Electrolyte imbalances as poor prognostic markers in COVID-19: a systemic review and meta-analysis.

PURPOSE: Serum electrolyte imbalances are highly prevalent in COVID-19 patients. However, their associations with COVID-19 outcomes are inconsistent, and of unknown prognostic value. We aim to systematically clarify the associations and prognostic accuracy of electrolyte imbalances (sodium, calcium, potassium, magnesium, chloride and phosphate) in predicting poor COVID-19 clinical outcome. METHODS: PubMed, Embase and Cochrane Library were searched. Odds of poor clinical outcome (a composite of mortality, intensive-care unit (ICU) admission, need for respiratory support and acute respiratory distress syndrome) were pooled using mixed-effects models. The associated prognostic sensitivity, positive and negative likelihood ratios (LR + , LR-) and predictive values (PPV, NPV; assuming 25% pre-test probability), and area under the curve (AUC) were computed. RESULTS: We included 28 observational studies from 953 records with low to moderate risk-of-bias. Hyponatremia (OR = 2.08, 95% CI = 1.48-2.94, I2 = 93%, N = 8), hypernatremia (OR = 4.32, 95% CI = 3.17-5.88, I2 = 45%, N = 7) and hypocalcemia (OR = 3.31, 95% CI = 2.24-4.88, I2 = 25%, N = 6) were associated with poor COVID-19 outcome. These associations remained significant on adjustment for covariates such as demographics and comorbidities. Hypernatremia was 97% specific in predicting poor outcome (LR + 4.0, PPV = 55%, AUC = 0.80) despite no differences in CRP and IL-6 levels between hypernatremic and normonatremic patients. Hypocalcemia was 76% sensitive in predicting poor outcome (LR- 0.44, NPV = 87%, AUC = 0.71). Overall quality of evidence ranged from very low to moderate. CONCLUSION: Hyponatremia, hypernatremia and hypocalcemia are associated with poor COVID-19 clinical outcome. Hypernatremia is 97% specific for a poor outcome, and the association is independent of inflammatory marker levels. Further studies should evaluate if correcting these imbalances help improve clinical outcome.

Adherence to clozapine vs. other antipsychotics in schizophrenia.

BACKGROUND: To date, there have been no studies evaluating adherence to clozapine with electronic adherence monitoring (EAM) such as the Medication Event Monitoring System (MEMS® ). METHODS: In outpatients with schizophrenia, we conducted a 3-month prospective study investigating antipsychotic adherence with EAM (eCAP® ). Participants were treated with different oral antipsychotics, including clozapine, and blind to EAM monitoring; all were on antipsychotic monotherapy administered once daily. Outcome measures included adherence rate, missed dose, and medication gap. Adherence trajectory patterns were also analyzed for clozapine vs. other antipsychotics collectively. RESULTS: A total of 111 patients were included in the study; 33 and 78 patients received clozapine or other antipsychotics, respectively. Adherence rates, defined as proportion of days that the subject took the medication at the prescribed time ± 3 h and proportion of subjects with ≥80% adherence, were numerically higher in patients receiving clozapine vs. other antipsychotics (72.0% vs. 65.1%, P = 0.10; 49.5% vs. 35.7%, P = 0.11, respectively). Along similar lines, some of the missed dose and medication gap outcomes were significantly better in patients receiving clozapine vs. other antipsychotics. Three adherence trajectory patterns were identified for both clozapine and other antipsychotics, with two shared by both groups (i.e., low adherence with a slight decrease over time; high and stable adherence). CONCLUSION: Findings suggest that in patients with schizophrenia clozapine adherence is at least comparable, if not slightly better, compared with other antipsychotics.

Cost Effectiveness of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Management of Colorectal Peritoneal Carcinomatosis.

