Development of the first edition of African treatment guidelines for common bacterial infections and syndromes

Standard treatment guidelines (STGs) are an important tool for ensuring high quality clinical care and prudent antimicrobial use (AMU) and stewardship (AMS). In 2018, African Union (AU) member state representatives recognized the lack of STGs as a barrier to AMS at national and facility levels. Previous research reported that only 17 of 55 (31%) member states had STGs that provided disease- or pathogen-specific antimicrobial treatment recommendations, excluding those that covered only treatment of HIV, malaria, and tuberculosis). The Africa Centres for Disease Control and Prevention convened expert panels to develop first edition antibiotic treatment guidelines for priority infectious diseases and clinical syndromes for pediatric and adult patient populations in Africa. The purpose of the guidelines is to provide healthcare workers with treatment guidance by harmonising existing national STGs, filling gaps where existing STGs are not available, and serving as a model for future guidelines. Two expert panels of 28 total clinicians, pharmacists, and other relevant stakeholders from 14 AU member states representing each continental region convened to develop consensus treatment recommendations for select priority bacterial infections and clinical syndromes. In developing recommendations, the panels considered treatment recommendations from existing STGs, drug availability, clinical experience, and available antimicrobial resistance data. The guidelines underwent an external review process where clinical stakeholders who did not serve on either panel were invited to submit feedback prior to their publication. The guidelines provide empiric antibiotic therapy guidelines – including drug selection, route of administration, formulation, dosage, and therapy duration – and principles of stewardship for 28 bacterial infections or clinical syndromes. The first edition guidelines for the treatment of common infectious diseases and clinical syndromes in Africa aims to improve clinical treatment and antimicrobial stewardship and will serve as a template for future regional guidelines.

Signature laminar distributions of pathology in frontotemporal lobar degeneration

Frontotemporal lobar degeneration (FTLD) with either tau (FTLD-tau) or TDP-43 (FTLD-TDP) inclusions are distinct proteinopathies that frequently cause similar frontotemporal dementia (FTD) clinical syndromes. FTD syndromes often display macroscopic signatures of neurodegeneration at the level of regions and networks, but it is unclear if subregional laminar pathology display patterns unique to proteinopathy or clinical syndrome. We hypothesized that FTLD-tau and FTLD-TDP accumulate pathology in relatively distinct cortical layers independent of clinical syndrome, with greater involvement of lower layers in FTLD-tau. The current study examined 170 patients with either FTLD-tau (n = 73) or FTLD-TDP (n = 97) spanning dementia and motor phenotypes in the FTD spectrum. We digitally measured the percent area occupied by tau and TDP-43 pathology in upper layers (I–III), lower layers (IV–VI), and juxtacortical white matter (WM) from isocortical regions in both hemispheres where available. Linear mixed-effects models compared ratios of upper to lower layer pathology between FTLD groups and investigated relationships with regions, WM pathology, and global cognitive impairment while adjusting for demographics. We found lower ratios of layer pathology in FTLD-tau and higher ratios of layer pathology in FTLD-TDP, reflecting lower layer-predominant tau pathology and upper layer-predominant TDP-43 pathology, respectively (p < 0.001). FTLD-tau displayed lower ratios of layer pathology related to greater WM tau pathology (p = 0.002) and to earlier involved/severe pathology regions (p = 0.007). In contrast, FTLD-TDP displayed higher ratios of layer pathology not related to either WM pathology or regional severity. Greater cognitive impairment was associated with higher ratios of layer pathology in FTLD-tau (p = 0.018), but was not related to ratios of layer pathology in FTLD-TDP. Lower layer-predominant tau pathology and upper layer-predominant TDP-43 pathology are proteinopathy-specific, regardless of clinical syndromes or regional networks that define these syndromes. Thus, patterns of laminar change may provide a useful anatomical framework for investigating how degeneration of select cells and corresponding laminar circuits influence large-scale networks and clinical symptomology in FTLD.

Rare Brain Tumors with Infrequent Clinical Manifestations: Illustrative Cases

This chapter describes the epidemiology, clinical and neuroimaging features, histological characteristics, surgical approach, outcomes, and prognostic factors of different cases of very rare intracranial tumors, associated with complex clinical syndromes. Highlighting the important aspects in the diagnosis and management that were considered relevant through the experience of our center. Here we included an intracranial Rosai-Dorfman disease manifested as an apparent multiple meningiomatosis, a choroid plexus papilloma clinically manifested as a hemifacial spasm originated by a compression of the facial colliculus, and a neuroenteric cyst associated with Klippel-Feil syndrome. This type of tumor presents a challenge to the neurosurgeon, originating various questions about its management. In this chapter, we present the experience we had with these pathologies to establish the most appropriate management decisions.

