Capsule endoscopy retention as a helpful tool in the management of a young patient with suspected small-bowel disease

Capsule endoscopy is an easy and painless procedure permitting visualization of the entire small-bowel during its normal peristalsis. However, important problems exist concerning capsule retention in patients at risk of small bowel obstruction. The present report describes a young patient who had recurrent episodes of overt gastrointestinal bleeding of obscure origin, 18 years after small bowel resection in infancy for ileal atresia. Capsule endoscopy was performed, resulting in capsule retention in the distal small bowel. However, this event contributed to patient management by clearly identifying the site of obstruction and can be used to guide surgical intervention, where an anastomotic ulcer is identified.     

An Intensive Intervention to Reduce Readmissions for Frequently Hospitalized Patients: the CHAMP Randomized Controlled Trial

BackgroundA small number of patients are disproportionally readmitted to hospitals. The Complex High Admission Management Program (CHAMP) was established as a multidisciplinary program to improve continuity of care and reduce readmissions for frequently hospitalized patients.ObjectiveTo compare hospital utilization metrics among patients enrolled in CHAMP and usual care.DesignPragmatic randomized controlled trial.ParticipantsInclusion criteria were as follows: 3 or more, 30-day inpatient readmissions in the previous year; or 2 inpatient readmissions plus either a referral or 3 observation admissions in previous 6 months.InterventionsPatients randomized to CHAMP were managed by an interdisciplinary team including social work, physicians, and pharmacists. The CHAMP team used comprehensive care planning and inpatient, outpatient, and community visits to address both medical and social needs. Control patients were randomized to usual care and contacted 18 months after initial identification if still eligible.Main MeasuresPrimary outcome was number of 30-day inpatient readmissions 180 days following enrollment. Secondary outcomes were number of hospital admissions, total hospital days, emergency department visits, and outpatient clinic visits 180 days after enrollment.Key ResultsThere were 75 patients enrolled in CHAMP, 76 in control. Groups were similar in demographic characteristics and baseline readmissions. At 180 days following enrollment, CHAMP patients had more inpatient 30-day readmissions [CHAMP incidence rate 1.3 (95% CI 0.9–1.8) vs. control 0.8 (95% CI 0.5–1.1), p=0.04], though both groups had fewer readmissions compared to 180 days prior to enrollment. We found no differences in secondary outcomes.ConclusionsFrequently hospitalized patients experienced reductions in utilization over time. Though most outcomes showed no difference, CHAMP was associated with higher readmissions compared to a control group, possibly due to consolidation of care at a single hospital. Future research should seek to identify subsets of patients with persistently high utilization for whom tailored interventions may be beneficial.Trial RegistrationClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03097640","term_id":"NCT03097640"}}NCT03097640; https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT03097640","term_id":"NCT03097640"}}NCT03097640KEY WORDS: care transitions, readmissions, care models, continuity of care, randomized controlled trial

A small number of patients account for a disproportionate number of hospital readmissions.¹ While medically diverse, many patients who are frequently hospitalized have behavioral or social needs that require holistic care models emphasizing more than medical care alone.² This population challenges a system of care that fragments hospital-based care and ambulatory care, creating systematic discontinuity for patients who may require longitudinal relationship-based care to meet their complex needs.³ In qualitative studies, patients who are frequently hospitalized report frustration with care fragmentation, causing them to perceive a lack of continuity and a loss of trust with the medical system.⁴Innovative care models have sought to reduce readmissions through redesigning care delivery, improving care coordination, and connecting patients to existing resources.^5–8 A systematic review of interventions for frequently hospitalized patients found a heterogeneous group of care models.⁹ Importantly, the majority of studies were observational. Many patients experience a reduction in utilization after an initial period of frequent admissions,¹⁰ limiting the ability of observational studies to measure a specific program’s effect due to the natural decline in readmissions over time. A randomized trial of a “healthcare hotspotting” intervention for patients in Camden, NJ, reported no change in hospitalization rates compared to a control group.¹¹ Though this intervention was an intensive interdisciplinary effort that enrolled patients while still hospitalized, it focused primarily on connecting patients to existing outpatient resources. Other intensive outpatient-only interventions have failed to reduce healthcare utilization.¹² Interventions that focus on improving care across clinical settings (i.e., both inside and outside of the hospital) may have a different effect.We created the Complex High Admission Management Program (CHAMP) as a quality improvement initiative to improve inpatient and outpatient care and reduce inpatient readmissions of patients frequently admitted to our hospital. The CHAMP multidisciplinary team works to foster longitudinal relationships with patients who suffer from systematic discontinuity. A pilot pre-post analysis of CHAMP observed reductions in readmission;¹³ however, results may have been confounded by the aforementioned tendency for utilization to decline over time.¹⁰ In this study, we conducted a randomized trial of CHAMP compared with usual care to accurately assess the program’s effect on hospital readmissions.     