BACKGROUND: Peritoneal carcinomatosis from colorectal cancer is a stage 4 disease for which palliative chemotherapy has traditionally been considered the mainstay of treatment. Since the development of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) by Sugarbaker, this combined method treatment has resulted in improved survival outcomes with acceptable morbidity for selected patients with peritoneal carcinomatosis. This study examined the cost effectiveness of CRS and HIPEC compared with palliative chemotherapy for patients with peritoneal carcinomatosis from colorectal cancer within the context of the Singaporean health care system. METHODS: A retrospective review of patients with peritoneal carcinomatosis from histologically proven colorectal cancer treated at the National Cancer Centre Singapore (NCCS) was conducted. RESULTS: The average cost of CRS and HIPEC per patient was S$83,680.26, and the median overall survival period was 47 months. The calculated cost per life year attained for a patient who underwent CRS and HIPEC was S$21,365.19 per life year. In comparison, the average cost of palliative chemotherapy was S$44,478.87, with a median overall survival of 9 months, and the calculated cost per life year attained for a patient in this treatment group was S$59,305.16 per life year. CONCLUSION: The findings show that CRS and HIPEC results in prolonged survival for selected patients with colorectal peritoneal carcinomatosis and a lower cost per life year attained than for the traditionally used palliative chemotherapy. It should logically be the preferred treatment of choice for selected patients with colorectal peritoneal metastasis.

19th-century and early 20th-century jaundice outbreaks, the USA.

Historical enquiry into diseases with morbidity or mortality predilections for particular demographic groups can permit clarification of their emergence, endemicity, and epidemicity. During community-wide outbreaks of hepatitis A in the pre-vaccine era, clinical attack rates were higher among juveniles rather than adults. In community-wide hepatitis E outbreaks, past and present, mortality rates have been most pronounced among pregnant women. Examination for these characteristic predilections in reports of jaundice outbreaks in the USA traces the emergence of hepatitis A and also of hepatitis E to the closing three decades of the 19th century. Thereafter, outbreaks of hepatitis A burgeoned, whereas those of hepatitis E abated. There were, in addition, community-wide outbreaks that bore features of neither hepatitis A nor E; they occurred before the 1870s. The American Civil War antedated that period. If hepatitis A had yet to establish endemicity, then it would not underlie the jaundice epidemic that was widespread during the war. Such an assessment may be revised, however, with the discovery of more extant outbreak reports.

Barriers and facilitators to starting insulin in patients with type 2 diabetes: a systematic review.

AIM: To identify the barriers and facilitators to start insulin in patients with type 2 diabetes. METHOD: This was a systematic review. We conducted a systematic search using PubMed, EMBASE, CINAHL and Web of Science (up to 5 June 2014) for original English articles using the terms 'type 2 diabetes', 'insulin', and free texts: 'barrier' or 'facilitate' and 'initiate'. Two pairs of reviewers independently assessed and extracted the data. Study quality was assessed with Qualsyst. RESULTS: A total of 9740 references were identified: 41 full-text articles were assessed for eligibility. Twenty-five articles (15 qualitative, 10 quantitative) were included in the review. Good inter-rater reliability was observed for the Qualsyst score (weighted kappa 0.7). Three main themes identified were as follows: patient-related, healthcare professional and system factors. The main patient-related barriers were fear of pain and injection (n = 18), concerns about side effects of insulin (n = 12), perception that insulin indicated end stage of diabetes (n = 11), inconvenience (n = 10), difficulty in insulin administration (n = 7), punishment (n = 7) and stigma and discrimination (n = 7). Healthcare professionals' barriers were as follows: poor knowledge and skills (n = 9), physician inertia (n = 5) and language barriers (n = 4). System barriers included lack of time (n = 5). The most common facilitators were understanding the benefits of insulin (n = 7), not being afraid of injections (n = 5), and patient education and information (n = 5). CONCLUSION: Major barriers to insulin initiation persist despite availability of newer and safer insulin. Healthcare professionals should explore and address these barriers. Targeted interventions should be developed to overcome these barriers.

A consensus on men's health status and policy in Asia: a Delphi survey.

OBJECTIVE: There is currently no documentation on the availability and implementation of policies related to men's health in Asia. This Delphi study aimed to achieve an Asian consensus on men's health policy based on the opinions and recommendations from men's health key opinion leaders. STUDY DESIGN: A two-phase Delphi online survey was used to gather information from men's health stakeholders across Asian countries. METHODS: All stakeholders were invited to participate in the survey through men's health conferences, personal contacts, recommendations from international men's health organizations and snowballing method. Stakeholders were asked about their concerns on 17 men's health key issues as well as their opinion on the availability and recommendations on men's health policies and programmes in their countries. RESULTS: There were a total of 128 stakeholders (policy makers, clinicians, researchers and consumers), from 28 Asian countries, who responded in the survey. Up to 85% of stakeholders were concerned about various men's health issues in Asia and in their respective country, particularly in smoking, ischaemic heart disease and high blood pressure. There is a lack of men's health policies and programmes in Asia (availability = 11.6-43.5%) and up to 92.9% of stakeholders recommended that these should be developed. CONCLUSIONS: These findings call for policy change and development, and more importantly a concerted effort to elevate men's health status in Asia.

