Characteristics and Management of Patients with Chronic Hepatitis B in an Integrated Care Setting

Background

Few population-based studies have described characteristics and management of patients with chronic hepatitis B (CHB) in the USA.

Methods

We retrospectively studied adults with CHB in the Northern California Kaiser Permanente Medical Care Program (KPNC) from July 2009 to December 2010 (n = 12,016). Laboratory tests, treatment patterns, and hepatocellular carcinoma (HCC) surveillance were ascertained during a “recent” 18-month study window (July 2009–December 2010), or as “ever” based on records dating to 1995.

Results

The mean age was 49 years; 51 % were men, 83 % Asian, and 87 % KPNC members >5 years. Overall, 51 % had ≥1 liver-related visit, 14 % with gastroenterology or infectious disease specialists, and 37 % with primary care providers (PCP) only. Less than 40 % of patients had both hepatitis B virus (HBV) DNA and ALT testing conducted recently, while 56 % of eligible patients had received HCC surveillance. Recent laboratory testing and HCC surveillance were more frequent in patients seen by a specialist versus PCP only (90 vs. 47 % and 92 vs. 73 %, respectively, p values <0.001). During the study period, 1,649 (14 %) received HBV treatment, while 5 % of untreated patients had evidence of treatment eligibility. Among 599 patients newly initiated on HBV therapy, 76 % had guideline-based indications for treatment.

Conclusions

Most patients initiated on HBV treatment met eligibility, and very few patients with evidence of needing treatment were left untreated. However, monitoring of ALT and HBV DNA levels, as well as HCC surveillance, were not frequent, underestimating the proportion of patients that warranted HBV therapy. Viral monitoring and cancer surveillance are therefore important targets for improving the scope of CHB care in the community setting.     

Test‐retest reliability of the default mode network in a multi‐centric fMRI study of healthy elderly: Effects of data‐driven physiological noise correction techniques

Understanding how to reduce the influence of physiological noise in resting state fMRI data is important for the interpretation of functional brain connectivity. Limited data is currently available to assess the performance of physiological noise correction techniques, in particular when evaluating longitudinal changes in the default mode network (DMN) of healthy elderly participants. In this 3T harmonized multisite fMRI study, we investigated how different retrospective physiological noise correction (rPNC) methods influence the within‐site test‐retest reliability and the across‐site reproducibility consistency of DMN‐derived measurements across 13 MRI sites. Elderly participants were scanned twice at least a week apart (five participants per site). The rPNC methods were: none (NPC), Tissue‐based regression, PESTICA and FSL‐FIX. The DMN at the single subject level was robustly identified using ICA methods in all rPNC conditions. The methods significantly affected the mean z‐scores and, albeit less markedly, the cluster‐size in the DMN; in particular, FSL‐FIX tended to increase the DMN z‐scores compared to others. Within‐site test‐retest reliability was consistent across sites, with no differences across rPNC methods. The absolute percent errors were in the range of 5–11% for DMN z‐scores and cluster‐size reliability. DMN pattern overlap was in the range 60–65%. In particular, no rPNC method showed a significant reliability improvement relative to NPC. However, FSL‐FIX and Tissue‐based physiological correction methods showed both similar and significant improvements of reproducibility consistency across the consortium (ICC = 0.67) for the DMN z‐scores relative to NPC. Overall these findings support the use of rPNC methods like tissue‐based or FSL‐FIX to characterize multisite longitudinal changes of intrinsic functional connectivity. Hum Brain Mapp 37:2114–2132, 2016. © 2016 Wiley Periodicals, Inc.     

Host density drives the postglacial migration of the tree parasite,Epifagus virginiana

To survive changes in climate, successful species shift their geographic ranges to remain in suitable habitats. For parasites and other highly specialized species, distributional changes not only are dictated by climate but can also be engineered by their hosts. The extent of host control on parasite range expansion is revealed through comparisons of host and parasite migration and demographic histories. However, understanding the codistributional history of entire forest communities is complicated by challenges in synthesizing datasets from multiple interacting species of differing datatypes. Here we integrate genetic and fossil pollen datasets from a host–parasite pair; specifically, the population structure of the parasitic plant (Epifagus virginiana) was compared with both its host (Fagus grandifolia) genetic patterns and abundance data from the paleopollen record of the last 21,000 y. Through tests of phylogeographic structure and spatial linear regression models we find, surprisingly, host range changes had little effect on the parasite''s range expansion and instead host density is the main driver of parasite spread. Unlike other symbionts that have been used as proxies to track their host''s movements, this parasite''s migration routes are incongruent with the host and instead reflect the greater importance of host density in this community''s assembly. Furthermore, these results confirm predictions of disease ecological models regarding the role of host density in the spread of pathogens. Due to host density constraints, highly specialized species may have low migration capacities and long lag times before colonization of new areas.     

Effects of rocking on neuromuscular development in the premature

It has been postulated that motion stimulation accelerates postnatal development. To test this hypothesis, 26 premature infants participated in a randomized controlled study of the effects of rocking on body weight gain and measures of neuromuscular development. Treatment infants were exposed to 15-min sessions of sinusoidal oscillation about the longitudinal axis, three times a day for 2 weeks. Infants were evaluated at the beginning and end of the 2-week treatment period and 2 weeks later. Neuromuscular development at these three times was measured with the comprehensive Dubowitz examination. Following treatment, large as compared with small premature infants showed a marked, but not statistically significant increase in weight gain. Duration of treatment appears to be a critical factor in influencing weight gain. All infants exposed to motion stimulation showed significant gains over controls in overall neuromuscular development. Passive muscle tone (posture, arm recoil and popliteal angle) and active motility (arm traction, head lag and ventral suspension) showed significant improvement in the treatment group at posttest. Similar results were recorded with auditory and visual orientation, alertness and defensive reaction. These specific areas of behavior have been recognized to be delayed in premature infants not exposed to a program of sensory stimulation.     

