Routine HIV Testing in Adolescents and Young Adults Presenting to an Outpatient Clinic in Durban,South Africa

Objectives

Although youth (12–24 years) in Sub-Saharan Africa have a high HIV risk, many have poor access to HIV testing services and are unaware of their status. Our objective was to evaluate the proportion of adolescents (12–17 years) and young adults (18–24 years) who underwent HIV testing and the prevalence among those tested in an urban adult outpatient clinic with a routine HIV testing program in Durban, South Africa.

Design

We conducted a retrospective cross-sectional analysis of adolescent and young adult outpatient records between February 2008 and December 2009.

Methods

We determined the number of unique outpatient visitors, HIV tests, and positive rapid tests among those tested.

Results

During the study period, 956 adolescents registered in the outpatient clinic, of which 527 (55%) were female. Among adolescents, 260/527 (49%, 95% CI 45–54%) females underwent HIV testing compared to 129/429 (30%, 95% CI 26–35%) males (p<0.01). The HIV prevalence among the 389 (41%, 95% CI 38–44%) adolescents who underwent testing was 16% (95% CI 13–20%) and did not vary by gender (p = 0.99). During this period, there were 2,351 young adult registrations, and of these 1,492 (63%) were female. The proportion consenting for HIV testing was similar among females 980/1,492 (66%, 95% CI 63–68%) and males 543/859 (63%, 95% CI 60–66%, p = 0.25). Among the 1,523 (65%, 95% CI 63–67%) young adults who underwent testing, the HIV prevalence was 22% (95% CI 19–24%) in females versus 14% in males (95% CI 11–17%, p<0.01).

Conclusions

Although the HIV prevalence is high among youth participating in an adult outpatient clinic routine HIV program, the uptake of testing is low, especially among 12–17 year old males. There is an urgent need to offer targeted, age-appropriate routine HIV testing to youth presenting to outpatient clinics in epidemic settings.     

Research Activity and the Association with Mortality

IntroductionThe aims of this study were to describe the key features of acute NHS Trusts with different levels of research activity and to investigate associations between research activity and clinical outcomes.MethodsNational Institute for Health Research (NIHR) Comprehensive Clinical Research Network (CCRN) funding and number of patients recruited to NIHR Clinical Research Network (CRN) portfolio studies for each NHS Trusts were used as markers of research activity. Patient-level data for adult non-elective admissions were extracted from the English Hospital Episode Statistics (2005-10). Risk-adjusted mortality associations between Trust structures, research activity and, clinical outcomes were investigated.ResultsLow mortality Trusts received greater levels of funding and recruited more patients adjusted for size of Trust (n = 35, 2,349 £/bed [95% CI 1,855–2,843], 5.9 patients/bed [2.7–9.0]) than Trusts with expected (n = 63, 1,110 £/bed, [864–1,357] p<0.0001, 2.6 patients/bed [1.7–3.5] p<0.0169) or, high (n = 42, 930 £/bed [683–1,177] p = 0.0001, 1.8 patients/bed [1.4–2.1] p<0.0005) mortality rates. The most research active Trusts were those with more doctors, nurses, critical care beds, operating theatres and, made greater use of radiology. Multifactorial analysis demonstrated better survival in the top funding and patient recruitment tertiles (lowest vs. highest (odds ratio & 95% CI: funding 1.050 [1.033–1.068] p<0.0001, recruitment 1.069 [1.052–1.086] p<0.0001), middle vs. highest (funding 1.040 [1.024–1.055] p<0.0001, recruitment 1.085 [1.070–1.100] p<0.0001).ConclusionsResearch active Trusts appear to have key differences in composition than less research active Trusts. Research active Trusts had lower risk-adjusted mortality for acute admissions, which persisted after adjustment for staffing and other structural factors.     

Identifying Adult Dengue Patients at Low Risk for Clinically Significant Bleeding

Background

Clinically significant bleeding is important for subsequent optimal case management in dengue patients, but most studies have focused on dengue severity as an outcome. Our study objective was to identify differences in admission parameters between patients who developed clinically significant bleeding and those that did not. We sought to develop a model for discriminating between these patients.

Methods

We conducted a retrospective study of 4,383 adults aged >18 years who were hospitalized with dengue infection at Tan Tock Seng Hospital, Singapore from 2005 to 2008. Patients were divided into those with clinically significant bleeding (n = 188), and those without (n = 4,195). Demographic, clinical, and laboratory variables on admission were compared between groups to determine factors associated with clinically significant bleeding during hospitalization.

Results

On admission, female gender (p<0.001); temperature >38°C (p<0.001); nausea/vomiting (p = 0.009) and abdominal pain/tenderness (p = 0.005); lower systolic blood pressure (p<0.001); higher pulse rate (p<0.001); increased absolute neutrophil count (ANC; p<0.001); reduced absolute lymphocyte count (ALC; p<0.001), haematocrit percentage (p<0.001) and platelet count (p = 0.04), and increased prothrombin time (p = 0.003) were significantly associated with clinically significant bleeding on univariate analysis. Multivariate analysis showed that independent variables in the final model were female gender (aOR 2.85; 95% CI: 1.9–4.33); temperature >38°C (aOR 1.81; 95% CI: 1.27–2.61), nausea/vomiting (aOR 1.39; 95% CI: 0.94–2.12), ANC (aOR 1.3; 95% CI: 1.15–1.46), ALC (aOR 0.4; 95% CI: 0.25–0.64), hematocrit percentage (aOR 0.96; 95% CI: 0.92–1.002) and platelet count (aOR 0.993; 95% CI: 0.988–0.998). At the cutoff of -3.919, the model achieved an AUC of 0.758 (sensitivity:0.87, specificity: 0.38, PPV: 0.06, NPV: 0.98).

Conclusion

Clinical risk factors associated with clinically significant bleeding were identified. This model may be useful to complement clinical judgement in triaging adult dengue patients given the dynamic nature of acute dengue, particularly in pre-identifying those less likely to develop clinically significant bleeding.     

Hyperthermia in Human Ischemic and Hemorrhagic Stroke: Similar Outcome,Different Mechanisms

Hyperthermia is a predictor of poor outcome in ischemic (IS) and intracerebral hemorrhagic (ICH) stroke. Our aim was to study the plausible mechanisms involved in the poor outcome associated to hyperthermia in stroke. We conducted a case-control study including patients with IS (n = 100) and ICH (n = 100) within the first 12 hours from symptom onset. Specifically, IS and ICH patients were consecutively included into 2 subgroups, according to the highest body temperature within the first 24 hours: Tmax <37.5°C and Tmax ≥37.5°C, up to reach 50 patients per subgroup of temperature for both IS and ICH patients. Body temperature was determined at admission and every 4 hours during the first 48 hours. Main outcome variable was poor functional outcome (modified Rankin scale score >2) at 3 months. Serum levels of glutamate and active MMP-9 were measured at admission. Our results showed that Tmax ≥37.5°C within the first 24 hours was independently associated with poor outcome in both IS (OR, 12.43; 95% CI, 3.73–41.48; p<0.0001) and ICH (OR, 4.29; 95% CI, 1.32–13.91; p = 0.015) after adjusting for variables with a proven biological relevance for outcome. However, when molecular markers levels were included in the logistic regression model, we observed that glutamate (OR, 1.01; 95% CI, 1.00–1.02; p = 0.001) and infarct volume (OR, 1.06; 95% CI, 1.01–1.10; p = 0.015) were the only variables independently associated to poor outcome in IS, and active MMP-9 (OR, 1.04; 95% CI, 1.00–1.08; p = 0.002) and National Institute of Health Stroke Scale (NIHSS) at admission (OR, 1.29; 95% CI, 1.13–1.49; p<0.0001) in ICH. In conclusion, these results suggest that although the outcome associated to hyperthermia is similar in human IS and ICH, the underlying mechanisms may be different.     

Association of Left Ventricular Mass with All-Cause Mortality,Myocardial Infarction and Stroke

Background

Our aim was to assess the association of left ventricular mass with mortality and nonfatal cardiovascular events.

Methodology/Principal Findings

Left ventricular mass was measured by echocardiography in 40138 adult patients (mean age 61.1±16.4 years, 52.5% male). The primary endpoint was all-cause mortality. Secondary endpoints included nonfatal myocardial infarction and nonfatal stroke. During a mean follow-up period of 5.6±3.9 years, 9181 patients died, 901 patients had a nonfatal myocardial infarction, and 2139 patients had a nonfatal stroke. Cumulative 10-year mortality was 26.8%, 31.9%, 37.4% and 46.4% in patients with normal, mildly, moderately and severely increased left ventricular mass, respectively (p<0.001). Ten-year rates of nonfatal myocardial infarction and stroke ranged from 3.2% and 6.7% in patients with normal left ventricular mass to 5.3% and 12.7% in those with severe increase in left ventricular mass, respectively. After multivariate adjustment, left ventricular mass remained an independent predictor of all-cause mortality (hazard ratio [HR] per 100 g increase 1.21, 95% confidence interval [CI] 1.14–1–27, p<0.001 in women, and HR 1.09, 95% CI 1.04–1–13, p<0.001 in men), myocardial infarction (HR 1.60, 95% CI 1.31–1.94, p<0.001 in women and HR 1.15, 95% CI 1.02–1.29, p = 0.019 in men) and stroke (HR 1.26, 95% CI 1.13–1.40, p<0.001 in women and HR 1.19, 95% CI 1.09–1.30, p<0.001 in men).

Conclusions/Significance

Left ventricular mass has a graded and independent association with all-cause mortality, myocardial infarction and stroke.     

Epidemiology of soil-transmitted helminth infections in Semarang,Central Java,Indonesia

Soil-transmitted helminth (STH) infections are endemic in Indonesia. However, prevalence data for many parts of the country are incomplete. The aim of this study was to determine human STH prevalence and knowledge and practices relating to STH risk behaviour, to provide a current view of the status of STH infection in rural communities in Central Java. A cross-sectional survey of 16 villages was conducted in Semarang, Central Java in 2015. Demographic and household data together with information about knowledge and practices relating to STH and hygiene were elicited through face-to-face interviews. Stool samples were collected and examined using the flotation method. Children (aged 2–12 years) also had their haemoglobin (Hb) levels, height and weight data collected, and BMI estimated. Data were analysed using univariate logistic regression analysis. A total of 6,466 individuals with a mean age of 33.5 years (range: 2–93) from 2,195 households were interviewed. The overall prevalence of STH was 33.8% with Ascaris lumbricoides (roundworm) the predominant nematode identified (prevalence = 26.0%). Hookworm and Trichuris trichiura (whipworm) were found in 7.9% and 1.8% of participants, respectively. Females were at increased odds of infection with A. lumbricoides (adjusted OR 1.14, 95% CI [1.02–1.29], p = 0.02). Adults in age groups 51–60 and over 60 years had the highest odds of being infected with hookworm (adjusted OR 3.01, 95% CI [1.84–4.91], p<0.001 and adjusted OR 3.79, 95% CI [2.30–6.26], p<0.001, respectively) compared to 6–12 year olds. Farmers also had higher odds of being infected with hookworm (adjusted OR 2.36, 95% CI [1.17–4.76], p = 0.02) compared to other occupation categories. Poverty (OR 2.14, 95% CI [1.77–2.58], p<0.001), overcrowding (OR 1.35, 95% CI [1.27–1.44], p<0.001), goat ownership (OR 1.61, 95% CI [1.10–2.41], p = 0.02) and the presence of dry floor space in the home (OR 0.73, 95% CI [0.58–0.91], p = 0.01) were all household factors significantly associated with an increased odds of infection. Infection with STH was not significantly associated with the gastrointestinal illness (p>0.05), BMI or Hb levels; however, one third of all 2–12 year olds surveyed were found to be anaemic (i.e. Hb concentrations below 110g/l or 115g/l for children under 5 and 5 years or older, respectively), with a greater proportion of school-age children at risk. Knowledge and behaviour related to hygiene and gastrointestinal diseases varied widely and were generally not associated with STH infection. The study revealed that STH infection remains endemic in Central Java despite ongoing deworming programs. Current control efforts would benefit from being re-evaluated to determine a more effective way forward.     

Prolonged Delayed Graft Function Is Associated with Inferior Patient and Kidney Allograft Survivals

It is unclear if there is an association between the duration of delayed graft function (DGF) and kidney transplant (KT) outcomes. This study investigated the impact of prolonged DGF on patient and graft survivals, and renal function one year after KT. This single center retrospective analysis included all deceased donor KT performed between Jan/1998 and Dec/2008 (n = 1412). Patients were grouped in quartiles according to duration of DGF (1–5, 6–10, 11–15, and >15 days, designated as prolonged DGF). The overall incidence of DGF was 54.2%. Prolonged DGF was associated with retransplantation (OR 2.110, CI95% 1.064–4.184,p = 0.033) and more than 3 HLA mismatches (OR 1.819, CI95% 1.117–2.962,p = 0.016). The incidence of acute rejection was higher in patients with DGF compared with those without DGF (36.2% vs. 12.2%, p<0.001). Compared to patients without DGF, DGF(1–5), DGF(6–10), and DGF(11–15), patients with prolonged DGF showed inferior one year patient survival (95.2% vs. 95.4% vs. 95.5% vs. 93.4% vs. 88.86%, p = 0.003), graft survival (91% vs. 91.4% vs. 92% vs. 88.7% vs. 70.5%, p<0.001), death-censored graft survival (95.7% vs. 95.4% vs. 96.4% vs. 94% vs. 79.3%, p<0.001), and creatinine clearance (58.0±24.6 vs. 55.8±22.2 vs. 53.8±24.1 vs. 53.0±27.2 vs. 36.8±27.0 mL/min, p<0.001), respectively. Multivariable analysis showed that prolonged DGF was an independent risk factor for graft loss (OR 3.876, CI95% 2.270–6.618, p<0.001), death censored graft loss (OR 4.103, CI95% 2.055–8.193, p<0.001), and death (OR 3.065, CI95% 1.536–6.117, p = 0.001). Prolonged DGF, determined by retransplantation and higher HLA mismatches, was associated with inferior renal function, and patient and graft survivals at one year.     

Association between Cytomegalovirus Antibody Levels and Cognitive Functioning in Non-Elderly Adults

Background

Elevated levels of antibodies to Cytomegalovirus (CMV) have been associated with cognitive impairment, but the quantitative relationship between CMV antibody levels and domains of cognitive functioning in younger adults has not been established.

Methods

We measured IgG class antibodies to Cytomegalovirus in 521 individuals, mean age 32.8 years. Participants were selected for the absence of psychiatric disorder and of a serious medical condition that could affect brain functioning. Cognitive functioning was measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Wisconsin Card Sorting Test, Trail Making Test part A, and the WAIS III Letter Number Sequencing subtest. Linear regression analyses were used to measure the quantitative association between cognitive scores and Cytomegalovirus IgG antibody level. Logistic regression analyses were used to measure the odds of low cognitive scores and elevated antibody levels defined as an antibody level > = 50^th, 75^th, and 90^th percentile of the group.

Results

Higher levels of CMV antibodies were associated with lower performance on RBANS Total (coefficient −1.03, p<.0002), Delayed Memory (coefficient −0.94, p<.001), Visuospatial/Constructional (coefficient −1.77, p<5×10⁻⁷), and Letter Number Sequencing (coefficient −0.15, p<.03). There was an incremental relationship between the level of CMV antibody elevation and the odds of a low RBANS Total score. The odds of a low total cognitive score were 1.63 (95^th % CI 1.01, 2.64; p<.045), 2.22 (95^th % CI 1.33, 3.70; p<.002), and 2.46 (95^th % CI 1.24, 4.86; p<.010) with a CMV antibody level greater than or equal to the 50^th, 75^th, and 90^th percentile respectively.

Conclusions

Higher levels of Cytomegalovirus antibodies are associated with lower levels of cognitive functioning in non-elderly adults. Methods for the prevention and treatment of CMV infection should be evaluated to determine if they result in an improvement in cognitive functioning in otherwise healthy adults.     

Gender Differences in In-Hospital Clinical Outcomes after Percutaneous Coronary Interventions: An Insight from a Japanese Multicenter Registry

Background

Gender differences in clinical outcomes after percutaneous coronary intervention (PCI) among different age groups are controversial in the era of drug-eluting stents, especially among the Asian population who are at higher risk for bleeding complications.

Methods and Results

We analyzed data from 10,220 patients who underwent PCI procedures performed at 14 Japanese hospitals from September 2008 to April 2013. A total of 2,106 (20.6%) patients were women. Women were older (72.7±9.7 vs 66.6±10.8 years, p<0.001), and had a lower body mass index (23.4±4.0 vs 24.3±3.5, p<0.001), with a higher prevalence of hypertension (p<0.001), hyperlipidemia (p<0.001), insulin-dependent diabetes (p<0.001), renal failure (p<0.001), and heart failure (p<0.001) compared with men. Men tended to have more bifurcation lesions (p = 0.003) and chronic totally occluded lesions (p<0.001) than women. Crude overall complications (14.8% vs 9.5%, p<0.001) and the rate of bleeding complications (5.3% vs 2.8%, p<0.001) were significantly higher in women than in men. On multivariate analysis in the total cohort, female sex was an independent predictor of overall complications (OR, 1.47; 95% CI, 1.26–1.71; p<0.001) and bleeding complications (OR, 1.74; 95% CI, 1.36–2.24; p<0.001) after adjustment for confounding variables. A similar trend was observed across the middle-aged group (≥55 and <75 years) and old age group (≥75 years).

Conclusions

Women are at higher risk than men for post-procedural complications after PCI, regardless of age.     

Multiple Marker Detection in Peripheral Blood for NSCLC Diagnosis

Background

Non-invasive early detection of lung cancer could reduce the number of patients diagnosed with advanced disease, which is associated with a poor prognosis. We analyzed the diagnostic accuracy of a panel of peripheral blood markers in detecting non small cell lung cancer (NSCLC).

Methods

100 healthy donors and 100 patients with NSCLC were enrolled onto this study. Free circulating DNA, circulating mRNA expression of peptidylarginine deiminase type 4 (PAD4/PADI4), pro-platelet basic protein (PPBP) and haptoglobin were evaluated using a Real-Time PCR-based method.

Results

Free circulating DNA, PADI4, PPBP and haptoglobin levels were significantly higher in NSCLC patients than in healthy donors (p<0.0001, p<0.0001, p = 0.0002 and p = 0.0001, respectively). The fitted logistic regression model demonstrated a significant direct association between marker expression and lung cancer risk. The odds ratios of individual markers were 6.93 (95% CI 4.15–11.58; p<0.0001) for free DNA, 6.99 (95% CI 3.75–13.03; p<0.0001) for PADI4, 2.85 (95% CI 1.71–4.75; p<0.0001) for PPBP and 1.16 (95% CI 1.01–1.33; p = 0.031) for haptoglobin. Free DNA in combination with PPBP and PADI4 gave an area under the ROC curve of 0.93, 95% CI = 0.90–0.97, with sensitivity and specificity over 90%.

Conclusions

Free circulating DNA analysis combined with PPBP and PADI4 expression determination appears to accurately discriminate between healthy donors and NSCLC patients. This non-invasive multimarker approach warrants further research to assess its potential role in the diagnostic or screening workup of subjects with suspected lung cancer.     

Depression in Atrial Fibrillation in the General Population

Background

Initial evidence suggests that depressive symptoms are more frequent in patients with atrial fibrillation. Data from the general population are limited.

Methods and Results

In 10,000 individuals (mean age 56±11 years, 49.4% women) of the population-based Gutenberg Health Study we assessed depression by the Patient Health Questionnaire (PHQ-9) and a history of depression in relation to manifest atrial fibrillation (n = 309 cases). The median (25th/75th percentile) PHQ-9 score of depressive symptoms was 4 (2/6) in atrial fibrillation individuals versus 3 (2/6) individuals without atrial fibrillation, . Multivariable regression analyses of the severity of depressive symptoms in relation to atrial fibrillation in cardiovascular risk factor adjusted models revealed a relation of PHQ-9 values and atrial fibrillation (odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01–1.08; P = 0.023). The association was stronger for the somatic symptom dimension of depression (OR 1.08, 95% CI 1.02–1.15; P = 0.0085) than for cognitive symptoms (OR 1.05, 95% CI 0.98–1.11; P = 0.15). Results did not change markedly after additional adjustment for heart failure, partnership status or the inflammatory biomarker C-reactive protein. Both, self-reported physical health status, very good/good versus fair/bad, (OR 0.54, 95% CI 0.41–0.70; P<0.001) and mental health status (OR 0.61 (0.46–0.82); P = 0.0012) were associated with atrial fibrillation in multivariable-adjusted models.

Conclusions

In a population-based sample we observed a higher burden of depressive symptoms driven by somatic symptom dimensions in individuals with atrial fibrillation. Depression was associated with a worse perception of physical or mental health status. Whether screening and treatment of depressive symptoms modulates disease progression and outcome needs to be shown.     

Comparison of Retinal Nerve Fiber Layer Thickness In Vivo and Axonal Transport after Chronic Intraocular Pressure Elevation in Young versus Older Rats

Purpose

To compare in young and old rats longitudinal measurements of retinal nerve fiber layer thickness (RNFLT) and axonal transport 3-weeks after chronic IOP elevation.

Method

IOP was elevated unilaterally in 2- and 9.5-month-old Brown-Norway rats by intracameral injections of magnetic microbeads. RNFLT was measured by spectral domain optical coherence tomography. Anterograde axonal transport was assessed from confocal scanning laser ophthalmolscopy of superior colliculi (SC) after bilateral intravitreal injections of cholera toxin-B-488. Optic nerve sections were graded for damage.

Results

Mean IOP was elevated in both groups (young 37, old 38 mmHg, p = 0.95). RNFL in young rats exhibited 10% thickening at 1-week (50.9±8.1 µm, p<0.05) vs. baseline (46.4±2.4 µm), then 7% thinning at 2-weeks (43.0±7.2 µm, p>0.05) and 3-weeks (43.5±4.4 µm, p>0.05), representing 20% loss of dynamic range. RNFLT in old rats showed no significant change at 1-week (44.9±4.1 µm) vs. baseline (49.2±5.3 µm), but progression to 22% thinning at 2-weeks (38.0±3.7 µm, p<0.01) and 3-weeks (40.0±6.6 µm, p<0.05), representing 59% loss of dynamic range. Relative SC fluorescence intensity was reduced in both groups (p<0.001), representing 77–80% loss of dynamic range and a severe transport deficit. Optic nerves showed 75–95% damage (p<0.001). There was greater RNFL thinning in old rats (p<0.05), despite equivalent IOP insult, transport deficit and nerve damage between age groups (all p>0.05).

Conclusion

Chronic IOP elevation resulted in severely disrupted axonal transport and optic nerve axon damage in all rats, associated with mild RNFL loss in young rats but a moderate RNFL loss in old rats despite the similar IOP insult. Hence, the glaucomatous injury response within the RNFL depends on age.     

Early Vascular Aging in Young and Middle-Aged Ischemic Stroke Patients: The Norwegian Stroke in the Young Study

Background

Ischemic stroke survivors have high risk of cardiovascular morbidity and mortality even at young age, suggesting that early arterial aging is common among such patients.

Methods

We measured aortic stiffness by carotid-femoral pulse wave velocity (PWV) in 205 patients (69% men) aged 15–60 years with acute ischemic stroke in the prospective Norwegian Stroke in the Young Study. High for age carotid-femoral PWV was identified in the reference normogram.

Results

Patients were on average 49±10 years old, 34% had a history of hypertension and 37% had metabolic syndrome (MetS). In the total study population, higher PWV was associated with history of hypertension (β = 0.18), higher age (β = 0.34), systolic blood pressure (BP) (β = 0.28) and serum creatinine (β = 0.18) and lower high-density lipoprotein (HDL) cholesterol (β = –0.10, all p<0.01) in multivariate linear regression analysis (multiple R² = 0.42, p<0.001). High for age PWV was found in 18% of patients. In univariate analyses, known hypertension was associated with a 6-fold, MetS with a 4-fold and presence of carotid plaque with a 3.7-fold higher risk for high for age PWV (all p<0.01). In multiple logistic regression analysis higher systolic BP (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.02–1.06; p<0.01), history of hypertension (OR 3.59; 95% CI 1.52–8.51; p<0.01), low HDL cholesterol (OR 3.03; 95% CI 1.00–9.09; p = 0.05) and higher serum creatinine (OR 1.04; 95% CI 1.01–1.06; p<0.01) were associated with high for age PWV.

Conclusions

Higher PWV is common in younger and middle-aged ischemic stroke patients and associated with a clustering of classical cardiovascular risk factors.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01597453","term_id":"NCT01597453"}}NCT01597453     

Risk Factors for Central Lymph Node Metastasis in CN0 Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis

Background

Central lymph node metastasis (CLNM) is common in papillary thyroid carcinoma (PTC). Prophylactic central lymph node dissection (PCLND) for patients with clinically negative central compartment lymph nodes (CN0) remains controversial. The phrase “clinically negative” is used to indicate that patients exhibited no clinical evidence of CLNM by ultrasonography (US) or computerized tomography (CT) preoperatively. In this study, we analyze the risk factors for CLNM in CN0 patients.

Methods

The PUBMED and SCIE databases were systematically searched for works published through January 31, 2015. All of the patients included in this study underwent thyroidectomy+PCLND. Revman 5.3 software was used to analyze the data.

Results

Twenty studies and 9084 patients were included in this meta-analysis. The following variables were associated with an increased risk of CLNM in CN0 patients: age < 45 years (OR = 1.59, 95% CI = 1.42–1.78, p<0.00001), male sex (OR = 1.95, 95% CI = 1.63–2.32, p<0.00001), multifocality (OR = 1.43, 95% CI = 1.22–1.67, p<0.00001), tumor size > 2 cm for PTC patients (OR = 2.98, 95% CI 2.08–4.28, p<0.00001) or tumor size > 0.5 cm for papillary thyroid microcarcinoma (PTMC) patients (OR = 2.30, 95% CI = 1.71–3.09, p<0.00001), location of the primary tumor in the central area and low pole (OR = 1.86, 95% CI = 1.48–2.33, p<0.00001), lymphovascular invasion (OR = 4.35, 95% CI = 2.24–8.46, p<0.0001), extrathyroidal extension (OR = 2.27, 95% CI = 1.76–2.94, p<0.00001), and capsular invasion (OR = 1.72, 95% CI = 1.39–2.41, p<0.00001). PTC (tumor size>1cm) exhibited a higher risk factor associated with CLNM than PTMC (tumor size<1cm) (OR = 2.83, 95% CI = 2.15–3.72, p<0.00001). Bilateral tumors (OR = 1.21, 95% CI = 0.92–1.58, p = 0.17) and lymphocytic thyroiditis (OR = 0.88, 95% CI = 0.71–1.09, p = 0.25) had no association with CLNM in CN0 patients.

Conclusions

Our systematic review identified several clinical features associated with CLNM in CN0 patients, including age, sex, multifocality, size, location, lymphovascular invasion, capsular invasion, and extrathyroidal extension. These factors should guide the application of PCLND in CN0 patients.     

Whole-Body CT in Haemodynamically Unstable Severely Injured Patients – A Retrospective,Multicentre Study

Background

The current common and dogmatic opinion is that whole-body computed tomography (WBCT) should not be performed in major trauma patients in shock. We aimed to assess whether WBCT during trauma-room treatment has any effect on the mortality of severely injured patients in shock.

Methods

In a retrospective multicenter cohort study involving 16719 adult blunt major trauma patients we compared the survival of patients who were in moderate, severe or no shock (systolic blood pressure 90–110,<90 or >110 mmHg) at hospital admission and who received WBCT during resuscitation to those who did not. Using data derived from the 2002–2009 version of TraumaRegister®, we determined the observed and predicted mortality and calculated the standardized mortality ratio (SMR) as well as logistic regressions.

Findings

9233 (55.2%) of the 16719 patients received WBCT. The mean injury severity score was 28.8±12.1. The overall mortality rate was 17.4% (SMR  = 0.85, 95%CI 0.81–0.89) for patients with WBCT and 21.4% (SMR = 0.98, 95%CI 0.94–1.02) for those without WBCT (p<0.001). 4280 (25.6%) patients were in moderate shock and 1821 (10.9%) in severe shock. The mortality rate for patients in moderate shock with WBCT was 18.1% (SMR 0.85, CI95% 0.78–0.93) compared to 22.6% (SMR 1.03, CI95% 0.94–1.12) to those without WBCT (p<0.001, p = 0.002 for the SMRs). The mortality rate for patients in severe shock with WBCT was 42.1% (SMR 0.99, CI95% 0.92–1.06) compared to 54.9% (SMR 1.10, CI95% 1.02–1.16) to those without WBCT (p<0.001, p = 0.049 for the SMRs). Adjusted logistic regression analyses showed that WBCT is an independent predictor for survival that significantly increases the chance of survival in patients in moderate shock (OR = 0.73; 95%CI 0.60–0.90, p = 0.002) as well as in severe shock (OR = 0.67; 95%CI 0.52–0.88, p = 0.004). The number needed to scan related to survival was 35 for all patients, 26 for those in moderate shock and 20 for those in severe shock.

Conclusions

WBCT during trauma resuscitation significantly increased the survival in haemodynamically stable as well as in haemodynamically unstable major trauma patients. Thus, the application of WBCT in haemodynamically unstable severely injured patients seems to be safe, feasible and justified if performed quickly within a well-structured environment and by a well-organized trauma team.     

Adverse childhood experiences,adult depression,and suicidal ideation in rural Uganda: A cross-sectional,population-based study

BackgroundDepression is recognized globally as a leading cause of disability. Early-life adverse childhood experiences (ACEs) have been shown to have robust associations with poor mental health during adulthood. These effects may be cumulative, whereby a greater number of ACEs are progressively associated with worse outcomes. This study aimed to estimate the associations between ACEs and adult depression and suicidal ideation in a cross-sectional, population-based study of adults in Uganda.Methods and findingsBetween 2016 and 2018, research assistants visited the homes of 1,626 adult residents of Nyakabare Parish, a rural area in southwestern Uganda. ACEs were assessed using a modified version of the Adverse Childhood Experiences-International Questionnaire, and depression symptom severity and suicidal ideation were assessed using the Hopkins Symptom Checklist for Depression (HSCL-D). We applied a validated algorithm to determine major depressive disorder diagnoses. Overall, 1,458 participants (90%) had experienced at least one ACE, 159 participants (10%) met criteria for major depressive disorder, and 28 participants (1.7%) reported suicidal ideation. We fitted regression models to estimate the associations between cumulative number of ACEs and depression symptom severity (linear regression model) and major depressive disorder and suicidal ideation (Poisson regression models). In multivariable regression models adjusted for age, sex, primary school completion, marital status, self-reported HIV status, and household asset wealth, the cumulative number of ACEs was associated with greater depression symptom severity (b = 0.050; 95% confidence interval [CI], 0.039–0.061, p < 0.001) and increased risk for major depressive disorder (adjusted relative risk [ARR] = 1.190; 95% CI, 1.109–1.276; p < 0.001) and suicidal ideation (ARR = 1.146; 95% CI, 1.001–1.311; p = 0.048). We assessed the robustness of our findings by probing for nonlinearities and conducting analyses stratified by age. The limitations of the study include the reliance on retrospective self-report as well as the focus on ACEs that occurred within the household.ConclusionsIn this whole-population, cross-sectional study of adults in rural Uganda, the cumulative number of ACEs had statistically significant associations with depression symptom severity, major depressive disorder, and suicidal ideation. These findings highlight the importance of developing and implementing policies and programs that safeguard children, promote mental health, and prevent trajectories toward psychosocial disability.

In a cross-sectional, population based study of adults in rural Uganda, Emily Satinsky and colleagues investigate adverse childhood experiences and associations with depression and suicidal ideation.     

Placental Growth Factor for the Prediction of Adverse Outcomes in Patients with Suspected Preeclampsia or Intrauterine Growth Restriction

Background

The circulating concentration of PlGF is reported to be lower in patients experiencing preeclampsia and patients delivering a small for gestational age (SGA) neonate. To evaluate the predictive value of circulating PlGF for preeclampsia and adverse outcome in patients with suspected preeclampsia or intrauterine growth restriction (IUGR).

Methodology/Principal Findings

A double blind prospective study. We enrolled 96 women for suspected preeclampsia or IUGR, and measured plasma levels of PlGF (Triage®) at enrolment. We defined adverse outcome as severe preeclampsia, SGA neonate (<10^th centile) or elective delivery for maternal or fetal complication. Severe adverse outcome was studied among patients included <34 weeks gestation (WG) and defined as eclampsia, HELLP syndrome, very SGA (<3^rd centile) or elective delivery <34 WG. The mean logtransformed PlGF level was lower for women who experienced preeclampsia (2.9 vs 3.7, p = 0.02), and was markedly lower for patients who experienced adverse outcome (2.9 vs 4.3, p<0.001). The odds of presenting an adverse outcome were higher for the lowest tertile of PlGF compared to the higher (OR = 13 , 95% CI [3–50]). For severe adverse outcome, odds were respectively for the lowest and intermediate tertile as compared with the higher tertile : OR = 216, 95% CI [18–2571]; and OR = 17, 95% CI [3–94]. When included <34 WG, patients with a PlGF level <12 pg/ml experienced a severe adverse outcome in 96% of cases (24/25), and only 1 of 20 patients with a PlGF level >5^th centile experienced a severe adverse outcome within 15 days (5%).

Conclusions/Significance

Among women with suspected preeclampsia or IUGR, PlGF helps identify women who will experience an adverse outcome and those who will not within a time period of 15 days.     

High Prevalence of Illicit Drug Use in Men Who Have Sex with Men with HIV-1 Infection in Japan

Objective

To examine the prevalence of illicit drug use among men who have sex with men (MSM) with HIV-1 infection in Japan, where the life-time prevalence of illicit drug use in the general population is only 2.9%.

Design

A single-center cross-sectional study at a large HIV clinic in Tokyo, which treats approximately 15% of HIV-1 infected patients in Japan.

Methods

The prevalence of illicit drug use and the assciation of characteristics and social demographics of the patients with illicit drug use were examined. Patients who visited the clinic for the first time from 2005 to 2010 were enrolled. Relevant variables were collected using a structured interview and from the medical records. Multivariate logistic regression analyses were applied to estimate the odds of association of MSM over non-MSM HIV-infected patients with illicit drug use.

Results

1,196 patients were enrolled. They were mostly Japanese men of relatively young age. Illicit drug use (including injection drugs) was reported by 35% of the patients (by 40% of MSM), and 4% were IDU while 5% were on methamphetamine. 2% of the population was arrested due to illicit drugs. MSM was significantly associated with illicit drug use (adjusted OR = 4.60; 95% CI, 2.88–7.36; p<0.01). Subgroup analysis of the patients stratified by three age groups (≤30, 31 to 40, and >40) showed that the odds of association of MSM with illicit drug use was the strongest in the youngest age group (≤30 years: adjusted OR = 7.56; 95% CI, 2.86–20.0; p<0.01), followed by the oldest (>40 years: adjusted OR = 6.15; 95% CI, 2.40–15.8; p<0.01), and the weakest in the group aged 31 to 40 (adjusted OR = 3.39; 95% CI, 1.73–6.63; p<0.01).

Conclusions

The prevalence of illicit drug use is high among MSM patients with HIV-1 infection in Japan. Effective intervention for illicit drug use in this population is warranted.     

Clinical characteristics and risk factors for severe scrub typhus in pediatric and elderly patients

BackgroundScrub typhus (ST) is a life-threatening infectious disease if appropriate treatment is unavailable. Large discrepancy of clinical severity of ST patients was reported among age groups, and the underlying risk factors for severe disease are unclear.MethodsClinical and epidemiological data of ST patients were collected in 55 surveillance hospitals located in Guangzhou City, China, from 2012 to 2018. Severe prognosis and related factors were determined and compared between pediatric and elderly patients.ResultsA total of 2,074 ST patients including 209 pediatric patients and 1,865 elderly patients were included, with a comparable disease severity rate of 11.0% (95% CI 7.1%–16.1%) and 10.3% (95% CI 9.0%–11.8%). Different frequencies of clinical characteristics including lymphadenopathy, skin rash, enlarged tonsils, etc. were observed between pediatric and elderly patients. Presence of peripheral edema and decreased hemoglobin were the most important predictors of severe illness in pediatric patients with adjusted ORs by 38.99 (9.96–152.67, p<0.001) and 13.22 (1.54–113.50, p = 0.019), respectively, while presence of dyspnea and increased total bilirubin were the potential determinants of severe disease in elderly patients with adjusted ORs by 11.69 (7.33–18.64, p<0.001) and 3.17 (1.97–5.11, p<0.001), respectively. Compared with pediatric patients, elderly patients were more likely to receive doxycycline (64.8% v.s 9.9%, p<0.001), while less likely to receive azithromycin therapy (5.0% v.s 41.1%, p<0.001).ConclusionThe disease severity rate is comparable between pediatric and elderly ST patients, while different clinical features and laboratory indicators were associated with development of severe complications for pediatric and elderly patients, which is helpful for diagnosis and progress assessment of disease for ST patients.     

Sleepiness,Long Distance Commuting and Night Work as Predictors of Driving Performance

Few studies have examined the effect of working night shift and long distance commuting. We examined the association between several sleep related and demographic variables, commuting distance, night work and use of mobile phones on driving performance. We used a prospective design to recruit participants and conducted a telephone survey (n = 649). The survey collected demographic and journey details, work and sleep history and driving performance concerning the day the participant was recruited. Participants also completed the Karolinska Sleepiness Scale and the Epworth Sleepiness Scale. Night workers reported significantly more sleepiness, shorter sleep duration and commuting longer distances. Seven variables were significant predictors of lane crossing. The strongest predictor was acute sleepiness (OR = 5.25, CI, 1.42–19.49, p<0.01) followed by driving ≥150 kms (OR = 3.61, CI, 1.66–7.81, p<0.001), obtaining less than 10 hours sleep in the previous 48 hours (OR = 2.58, CI, 1.03–6.46, p<0.05), driving after night shift (OR = 2.19, CI, 1.24–3.88, p<0.001), being <43 years old (OR = 1.95, CI, 1.11–3.41, p<0.05) and using mobile phones during the journey (OR = 1.90, CI, 1.10–3.27, p<0.05). Sleep related variables, long-distance commuting and night work have a major impact on lane crossing. Several interventions should be considered to reduce the level of sleepiness in night workers.