Blue dye is sufficient for sentinel lymph node biopsy in breast cancer.

BACKGROUND: Most previous studies have reported superior results when blue dye and radiocolloids were used together for sentinel lymph node (SLN) biopsy in early breast cancer. Blue dye was reported to perform poorly when used alone, although more recent studies have found otherwise. This study reviewed the authors' practice of performing SLN biopsy with blue dye alone. METHODS: This was a retrospective review of patients who underwent SLN biopsy using blue dye alone from 2001 to 2005, when SLN biopsy was performed selectively and always followed by axillary lymph node dissection (ALND), and from 2006 to 2010, when SLN biopsy was offered to all suitable patients and ALND done only when the SLN was not identified or positive for metastasis. RESULTS: Between 2001 and 2005, 170 patients underwent SLN biopsy with blue dye alone. The overall SLN non-identification rate was 8·4 per cent. The overall false-negative rate was 34 per cent, but decreased with each subsequent year to 13 per cent in 2005. From 2006 to 2010, 610 patients underwent SLN biopsy with blue dye alone. The SLN was not identified in 12 patients (2·0 per cent) and no significant contributing factor was identified. A median of 2 (range 1-11) SLNs were identified. A non-SLN was found to be positive for metastasis in two patients with negative SLNs. Axillary nodal recurrence developed in one patient; none developed internal mammary nodal recurrence. Anaphylaxis occurred in one patient. CONCLUSION: Blue dye performed well as a single modality for SLN biopsy. Non-identification, axillary nodal recurrence and serious allergic reactions were uncommon.

Intracranial pial arteriovenous fistula in infancy: a case report and literature review.

Intracranial pial arteriovenous fistulas (AVF) are rare vascular malformation especially in the first 2 years of life. The pathology in this age group is associated with greater morbidity and mortality. We report a rare case of 36-day-old male infant with a pial AVF associated with an arterial aneurysm, who presented with intraventricular hemorrhage and hydrocephalus. In addition, an online review of the literatures on pediatric pial AVF was performed using PubMed on published case reports and articles from 1980 to April 2013.

An innovative model of delivering cancer care in the community: the experience of a tertiary cancer centre in Singapore.

BACKGROUND: Cancer care has evolved rapidly, increasing the demand on healthcare resources. While many non-oral cancer treatments are administered in the hospital, not all necessitate complex medical care. Treatments that can be administered subcutaneously, intramuscularly, or as short intravenous infusions with a low risk of extravasation can be safely administered in the community. PATIENTS AND METHODS: Since 2017, the National University Cancer Institute, Singapore (NCIS) has operated a program called NCIS on-the-go (NOTG) comprising a network of community cancer treatment clinics located within 20 km of the hospital. NOTG provides 17 low-risk treatments and nursing services run by oncology-trained nurses without on-site physicians. Patients who receive their first dose of cancer treatment uneventfully in the cancer centre can opt-in to receive subsequent doses at any NOTG clinic. RESULTS: Treatment at NOTG has become more mainstream over the years, with its workload increasing by over sevenfold since 2017, and is now responsible for ∼10% of the total main cancer centre workload. The program is sustainable and financially viable to operate. A survey of 155 patients revealed a 96.8% user satisfaction rate, with the majority reporting tangible savings in travelling time, waiting time, and travelling costs. The diversion of low-risk treatments to NOTG has indirectly increased capacity and reduced waiting times at the main cancer centre for patients requiring complex cancer treatments, resulting in a win-win situation. CONCLUSIONS: NOTG represents an innovative model of care to deliver low-risk cancer treatments safely in the community and can be easily replicated in other countries.

Hepatitis B virus transmission in pre-adolescent schoolchildren in four multi-ethnic areas of England.