CD4 cell and CD8 cell-mediated resistance to HIV-1 infection in exposed uninfected intravascular drug users in Vietnam

OBJECTIVE: To identify mechanisms of resistance to HIV-1 infection in exposed uninfected individuals. DESIGN: We examined in-vitro cell susceptibility to HIV-1 infection in highly exposed Vietnamese intravascular drug users (IDU) who, despite a history of more than 10 years of drug use and a high prevalence of other blood-borne viral infections, remain apparently HIV uninfected. METHODS: Forty-five exposed uninfected IDU and 50 blood donors were included in the study. Peripheral blood mononuclear cells (PBMC) or CD4 cell susceptibilities to HIV infection were evaluated using three HIV-1 isolates with different tropisms. Polymerase chain reaction analysis of HIV-1-DNA replication intermediates was used to characterize the restriction of HIV-1 replication in CD4 cells. Homologous CD8 cells were mixed with infected CD4 cells to evaluate their role in virus suppression. RESULTS: We observed a relative resistance to PBMC infection with HIV-1 in 21 out of 45 exposed uninfected IDU, but only in five out of 50 unexposed controls (P < 0.001). PBMC resistance was related either to an inhibition of HIV-1 replication in CD4 cells or to CD8 cell-mediated viral suppression. HIV-1 replication in CD4 cells was restricted at the early stages of the viral cycle. CONCLUSION: Reduced PBMC susceptibility to HIV-1 infection was associated with resistance to infection in exposed uninfected IDU. Distinct mechanisms are involved in in-vitro resistance and may contribute to the apparent protection from HIV-1 transmission in this systemically exposed population.     

Effects of CCR5-Delta32 and CCR2-64I alleles on HIV-1 disease progression: the protection varies with duration of infection

OBJECTIVE: To examine temporal variation in the effects of CCR5-Delta32 and CCR2-64I chemokine receptor gene polymorphisms on HIV-1 disease progression. DESIGN: Pooled analysis of individual patient data from 10 cohorts of HIV-1 seroconverters from the United States, Europe, and Australia. METHODS: We studied HIV-1 seroconverters of European (n = 1635) or African (n = 215) ancestry who had been genotyped for CCR5-Delta32 and CCR2-64I. We used Cox proportional hazards models with time-varying coefficients to determine whether the genetic protection against AIDS (1987 case definition) and death varied with time since seroconversion. RESULTS: Protection against AIDS conferred by CCR5-Delta32 held constant at a 31% (RH 0.69, 95% CI 0.54, 0.88) reduction in risk over the course of HIV-1 infection, whereas protection against death held constant at a 39% reduction in risk (RH 0.61, 95% CI 0.45, 0.88). When the period from AIDS to death was isolated, the survival benefit of CCR5-Delta32 diminished 2 years after AIDS. Protection against AIDS conferred by CCR2-64I was greatest early in the disease course. Compared with individuals without CCR5-Delta32 or CCR2-64I, individuals with one or two copies of CCR2-64I had a 58% lower risk of AIDS during the first 4 years after seroconversion (RH 0.42, 95% CI 0.23, 0.76), a 19% lower risk during the subsequent 4 years (RH 0.81, 95% CI 0.59, 1.12), and no significant protection thereafter. CONCLUSION: The protection against AIDS provided by CCR5-Delta32 is continuous during the course of infection. In contrast, the protection provided by CCR2-64I is greatest early in the course of infection.     

Alcohol Outcome Expectancies Mediate the Relationship Between Social Anxiety and Alcohol Drinking in University Students: The Role of Gender

College alcohol drinking is a public health concern worldwide. A line of research indicates that higher social anxiety is associated with more severe college drinking. However, other studies reveal a protective role of social anxiety against alcohol drinking in college students. Attempting to reconcile contradictory findings, we examined the hypothesis that there are multiple antagonistic pathways that could explain the social anxiety-college drinking relationship. In addition, there may be individual difference variables that moderate these processes. Furthermore, it was expected that the processes could vary as a function of the alcohol drinking outcomes examined. Expectancy theory emphasizes the role of alcohol outcome expectancies in alcohol drinking. Thus, in the present study we tested whether global positive and negative alcohol outcome expectancies partially mediate the relationship between social anxiety, alcohol consumption, and alcohol-related problems in a sample of 245 university students. We also examined the moderating role of gender in these mediating processes. Results revealed parallel but oppositional processes. Higher social anxiety was associated with heavier alcohol drinking and more serious alcohol-related problems via stronger positive alcohol outcome expectancies. However, the mediating role of positive alcohol outcome expectancies varied as a function of gender. It appears that in female students the mediating effect of positive alcohol outcome expectancies was stronger than in male students. On the other hand, higher social anxiety had a protective role against alcohol consumption but not against alcohol-related problems via stronger negative alcohol outcome expectancies. Finally, there was an inverse direct relationship between social anxiety and alcohol consumption.     

