The coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving global emergency that continues to strain healthcare systems. Emerging research describes a plethora of patient ...factors-including demographic, clinical, immunologic, hematological, biochemical, and radiographic findings-that may be of utility to clinicians to predict COVID-19 severity and mortality. We present a synthesis of the current literature pertaining to factors predictive of COVID-19 clinical course and outcomes. Findings associated with increased disease severity and/or mortality include age > 55 years, multiple pre-existing comorbidities, hypoxia, specific computed tomography findings indicative of extensive lung involvement, diverse laboratory test abnormalities, and biomarkers of end-organ dysfunction. Hypothesis-driven research is critical to identify the key evidence-based prognostic factors that will inform the design of intervention studies to improve the outcomes of patients with COVID-19 and to appropriately allocate scarce resources.
Summary Background Tuberculous meningitis disproportionately affects young children. We aimed to characterise treatment outcomes for this deadliest and most debilitating form of tuberculosis. Methods ...We did a systematic review and meta-analysis of childhood tuberculous meningitis studies published up to Oct 12, 2012. We included study reports that applied predefined diagnostic criteria and described treatment regimens and outcomes. We pooled risks of death during treatment and neurological sequelae among survivors. As secondary objectives, we assessed study-level characteristics as sources of heterogeneity, and we pooled frequencies of presenting symptoms and diagnostic findings. For all meta-analyses we used random-effects models with the exact binomial likelihood method. Findings 19 studies met our inclusion criteria, with reported treatment outcomes for 1636 children. Risk of death was 19·3% (95% CI 14·0–26·1) and probability of survival without neurological sequelae was 36·7% (27·9–46·4). Among survivors, risk of neurological sequelae was 53·9% (95% CI 42·6–64·9). Diagnosis in the most advanced disease stage (3) occurred in 307 (47%) of 657 patients and was associated with worse outcomes than was earlier diagnosis. The most common findings at presentation were cerebrospinal fluid (CSF) leucocytosis (frequency 99·9%, 95% CI 68·5–100·0), CSF lymphocytosis (97·9%, 51·9–100·0), fever (89·8%, 79·8–95·2), and hydrocephalus (86·1%, 68·6–94·6). Frequency of CSF acid-fast-bacilli smear positivity was 8·9% (95% CI 5·0–15·4), and frequency of CSF culture positivity for Mycobacterium tuberculosis was 35·1% (16·8–59·2). Interpretation Despite treatment, childhood tuberculous meningitis has very poor outcomes. Poor prognosis and difficult early diagnosis emphasise the importance of preventive therapy for child contacts of patients with tuberculosis and low threshold for empirical treatment of tuberculous meningitis suspects. Implementation of consensus definitions, standardised reporting of data, and high-quality clinical trials are needed to clarify optimum therapy. Funding None.
Background In order for healthcare systems to prepare for future waves of COVID-19, an in-depth understanding of clinical predictors is essential for efficient triage of hospitalized patients. ...Methods We performed a retrospective cohort study of 259 patients admitted to our hospitals in Rhode Island to examine differences in baseline characteristics (demographics and comorbidities) as well as presenting symptoms, signs, labs, and imaging findings that predicted disease progression and in-hospital mortality. Results Patients with severe COVID-19 were more likely to be older (p = 0.02), Black (47.2% vs. 32.0%, p = 0.04), admitted from a nursing facility (33.0% vs. 17.9%, p = 0.006), have diabetes (53.9% vs. 30.4%, p<0.001), or have COPD (15.4% vs. 6.6%, p = 0.02). In multivariate regression, Black race (adjusted odds ratio aOR 2.0, 95% confidence interval CI: 1.1-3.9) and diabetes (aOR 2.2, 95%CI: 1.3-3.9) were independent predictors of severe disease, while older age (aOR 1.04, 95% CI: 1.01-1.07), admission from a nursing facility (aOR 2.7, 95% CI 1.1-6.7), and hematological co-morbidities predicted mortality (aOR 3.4, 95% CI 1.1-10.0). In the first 24 hours, respiratory symptoms (aOR 7.0, 95% CI: 1.4-34.1), hypoxia (aOR 19.9, 95% CI: 2.6-152.5), and hypotension (aOR 2.7, 95% CI) predicted progression to severe disease, while tachypnea (aOR 8.7, 95% CI: 1.1-71.7) and hypotension (aOR 9.0, 95% CI: 3.1-26.1) were associated with increased in-hospital mortality. Conclusions Certain patient characteristics and clinical features can help clinicians with early identification and triage of high-risk patients during subsequent waves of COVID-19.
In high burden settings, the risk of infection with
increases throughout childhood due to cumulative exposure. However, the risk of progressing from tuberculosis (TB) infection to disease varies by ...age. Young children (<5 years) have high risk of disease progression following infection. The risk falls in primary school children (5 to <10 years), but rises again during puberty. TB disease phenotype also varies by age: generally, young children have intrathoracic lymph node disease or disseminated disease, while adolescents (10 to <20 years) have adult-type pulmonary disease. TB risk also exhibits a gender difference: compared to adolescent boys, adolescent girls have an earlier rise in disease progression risk and higher TB incidence until early adulthood. Understanding why primary school children, during what we term the "Wonder Years," have low TB risk has implications for vaccine development, therapeutic interventions, and diagnostics. To understand why this group is at low risk, we need a better comprehension of why younger children and adolescents have higher risks, and why risk varies by gender. Immunological response to
is central to these issues. Host response at key stages in the immunopathological interaction with
influences risk and disease phenotype. Cell numbers and function change dramatically with age and sexual maturation. Young children have poorly functioning innate cells and a Th2 skew. During the "Wonder Years," there is a lymphocyte predominance and a Th1 skew. During puberty, neutrophils become more central to host response, and CD4+ T cells increase in number. Sex hormones (dehydroepiandrosterone, adiponectin, leptin, oestradiol, progesterone, and testosterone) profoundly affect immunity. Compared to girls, boys have a stronger Th1 profile and increased numbers of CD8+ T cells and NK cells. Girls are more Th2-skewed and elicit more enhanced inflammatory responses. Non-immunological factors (including exposure intensity, behavior, and co-infections) may impact disease. However, given the consistent patterns seen across time and geography, these factors likely are less central. Strategies to protect children and adolescents from TB may need to differ by age and sex. Further work is required to better understand the contribution of age and sex to
immunity.
Tuberculosis (TB) stigma remains a barrier to early diagnosis and treatment completion. Increased understanding of stigma is necessary for improved interventions to minimise TB stigma and its ...effects. The purpose of this study is to quantitatively measure TB stigma and to explore qualitatively its manifestation among TB patients in a rural Kenyan community.
This hospital based study using explanatory sequential mixed methods approach was conducted in 2016. In the quantitative part of the study, a questionnaire containing socio-demographic characteristics and scales measuring perceived TB stigma and experienced TB stigma, was administered to 208 adult pulmonary TB patients receiving treatment in West Pokot County. Respondents with high stigma were purposively selected to take part in in-depth interviews and focus group discussions. The qualitative data were collected through 15 in-depth interviews and 6 focus group discussions with TB patients. Descriptive and bivariate analysis was done for the quantitative data while the thematic analysis was done for qualitative data.
The internal consistency reliability coefficients were satisfactory with Cronbach alphas of 0.87 and 0.86 for the 11-item and 12-item stigma measurement scale. The investigation revealed that TB stigma was high. The key drivers of TB stigma were the association of TB with HIV/AIDS and the fear of TB transmission. TB stigma was exemplified through patients being isolated by others, self-isolation, fear to disclose TB diagnosis, association of TB with human immunodeficiency virus (HIV) and lack of social support. Being a woman was significantly associated with high levels of both experienced stigma (p = 0.007) and perceived stigma (p = 0.005) while age, marital status, occupation and the patient's religion were not.
There is a need to implement stigma reduction interventions in order to improve TB program outcomes.
To evaluate the diagnostic value of symptoms used by daycares and schools to screen children and adolescents for SARS-CoV-2 infection, we analyzed data from a primary care setting.
This cohort study ...included all patients ≤17 years old who were evaluated at Providence Community Health Centers (PCHC; Providence, U.S.), for COVID-19 symptoms and/or exposure, and received SARS-CoV-2 polymerase chain reaction (PCR) testing between March-June 2020. Participants were identified from PCHC electronic medical records. For three age groups- 0-4, 5-11, and 12-17 years-we estimated the sensitivity, specificity, and area under the receiver operating curve (AUC) of individual symptoms and three symptom combinations: a case definition published by the Rhode Island Department of Health (RIDOH), and two novel combinations generated by different statistical approaches to maximize sensitivity, specificity, and AUC. We evaluated symptom combinations both with and without consideration of COVID-19 exposure. Myalgia, headache, sore throat, abdominal pain, nausea, anosmia, and ageusia were not assessed in 0-4 year-olds due to the lower reliability of these symptoms in this group.
Of 555 participants, 217 (39.1%) were SARS-CoV-2-infected. Fever was more common among 0-4 years-olds (p = 0.002); older children more frequently reported fatigue (p = 0.02). In children ≥5 years old, anosmia or ageusia had 94-98% specificity. In all ages, exposure history most accurately predicted infection. With respect to individual symptoms, cough most accurately predicted infection in <5 year-olds (AUC 0.69) and 12-17 year-olds (AUC 0.62), while headache was most accurate in 5-11 year-olds (AUC 0.62). In combination with exposure history, the novel symptom combinations generated statistically to maximize test characteristics had sensitivity >95% but specificity <30%. No symptom or symptom combination had AUC ≥0.70.
Anosmia or ageusia in children ≥5 years old should raise providers' index of suspicion for COVID-19. However, our overall findings underscore the limited diagnostic value of symptoms.
New Diagnostics for Childhood Tuberculosis Chiang, Silvia S; Swanson, Douglas S; Starke, Jeffrey R
Infectious disease clinics of North America,
09/2015, Letnik:
29, Številka:
3
Journal Article
Recenzirano
The challenge of diagnosing childhood tuberculosis (TB) results from its paucibacillary nature and the difficulties of sputum collection in children. Mycobacterial culture, the diagnostic gold ...standard, provides microbiological confirmation in only 30% to 40% of childhood pulmonary TB cases and takes up to 6 weeks to result. Conventional drug susceptibility testing requires an additional 2 to 4 weeks after culture confirmation. In response to the low sensitivity and long wait time of the traditional diagnostic approach, many new assays have been developed. These new tools have shortened time to result; however, none of them offer greater sensitivity than culture.
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