Clinical and microbiological profile of adult inpatients with community acquired pneumonia in Ilorin,North Central,Nigeria

BackgroundThe optimal management of community acquired pneumonia (CAP) depends on the clinical and microbiological profile in the locality.ObjectivesTo determine the clinical and microbiological profile of patients admitted with CAP in Ilorin, Nigeria.MethodsOne hundred and two consenting consecutively selected patients with clinical and radiologic confirmation of CAP were recruited in 12 months. The socio-demographic, physical examination and laboratory/radiologic parameters were documented in a questionnaire. Microbiological evaluation of their sputum was done and blood samples were taken for complete blood count, culture, serum urea and serological evaluation for atypical bacteria and some viral pathogens.ResultsCAP constituted 5.9% of the total medical admissions during the one-year study period. The mean age of the patients was 49 ± 22 years with the largest frequency in those aged 65 years and above. The commonest symptoms were shortness of breath (96.1%) and cough (94.1%), with a median duration of 3 days from symptom onset to admission. Systemic hypertension was the commonest comorbid illness (25/102; 24.5%). Klebsiella pneumoniae was the predominant pathogen isolated (20/102; 28.1%). The susceptible antibiotics were Imipenem, Ceftazidime and Ceftriaxone. Intra-hospital mortality was 17.6%. CURB – 65 score of ≥ 2 and the presence of complications of CAP were the independent predictors of mortality.ConclusionCAP constitutes a significant disease burden in Ilorin, Nigeria. Typical bacteria accounted for over half of the pathogens isolated from the patients with gram negative agents predominating. This highlights a possible shift in the microbiological profile which could guide empirical treatment.     

A Systematic Review of the Evidence for the Decipher Genomic Classifier in Prostate Cancer

ContextMolecular biomarkers aim to address the established limitations of clinicopathologic factors to accurately risk stratify patients with prostate cancer (PCa). Questions remain as to whether sufficient evidence supports adoption of these biomarkers for clinical use.ObjectiveTo perform a systematic review of the available evidence supporting the clinical utility of the Decipher genomic classifier (GC).Evidence acquisitionThe review was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines by searching PubMed and conference abstracts from January 2010 to June 2020. Evidence was then graded using the criteria of Simon et al (Simon RM, Paik S, Hayes DF. Use of archived specimens in evaluation of prognostic and predictive biomarkers. J Natl Cancer Inst 2009;101:1446–52) and American Urology Association (AUA) criteria.Evidence synthesisIn total, 42 studies and 30 407 patients were included. GC performance data were available for localized, postprostatectomy, nonmetastatic castration-resistant, and metastatic hormone-sensitive PCa as part of retrospective studies (n = 12 141), prospective registries (n = 17 053), and prospective and post hoc randomized trial analyses (n = 1213). In 32 studies (n = 12 600), the GC was independently prognostic for all study endpoints (adverse pathology, biochemical failure, metastasis, and cancer-specific and overall survival) on multivariable analysis and improved the discrimination over standard of care in 24 studies (n = 8543). GC use changed the management in active surveillance (number needed to test [NNT] = 9) and postprostatectomy (NNT = 1.5–4) settings in five studies (n = 4331). Evidence strength was levels 1 and 2 by the Simon criteria for all disease states other than high-risk PCa, and grades A and B by AUA criteria depending on disease state.ConclusionsConsistent data are now present from diverse levels of evidence, which when viewed together, have demonstrated clinical utility of the GC in PCa. The utility of the GC is strongest for intermediate-risk PCa and postprostatectomy decision-making.Patient summaryIn this paper, we review the evidence of the Decipher genomic classification tool for men with prostate cancer. We found consistent evidence that the test helps identify which cancers are more or less aggressive, which in turn aids in personalized treatment decision-making.     