Clinical relevance of balance between type 1 and type 2 immune responses of lymphocyte subpopulations in aplastic anaemia patients

Immune dysfunction, which leads to the suppression of haemopoiesis by cytokines that are secreted by activated T lymphocytes, is considered to play a key role in the pathogenesis of acquired aplastic anaemia (AAA). We investigated the intracytoplasmic expression of type-1 [interferon gamma (IFN-gamma), interleukin (IL)-2] and type-2 (IL-4, IL-10) cytokines in CD4+ and CD8+ T cells before and after in vitro activation in 16 patients with AAA and 17 normal controls. Untreated or refractory patients had a significantly higher proportion of unstimulated CD4+ and CD8+ T cells that produced IFN-gamma and IL-2 whereas the IL-4 and IL-10 producing T cells did not differ from that of controls, resulting in a shift of IFN-gamma/IL-4 ratio towards a type-1 response. Patients in remission had also increased proportion of IFN-gamma-producing unstimulated CD4+ and CD8+ cells, with a parallel rise of IL-4- and IL-10-producing cells and normal IFN-gamma/IL-4 ratio. These data indicate that, in newly diagnosed and refractory patients with AAA, CD4+ cells are polarized towards a type-1 response that in turn leads to activation of cytotoxic CD8+ cells and finally to haemopoietic stem cell destruction. The type-1 response persists in patients in remission although this effect is compensated by the increase of IL-4 and IL-10 production.     

High occurence of DRB1 11 in chronic lymphocytic leukaemia families

Recently, linkage analysis of a series of familial chronic lymphocytic leukaemia (CLL) showed that affected sibling pairs did not share common major histocompatibilty complex haplotypes. We analysed Class I and II antigens in 11 Italian families with familial CLL. Although there was no association of disease status with any particular human leucocyte antigen, there was an overrepresentation of DRB1 11 alleles in these families (P = 0.009). A similar trend was also observed in a second series of nine French families (P = 0.002). Larger studies are needed to determine whether non-inherited paternal or maternal DRB1 antigens play a role in familial CLL development.     

IL28B alleles associated with poor hepatitis C virus (HCV) clearance protect against inflammation and fibrosis in patients infected with non-1 HCV genotypes

Genetic polymorphisms near IL28B are associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV), two processes that require the appropriate activation of the host immune responses. Intrahepatic inflammation is believed to mirror such activation, but its relationship with IL28B polymorphisms has yet to be fully appreciated. We analyzed the association of IL28B polymorphisms with histological and follow-up features in 2335 chronically HCV-infected Caucasian patients. Assessable phenotypes before any antiviral treatment included necroinflammatory activity (n = 1,098), fibrosis (n = 1,527), fibrosis progression rate (n = 1,312), and hepatocellular carcinoma development (n = 1,915). Associations of alleles with the phenotypes were evaluated by univariate analysis and multivariate logistic regression, accounting for all relevant covariates. The rare G allele at IL28B marker rs8099917-previously shown to be at risk of treatment failure-was associated with lower activity (P = 0.04), lower fibrosis (P = 0.02) with a trend toward lower fibrosis progression rate (P = 0.06). When stratified according to HCV genotype, most significant associations were observed in patients infected with non-1 genotypes (P = 0.003 for activity, P = 0.001 for fibrosis, and P = 0.02 for fibrosis progression rate), where the odds ratio of having necroinflammation or rapid fibrosis progression for patients with IL28B genotypes TG or GG versus TT were 0.48 (95% confidence intervals 0.30-0.78) and 0.56 (0.35-0.92), respectively. IL28B polymorphisms were not predictive of the development of hepatocellular carcinoma. CONCLUSION: In chronic hepatitis C, IL28B variants associated with poor response to interferon therapy may predict slower fibrosis progression, especially in patients infected with non-1 HCV genotypes.     

Treatment of bladder carcinoma with irradiation combined with misonidazole

One hundred patients suffering from cancer of the bladder were treated by external beam irradiation, 400 cGy twice a week to a total dose of 4800 cGy. One half of the patients were randomized to receive the electron affinic sensitizer agent, misonidazole, at a dose of 1 gr/m2 and a total dose of 12 gr/m2. There was no statistically significant difference in tumor responses and in recurrence--free survival time between the patients who received irradiation and misonidazole as compared to those who received irradiation and placebos.