The aim of this study was to estimate the amount of childhood hepatitis B virus transmission in children born in the UK, a very low-prevalence country, that is preventable only by universal hepatitis B immunization of infants. Oral fluid specimens were collected from schoolchildren aged 7-11 years in four inner city multi-ethnic areas and tested for the presence of antibody to hepatitis B core antigen (anti-HBc). Those found positive or indeterminate were followed up with testing on serum to confirm their hepatitis B status. The overall prevalence of anti-HBc in children was low [0.26%, 95% confidence interval (CI) 0.14-0.44]. The estimated average annual incidence of hepatitis B was estimated to be 29.26/100 000 children (95% CI 16.00-49.08). The total incidence that is preventable only by a universal infant immunization programme in the UK was estimated to be between 5.00 and 12.49/100 000. The study demonstrates that the extent of horizontal childhood hepatitis B virus transmission is low in children born in the UK and suggests that schools in the UK are an uncommon setting for the transmission of the virus. Targeted hepatitis B testing and immunization of migrants from intermediate- and high-prevalence countries is likely to be a more effective measure to reduce childhood transmission than a universal infant immunization programme.

Association of ethnicity with antipsychotic dosage using STRUCTURE analysis.

Several studies have examined whether ethnicity as an independent factor can influence the individual's dosage of antipsychotics. However, there has been inconsistency in the results of these studies, particularly between white and non-white populations. This retrospective study tests the hypothesis of different dosing of antipsychotics in white Europeans vs. non-white Europeans considering both the self-reported ethnicity and the geographical ancestry calculated using 196 DNA markers.We collected self-reported ethnicity and DNA samples from 209 schizophrenia patients. We tested the association between self-reported and genetically-determined ethnicity with the chlorpromazine equivalent dose of each antipsychotic prescribed at the time of the assessment.We did not find any significant difference between self-reported white European -ethnicity and chlorpromazine equivalent doses (p=0.972). Furthermore, when we considered the geographical ancestry determined by the 196 SNPs, we could not find any correlation between the European ancestry and chlorpromazine equivalent dose.Our preliminary analysis shows that there is no evidence that different ethnic groups receive different dose of antipsychotics.

Subablative Er:YAG laser effect on enamel demineralization.

OBJECTIVES: To characterize the cariostatic potential of a low-energy Er:YAG laser treatment. METHODS: Twelve sound premolars were selected. Two 2 × 1 mm windows were created on each tooth and randomly assigned to L(1) and L(2) groups. Three sites in each window were chosen with the middle site as the control and the left and right ones receiving Er:YAG laser treatment of 5.1 J/cm(2) (L(1)) or 2.0 J/cm(2) (L(2)), respectively. The teeth were further subjected to 4-day pH cycling to create caries-like lesions. After mineral quantification using a micro-computed tomography scanner, the preventive effects (ΔML = mineral loss of the control area minus that of the lased area) of L(1) and L(2) treatments were calculated based on the difference in the gray value of the control and lased sites. RESULTS: Significant inhibitory effects of L(1) and L(2) on enamel demineralization were demonstrated (both p ≤ 0.001), with the L(1) treatment having a greater effect (45.2%) than the L(2) treatment (25.2%, p = 0.004). CONCLUSIONS: Subablative low-energy Er:YAG laser irradiation can significantly prevent enamel demineralization potentially through the retardation of enamel diffusion. This study confirmed that high-energy laser treatment, which may damage the peripheral and underlying tissues, may not be needed for caries prevention.

Post mortem changes in relation to different types of clothing.