Detection and typing of papillomavirus DNA in formaldehyde-fixed paraffin-embedded tissue

Clinical specimens from nine patients with papillomatosis of the vocal cords and three patients with vocal cord polyps were evaluated for the presence of human papillomavirus (HPV) DNA using two complementary molecular hybridization techniques. In one method, involving polymerase chain reaction (PCR) amplification, HPV DNA sequences were replicated in vitro from tissue DNA extracted from paraffin sections prior to hybridization. Polymerase chain reaction amplification was compared with the standard method of Southern blot hybridization. Results of the two techniques for all nine laryngeal papillomas agreed completely: five patients harbored HPV type 6 and four HPV type 11. Both PCR amplification and Southern blot hybridization found two of the three polyps to be free of HPV infection, while PCR detected HPV type 18 in one polyp specimen that was reported negative by Southern blot hybridization, suggesting a greater sensitivity of PCR. Our results demonstrate that PCR amplification is as reliable and at least as sensitive as Southern blot hybridization. Moreover the PCR technique opens the way to the undertaking of a whole variety of retrospective studies using formaldehyde-fixed paraffin-embedded tissues.     

APRIL/TRDL-1, a tumor necrosis factor-like ligand, stimulates cell death

We have examined the activity of a new member of the tumor necrosis factor (TNF) family identified through Expressed Sequence Tag database searching using TNFalpha protein as the search query. We have termed this protein TNF-related death ligand-la (TRDL-1alpha). Traditional cDNA library screening identified two additional splice variants designated TRDL-1beta and TRDL-1gamma that differed from TRDL-1alpha by the deletion of two small regions within the protein coding region. TRDL-1alpha is identical in sequence to the recently described molecule, APRIL, that may induce cell proliferation. We found, however, that purified, FLAG-tagged TRDL-1alpha caused Jurkat cell death with kinetics that paralleled FasL. In vitro binding experiments demonstrated that TRDL-1alpha coprecipitated Fas and HVEM and suggested TRDL-1alpha as an alternate ligand for these receptors. TRDL-1 localized to chromosome 17p13.3 and its expression was widespread in normal tissues. Examination of 48 tumor samples revealed high levels of TRDL-1 expression in several tumors, including those from the gastrointestinal tract. Expression of TRDL-1 in COS-1 cells confirmed membrane association of TRDL-1, typical of TNF family members.     

Characteristics of women refusing follow-up for tests or symptoms suggestive of breast cancer

BACKGROUND: Delay in diagnosis of breast cancer can occur at several points on the diagnostic pathway. We examined characteristics of women with breast cancer who before diagnosis actively refused recommended follow-up of tests or symptoms suggestive of breast cancer. METHODS: We identified women aged 50 years or older diagnosed with late-stage (metastatic disease or tumors > or = 3 cm at diagnosis) and a matched sample of women with early-stage (tumors < 3 cm) breast cancer from 1995 to 1999. Using medical records, we investigated clinical characteristics, use of health care, and documentation of care refusal during the 3 years before diagnosis. We used logistic regression models to compare refusers to nonrefusers. RESULTS: Of the 2694 women studied, 7.2% refused provider follow-up advice during the 3 years. These women were more likely to have late-stage breast cancer at diagnosis than were nonrefusers (odds ratio [OR] = 1.9, 95% confidence interval [CI] = 1.4 to 2.6). They were more likely to be aged 75 years or older (OR = 1.9, 95% CI = 1.4 to 2.7 compared with age 50-64) or to have six or more children (OR = 2.3, 95% CI = 1.3 to 4.2 compared to women with one to two children). Clinical factors associated with refusal included low use of mammography, high use of clinical breast exam, and missed appointments. A minority of women who refused had a reason documented in the medical record; the most frequent reasons were avoidance-denial-fatalism, fear of diagnostic tests, and fear of surgery or disfigurement. CONCLUSIONS: Our results suggest that certain demographic and clinical characteristics are associated with women's refusal of diagnostic testing for breast cancer. Further study is needed on refusers' characteristics and on how such refusals affect outcomes. Efforts aimed at identifying and counseling women with abnormal results who refuse follow-up are warranted.     

Gradual withdrawal of antiparkinson medication in chronic schizophrenics: any better than the abrupt?

Twenty-four months after the completion of a double blind study of antiparkinson (AP) medication abrupt withdrawal in which 100 chronic schizophrenics took part, 42 patients out of that study's 75 patient placebo group were found in the ward. In a new double blind 8-week study of 3-week gradual withdrawal of AP medication, 70-6 per cent of the 34 patient placebo group (vs. none of the active) presented severe extrapyramidal symptoms (EPS) necessitating early termination, 23.5 per cent (vs. 12.5 per cent of the active) presented worsening but not to a point necessitating early termination, and only 5.9 per cent (vs. 87.5 per cent of the active) completed the 8-week period unchanged. Furthermore, 41.17 and 23.52 per cent of the placebo group (vs none of the active) presented EPS-related severe complaints and or psychotic symptomatology, respectively. These results were almost identical to those of the study of abrupt withdrawal. Thus, it seems that AP medication withdrawal in chronic schizophrenics remains problematic, even if the medication is withdrawn gradually.