Adverse pregnancy and neonatal outcomes associated with <i>Neisseria gonorrhoeae:</i> systematic review and meta-analysis.

ObjectiveTo examine associations between Neisseria gonorrhoeae (NG) infection during pregnancy and the risk of preterm birth, spontaneous abortion, premature rupture of membranes, perinatal mortality, low birth weight and ophthalmia neonatorum.Data sourcesWe searched Medline, EMBASE, the Cochrane Library and Cumulative Index to Nursing and Allied Health Literature for studies published between 1948 and 14 January 2020.MethodsStudies were included if they reported testing for NG during pregnancy and compared pregnancy, perinatal and/or neonatal outcomes between women with and without NG. Two reviewers independently assessed papers for inclusion and extracted data. Risk of bias was assessed using established checklists for each study design. Summary ORs with 95% CIs were generated using random effects models for both crude and, where available, adjusted associations.ResultsWe identified 2593 records and included 30 in meta-analyses. Women with NG were more likely to experience preterm birth (OR 1.55, 95% CI 1.21 to 1.99, n=18 studies); premature rupture of membranes (OR 1.41, 95% CI 1.02 to 1.92, n=9); perinatal mortality (OR 2.16, 95% CI 1.35 to 3.46, n=9); low birth weight (OR 1.66, 95% CI 1.12 to 2.48, n=8) and ophthalmia neonatorum (OR 4.21, 95% CI 1.36 to 13.04, n=6). Summary adjusted ORs were, for preterm birth 1.90 (95% CI 1.14 to 3.19, n=5) and for low birth weight 1.48 (95% CI 0.79 to 2.77, n=4). In studies with a multivariable analysis, age was the variable most commonly adjusted for. NG was more strongly associated with preterm birth in low-income and middle-income countries (OR 2.21, 95% CI 1.40 to 3.48, n=7) than in high-income countries (OR 1.38, 95% CI 1.04 to 1.83, n=11).ConclusionsNG is associated with a number of adverse pregnancy and newborn outcomes. Further research should be done to determine the role of NG in different perinatal mortality outcomes because interventions that reduce mortality will have the greatest impact on reducing the burden of disease in low-income and middle-income countries.Prospero registration numberCRD42016050962

Moving in an environment of induced sensorimotor incongruence does not influence pain sensitivity in healthy volunteers: A randomised within-subject experiment

Objectives: It has been proposed that in the same way that conflict between vestibular and visual inputs leads to motion sickness, conflict between motor commands and sensory information associated with these commands may contribute to some chronic pain states. Attempts to test this hypothesis by artificially inducing a state of sensorimotor incongruence and assessing self-reported pain have yielded equivocal results. To help clarify the effect sensorimotor incongruence has on pain we investigated the effect of moving in an environment of induced incongruence on pressure pain thresholds (PPT) and the pain experienced immediately on completion of PPT testing. Methods: Thirty-five healthy subjects performed synchronous and asynchronous upper-limb movements with and without mirror visual feedback in random order. We measured PPT over the elbow and the pain evoked by testing. Generalised linear mixed-models were performed for each outcome. Condition (four levels) and baseline values for each outcome were within-subject factors. Results: There was no effect of condition on PPT (p = 0.887) or pressure-evoked pain (p = 0.771). A sensitivity analysis using only the first PPT measure after each condition confirmed the result (p = 0.867). Discussion: Inducing a state of movement related sensorimotor incongruence in the upper-limb of healthy volunteers does not influence PPT, nor the pain evoked by testing. We found no evidence that sensorimotor incongruence upregulates the nociceptive system in healthy volunteer

Comparative effectiveness and safety of analgesic medicines for adults with non-specific acute low back pain: systematic review and network meta-analysis