Quality assurance management methods applied to a local-level primary health care system in rural Nigeria

Introduction. Management of primary health care (PHC) systems in less developed countries is often impeded by factors such as poorly trained personnel, limited financial resources, and poor worker morale. This study explored the ability of local-level PHC supervisors in rural Nigeria to use quality assurance (QA) management methods to improve the quality of the PHC system. Methods. PHC supervisors from Bama Local Government Area were trained for 3 days in the use of QA methods and tools. The supervisors targeted the supervisory system and the health information system (HIS) for improvement. Health worker performance in diarrhoea case management was assessed, using a simulated case, to measure the impact of supervision. A HIS audit assessed data collection forms used by 17 PHC facilities. Gaps in quality were monitored over a 2-month study period and flaws in work processes were modified. Results. PHC supervisors introduced a checklist during monthly visits to facilities to monitor how workers managed cases of diarrhoea. Performance in history-taking, physical examination, disease classification, treatment and counselling improved over the evaluation period. The HIS audit found that a variety of reporting forms were used at PHC facilities. After HIS reporting was standardized, the number of health facilities using a daily disease registry significantly improved during the study period. Conclusions. QA management methods were used by PHC supervisors in Nigeria to improve supervision and the HIS. QA management methods are appropriate for improving the quality of the PHC in Nigeria and in other less developed countries where at least a minimal PHC infrastructure exists.     

Primed-burst potentiation in adult rat visual cortex in vitro

The effectiveness of θ pattern primed-bursts (PBs) on development of PB potentiation was investigated in layer II/III of the adult rat visual cortex in vitro. Experiments were carried out in the visual cortical slices. Population excitatory postsynaptic potentials (pEPSPs) were evoked in layer II/III by stimulation of either white matter or layer IV. To induce long-term potentiation (LTP), eight episodes of PBs were delivered at 0.1 Hz. Regardless of stimulation site, field potential recorded in layer II/III consisted of two components: a short latency and high amplitude response called pEPSP1, and a long latency and low amplitude response called pEPSP2. The incidence of LTP produced by PBs of layer IV was higher than that of the white matter tetanization. In contrast, PBs of both layer IV and white matter reliably produced LTP of pEPSP2 in layer II/III. It is concluded that PBs, as a type of activity pattern, of either white matter or layer IV can gain access to the modifiable synapses that are related to pEPSP2 in layer II/III, but accessibility of the modifiable synapses that are related to pEPSP1 depends on tetanization site. Relevancy of the results to the plasticity gate hypothesis is also discussed.     

Elevated hippocampal resting-state connectivity underlies deficient neurocognitive function in aging

The brain is not idle during rest. Functional MRI (fMRI) studies have identified several resting-state networks, including the default mode network (DMN), which contains a set of cortical regions that interact with a hippocampus (HC) subsystem. Age-related alterations in the functional architecture of the DMN and HC may influence memory functions and possibly constitute a sensitive biomarker of forthcoming memory deficits. However, the exact form of DMN–HC alterations in aging and concomitant memory deficits is largely unknown. Here, using both task and resting data from 339 participants (25–80 y old), we have demonstrated age-related decrements in resting-state functional connectivity across most parts of the DMN, except for the HC network for which age-related elevation of connectivity between left and right HC was found along with attenuated HC–cortical connectivity. Elevated HC connectivity at rest, which was partly accounted for by age-related decline in white matter integrity of the fornix, was associated with lower cross-sectional episodic memory performance and declining longitudinal memory performance over 20 y. Additionally, elevated HC connectivity at rest was associated with reduced HC neural recruitment and HC–cortical connectivity during active memory encoding, which suggests that strong HC connectivity restricts the degree to which the HC interacts with other brain regions during active memory processing revealed by task fMRI. Collectively, our findings suggest a model in which age-related disruption in cortico–hippocampal functional connectivity leads to a more functionally isolated HC at rest, which translates into aberrant hippocampal decoupling and deficits during mnemonic processing.The brain is not idle at rest (1). Rather, intrinsic neuronal signaling, which manifests as spontaneous fluctuations in the blood oxygen level-dependent (BOLD) functional MRI (fMRI) signal, is ubiquitous in the human brain and consumes a substantial portion of the brain’s energy (2). Coherent spontaneous activity has been revealed in a hierarchy of networks that span large-scale functional circuits in the brain (3–6). These resting-state networks (RSNs) show moderate-to-high test–retest reliability (7) and replicability (8), and some have been found in the monkey (9) and infant (10) brain. In the adult human brain, RSNs include sensory motor, visual, attention, and mnemonic networks, as well as the default mode network (DMN). There is evidence that the DMN entails interacting subsystems and hubs that are implicated in episodic memory (11–13). One major hub encompasses the posterior cingulate cortex and the retrosplenial cortex. Other hubs include the lateral parietal cortex and the medial prefrontal cortex. In addition, a hippocampus (HC) subsystem is distinct from, yet interrelated with, the major cortical DMN hubs (12, 14).The functional architecture of the DMN and other RSNs is affected by different conditions, such as Alzheimer’s disease (AD), Parkinson’s disease, and head injury, suggesting that measurements of the brain’s intrinsic activity may be a sensitive biomarker and a putative diagnostic tool (for a review, see ref. 15). Alterations of the DMN have also been shown in age-comparative studies (16, 17), but the patterns of alterations are not homogeneous across different DMN components (18). Reduced functional connectivity among major cortical DMN nodes has been reported in aging (16, 17) and also in AD (19) and for asymptomatic APOE e4 carriers at increased risk of developing AD (20). Reduced cortical DMN connectivity has been linked to age-impaired performance on episodic memory (EM) tasks (21, 22). For instance, Wang and colleagues (21) showed that functional connectivity between cortical and HC hubs promoted performance on an EM task and was substantially weaker among low-performing elderly. This and other findings suggest that reductions in the DMN may be a basis for age-related EM impairment. However, elevated connectivity has been observed for the HC in individuals at genetic risk for AD (23, 24) and for elderly with memory complaints (25). Furthermore, a trend toward elevated functional connectivity for the medial temporal lobe (MTL) subsystem was observed in healthy older adults (26). Critically, higher subcortical RSN connectivity was found to correlate negatively with EM performance in an aging sample (27). Moreover, a recent combined fMRI/EEG study observed age increases in HC EEG beta power during rest (28).Thus, the association of aging with components of the DMN is complex, and it has been argued that age-related increases in functional connectivity need further examination (18). Such increases could reflect a multitude of processes, including age-related degenerative effects on the brain’s gray and white matter (18). Additionally, increases in HC functional connectivity may reflect alterations in proteolytic processes, such as amyloid deposition (29). Amyloid deposition is most prominent in posterior cortical regions of the DMN (29). It has been argued that there is a topological relationship between high neural activity over a lifetime within the DMN and amyloid deposition (30). Increased amyloid β protein burden within the posterior cortical DMN may cause cortico–hippocampal functional connectivity disruption (31), leading to a more functionally isolated HC network, which translates into aberrant hippocampal decoupling (30, 32, 33). Correspondingly, a recent model hypothesized that progressively less inhibitory cortical input would cause HC hyperactivity in aging (34).Elevated HC resting-state connectivity might thus be a sign of brain dysfunction, but the evidence remains inconclusive. Here, using data from a population-based sample covering the adult age span (n = 339, 25–80 y old), we tested the hypothesis that aging differentially affects distinct DMN components. A data-driven approach, independent component analysis (ICA), was used to identify DMN subsystems (4). We expected to observe age-related decreases in the connectivity of the cortical DMN. We also examined age-related alterations of HC RSN connectivity, and tested whether such alterations were related to HC volume and white matter integrity. We predicted that if increased HC connectivity was found, it would be accompanied by age-related decreases in internetwork connectivity of the HC RSN with cortical DMN regions. To constrain interpretations of age-related alterations, the DMN components were related to cognitive performance. Elevated HC RSN should negatively correlate with level and longitudinal change in EM performance. Such negative correlations could reflect an inability to flexibly recruit the HC and functionally associated areas during EM task performance due to aberrant hippocampal decoupling (23, 24). We tested this prediction by relating the HC RSN, within-person, to HC recruitment during an EM fMRI task (35, 36).