Post mortem changes are important in estimating post mortem interval (PMI). This project's aim was to study the effect of burial and type of clothing on rate of decomposition, which can contribute to estimating PMI for victims. 12 rabbits (Oryctolagus cuniculus) carcasses were separated into 3 groups: no clothing, light clothing and heavy clothing. Control subjects were placed on the ground surface while test subjects were buried at 30 cm depth graves. Soil samples prior and after decomposition were collected for soil pH and moisture analysis. Post mortem change was assessed using a Total Body Score system. The head, neck and limb regions were found to decay faster than the body trunk region. Mummifi cation occurred on body parts that were exposed directly to the atmosphere while adipocere formed on some buried subjects. Burial delayed decomposition due to lower insect activity and lower soil temperature. The soil layer also blocked the accessibility of majority of the arthropods, causing further delay in decomposition. Clothing enhanced decay for bodies on ground surface because it provided protection for maggots and retained moisture on tissues. However, clothing delayed decomposition in buried bodies because it physically separated the bodies from soil and arthropods. Higher sun exposure and repetitive exhumation showed acceleration of decomposition. The decomposition process increased soil pH and moisture percentage values. Soil pH initially increased until pH 8.0-8.4 followed by a slight decrease while soil moisture percentage changed inconsistently. Burial was significant in affecting post mortem change, F(1,11)=12.991, p<0.05 while type of clothing was not significant, F(2,9)=0.022, p=0.978 and combination of both type of clothing and burial factors were also not significant, F(2,3)=0.429, p=0.686. For validation, an accuracy of 83.33% was achieved based on soil pH and soil moisture percentage analysis.

Contamination of the central medical air supply with water leading to mass ventilator failure.

Here, we present a case of mass ventilator failure due to contaminated medical air. Multiple ventilators failed routine tests, including almost all of the ventilators in our intensive care unit. A faulty air compressor had led to water contamination of our centre's supply of medical air. Water entered the pipeline supply of air and, hence the ventilators and anaesthetic machines. The disruption of the machines' proportional mixer valve resulted in unreliable delivery of fresh gas flow. This malfunction was discovered during routine pre-use checks, and backup ventilators were available to replace the faulty ventilators. A shortage of equipment was averted due to a serendipitous availability of ventilator stockpiles prepared for the COVID-19 pandemic. Ventilator shortages are commonly described in mass casualty and pandemic scenarios. While there are multiple strategies described in literature to augment and maximise equipment available for mechanical ventilation, stockpiling equipment remains an expensive but necessary component of disaster contingency planning.

Fatal outbreaks of jaundice in pregnancy and the epidemic history of hepatitis E.

Space-time clustering of people who fall acutely ill with jaundice, then slip into coma and death, is an alarming phenomenon, more markedly so when the victims are mostly or exclusively pregnant. Documentation of the peculiar, fatal predisposition of pregnant women during outbreaks of jaundice identifies hepatitis E and enables construction of its epidemic history. Between the last decade of the 18th century and the early decades of the 20th century, hepatitis E-like outbreaks were reported mainly from Western Europe and several of its colonies. During the latter half of the 20th century, reports of these epidemics, including those that became serologically confirmed as hepatitis E, emanated from, first, the eastern and southern Mediterranean littoral and, thereafter, Southern and Central Asia, Eastern Europe, and the rest of Africa. The dispersal has been accompanied by a trend towards more frequent and larger-scale occurrences. Epidemic and endemic hepatitis E still beset people inhabiting Asia and Africa, especially pregnant women and their fetuses and infants. Their relief necessitates not only accelerated access to potable water and sanitation but also vaccination against hepatitis E.

CdSe/ZnS quantum dot size dependent carrier relaxation in hybrid organic/inorganic system.

We have studied the CdSe/ZnS quantum dot (QD) size dependent carrier relaxation dynamics in hybrid organic/inorganic system for the first time. The QD size was from 5.0 to 2.0 nm. The optical narrow emission of quantum dots shift to higher energies as the size of dots gets smaller due to the 3-D confinement which splits the continuous band into a series of discrete quantum states and increases the band gap. The carrier relaxation time in QDs was found to increases as the pump power increased and reached saturation at approximately 326 microW excitation, probably due to the saturation of traps with the photoexcited charge carriers within individual nanoparticles. The relaxation rate was also increased with pump power, indicating that new relaxation processes e.g., Auger processes and faster carrier trapping were present. The slow decay component remained at the lowest power (51microW) excitation with no fast decay present. The decrease of CdSe/ZnS QD size increased the fast component relaxation rate probably due to a higher number of surface defects hence inducing faster trapping of carriers by shallow trap state.

The SINgapore GERiatric Intervention Study to Reduce Cognitive Decline and Physical Frailty (SINGER): Study Design and Protocol.

