Cohort studies in public health practice and their significance / 上海预防医学

Cohort studies play an important role in elucidating the association between risk factors and diseases， and are widely used in etiology research， the assessment of disease prognosis， understanding the natural history of diseases， and the surveillance following the market release of new drugs. The data produced by cohort studies possess great scientific value and can provide essential evidence for public health practice. A well-conceived scientific design is a prerequisite to conducting a cohort study， and the design should focus on aspects such as sample size， selection of exposed and non-exposed populations， follow-up procedures， outcome assessments， research duration， and the choice of analytical indicators and methods. Cohort studies have become an important way to obtain scientific evidence. Internationally renowned population-based cohorts， such as China Kadoorie biobank and the Framingham heart study cohort， have provided a wealth of scientifically valuable evidence for promoting human health. The quality of data produced by a cohort study is extremely important， and a cohort study should continuously incorporate new technologies and methods to provide objective， accurate， and reliable means to determine exposure and outcomes， as well as control for bias. Cohort studies have great potential for application and will continue to provide abundant high-quality scientific evidence for the development of strategies and measures to enhance human health.

The Way of Water: Unravelling White Spot Syndrome Virus (WSSV) Transmission Dynamics in Litopenaeus vannamei Shrimp.

White spot disease (WSD) is a severe viral threat to the global shrimp aquaculture industry. However, little is known about white spot syndrome virus (WSSV) transmission dynamics. Our aim was to elucidate this in Litopenaeus vannamei using peroral in vivo WSSV challenge experiments. We demonstrated that WSD progression was rapid and irreversible, leading to death within 78 h. Viral DNA shedding was detected within 6 h of disease onset. This shedding intensified over time, reaching a peak within 12 h of the time of death. Isolating shrimp (clinically healthy and diseased) from infected populations at different time points post-inoculation showed that host-to-host WSSV transmission was occurring around the time of death. Exposing sentinels to environmental components (i.e., water, feces, molts) collected from tanks housing WSSV-infected shrimp resulted in a significantly (p-value < 0.05) increased infection risk after exposure to water (1.0) compared to the risk of infection after exposure to feces (0.2) or molts (0.0). Furthermore, ingestion of WSSV-infected tissues (cannibalism) did not cause a significantly higher number of WSD cases compared to immersion in water in which the same degree of cannibalism had taken place.

Hepatitis B virus genotypes and subgenotypes and the natural history and epidemiology of hepatitis B.

INTRODUCTION AND OBJECTIVES: Espírito Santo state is considered a region with a higher frequency of hepatitis B virus infection. This study characterized demographic, epidemiological, laboratory, virological and clinical aspects of 587 chronic HBV carriers followed up at the University of Espírito Santo Hospital. MATERIALS AND METHODS: Demographic, epidemiological, laboratory and clinical data were extracted from medical records during the entire follow-up period. Classification of the evolutionary phases of chronic hepatitis B was defined as immunotolerant; inactive carrier; chronic active hepatitis HBeAg (+)  and HBeAg (-). Characterization of HBV genotypes/subgenotypes was performed by sequencing of overlapping surface antigens and HBV DNA polymerase genes. Phylogenetic relationships were determined using BEAST 1.8.3 software. RESULTS: and Conclusions: Genotypes found were A (132/65.3%) [A1 = 129 (63.9%) and A2 = 3 (1.5%)], D (66/32.7%) [D3 = 56 (27.7%), D4 = 8 (4.0%) and D2 = 2 (1.0%)] and F (4/2.0%) - all F2a. Subgenotypes A1 or D3 were not associated with age, sex, HIV/HCV co-infection, viral load, antiviral usage, HBeAg status or clinical stages of chronic hepatitis B. Mother -to-child-transmission (MTCT) was associated with the subgenotype A1 and intrafamilial transmission with subgenotype D3. Subgenotype A1 was more frequent than D3 among individuals born outside ES compared to those born in ES. CONCLUSIONS: The most predominant clinical phases were HBeAg (-), inactive carrier and chronic active hepatitis HBeAg (-). Subgenotypes A1 and D3 were most frequent and were associated were MTCT and intrafamilial transmission of HBV, respectively.

Clinical disease progression and biomarkers in Niemann-Pick disease type C: a prospective cohort study.

BACKGROUND: Niemann-Pick disease type C (NPC) is a rare, progressive, neurodegenerative disease associated with neurovisceral manifestations resulting from lysosomal dysfunction and aberrant lipid accumulation. A multicentre, prospective observational study (Clinical Trials.gov ID: NCT02435030) of individuals with genetically confirmed NPC1 or NPC2 receiving routine clinical care was conducted, to prospectively characterize and measure NPC disease progression and to investigate potential NPC-related biomarkers versus healthy individuals. Progression was measured using the abbreviated 5-domain NPC Clinical Severity Scale (NPCCSS), 17-domain NPCCSS and NPC clinical database (NPC-cdb) score. Cholesterol esterification and heat shock protein 70 (HSP70) levels were assessed from peripheral blood mononuclear cells (PBMCs), cholestane-3ß,5α-,6ß-triol (cholestane-triol) from serum, and unesterified cholesterol from both PBMCs and skin biopsy samples. The inter- and intra-rater reliability of the 5-domain NPCCSS was assessed by 13 expert clinicians' rating of four participants via video recordings, repeated after ≥ 3 weeks. Intraclass correlation coefficients (ICCs) were calculated. RESULTS: Of the 36 individuals with NPC (2-18 years) enrolled, 31 (86.1%) completed the 6-14-month observation period; 30/36 (83.3%) were receiving miglustat as part of routine clinical care. A mean (± SD) increase in 5-domain NPCCSS scores of 1.4 (± 2.9) was observed, corresponding to an annualized progression rate of 1.5. On the 17-domain NPCCSS, a mean (± SD) progression of 2.7 (± 4.0) was reported. Compared with healthy individuals, the NPC population had significantly lower levels of cholesterol esterification (p < 0.0001), HSP70 (p < 0.0001) and skin unesterified cholesterol (p = 0.0006). Cholestane-triol levels were significantly higher in individuals with NPC versus healthy individuals (p = 0.008) and correlated with the 5-domain NPCCSS (Spearman's correlation coefficient = 0.265, p = 0.0411). The 5-domain NPCCSS showed high ICC agreement in inter-rater reliability (ICC = 0.995) and intra-rater reliability (ICC = 0.937). CONCLUSIONS: Progression rates observed were consistent with other reports on disease progression in NPC. The 5-domain NPCCSS reliability study supports its use as an abbreviated alternative to the 17-domain NPCCSS that focuses on the most relevant domains of the disease. The data support the use of cholestane-triol as a disease monitoring biomarker and the novel methods of measuring unesterified cholesterol could be applicable to support NPC diagnosis. Levels of HSP70 in individuals with NPC were significantly decreased compared with healthy individuals. TRIAL REGISTRATION: CT-ORZY-NPC-001: ClincalTrials.gov NCT02435030, Registered 6 May 2015, https://clinicaltrials.gov/ct2/show/NCT02435030 ; EudraCT 2014-005,194-37, Registered 28 April 2015, https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-005194-37/DE . OR-REL-NPC-01: Unregistered.

Elizabethkingia miricola as an opportunistic oral pathogen associated with superinfectious complications in humoral immunodeficiency: a case report.

BACKGROUND: Elizabethkingia miricola is a rare Gram-negative bacterium found in water and clinical specimens. Typical culturing methods often misidentify Elizabethkingia spp. as Flavobacterium or Chryseobacterium. Although diagnosis is based on culturing samples taken from sterile sites, such as blood, a proper identification of this bacterium requires an expertise that goes beyond the capabilities of a typical clinical laboratory. CASE PRESENTATION: A 35-year-old woman diagnosed with common variable immunodeficiency was admitted to our center. Previous treatment with antibiotics (amoxicillin plus clavulanate, first and third generation of cephalosporins, macrolides) and systemic corticosteroids (up to 120 mg/day of prednisolone) failed to arrest the spread of inflammation. Gingival recession was observed in her oral cavity, resulting in an apparent lengthening of her teeth. In addition to typical commensal bacteria, including streptococci and neisseriae, strains of Rothia mucilaginosa and Elizabethkingia miricola were identified upon a detailed microbiological examination using a MALDI-TOF MS Biotyper system. The presence of the latter strain correlated with severe periodontitis, lack of IgA in her saliva and serum, a very low IgG concentration (< 50 mg/dl), IgM-paraproteinemia, decreases in C3a and C5a and microvascular abnormality. High-dose immunoglobulin (to maintain IgG > 500 mg/dl) and targeted levofloxacin treatment resulted in immune system reconstitution, oral healing, and eradication of the Elizabethkingia infection. CONCLUSIONS: E. miricola rarely causes disease in healthy individuals. However, the overgrowth of commensal bacteria, lack of IgG/IgA, microvasculopathy and complement cascade activation in patients with humoral immunodeficiency may facilitate Elizabethkingia invasion. Overuse of antibiotics, particularly beta-lactams, may cause mucosal colonization by E. miricola, followed by its multiplication combined with periodontitis that prompts bacterial translocation. MALDI-TOF Biotyper analysis may become a method of choice for identification of Elizabethkingia infections.

Modelling the burden of hepatitis C infection among people who inject drugs in Norway, 1973-2030.

BACKGROUND: Lack of Hepatitis C virus (HCV) incidence data in (Norwegian) high-risk groups impedes the ability to make informed decisions on prevention measures. Thus we rely on modelling to estimate the incidence and burden of HCV infections. METHODS: We constructed a compartmental model for HCV infections in Norway among active and former people who inject drugs (PWIDs). We based yearly transition rates on literature. The model was fitted to absolute numbers of hepatitis C associated cirrhosis, hepatocellular carcinoma (HCC) and death from national data sources (2000-2013). We estimated the number (95%CI) of HCV infections, cirrhosis, HCC and death and disability adjusted life years (DALYs) due to HCV infections in Norway, 1973-2030. We assumed treatment rates in the projected period were similar to those in 2013. RESULTS: The estimated proportion of chronic HCV (including those with cirrhosis and HCC) among PWIDs was stable from 2000 (49%; 4441/9108) to 2013 (43%; 3667/8587). We estimated that the incidence of HCV among PWIDs was 381 new infections in 2015. The estimated number of people with cirrhosis, HCC, and liver transplant was predicted to increase until 2022 (1537 people). DALYs among active PWIDs estimated to peak in 2006 (3480 DALYs) and decrease to 1870 DALYs in 2030. Chronic HCV infection contributes most to the total burden of HCV infection, and peaks at 1917 DALYs (52%) in 2007. The burden of HCV related to PWID increased until 2006 with 81/100,000 DALYs inhabitants and decreased to 68/100,000 DALYs in 2015. CONCLUSION: The burden of HCV associated with injecting drug use is considerable, with chronic HCV infection contributing most to the total burden. This model can be used to estimate the impact of different interventions on the HCV burden in Norway and to perform cost-benefit analyses of various public health measures.

Natural history of patients with tuberous sclerosis complex related renal angiomyolipoma.

OBJECTIVE: To examine temporal relationships between tuberous sclerosis complex (TSC) and renal angiomyolipoma diagnosis and outcomes, treatment, and healthcare utilization. METHODS: Administrative data from the MarketScan Commercial Database was used to select TSC-related renal angiomyolipoma patients during 1 January 2000-31 March 2013. Patients were followed until the earliest of inpatient death or end of enrollment or study. Occurrence of kidney-related outcomes, kidney-related procedures, and all-cause healthcare utilization and time to occurrence were reported. Kaplan-Meier curves were used to display the unadjusted distribution of time to outcome. RESULTS: A total of 605 patients were selected (<18 years N = 225; ≥18 years N = 380). Mean time from TSC to renal angiomyolipoma diagnosis was 25.7 months in younger and 16.9 months in older patients. Patients ≥18 years had higher rates of chronic kidney disease (CKD), hematuria, kidney failure, embolization (EMB), and partial and complete nephrectomy compared to patients <18 years (all p < .05). Mean time from TSC-related renal angiomyolipoma diagnosis to CKD, hematuria, kidney failure, EMB, first emergency room and inpatient visits was shorter in older compared to younger patients (all p < .05). Probability of developing CKD was approximately 0.8 and 0.95 within 3 years in younger and older patients, respectively. CONCLUSIONS: Patients with TSC-related renal angiomyolipoma had high rates of kidney-related outcomes and procedures. These events sometimes preceded the angiomyolipoma diagnosis. A key study limitation was that due to the small sample size, results may have been biased by outliers. Research is needed to determine whether earlier angiomyolipoma diagnosis can impact occurrence of events and reduce healthcare utilization.

Cystic Adverse Local Tissue Reactions in Asymptomatic Modular Metal-on-Metal Total Hips May Decrease Over Time.

BACKGROUND: The presence of pain as a harbinger of bearing-related problems has recently been challenged. Adverse local tissue reactions (ALTRs) have been noted on cross-sectional imaging even in asymptomatic patients. The purpose of this study was to determine the natural history of such lesions in asymptomatic patients. METHODS: Eighty-three asymptomatic patients with modular metal-on-metal total hip arthroplasties underwent metal ion reports and metal artifact reduction sequence magnetic resonance imaging (MARS MRI). MARS MRI images were reviewed and evaluated for the presence or absence of an ALTR lesion by a musculoskeletal radiologist and the senior author. We defined an ALTR lesion as abnormal fluid collections, solid or semisolid pseudotumors, or muscle or bone damage and was classified according to the MRI Classification System of Hart et al. In addition, serum cobalt and chromium levels were measured and analyzed at the time of MRI. RESULTS: Twenty-six of 83 (31%) asymptomatic patients had cystic lesions identified. All patients with positive MRIs were contacted to have repeat studies a year later. Nineteen of 26 were available for follow-up. Three patients who became symptomatic were revised. Most ALTRs in asymptomatic patients with modular metal-on-metal total hip arthroplasties that underwent repeat MARS MRI decreased in size (15 of 19 [79%]); 3 lesions increased, whereas 1 remained the same. All patients in the series had Co and Cr ion levels below the threshold of 7 ppb. CONCLUSION: Although most cystic lesions decreased in size, vigilance is still required as 3 patients became symptomatic requiring revision.