MEG-Derived Symptom-Sensitive Biomarkers with Long-Term Test-Retest Reliability

Neuroelectric measures derived from human magnetoencephalographic (MEG) recordings hold promise as aides to diagnosis and treatment monitoring and targeting for chronic sequelae of traumatic brain injury (TBI). This study tests novel MEG-derived regional brain measures of tonic neuroelectric activation for long-term test-retest reliability and sensitivity to symptoms. Resting state MEG recordings were obtained from a normative cohort (CamCAN, baseline: n = 613; mean 16-month follow-up: n = 245) and a chronic symptomatic TBI cohort (TEAM-TBI, baseline: n = 62; mean 6-month follow-up: n = 40). The MEG-derived neuroelectric measures were corrected for the empty-room contribution using a random forest classifier. The mean 16-month correlation between baseline and 16-month follow-up CamCAN measures was 0.67; test-retest reliability was markedly improved in this study compared with previous work. The TEAM-TBI cohort was screened for depression, somatization, and anxiety with the Brief Symptom Inventory and for insomnia with the Insomnia Severity Index and was assessed via adjudication for six clinical syndromes: chronic pain, psychological health, and oculomotor, vestibular, cognitive, and sleep dysfunction. Linear classifiers constructed from the 136 regional measures from each TEAM-TBI cohort member distinguished those with and without each symptom, p < 0.0003 for each, i.e., the tonic regional neuroelectric measures of activation are sensitive to the presence/absence of these symptoms and clinical syndromes. The novel regional MEG-derived neuroelectric measures obtained and tested in this study demonstrate the necessary and sufficient properties to be clinically useful, i.e., good test-retest reliability, sensitivity to symptoms in each individual, and obtainable using automatic processing without human judgement or intervention.

Personality, Interpersonal Problems, and Anxiety Among Older Adults

Introduction: This study examined relationships between personality disorder (PD) features, Big Five personality traits, and interpersonal problems with anxiety. Method: Older adults ( N = 130) completed the Geriatric Anxiety Scale, Coolidge Axis Two Inventory, Big Five Inventory-2, and Circumplex Scales of Interpersonal Problems. Pearson correlation analyses were used to assess simple relationships between anxiety with PD features (CATI scales), Big Five personality domains (BFI-2 scales), and interpersonal problems (CSIP scales). Multiple linear regression analyses were performed to determine the extent to which the PD scales of the CATI, the personality scales of the BFI-2, and the scales of the CSIP explained variance in anxiety. Results: Anxiety was positively correlated with 13 of 14 PD scales, ranging from .23 (Narcissistic) to .61 (Depressive). Regarding Big Five personality traits, anxiety was negatively associated with Agreeableness (−.23), Conscientiousness (−.30), and Extraversion (−.31) but was positively associated with Negative Emotionality (.56). Regarding interpersonal problems, anxiety was positively related to all eight CSIP scales, ranging from Self-sacrificing (.30) to Distant/Cold (.62). Regression analyses indicated that PD features accounted for the most variance in anxiety symptoms (53%), followed by interpersonal problems (46%), and Big Five personality traits (33%). Discussion: Anxiety appears to be meaningfully associated with PD features, several aspects of Big Five personality traits, and interpersonal problems, suggesting that these variables may play important roles in the development and maintenance of anxiety, or vice versa. Our findings especially speak to the growing awareness of the deleterious impact of PD features on clinical syndromes in later life, as evidenced by strong comorbidities with anxiety.

Neuroendocrine Tumors of the Pancreas

Pancreatic neuroendocrine tumors (PNETs) comprise a diverse, heterogeneous group of tumours that range in presentation and biologic behavior, including small, asymptomatic, incidentally discovered, nonfunctional neoplasms, functional tumors (both localizable and unlocalizable) with associated clinical syndromes, and diffuse metastatic disease. Based on its functional status, the malignancy of a PNET can vary, from the benign (insulinoma) to that which is commonly malignant more than 50% of the time (gastrinoma, somatostatinoma). According to a recent study, PNETs appear to be increasing in incidence or at least in clinical detection; currently the disorder accounts for 1 to 2% of pancreatic tumors and with a reported clinical incidence of one to five cases per million persons annually in the United States. Nonfunctional PNETs make up the majority of cases, and comprise 2% of all pancreatic malignancies. Treatment has been primarily done through surgical management, particularly via resection. However, medical management has played a more increased role for patients where the disease is advanced, encompassing biotherapy, chemotherapy, and targeted therapies such as peptide receptor radionuclide therapy (PRRT). For nonfunctional PNETs—insulinomas, gastrinomas, glucagonomas, somatostatinomas, and VIPomas—the epidemiology, biology of disease, clinical presentation and diagnosis, localization of tumor, operative management considerations, surgical management of primary tumor, and prognosis and outcomes of each are discussed. This review contains 6 figures, 18 tables, and 58 references Keywords: Pancreas, neuroendocrine tumor, gastrinoma, somatostatinoma, VIPoma, insulinoma, incidentaloma, glucagonoma, enucleation