Objective To evaluate the comparative effectiveness and safety of analgesic medicines for acute non-specific low back pain. Design Systematic review and network meta-analysis. Data sources Medline, PubMed, Embase, CINAHL, CENTRAL, ClinicalTrials.gov, clinicialtrialsregister.eu, and World Health Organization’s International Clinical Trials Registry Platform from database inception to 20 February 2022. Eligibility criteria for study selection Randomised controlled trials of analgesic medicines (eg, non-steroidal anti-inflammatory drugs, paracetamol, opioids, anti-convulsant drugs, skeletal muscle relaxants, or corticosteroids) compared with another analgesic medicine, placebo, or no treatment. Adults (≥18 years) who reported acute non-specific low back pain (for less than six weeks). Data extraction and synthesis Primary outcomes were low back pain intensity (0-100 scale) at end of treatment and safety (number of participants who reported any adverse event during treatment). Secondary outcomes were low back specific function, serious adverse events, and discontinuation from treatment. Two reviewers independently identified studies, extracted data, and assessed risk of bias. A random effects network meta-analysis was done and confidence was evaluated by the Confidence in Network Meta-Analysis method. Results 98 randomised controlled trials (15 134 participants, 49% women) included 69 different medicines or combinations. Low or very low confidence was noted in evidence for reduced pain intensity after treatment with tolperisone (mean difference −26.1 (95% confidence intervals −34.0 to −18.2)), aceclofenac plus tizanidine (−26.1 (−38.5 to −13.6)), pregabalin (−24.7 (−34.6 to −14.7)), and 14 other medicines compared with placebo. Low or very low confidence was noted for no difference between the effects of several of these medicines. Increased adverse events had moderate to very low confidence with tramadol (risk ratio 2.6 (95% confidence interval 1.5 to 4.5)), paracetamol plus sustained release tramadol (2.4 (1.5 to 3.8)), baclofen (2.3 (1.5 to 3.4)), and paracetamol plus tramadol (2.1 (1.3 to 3.4)) compared with placebo. These medicines could increase the risk of adverse events compared with other medicines with moderate to low confidence. Moderate to low confidence was also noted for secondary outcomes and secondary analysis of medicine classes. Conclusions The comparative effectiveness and safety of analgesic medicines for acute non-specific low back pain are uncertain. Until higher quality randomised controlled trials of head-to-head comparisons are published, clinicians and patients are recommended to take a cautious approach to manage acute non-specific low back pain with analgesic medicines.MAW was supported by a Postgraduate Scholarship from the National Health and Medical Research Council of Australia, a School of Medical Sciences Top-Up Scholarship from the University of New South Wales, and a PhD Supplementary Scholarship from Neuroscience Research Australia. MKB was supported by a PhD Candidature Scholarship and Supplementary Scholarship from Neuroscience Research Australia. MCF was supported by an Australian Government Research Training Program Scholarship, a PhD Supplementary Scholarship from Neuroscience Research Australia, and the Edward C Dunn Foundation Scholarship. RRNR was supported by the School of Medical Sciences Postgraduate Research Scholarship from the University of New South Wales and a PhD Supplementary Scholarship from Neuroscience Research Australia. HBL was supported by an Australian Government Research Training Program Scholarship. SSh was supported by the International Association for the Study of Pain John J Bonica Postdoctoral Fellowship. CGM was supported by an NHMRC Leadership 3 Fellowship (App 1194283). SMG was supported by a Research Fellowship from the Rebecca L Cooper Foundation. AN was supported by personal fellowship (P400PM_186723) from the Swiss National Science Foundation. This study received project support funding from a 2020 Exercise Physiology Research (Consumables) Grant from the University of New South Wales, which was used to obtain translations of studies published in languages other than English. The funder had played no part in the design, conduct, or analysis of the study

Paracetamol, NSAIDS and opioid analgesics for chronic low back pain: A network meta-analysis

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To answer the clinical question: ‘what analgesic medicine shall I prescribe this patient with chronic low back pain to reduce their pain?’. The objectives are to determine the analgesic effects, safety, effect on function, and relative rank according to analgesic effect, safety and effect on function of a single course of opioid analgesics, NSAIDs or paracetamol or combinations of these medicines

The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Curation Expert Panel consensus guidelines for LDLR variant classification

PURPOSE: In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published consensus standardized guidelines for sequence-level variant classification in Mendelian disorders. To increase accuracy and consistency, the Clinical Genome Resource Familial Hypercholesterolemia (FH) Variant Curation Expert Panel was tasked with optimizing the existing ACMG/AMP framework for disease-specific classification in FH. In this study, we provide consensus recommendations for the most common FH-associated gene, LDLR, where >2300 unique FH-associated variants have been identified. METHODS: The multidisciplinary FH Variant Curation Expert Panel met in person and through frequent emails and conference calls to develop LDLR-specific modifications of ACMG/AMP guidelines. Through iteration, pilot testing, debate, and commentary, consensus among experts was reached. RESULTS: The consensus LDLR variant modifications to existing ACMG/AMP guidelines include (1) alteration of population frequency thresholds, (2) delineation of loss-of-function variant types, (3) functional study criteria specifications, (4) cosegregation criteria specifications, and (5) specific use and thresholds for in silico prediction tools, among others. CONCLUSION: Establishment of these guidelines as the new standard in the clinical laboratory setting will result in a more evidence-based, harmonized method for LDLR variant classification worldwide, thereby improving the care of patients with FH

Savannahs of Asia: Antiquity, biogeography, and an uncertain future

The savannahs of Asia remain locally unrecognized as distinctive ecosystems, and continue to be viewed as degraded forests or seasonally dry tropical forests. These colonial-era legacies are problematic, because they fail to recognize the unique diversity of Asian savannahs and the critical roles of fire and herbivory in maintaining ecosystem health and diversity. In this review, we show that: the palaeo-historical evidence suggests that the savannahs of Asia have existed for at least 1 million years, long before widespread landscape modification by humans; savannah regions across Asia have levels of C4 grass endemism and diversity that are consistent with area-based expectations for non-Asian savannahs; there are at least three distinct Asian savannah communities, namely deciduous broadleaf savannahs, deciduous fine-leafed and spiny savannahs and evergreen pine savannahs, with distinct functional ecologies consistent with fire- and herbivory-driven community assembly. Via an analysis of savannah climate domains on other continents, we map the potential extent of savannahs across Asia. We find that the climates of African savannahs provide the closest analogues for those of Asian deciduous savannahs, but that Asian pine savannahs occur in climates different to any of the savannahs in the southern continents. Finally, we review major threats to the persistence of savannahs in Asia, including the mismanagement of fire and herbivory, alien woody encroachment, afforestation policies and future climate uncertainty associated with the changing Asian monsoon. Research agendas that target these issues are urgently needed to manage and conserve these ecosystems. This article is part of the themed issue ‘Tropical grassy biomes: linking ecology, human use and conservation’

Phylodynamics of HIV-1 Subtype B among the Men-Having-Sex-with-Men (MSM) Population in Hong Kong

The men-having-sex-with-men (MSM) population has become one of the major risk groups for HIV-1 infection in the Asia Pacific countries. Hong Kong is located in the centre of Asia and the transmission history of HIV-1 subtype B transmission among MSM remained unclear. The aim of this study was to investigate the transmission dynamics of HIV-1 subtype B virus in the Hong Kong MSM population. Samples of 125 HIV-1 subtype B infected MSM patients were recruited in this study. Through this study, the subtype B epidemic in the Hong Kong MSM population was identified spreading mainly among local Chinese who caught infection locally. On the other hand, HIV-1 subtype B infected Caucasian MSM caught infection mainly outside Hong Kong. The Bayesian phylogenetic analysis also indicated that 3 separate subtype B epidemics with divergence dates in the 1990s had occurred. The first and latest epidemics were comparatively small-scaled; spreading among the local Chinese MSM while sauna-visiting was found to be the major sex partner sourcing reservoir for the first subtype B epidemic. However, the second epidemic was spread in a large-scale among local Chinese MSM with a number of them having sourced their sex partners through the internet. The epidemic virus was estimated to have a divergence date in 1987 and the infected population in Hong Kong had a logistic growth throughout the past 20 years. Our study elucidated the evolutionary and demographic history of HIV-1 subtype B virus in Hong Kong MSM population. The understanding of transmission and growth model of the subtype B epidemic provides more information on the HIV-1 transmission among MSM population in other Asia Pacific high-income countries

