bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Role of Phospholipases in Virulence and Fungal Pathogenesis
Authors: Ghannoum Mahmoud A.
Published: October 2018

Microbial pathogens use a number of genetic strategies to invade the host and cause infection. These common themes are found throughout microbial systems. Secretion of enzymes, such as phospholipase, has been proposed as one of these themes that are used by bacteria, parasites, and pathogenic fungi. The role of extracellular phospholipase as a potential virulence factor in pathogenic fungi, including Candida albicans, Cryptococcus neoformans, and Aspergillus, has gained credence recently. In this review, data implicating phospholipase as a virulence factor in C. albicans, Candida glabrata, C. neoformans, and A. fumigatus are presented. A detailed description of the molecular and biochemical approaches used to more definitively delineate the role of phospholipase in the virulence of C. albicans is also covered. These approaches resulted in cloning of three genes encoding candidal phospholipases (caPLP1, caPLB2, and PLD). By using targeted gene disruption, C. albicans null mutants that failed to secrete phospholipase B, encoded by caPLB1, were constructed. When these isogenic strain pairs were tested in two clinically relevant murine models of candidiasis, deletion of caPLB1 was shown to lead to attenuation of candidal virulence. Importantly, immunogold electron microscopy studies showed that C. albicans secretes this enzyme during the infectious process. These data indicate that phospholipase B is essential for candidal virulence. Although the mechanism(s) through which phospholipase modulates fungal virulence is still under investigations, early data suggest that direct host cell damage and lysis are the main mechanisms contributing to fungal virulence. Since the importance of phospholipases in fungal virulence is already known, the next challenge will be to utilize these lytic enzymes as therapeutic and diagnostic targets.
Drug Resistance in Human Helminths: Current Situation and Lessons from Livestock
Authors: Geerts S. , Gryseels B.
Published: October 2018

In this review the available reports on drug resistance in human helminths, particularly hookworms and schistosomes, are critically analyzed. The experiences with helminths of livestock are then reviewed, in particular the factors contributing to the development of anthelmintic resistance, the mechanisms and genetics of resistance to various anthelmintic classes, and the methods available for detection. These experiences appear to be worryingly similar and relevant to the potential development of drug resistance in human helminths. Recommendations to reduce its risks are suggested.
Worldwide
Haemophilus influenzae
Type b Disease at the Beginning of the 21st Century: Global Analysis of the Disease Burden 25 Years after the Use of the Polysaccharide Vaccine and a Decade after the Advent of Conjugates
Authors: Peltola Heikki
Published: October 2018

Vaccination against Haemophilus influenzae type b (Hib) diseases began a quarter of a century ago with a polysaccharide vaccine; this vaccine was followed by four different conjugates 10 years later. In this review, the burden of global Hib disease is quantified following this 25-year period of vaccine availability to determine the potential impact of conjugate vaccines. This task was accomplished by analysis of data available in 10 languages in 75 geographical regions of over 50 countries. All severe Hib diseases, not only meningitis, were characterized, and special attention was paid to the most vulnerable age group, i.e., children aged 0 to 4 years. Prior to vaccination, the weighted worldwide incidence of meningitis in patients younger than 5 years was 57/100,000, and for all Hib diseases except nonbacteremic pneumonia, it was 71/100,000, indicating 357,000 and 445,000 cases per year, respectively. At least 108,500 of these children died. For all age groups combined, there were 486,000 cases of Hib disease, excluding pneumonia, with 114,200 deaths and probably an equal number of sequelae per annum. If the figures for nonbacteremic pneumonia are included, a conservative estimate is that over 2.2 million cases of infection and 520,000 deaths from Hib disease occurred worldwide, but the true numbers might have been greater. Despite these large numbers and availability of safe and efficacious vaccines, only 38,000 cases annually are prevented—a meager 8% or less than a 2% reduction in cases, depending on whether nonbacteremic pneumonia is included in the calculations. Although vaccination has had great success in some affluent countries, the current level of activity has had a very small impact globally. The use of conjugates, preferably with a reduced number of doses and in combination with other vaccines or perhaps in fractional doses, should be extended to less privileged countries, where most Hib disease occurs.
Risk and Management of Blood-Borne Infections in Health Care Workers
Authors: Beltrami Elise M. , Williams Ian T. , Shapiro Craig N. , Chamberland Mary E.
Published: October 2018

Exposure to blood-borne pathogens poses a serious risk to health care workers (HCWs). We review the risk and management of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections in HCWs and also discuss current methods for preventing exposures and recommendations for postexposure prophylaxis. In the health care setting, blood-borne pathogen transmission occurs predominantly by percutaneous or mucosal exposure of workers to the blood or body fluids of infected patients. Prospective studies of HCWs have estimated that the average risk for HIV transmission after a percutaneous exposure is approximately 0.3%, the risk of HBV transmission is 6 to 30%, and the risk of HCV transmission is approximately 1.8%. To minimize the risk of blood-borne pathogen transmission from HCWs to patients, all HCWs should adhere to standard precautions, including the appropriate use of hand washing, protective barriers, and care in the use and disposal of needles and other sharp instruments. Employers should have in place a system that includes written protocols for prompt reporting, evaluation, counseling, treatment, and follow-up of occupational exposures that may place a worker at risk of blood-borne pathogen infection. A sustained commitment to the occupational health of all HCWs will ensure maximum protection for HCWs and patients and the availability of optimal medical care for all who need it.
Bartonella Infection in Animals: Carriership, Reservoir Potential, Pathogenicity, and Zoonotic Potential for Human Infection
Authors: Breitschwerdt Edward B. , Kordick Dorsey L.
Published: October 2018

Recent observations have begun to support a role for Bartonella spp. as animal as well as human pathogens. Bartonella spp. are vector-transmitted, blood-borne, intracellular, gram-negative bacteria that can induce prolonged infection in the host. Persistent infections in domestic and wild animals result in a substantial reservoir of Bartonella organisms in nature that can serve as a source for inadvertent human infection. The prevalence of bacteremia can range from 50 to 95% in selected rodent, cat, deer, and cattle populations. Dogs infected with Bartonella spp. can develop lameness, endocarditis, granulomatous lymphadenitis, and peliosis hepatis, lesions that have also been reported in association with human infection. Understanding the role of Bartonella spp. as pathogens in cats and other wild or domestic animals awaits the results of additional studies. Considering the extensive animal reservoirs and the large number of insects that have been implicated in the transmission of Bartonella spp., both animal and human exposure to these organisms may be more substantial than is currently believed.
Polysaccharide Immunomodulators as Therapeutic Agents: Structural Aspects and Biologic Function
Authors: Tzianabos Arthur O.
Published: October 2018

Polysaccharide immunomodulators were first discovered over 40 years ago. Although very few have been rigorously studied, recent reports have revealed the mechanism of action and structure-function attributes of some of these molecules. Certain polysaccharide immunomodulators have been identified that have profound effects in the regulation of immune responses during the progression of infectious diseases, and studies have begun to define structural aspects of these molecules that govern their function and interaction with cells of the host immune system. These polymers can influence innate and cell-mediated immunity through interactions with T cells, monocytes, macrophages, and polymorphonuclear lymphocytes. The ability to modulate the immune response in an appropriate way can enhance the host's immune response to certain infections. In addition, this strategy can be utilized to augment current treatment regimens such as antimicrobial therapy that are becoming less efficacious with the advent of antibiotic resistance. This review focuses on recent studies that illustrate the structural and biologic activities of specific polysaccharide immunomodulators and outlines their potential for clinical use.
Endemic mycoses in AIDS: a clinical review
Authors: Wheat J
Published: October 2018

Histoplasmosis and coccidioidomycosis are serious opportunistic infections in patients with AIDS who reside in areas of endemicity of the United States and Central and South America. Blastomycosis, although less common, also must be recognized as an opportunistic infection in patients with AIDS. Prompt diagnosis requires knowledge of the clinical syndromes and diagnostic tests as well as a high index of suspicion. Histoplasmosis and blastomycosis respond well to antifungal treatment, but relapse is common without chronic suppressive therapy. Improvements in treatment are needed in coccidioidomycosis. Research is needed to identify preventive strategies for patients at risk. These strategies may include use of prophylactic antifungal therapy or vaccination.
Feline immunodeficiency virus: an interesting model for AIDS studies and an important cat pathogen
Authors: Bendinelli M , Pistello M , Lombardi S , Poli A , Garzelli C , Matteucci D , Ceccherini-Nelli L , Malvaldi G , Tozzini F
Published: October 2018

The lentivirus feline immunodeficiency virus (FIV) is a widespread pathogen of the domestic cat that is mainly transmitted through bites, although other means of transmission are also possible. Its prevalence ranges from 1 to 10% in different cat populations throughout the world, thus representing a large reservoir of naturally infected animals. FIV resembles the human immunodeficiency virus (HIV) in many respects. Similarities include the structural features of the virion, the general organization and great variability of the genome, the life cycle in the infected host, and most importantly, the pathogenic potential. Infection is associated with laboratory signs of immunosuppression as well as with a large variety of superinfections, tumors, and neurological manifestations. Our understanding of FIV is steadily improving and is providing important clues to the pathogenesis of immunodeficiency-inducing lentiviruses. The cellular receptor for FIV is different from the feline equivalent of the human CD4 molecule used by HIV; nevertheless, the major hallmark of infection is a progressive loss of CD4+ T lymphocytes as in HIV infection. The mechanisms by which FIV escapes the host's immune responses are being actively investigated. FIV causes lysis of infected T cells and also appears to predispose these cells to apoptosis. Infection of macrophages and other cell types has also been documented. For reasons yet to be understood, antibody-mediated neutralization of fresh FIV isolates is very inefficient both in vitro and in vivo. Vaccination studies have provided some encouraging results, but the difficulties encountered appear to match those met in HIV vaccine development. FIV susceptibility to antiviral agents is similar to that of HIV, thus providing a valuable system for in vivo preclinical evaluation of therapies. It is concluded that in many respects FIV is an ideal model for AIDS studies.
Tuberculosis in the AIDS era
Authors: Sepkowitz K A , Raffalli J , Riley L , Kiehn T E , Armstrong D
Published: October 2018

A resurgence of tuberculosis has occurred in recent years in the United States and abroad. Deteriorating public health services, increasing numbers of immigrants from countries of endemicity, and coinfection with the human immunodeficiency virus (HIV) have contributed to the rise in the number of cases diagnosed in the United States. Outbreaks of resistant tuberculosis, which responds poorly to therapy, have occurred in hospitals and other settings, affecting patients and health care workers. This review covers the pathogenesis, epidemiology, clinical presentation, laboratory diagnosis, and treatment of Mycobacterium tuberculosis infection and disease. In addition, public health and hospital infection control strategies are detailed. Newer approaches to epidemiologic investigation, including use of restriction fragment length polymorphism analysis, are discussed. Detailed consideration of the interaction between HIV infection and tuberculosis is given. We also review the latest techniques in laboratory evaluation, including the radiometric culture system, DNA probes, and PCR. Current recommendations for therapy of tuberculosis, including multidrug-resistant tuberculosis, are given. Finally, the special problem of prophylaxis of persons exposed to multidrug-resistant tuberculosis is considered.
Endotoxemia: methods of detection and clinical correlates
Authors: Hurley J C
Published: October 2018

As an assay for endotoxin, the Limulus amebocyte lysate assay has several desirable properties: sensitivity, specificity, and potential for adaptation to a quantitative format. Several modifications have been developed to enhance its potential for clinical application. The modifications that allow quantitative measurement of endotoxin and also improve its application to blood samples are described in this review. In fluids other than blood, the detection of endotoxin with the Limulus amebocyte lysate assay can be used as an aid to identify the presence of gram-negative bacteria, and the assay has established utility. With blood, however, there are a range of factors that interfere with the detection of endotoxemia and there are disparate views with respect to the diagnostic and prognostic significance of the test results. In general, the clinical significance of the finding of endotoxemia broadly parallels the frequency and importance of gram-negative sepsis in the patient groups studied and a decline in endotoxin levels accompanies clinical improvement. However, with therapies designed to reduce levels of endotoxin, or to antagonize its effects, it is unclear whether clinical improvement occurs as a consequence of changes in the levels of endotoxemia.
Cervical cancer: is herpes simplex virus type II a cofactor?
Authors: Jones C
Published: October 2018

In many ways, cervical cancer behaves as a sexually transmitted disease. The major risk factors are multiple sexual partners and early onset of sexual activity. Although high-risk types of human papillomaviruses (HPV) play an important role in the development of nearly all cases of cervical cancer, other sexually transmitted infectious agents may be cofactors. Herpes simplex virus type 2 (HSV-2) is transmitted primarily by sexual contact and therefore has been implicated as a risk factor. Several independent studies suggest that HSV-2 infections correlate with a higher than normal incidence of cervical cancer. In contrast, other epidemiological studies have concluded that infection with HSV-2 is not a major risk factor. Two separate transforming domains have been identified within the HSV-2 genome, but continued viral gene expression apparently is not necessary for neoplastic transformation. HSV infections lead to unscheduled cellular DNA synthesis, chromosomal amplifications, and mutations. These observations suggest that HSV-2 is not a typical DNA tumor virus. It is hypothesized that persistent or abortive infections induce permanent genetic alterations that interfere with differentiation of cervical epithelium and subsequently induce abnormal proliferation. Thus, HSV-2 may be a cofactor in some but not all cases of cervical cancer.
Infections and antibiotic resistance in nursing homes
Authors: Nicolle L E , Strausbaugh L J , Garibaldi R A
Published: October 2018

Infections occur frequently in nursing home residents. The most common infections are pneumonia, urinary tract infection, and skin and soft tissue infection. Aging-associated physiologic and pathologic changes, functional disability, institutionalization, and invasive devices all contribute to the high occurrence of infection. Antimicrobial agent use in nursing homes is intense and usually empiric. All of these factors contribute to the increasing frequency of antimicrobial agent-resistant organisms in nursing homes. Programs that will limit the emergence and impact of antimicrobial resistance and infections in nursing homes need to be developed.
Activation of the complement system by pathogenic fungi
Authors: Kozel T R
Published: October 2018

Fungi have been studied as prototype activators of the complement cascade since the early 1900s. More recently, attention has focused on the role of the complement system in the pathogenesis of fungal infections. The interactions of Cryptococcus neoformans and Candida albicans with the complement system are the most widely characterized; however, all pathogenic fungi examined to date have the ability to initiate the complement cascade. The molecular mechanisms for initiation and regulation of the complement cascade differ from one fungus to another, most likely reflecting differences in the structure of the outer layers of the cell wall. The molecular bases for such differences remain to be identified. Studies of mycoses in experimental animals with induced or congenital deficiencies in the complement system demonstrate that complement is an important innate system for control of fungal infection. Contributions to host resistance include opsonization and generation of inflammatory mediators. Inflammation induced by chemotactic products of the complement system may contribute to the pathogenesis of some fungal infections.
Bartonella (Rochalimaea) quintana infections
Authors: Maurin M , Raoult D
Published: October 2018

Bartonella (formerly Rochalimaea) quintana is the etiological agent of trench fever, a disease extensively reported during the World Wars. Recent molecular biology approaches have allowed dramatic extension of the spectrum of Bartonella infections. B. quintana is now also recognized as an etiological agent of fever and bacteremia, endocarditis, bacillary angiomatosis, and chronic lymphadenopathy. Human immunodeficiency virus-infected patients and/or homeless people are the most vulnerable to infection. Poverty and louse infestation were the main epidemiological factors associated with B. quintana infections during wartime. Although poverty and chronic alcoholism have been associated with modern cases of trench fever and bacteremia due to B. quintana in Europe and the United States, vectors for B. quintana have not been clearly identified and B. quintana has not been isolated from modern-day lice. Microscopic bacillary angiomatosis lesions are characterized by tumor-like capillary lobules, with proliferating endothelial cells. In vitro experiments have shown that B. quintana survives within endothelial cells and stimulates cell proliferation. These observations, together with the finding that lesions may regress when antibiotic therapy is administered, strongly suggest that B. quintana itself stimulates angiogenesis. Bartonella infections are characterized by a high frequency of relapses after brief courses of antibiotic therapy. It is to be noted that in vitro, although Bartonella species are highly susceptible to antibiotics, only the aminoglycosides have proved to be bactericidal. However, the most effective antibiotic regimen for Bartonella infections remains to be established.
Immunopathogenesis of recurrent vulvovaginal candidiasis
Authors: Fidel P L , Sobel J D
Published: October 2018

Recurrent vulvovaginal candidiasis (RVVC) is a prevalent opportunistic mucosal infection, caused predominantly by Candida albicans, which affects a significant number of otherwise healthy women of childbearing age. Since there are no known exogenous predisposing factors to explain the incidence of symptomatic vaginitis in most women with idiopathic RVVC, it has been postulated that these particular women suffer from an immunological abnormality that prediposes them to RVVC. Because of the increased incidence of mucosal candidiasis in individuals with depressed cell-mediated immunity (CMI), defects in CMI are viewed as a possible explanation for RVVC. In this review, we attempt to place into perspective the accumulated information regarding the immunopathogenesis of RVVC, as well as to provide new immunological perspectives and hypotheses regarding potential immunological deficiencies that may predispose to RVVC and potentially other mucosal infections by the same organism. The results of both clinical studies and studies in an animal model of experimental vaginitis suggest that systemic CMI may not be the predominant host defense mechanism against C. albicans vaginal infections. Rather, locally acquired mucosal immunity, distinct from that in the peripheral circulation, is now under consideration as an important host defense at the vaginal mucosa, as well as the notion that changes in local CMI mechanism(s) may predispose to RVVC.
Pediatric human immunodeficiency virus infection
Authors: Domachowske J B
Published: October 2018

In the past decade, an increase in pediatric human immunodeficiency virus (HIV) infection has had a substantial impact on childhood morbidity and mortality worldwide. The vertical transmission of HIV from mother to infant accounts for the vast majority of these cases. Identification of HIV-infected pregnant women needs to be impoved so that appropriate therapy can be initiated for both mothers and infants. While recent data demonstrate a dramatic decrease in HIV transmission from a subset of women treated with zidovudine during pregnancy, further efforts at reducing transmission are desperately needed. This review focuses on vertically transmitted HIV infection in children, its epidemiology, diagnostic criteria, natural history, and clinical manifestations including infectious and noninfectious complications. An overview of the complex medical management of these children ensues, including the use of antiretroviral therapy. Opportunistic infection prophylaxis is reviewed, along with the important role of other supportive therapies.
Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases
Authors: Lucey D R , Clerici M , Shearer G M
Published: October 2018

In the mid-1980s, Mosmann, Coffman, and their colleagues discovered that murine CD4+ helper T-cell clones could be distinguished by the cytokines they synthesized. The isolation of human Th1 and Th2 clones by Romagnani and coworkers in the early 1990s has led to a large number of reports on the effects of Th1 and Th2 on the human immune system. More recently, cells other than CD4+ T cells, including CD8+ T cells, monocytes, NK cells, B cells, eosinophils, mast cells, basophils, and other cells, have been shown to be capable of producing "Th1" and "Th2" cytokines. In this review, we examine the literature on human diseases, using the nomenclature of type 1 (Th1-like) and type 2 (Th2-like) cytokines, which includes all cell types producing these cytokines rather than only CD4+ T cells. Type 1 cytokines include interleukin-2 (IL-2), gamma interferon, IL-12 and tumor necrosis factor beta, while type 2 cytokines include IL-4, IL-5, IL-6, IL-10, and IL-13. In general, type 1 cytokines favor the development of a strong cellular immune response whereas type 2 cytokines favor a strong humoral immune response. Some of these type 1 and type 2 cytokines are cross-regulatory. For example, gamma interferon and IL-12 decrease the levels of type 2 cytokines whereas IL-4 and IL-10 decrease the levels of type 1 cytokines. We use this cytokine perspective to examine human diseases including infections due to viruses, bacteria, parasites, and fungi, as well as selected neoplastic, atopic, rheumatologic, autoimmune, and idiopathic-inflammatory conditions. Clinically, type 1 cytokine-predominant responses should be suspected in any delayed-type hypersensitivity-like granulomatous reactions and in infections with intracellular pathogens, whereas conditions involving hypergammaglobulinemia, increased immunoglobulin E levels, and/or eosinophilia are suggestive of type 2 cytokine-predominant conditions. If this immunologic concept is relevant to human diseases, the potential exists for novel cytokine-based therapies and novel cytokine-directed preventive vaccines for such diseases.
Surveillance for variant CJD: should more children with neurodegenerative diseases have autopsies?
Authors: Verity Christopher , Winstone Anne Marie , Will Robert , Powell Alison , Baxter Peter , de Sousa Carlos , Gissen Paul , Kurian Manju , Livingston John , McFarland Robert , Pal Suvankar , Pike Michael , Robinson Richard , Wassmer Evangeline , Zuberi Sameer
Published: October 2018

Objectives

To report investigations performed in children with progressive neurodegenerative diseases reported to this UK study.

Design

Since 1997 paediatric surveillance for variant Creutzfeldt-Jakob disease (vCJD) has been performed by identifying children aged less than 16 years with progressive intellectual and neurological deterioration (PIND) and searching for vCJD among them.

Setting

The PIND Study obtains case details from paediatricians who notify via the British Paediatric Surveillance Unit.

Participants

Between May 1997 and October 2017, a total of 2050 cases meeting PIND criteria had been notified and investigated.

Results

Six children had vCJD. 1819 children had other diagnoses, made in 12 cases by antemortem brain biopsy and in 15 by postmortem investigations. 225 children were undiagnosed: only 3 had antemortem brain biopsies and only 14 of the 108 who died were known to have had autopsies; postmortem neuropathological studies were carried out in just 10% (11/108) and only two had prion protein staining of brain tissue. Of the undiagnosed cases 43% were known to come from Asian British families.

Conclusions

Most of the notified children had a diagnosis other than vCJD to explain their neurological deterioration. None of the undiagnosed cases had the clinical phenotype of vCJD but brain tissue was rarely studied to exclude vCJD. Clinical surveillance via the PIND Study remains the only practical means of searching for vCJD in UK children.
Immunosuppressants and/or antivascular endothelial growth factor inhibitors in punctate inner choroidopathy? Follow-up results with optical coherence tomography angiography
Authors: Pohlmann Dominika , Pleyer Uwe , Joussen Antonia M , Winterhalter Sibylle
Published: October 2018

Purpose

To report the effectiveness of treatment with antivascular endothelial growth factor (VEGF)-inhibitor and/or immunosuppressants in punctate inner choroidopathy (PIC) using standard imaging modalities and optical coherence tomography angiography (OCTA) over a time period of 16 months.

Methods

In this prospective, unmasked, single-centre study, 23 individuals with PIC underwent imaging with spectral domain OCT, fluorescein angiography, indocyanine green angiography and OCTA. Two groups were formed based on systemic treatment. In case of choroidal neovascularisation (CNV) activity, intravitreal anti-VEGF injections were carried out in both groups.

Results

Group I included 12 patients (24 eyes) with 18 affected eyes (75%) who did not receive any systemic therapy at baseline. Group II contained 11 patients (22 eyes) who started systemic immunosuppressive therapy on average 2 years before baseline. All eyes with recurrence of CNV or residual fluid (group I: seven eyes; group II: six eyes) received anti-VEGF agents. Group I showed a significant reduction of CNV size (p=0.0078), as well as a decrease of fluid retention (p=0.0078) on OCTA after anti-VEGF injection. Group II did not demonstrate any significant reduction of CNV size, vessel shape or fluid retention post injection. But overall, fluid accumulation was significantly lower in group II (median=0.03 mm2) than in group I (median=0.32 mm2) (p=0.0028).

Conclusion

Immunosuppressants in addition to anti-VEGF agents showed a significant reduction of fluid accumulation, that is, reduced disease activity. We conclude that there is a benefit and effectiveness of immunosuppressants to control inflammatory secondary CNV in PIC.
Glucose responses to acute and chronic exercise during pregnancy: a systematic review and meta-analysis
Authors: Davenport Margie H , Sobierajski Frances , Mottola Michelle F , Skow Rachel J , Meah Victoria L , Poitras Veronica J , Gray Casey E , Jaramillo Garcia Alejandra , Barrowman Nick , Riske Laurel , James Marina , Nagpal Taniya S , Marchand Andree-Anne , Slater Linda G , Adamo Kristi B , Davies Gregory A , Barakat Ruben , Ruchat Stephanie-May
Published: October 2018

Objective

To perform a systematic review and meta-analysis to explore the relationship between prenatal exercise and glycaemic control.

Design

Systematic review with random-effects meta-analysis and meta-regression.

Data sources

Online databases were searched up to 6 January 2017.

Study eligibility criteria

Studies of all designs were included (except case studies and reviews) if they were published in English, Spanish or French, and contained information on the population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of acute or chronic exercise, alone (‘exercise-only’) or in combination with other intervention components (eg, dietary; ‘exercise+cointervention’) at any stage of pregnancy), comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and outcome (glycaemic control).

Results

A total of 58 studies (n=8699) were included. There was ‘very low’ quality evidence showing that an acute bout of exercise was associated with a decrease in maternal blood glucose from before to during exercise (6 studies, n=123; mean difference (MD) −0.94 mmol/L, 95% CI −1.18 to −0.70, I2=41%) and following exercise (n=333; MD −0.57 mmol/L, 95% CI −0.72 to −0.41, I2=72%). Subgroup analysis showed that there were larger decreases in blood glucose following acute exercise in women with diabetes (n=26; MD −1.42, 95% CI −1.69 to −1.16, I2=8%) compared with those without diabetes (n=285; MD −0.46, 95% CI −0.60 to −0.32, I2=62%). Finally, chronic exercise-only interventions reduced fasting blood glucose compared with no exercise postintervention in women with diabetes (2 studies, n=70; MD −2.76, 95% CI −3.18 to −2.34, I2=52%; ‘low’ quality of evidence), but not in those without diabetes (9 studies, n=2174; MD −0.05, 95% CI −0.16 to 0.05, I2=79%).

Conclusion

Acute and chronic prenatal exercise reduced maternal circulating blood glucose concentrations, with a larger effect in women with diabetes.
US-based cross-sectional survey of clinicians’ knowledge and attitudes about shared decision-making across healthcare professions and specialties
Authors: Forcino Rachel C , Yen Renata West , Aboumrad Maya , Barr Paul J , Schubbe Danielle , Elwyn Glyn , Durand Marie-Anne
Published: October 2018

Objective

In this study, we aim to compare shared decision-making (SDM) knowledge and attitudes between US-based physician assistants (PAs), nurse practitioners (NPs) and physicians across surgical and family medicine specialties.

Setting

We administered a cross-sectional, web-based survey between 20 September 2017 and 1 November 2017.

Participants

272 US-based NPs, PA and physicians completed the survey. 250 physicians were sent a generic email invitation to participate, of whom 100 completed the survey. 3300 NPs and PAs were invited, among whom 172 completed the survey. Individuals who met the following exclusion criteria were excluded from participation: (1) lack of English proficiency; (2) area of practice other than family medicine or surgery; (3) licensure other than physician, PA or NP; (4) practicing in a country other than the US.

Results

We found few substantial differences in SDM knowledge and attitudes across clinician types, revealing positive attitudes across the sample paired with low to moderate knowledge. Family medicine professionals (PAs) were most knowledgeable on several items. Very few respondents (3%; 95% CI 1.5% to 6.2%) favoured a paternalistic approach to decision-making.

Conclusions

Recent policy-level promotion of SDM may have influenced positive clinician attitudes towards SDM. Positive attitudes despite limited knowledge warrant SDM training across occupations and specialties, while encouraging all clinicians to promote SDM. Given positive attitudes and similar knowledge across clinician types, we recommend that SDM is not confined to the patient-physician dyad but instead advocated among other health professionals.
Active surveillance of 2017 seasonal influenza vaccine safety: an observational cohort study of individuals aged 6 months and older in Australia
Authors: Pillsbury Alexis J , Glover Catherine , Jacoby Peter , Quinn Helen E , Fathima Parveen , Cashman Patrick , Leeb Alan , Blyth Christopher C , Gold Michael S , Snelling Thomas , Macartney Kristine K
Published: October 2018

Objective

To actively solicit adverse events experienced in the days following immunisation with quadrivalent inactivated influenza vaccine using Australia’s near real-time, participant-based vaccine safety surveillance system, AusVaxSafety.

Design and setting

Observational cohort study conducted in 194 sentinel surveillance immunisation sites (primary care, hospital and community-based clinics) across Australia.

Participants

Individuals aged ≥6 months who received a routine seasonal influenza vaccine at a participating site (n=102 911) and responded to a survey (via short message service or email) sent 3 days after vaccination about adverse events experienced (n=73 892; 71.8%).

Main outcome measure

Near real-time and cumulative participant-reported rates of any adverse event, fever or medical attendance experienced within 3 days after vaccination overall, by brand, age, pregnancy status and concomitant vaccine receipt.

Results

Participant median age was 57 years (range: 6 months to 102 years); 58.1% (n=42 869) were female and 2.7% (n=2018) were pregnant. Near real-time fast initial response cumulative summation and Bayesian analyses of weekly event rates did not demonstrate a safety signal. Children aged 6 months to 4 years had higher event rates (522/6180; 8.4%) compared with older ages; participants aged ≥65 years reported fewer events (1695/28 154; 6.0%). There were no clinically significant differences in safety between brands, by age group or overall. Cumulative data analysis demonstrated that concomitant vaccination was associated with increased rates of fever (2.1% vs 0.8%) and medical attendance (0.8% vs 0.4%), although all rates were low and did not exceed expected levels.

Conclusions

Novel, postmarketing AusVaxSafety surveillance demonstrated comparable and expected safety outcomes for the 2017 quadrivalent inactivated influenza vaccine brands used in Australia. These near real-time, participant-reported data are expected to encourage confidence in vaccine safety and promote uptake.
THUR 001 An unusual (ne)urological presentation
Authors: Alexander Stevenson , Katie Yoganathan , David Gleeson , Ravneeta Singh
Published: October 2018

We present the case of a 78-year-old female with a background of diabetes, who presented with acute-onset hemichorea whilst on the surgical ward under the care of the Urology team. She had an extensive past medical history including type two diabetes; additionally, she reported she had experienced similar transient symptoms during an admission ten months previously. CT and MRI brain demonstrated no acute ischaemic changes. A thorough drug history revealed no causative agent, and her blood tests were unremarkable. Her capillary blood glucose charts showed a severe hypoglycaemic episode two days prior to the onset of symptoms with similar hypoglycaemic episodes noted during her last admission. A diagnosis of hypoglycaemia-induced hemichorea was made and the patient was started on tetrabenazine. Our case of an elderly diabetic patient with new-onset hemichorea secondary to hypoglycaemia highlights the importance of identifying and optimising glycaemic control in this vulnerable cohort.
281 Predicting neurodegeneration after traumatic brain injury
Authors: SN Graham Neil , E Jolly Amy , J Bourke Niall , Gregory Scott , H Cole James , J Sharp David
Published: October 2018

Background

Dementia rates are elevated after traumatic brain injury (TBI) and a subgroup develops chronic traumatic encephalopathy. Post-traumatic neurodegeneration can be measured by brain atrophy rates derived from neuroimaging, but it is unclear how atrophy relates to the initial pattern of injury.

Objectives

To investigate the relationship between baseline TBI patterns and subsequent neurodegeneration measured by progressive brain atrophy.

Methods

55 patients after moderate-severe TBI (mean 3 years post-injury) and 20 controls underwent longitudinal MRI. Brain atrophy was quantified using the Jacobian determinant defined from volumetric T1 scans approximately one year apart. Diffuse axonal injury was measured using diffusion tensor imaging and focal injuries defined from T1 and FLAIR. Neuropsychological assessment was performed.

Results

Abnormal progressive brain atrophy was seen after TBI (~1.8%/year in white matter). This was accompanied by widespread reductions in fractional anisotropy, in keeping with the presence of diffuse axonal injury. There was a strong negative correlation between FA and brain atrophy, whereby areas of greater white matter damage showed greater atrophy over time.

Conclusions

The results show a strong relationship between the location of diffuse axonal injury and subsequent neurodegeneration. This suggests that TBI triggers progressive neurodegeneration through the long-lasting effects of diffuse axonal injury.
283 Quantifying muscle amyloid in inclusion body myositis using pet
Authors: B Lilleker James , Richard Hodgson , E Roberts Mark , Karl Herholz , James Howard , Rainer Hinz , Hector Chinoy
Published: October 2018

Objectives

Inclusion body myositis (IBM) shares some histopathological features with polymyositis (PM). Current investigations have low sensitivity for identification of amyloid deposits that are characteristic of IBM, contributing to frequent misdiagnosis. We compared muscle amyloid content, quantified using a novel positron emission tomography (PET) technique, in IBM and PM.

Methods

Ten cases with IBM and six controls with PM underwent clinical review, [18F]florbetapir PET/computed tomography, and magnetic resonance imaging (MRI) of whole-body skeletal musculature. [18F]florbetapir standardised uptake value ratios (SUVRs, reference=lumbar fat pad) in skeletal muscle were compared between cases and controls. The relationship in IBM of [18F]florbetapir SUVRs to clinical and MRI-derived measures of disease severity were also investigated.

Results

[18F]florbetapir SUVRs were significantly higher in those with IBM for all muscle regions assessed (total SUVR 1.45 [IQR 1.28–2.05] versus 1.01 [IQR 0.80–1.22], p=0.005). Strong negative correlation between MRI-derived muscle inflammation levels and [18F]florbetapir SUVRs were observed only in calf muscles bilaterally (right −0.73, p=0.02; left −0.68, p=0.03). No significant relationship between [18F]florbetapir SUVRs and clinical measures of disease severity were identified.

Conclusion

Muscle amyloid imaging using [18F]florbetapir PET may be useful in the diagnostic workup of IBM, particularly when differentiating from PM.
286 Hyperacute stroke unit and hyperacute neurology unit under one roof
Authors: Das Joyutpal , McKenzie Stefan , Gozzard Paul , Pattrick Michael , O’Malley Ronan , Payne Thomas , Grunewald Richard , Harkness Kirsty
Published: October 2018

The Acute neurology unit (ANU), located at the Royal Hallamshire Hospital, Sheffield is a regional centre for a population of approximately 1.5 million. We are unusual, as our neurologists manage both hyperacute stroke and hyperacute neurology. HASU is located within our ANU. We had 4026 neurology ward admissions, 3265 emergency cases and 761 elective cases last year. We receive acute admissions from Trust A and E, direct admissions from general practitioners and urgent transfers from DGHs.

We provide 24 hour stroke thrombolysis and a weekday working hours thrombectomy service. Overnight thrombolysis is supervised through a regional ‘Telemedicine’ system. A 2 week survey in July 2017 showed that only 59% patients, who were referred with suspected stroke, had stroke/TIA. Neurological conditions, such as migraine, seizure, syncope, acute vestibulopathy, Bell’s palsy and medically unexplained symptoms were common ‘stroke mimics’. 46% of patients with ‘stroke mimic’ were discharged on the day of admission. Average length of stay was 3 days. A separate survey of acute neurology referrals showed that 58% of patients did not require admission and were managed through an ambulatory care pathway. Patient satisfaction regarding their rapid assessment and diagnosis was high.

Co-location of ANU and HASU allows rapid and effective management of ‘stroke mimics’.
287 A new UK reproductive care pathway for women with serious MTDNA disease
Authors: Grainne Gorman , Robert McFarland , Jane Stewart , Catherine Feeney , Mary Herbert , Louise Heslop , Emma Blakeley , Robert Taylor , Julie Murphy , Doug Turnbull
Published: October 2018

In March 2015, the UK government passed into law, an amendment to the Human Fertilisation and Embryology Act 1990 to permit ‘Mitochondrial Donation’. This provided a unique legal framework for techniques that make it possible to ‘replace’ mutated mitochondrial DNA (mtDNA) in human oocytes or zygotes. As a group, primary mtDNA diseases are the most prevalent of the inherited neurometabolic disorders, affecting up to 1 in 5000 live births and can often have devastating clinical consequences. To date, treatments focus on palliation of symptoms, while the emergence of reproductive techniques, such as Mitochondrial Donation, offers the first real opportunity to prevent the maternal transmission of some serious forms of mtDNA disease. The Human Fertilization and Embryo Authority (HFEA), the statutory regulatory authority charged with regulating human embryo research in the UK, has devised, a detailed regulatory process for Mitochondrial Donation. To ensure compliance with the HFEA regulations we describe how we have established a high quality, integrated care pathway that provides care that is available to anyone in the UK, and comprehensively involves pathways for couples seeking reproductive advice, IVF pathway for potential mothers with pathogenic mtDNA mutations, a pathway for donors and long-term follow up of children born.
292 Mapping patient pathways for acute functional neurological symptoms
Authors: Clea Southall , Samantha Haley , Stefan Williams , D Graham Christopher , Jane Alty , Owen Johnson , Melissa Maguire
Published: October 2018

Introduction

Patients with Functional Neurological Symptoms (FNS) can present acutely, but many hospitals lack specific pathways or services for them. Outpatient FNS cohorts have been studied, but there is little data regarding acute FNS to inform service improvement.

Method

Over an 8 month period at Leeds Teaching Hospitals NHS Trust (UK), the on-call neurology and stroke teams were telephoned regularly. Acute referrals with possible FNS were recorded. Electronic documentation was searched for the following events: symptoms, first presentation, diagnosis, A and E, outpatient clinic, inpatient admission, investigation, and psychological/psychiatric referral. This data was analysed with process mapping software (Fluxicon disco).

Results

We present a dynamic care pathway map using real data, showing 205 patients with possible FNS moving through hospital services over time. Our map visualises the temporal relationships between healthcare utilisation, first presentation, diagnosis and therapy. The picture shows high healthcare burden, with incomplete and slow movement towards appropriate therapy (e.g. clear diagnosis documented in only 66%; referral to psychological therapy in 26%).

Conclusion

Patients with FNS are regularly referred to acute neurological services in Leeds. Our dynamic map shows a high healthcare burden, and slow or incomplete movement to appropriate care, which suggests potential targets for service improvement.
296 Longitudinal measurement of serum NFL in early familial AD
Authors: Philip Weston , Teresa Poole , Natalie Ryan , Yuying Liang , Simon Mead , Kaj Blennow , Martin Rossor , Jonathan Schott , Henrik Zetterberg , Nick Fox
Published: October 2018

A blood-based biomarker able to track early neurodegeneration in Alzheimer’s disease would be valuable. Serum neurofilament-light (NfL) is elevated in familial Alzheimer’s disease (FAD) mutation carriers prior to symptom onset, but exactly how early NfL becomes abnormal and whether it can track change within individuals is uncertain.

We recruited 18 symptomatic carriers of autosomal dominant FAD mutations, 19 presymptomatic carriers, and 11 non-carriers. Blood was taken at baseline, and 26 participants also gave at least one follow-up sample (mean interval=2.5 years). Serum NfL was measured on the SIMOA platform. A longitudinal mixed effects framework was used to model change in NfL over time.

Serum NfL was increased (p<0.05) in mutation carriers compared with non-carriers 11 years before the estimated time of symptom onset, with rate of change in NfL becoming significantly different 12 years before. However, there was high variability in the inter-individual rate of change in NfL between participants.

Serum NfL concentration, and its rate of change, are sensitive, at the group level at least, to very early AD-neurodegenration. However, the high variability between individuals in NfL rate of change may make it difficult at present to use this measure to track early change in individual patients.
THUR 051 Ictal asystole: return to the history
Authors: Gashirai Mbizvo , Chris Derry , Richard Davenport
Published: October 2018

In these two adult cases of transient loss of consciousness (TLoC), careful history-taking revealed a stereotyped prodrome of déjà vu suggestive of focal seizures. One patient had an implantable cardiac monitor fitted, the other a 48 hour Holter monitor. Each patient subsequently had a typical event of déjà vu followed by TLoC with rapid recovery and for both, the monitor showed cardiac asystole corresponding with this event. A permanent pacemaker (PPM) was inserted in both patients. This abolished TLoC. In its absence, déjà vu became more frequent, intense, and prolonged for one patient, resolving with levetiracetam. The other patient had a post-PPM episode of déjà vu followed by a generalised tonic-clonic seizure. It transpired that their lamotrigine had been withdrawn following PPM insertion. Seizure-freedom was achieved by restarting lamotrigine.

Ictal asystole, a rare complication of focal epilepsy, has a mean ventricular standstill duration of 20 s. This can be benign or progress to post-ictal asystole −fatal in 54% of cases. Careful attention should be paid to prodromal symptoms suggestive of focal seizures (including ‘auras’) in patients presenting with what might otherwise sound like syncope. These patients may have epilepsy presenting with ictal asystole and require antiepileptic drugs alongside their cardiac investigations/interventions.