studies evaluating women’s beliefs, medication adherence and community pharmacists’ counselling during pregnancy. All original descriptive and analytic epidemiological studies performed in Europe, North America and Australia, written in English and published from 2000 onwards were included. Results We included 14 studies reporting on women’s beliefs, 11 studies on medication adherence and 9 on community pharmacists’ counselling during pregnancy. Women are more reluctant to use medicines during pregnancy and tend to overestimate the teratogenic risk of medicines. Risk perception varies with type of medicine, level of health literacy, education level and occupation. Furthermore, low medication adherence during pregnancy is common. Finally, limited evidence showed current community pharmacists’ counselling is insufficient. Barriers hindering pharmacists are insufficient knowledge and limited access to reliable information. Conclusion Concerns about medication use and non-adherence are widespread among pregnant women. Community pharmacists’ counselling during pregnancy is insufficient. Further education, training and research are required to support community pharmacists in fulfilling all the opportunities they have when counselling pregnant women

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification. Funding: UK Research and Innovation and National Institute for Health Research

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials