Performance of Sepsis Scoring Systems in a developing country ­ a prospective cohort study

Background: Sepsis and its sequelae poses a significant socio-economic burden on health care systems globally. Risk stratification plays a fundamental role in emergency department management, since early and aggressive management in high-risk cohorts leads to improved outcomes. Several risk stratification tools exist but in the local setting (developing country with high chronic disease burden) there is no standardised recommendation for beside utilisation. Objectives: We aimed to compare the ability of the quick Sepsis-related Organ Failure Assessment (qSOFA) score with the Systemic Inflammatory Response Syndrome (SIRS) criteria and National Early Warning Score (NEWS) to detect and risk stratify patients with presumed sepsis outside of the intensive care unit (ICU). Methods: A prospective observational cohort study was conducted at a public tertiary hospital during the period May to June 2017. Ethical and institutional approval was secured and informed consent was sought from study participants aged eighteen (18) years and older. Demographic and clinical data were collected via a data collection instrument and statistical analysis was undertaken using IBM SPSS v23. Results: 304 patients were treated for presumed sepsis. The primary outcomes of in-hospital death or intensive care unit admission were seen in 14.8%. Discrimination for the primary outcome was highest for NEWS (AUROC 0.88 [95% CI 0.83-0.94]) followed by qSOFA (AUROC 0.82 [95% CI 0.74-0.89]) and SIRS (AUROC 0.69 [95% CI 0.61-0.77]). A NEWS value of ≥4 resulted in a sensitivity of 93.3%, and negative predictive value of 98.3% (p<0.001). A qSOFA score ≥2 demonstrated a specificity of 94.6 % and a negative predictive value of 91.4% (p<0.001). A SIRS criteria score ≥2 resulted in a sensitivity of 88.9%, and a negative predictive value of 95.0% (p=0.001). Univariate analysis showed that: need for supplemental oxygen, an oxygen saturation less than 91%, a Glasgow Coma Scale <15 and non-selfpresentation were associated with the highest odds ratios for death in-hospital or ICU admission. Conclusions: Urgent identification of high-risk patients with presumed infection is critical in achieving a positive outcome. NEWS was superior to both qSOFA AND SIRS in predicting in-hospital mortality and need for ICU admission A qSOFA score ≥2 demonstrated a high specificity but poor sensitivity, thus limiting its use as a bedside tool. The findings of this study are consistent with the Sepsis-3 guidelines, which recommend qSOFA as being superior to SIRS criteria. However, we found that NEWS had a superior predictive value to both. Its role in the identification of high-risk subjects should be further evaluated.

Can target-to-pons ratio be used as a reliable method for the analysis of [11C]PIB brain scans?

RATIONALE: (11)C]PIB is the most widely used PET imaging marker for amyloid in dementia studies. In the majority of studies the cerebellum has been used as a reference region. However, cerebellar amyloid may be present in genetic Alzheimer's (AD), cerebral amyloid angiopathy and prion diseases. Therefore, we investigated whether the pons could be used as an alternative reference region for the analysis of [(11)C]PIB binding in AD. The aims of the study were to: 1) Evaluate the pons as a reference region using arterial plasma input function and Logan graphical analysis of binding. 2) Assess the power of target-to-pons ratios to discriminate controls from AD subjects. 3) Determine the test-retest reliability in AD subjects. 4) Demonstrate the application of target-to-pons ratio in subjects with elevated cerebellar [(11)C]PIB binding. METHODS: 12 sporadic AD subjects aged 65 ± 4.5 yrs with a mean MMSE 21.4 ± 4 and 10 age-matched control subjects had [(11)C]PIB PET with arterial blood sampling. Three additional subjects (two subjects with pre-symptomatic presenilin-1 mutation carriers and one probable familial AD) were also studied. Object maps were created by segmenting individual MRIs and spatially transforming the gray matter images into standard stereotaxic MNI space and then superimposing a probabilistic atlas. Cortical [(11)C]PIB binding was assessed with an ROI (region of interest) analysis. Parametric maps of the volume of distribution (V(T)) were generated with Logan analysis. Additionally, parametric maps of the 60-90 min target-to-cerebellar ratio (RATIO(CER)) and the 60-90 min target-to-pons ratio (RATIO(PONS)) were computed. RESULTS: All three approaches were able to differentiate AD from controls (p<0.0001, nonparametric Wilcoxon rank sum test) in the target regions with RATIO(CER) and RATIO(PONS) differences higher than V(T) with use of an arterial input function. All methods had a good reproducibility (intraclass correlation coefficient>0.83); RATIO(CER) performed best closely followed by RATIO(PONS). The two subjects with presenilin-1 mutations and the probable familial AD case showed no significant differences in cortical binding using RATIO(CER), but the RATIO(PONS) approach revealed higher [(11)C]PIB binding in cortex and cerebellum. CONCLUSION: This study established 60-90 min target-to-pons RATIOs as a reliable method of analysis in [(11)C]PIB PET studies where cerebellum is not an appropriate reference region.

[¹8F]FDOPA uptake in the raphe nuclei complex reflects serotonin transporter availability. A combined [¹8F]FDOPA and [¹¹C]DASB PET study in Parkinson's disease.

Brain uptake of [(18)F]FDOPA, measured with PET, reflects the activity of aromatic amino acid decarboxylase, an enzyme largely expressed in monoaminergic nerve terminals. This enzyme catalyzes a number of decarboxylation reactions including conversion of l-dopa into dopamine and 5-hydroxytryptophan into serotonin. For more than 20years [(18)F]FDOPA PET has been used to assess dopaminergic nigrostriatal dysfunction in patients with Parkinson's disease (PD). More recently, however, [(18)F]FDOPA PET has also been employed as a marker of serotoninergic and noradrenergic function in PD patients. In this study, we provide further evidence in support of the view that [(18)F]FDOPA PET can be used to evaluate the distribution and the function of serotoninergic systems in the brain. Eighteen patients with PD were investigated with both [(18)F]FDOPA and [(11)C]DASB PET, the latter being a marker of serotonin transport (SERT) availability. We then assessed the relationship between measurements of the two tracers within brain serotoninergic structures. [(18)F]FDOPA uptake in the median raphe nuclei complex of PD patients was significantly correlated with SERT availability in the same structure. Trends towards significant correlations between [(18)F]FDOPA Ki values and [(11)C]DASB binding values were also observed in the hypothalamus and the anterior cingulate cortex, suggesting a serotoninergic contribution to [(18)F]FDOPA uptake in these regions. Conversely, no correlations were found in brain structures with mixed dopaminergic, serotoninergic and noradrenergic innervations, or with predominant dopaminergic innervation. These findings provide evidence that [(18)F]FDOPA PET represents a valid marker of raphe serotoninergic function in PD and supports previous studies where [(18)F]FDOPA PET has been used to assess serotoninergic function in PD.

Adenosine 2A receptor availability in dyskinetic and nondyskinetic patients with Parkinson disease.

OBJECTIVE: To investigate striatal adenosine A2A receptor availability in patients with Parkinson disease (PD) with and without levodopa-induced dyskinesias (LIDs). While providing effective relief from the motor symptoms of PD, chronic levodopa use is associated with development of LIDs. A2A receptors are expressed on the bodies of indirect pathway medium spiny striatal neurons and on dopamine terminals and play a role in modulating dopamine transmission. A2A antagonists have antiparkinsonian activity by boosting levodopa efficacy. We aimed to study A2A receptor availability in patients with PD with and without LIDs using PET and [¹¹C]SCH442416, an A2A antagonist. METHODS: Six patients with PD with and 6 without LIDs were studied withdrawn 12 hours from medication. Their PET findings were compared with 6 age-matched healthy controls. Using spectral analysis, [¹¹C]SCH442416 regional volumes of distribution (V(T)) were computed for the caudate, putamen, and thalamus and binding potentials (BP(ND)) reflecting the ratio of specific:nonspecific uptake were compared between groups. RESULTS: A2A binding in the caudate and putamen of subjects with PD with LIDs was far higher (p = 0.026 and p = 0.036, respectively) than that of subjects with PD without LIDs, which lay within the control range. Thalamic A2A availability was similar for all 3 groups. CONCLUSION: Patients with PD with LIDs show increased A2A receptor availability in the striatum. This finding is compatible with altered adenosine transmission playing a role in LIDs and provides a rationale for a trial of A2A receptor agents in the treatment of these motor complications.

Neuroleptic malignant syndrome and acute motor axonal neuropathy after Campylobacter jejuni infection.

We report the case of a patient with Parkinson's disease who developed rapidly progressive weakness of the four limbs due to an acute motor axonal neuropathy (AMAN). This occurred days after a neuroleptic malignant syndrome (NMS). Serologic evidence of a preceding Campylobacter jejuni infection was detected and treatment with intravenous immunoglobulins proved effective. This case suggests that the rarely described neuropathies occurring with NMS may have a postinfectious immune basis and respond to immunomodulatory therapy.

Ataxia Telangiectasia. A case report

The case of an eight year old girl with Ataxia Telangiectasia (AT) is described. She presented at seven years of age with gait problems and was found to have the neurological, dermatological and immunological features characteristic of AT along with a history of frequent sino-pulmonary infections. This report highlights the refractory nature of the disease, the difficulties in medical management, and the problems posed by late diagnosis which can compromise patient care. This is a rare inherited form of ataxia which has not been previously reported in West Indian literature.

Ataxia Telangiectasia. A case report.

The case of an eight year old girl with Ataxia Telangiectasia (AT) is described. She presented at seven years of age with gait problems and was found to have the neurological, dermatological and immunological features characteristic of AT along with a history of frequent sino-pulmonary infections. This report highlights the refractory nature of the disease, the difficulties in medical management, and the problems posed by late diagnosis which can compromise patient care. This is a rare inherited form of ataxia which has not been previously reported in West Indian literature.

Dengue in Trinidad: a survey of knowledge, attitudes, practices and beliefs in two communities in Trinidad, West Indies

This study was conducted to test the Health Belief Model as it relates to dengue fever in two urban communities, namely Curepe and Woodbrook, Trinidad using a knowledge, attitude, practices and beliefs questionnaire and entomological investigations. The knowledge of dengue symptomatology, its prevention and control suggested a high level of awareness about dengue and its aetiological agents among residents of both commuities, but the connection between the vector Aedes aegypti (L.) and dengue fever transmission was poorly understood. The major determinants for cues to action were demographics, prevention of water treatment and garbage collection and disposal. Data from the present study gave clear indications of the need for health education programs, defining what garbage is and the further studies using the transtheoretical model of change (Prochaska Model). With these tools a holistic approach to vector control using community participation, health education and conventional vector control strategies may be adopted for the prevention and control of dengue and its vector. Ae. aegypti, on a sustained basis in Trinidad and, possibly, the Caribbean region.(AU)

Ataxia Telangiectasia: A case report

The case of an eight year old girl with Ataxia Telangiectasia (AT) is described. She presented at seven years of age with gait problems and was found to have the neurological, dermatological and immunological features characteristic of AT along with a history of frequent sino-pulmonary infections. This report highlights the refractory nature of the disease, the difficulties in medical management, and the problems posed by late diagnosis which can comprise patient care. This is a rare inherited form of ataxia which has not been previously reported in West Indian literature. (AU)