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

The association between hip fracture and hip osteoarthritis: A case-control study

<p>Abstract</p> <p>Background</p> <p>There have been reports both supporting and refuting an inverse relationship between hip fracture and hip osteoarthritis (OA). We explore this relationship using a case-control study design.</p> <p>Methods</p> <p>Exclusion criteria were previous hip fracture (same side or contralateral side), age younger than 60 years, foreign nationality, pathological fracture, rheumatoid arthritis and cases were radiographic examinations were not found in the archives. We studied all subjects with hip fracture that remained after the exclusion process that were treated at Akureyri University Hospital, Iceland 1990-2008, n = 562 (74% women). Hip fracture cases were compared with a cohort of subjects with colon radiographs, n = 803 (54% women) to determine expected population prevalence of hip OA. Presence of radiographic hip OA was defined as a minimum joint space of 2.5 mm or less on an anteroposterior radiograph, or Kellgren and Lawrence grade 2 or higher. Possible causes of secondary osteoporosis were identified by review of medical records.</p> <p>Results</p> <p>The age-adjusted odds ratio (OR) for subjects with hip fracture having radiographic hip OA was 0.30 (95% confidence interval [95% CI] 0.12-0.74) for men and 0.33 (95% CI 0.19-0.58) for women, compared to controls. The probability for subjects with hip fracture and hip OA having a secondary cause of osteoporosis was three times higher than for subjects with hip fracture without hip OA.</p> <p>Conclusion</p> <p>The results of our study support an inverse relationship between hip fractures and hip OA.</p

Adenylyl Cyclases 1 and 8 Initiate a Presynaptic Homeostatic Response to Ethanol Treatment

BACKGROUND:Although ethanol exerts widespread action in the brain, only recently has progress been made in understanding the specific events occurring at the synapse during ethanol exposure. Mice deficient in the calcium-stimulated adenylyl cyclases, AC1 and AC8 (DKO), demonstrate increased sedation duration and impaired phosphorylation by protein kinase A (PKA) following acute ethanol treatment. While not direct targets for ethanol, we hypothesize that these cyclases initiate a homeostatic presynaptic response by PKA to reactivate neurons from ethanol-mediated inhibition. METHODOLOGY/PRINCIPAL FINDINGS:Here, we have used phosphoproteomic techniques and identified several presynaptic proteins that are phosphorylated in the brains of wild type mice (WT) after ethanol exposure, including synapsin, a known PKA target. Phosphorylation of synapsins I and II, as well as phosphorylation of non-PKA targets, such as, eukaryotic elongation factor-2 (eEF-2) and dynamin is significantly impaired in the brains of DKO mice. This deficit is primarily driven by AC1, as AC1-deficient, but not AC8-deficient mice also demonstrate significant reductions in phosphorylation of synapsin and eEF-2 in cortical and hippocampal tissues. DKO mice have a reduced pool of functional recycling vesicles and fewer active terminals as measured by FM1-43 uptake compared to WT controls, which may be a contributing factor to the impaired presynaptic response to ethanol treatment. CONCLUSIONS/SIGNIFICANCE:These data demonstrate that calcium-stimulated AC-dependent PKA activation in the presynaptic terminal, primarily driven by AC1, is a critical event in the reactivation of neurons following ethanol-induced activity blockade