Homeopathic use of modern drugs: therapeutic application of the organism paradoxical reaction or rebound effect

When Samuel Hahnemann systematized homeopathy and the effects of drugs on the state of human health, he described the primary action of drugs and the following secondary and opposite reaction of the organism. Seeking to apply this secondary action or vital reaction of the organism as therapeutic method, he postulated the principle of similitude, i.e. the prescription to ill individuals of drugs that cause similar symptoms in the healthy (similia similibus curentur). In modern pharmacology, secondary action (vital reaction) of drugs is known as rebound effect or paradoxical reaction of the organism. It has been observed after discontinuation of several classes of palliative (enantiopathic) drugs, namely those that act according to the principle of contraries (contraria contrariis curentur). Although in this case it is associated with severe and fatal iatrogenic events, rebound effect might awaken a healing reaction when the very same drug is employed according to the principle of similitude. The validity of the principle of similitude is proved by scientific evidence on rebound effect, whereas conventional drugs primary (therapeutic, adverse and side) effects might be equated to pathogenetic manifestations and thus be homeopathically applied. For this purpose a homeopathic materia medica and repertory comprising 1,251 modern drugs was elaborated using the monographs described in The United States Pharmacopeia Dispensing Information as source (www.newhomeopathicmedicines.com). Thus, the therapeutic range of homeopathy is broadened through the addition of hundreds of new medicines that might be employed in every kind of disease including countless modern clinical syndromes.

Post-release of the symposium «How to Deal with Pain in the 21st Century? Expert Opinions» (November 8, 2021, XII Interdisciplinary International Congress «Manage Pain»)

The article presents the chronology of the symposium «How to Deal with Pain in the 21st Century? Experts' opinions», which took place on November 8 during the XII interdisciplinary international congress «Manage Pain». The lectures discussed issues of non-steroidal anti-inflammatory drugs (NSAIDs), including etoricoxib (Atorika tabs), administration on the example of a clinical case, problems of terminology associated with the concepts of «lumbago» and «sciatica», rare clinical syndromes (for example, heavy-purse syndrome) that we need to differentiate nonspecific back pain with, strategies for choosing NSAIDs in patients with osteoarthritis, the importance of timely administration of NSAIDs in the prevention of chronic pain syndromes, the influence of emotional and cognitive factors on the back pain chronization. The benefits of etoricoxib (Atorika) in the treatment of chronic back pain were reviewed, as well as the evidence for its safety.

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Toward an Individualized Approach

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), characterized by the presence of autoantibodies to neutrophil cytoplasmic antigens, proteinase 3 (PR3), and myeloperoxidase (MPO), typically involves small blood vessels of the respiratory tract and kidneys. It includes distinct clinical syndromes: microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic GPA. GPA is commonly associated with PR3-ANCA, while MPA is associated with MPO-ANCA. AAVs have a complex pathogenesis, influenced by genetics and environmental factors. There is evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation and injury, with effector T cells and activation of the alternative pathway of the complement also involved. Advances in immunosuppressive treatment have drastically reduced mortality of AAV in the past decades, opting for a more individualized approach. Careful assessment of ANCA specificity, disease activity, organ damage, and quality of life allows for a tailored immunosuppressive therapy. Contemporary AAV treatment is characterized by regimens that minimize the cumulative exposure to glucocorticoids and cyclophosphamide, and novel approaches including complement blockage and immunosuppressant combinations might be the standard of care in the future. In this review, we examine the pathogenesis, clinical approach, and evidence-based treatment options for the management of AAV patients.

A Survey to Reduce STDs Infection in Mongolia and Big Data Virtualization Propagation

Sexually transmitted diseases refer to clinical syndromes and infections that are acquired and transmitted through sexual activity. Worldwide, more than 340 million cases of sexually transmitted disease occur each year, placing a great burden on individuals as well as communities and countries. The proportion of sexually transmitted diseases (STDs) in Mongolia is relatively high due to their inadequate treatment technologies, religious or local customs, and regional differences. It is rather difficult to grasp the exact number of patients as these diseases are considered ones that should not be disclosed to others. Therefore, this study aims to accurately identify sexually transmitted diseases in Mongolia and reduce infection through an analytic approach of big data virtualization propagation.