BACKGROUND: The SINgapore GERiatric intervention study to reduce cognitive decline and physical frailty (SINGER) randomised controlled trial (RCT) uses a multidomain lifestyle interventions approach, shown to be effective by the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) trial, to delay cognitive decline. OBJECTIVE: To investigate the efficacy and safety of the SINGER multidomain lifestyle interventions in older adults at risk for dementia to delay cognitive decline. PARTICIPANTS: 1200 participants between 60-77 years old, with Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score ≥6, fulfilling at least one of the following LIBRA index for diet, cognitive activity, physical activity and a Montreal Cognitive Assessment (MoCA) score ≥18, ≤27 points, will be recruited across Singapore. METHODS: SINGER is a 2-year multi-site RCT consisting of multidomain interventions: dietary advice, exercise, cognitive training, and vascular risk factors management. Participants will be randomised into either the Self-Guided Intervention (SGI; general lifestyle and health information and resources) or Structured Lifestyle Intervention (SLI) group. The SLI comprises diet training (6 group and 3 individual sessions over 12 months); exercise (supervised: 1-hour twice weekly for 6 months, unsupervised: 2-3/week for the rest of the study duration); cognitive sessions (15-30 minutes/session, 3/week for 6 months, together with 10 workshops in 24 months). Vascular management takes place every 3-6 months or otherwise as specified by study physicians. The primary outcome is global cognition measured using the modified Neuropsychological Battery assessing performance in various domains, such as episodic memory, executive function and processing speed. Secondary outcome measures include: domain-specific cognition and function, imaging evidence of brain and retinal changes, incidence and progression of chronic diseases, blood biomarkers, quality of life, mental health and cost-benefit analysis. CONCLUSIONS: SINGER is part of the Worldwide-FINGERS international network, which is at the forefront of harmonizing approaches to effective non-pharmacological interventions in delaying cognitive decline in older adults at risk of dementia. By establishing the efficacy of multidomain interventions in preventing cognitive decline, SINGER aims to implement the findings into public health and clinical practices by informing policy makers, and guiding the design of community- and individual-level health promotion initiatives.

Transmission of human immunodeficiency virus and hepatitis C virus from an organ donor to four transplant recipients.

In 2007, a previously uninfected kidney transplant recipient tested positive for human immunodeficiency virus type 1 (HIV) and hepatitis C virus (HCV) infection. Clinical information of the organ donor and the recipients was collected by medical record review. Sera from recipients and donor were tested for serologic and nucleic acid-based markers of HIV and HCV infection, and isolates were compared for genetic relatedness. Routine donor serologic screening for HIV and HCV infection was negative; the donor's only known risk factor for HIV was having sex with another man. Four organs (two kidneys, liver and heart) were transplanted to four recipients. Nucleic acid testing (NAT) of donor sera and posttransplant sera from all recipients were positive for HIV and HCV. HIV nucleotide sequences were indistinguishable between the donor and four recipients, and HCV subgenomic sequences clustered closely together. Two patients subsequently died and the transplanted organs failed in the other two patients. This is the first recognized cotransmission of HIV and HCV from an organ donor to transplant recipients. Routine posttransplant HIV and HCV serological testing and NAT of recipients of organs from donors with suspected risk factors should be considered as routine practice.

Differences in variability of hypervariable region 1 of hepatitis C virus (HCV) between acute and chronic stages of HCV infection.

Distinguishing between acute and chronic HCV infections is clinically important given that early treatment of infected patients leads to high rates of sustained virological response. Analysis of 2179 clonal sequences derived from hypervariable region 1 (HVR1) of the HCV genome in samples obtained from patients with acute (n = 49) and chronic (n = 102) HCV infection showed that intra-host HVR1 diversity was 1.8 times higher in patients with chronic than acute infection. Significant differences in frequencies of 5 amino acids (positions 5, 7, 12, 16 and 18) and the average genetic distances among intra-host HVR1 variants were found using analysis of molecular variance. Differences were also observed in the polarity, volume and hydrophobicity of 10 amino acids (at positions 1, 4, 5, 12, 14, 15, 16, 21, 22 and 29). Based on these properties, a classification model could be constructed, which permitted HVR1 variants from acute and chronic cases to be discriminated with an accuracy of 88%. Progression from acute to chronic stage of HCV infection is accompanied by characteristic changes in amino acid composition of HVR1. Identifying these changes may permit diagnosis of recent HCV infection.