A. Alfred Taubman Health Care Center

No abstract.

Helicobacter pylori (H. pylori) infection is a common worldwide infection that is an important cause of peptic ulcer disease and gastric cancer. H. pylori may also have a role in uninvestigated and functional dyspepsia, ulcer risk in patients taking low-dose aspirin or starting therapy with a non-steroidal anti-inflammatory medication, unexplained iron deficiency anemia, and idiopathic thrombocytopenic purpura. While choosing a treatment regimen for H. pylori, patients should be asked about previous antibiotic exposure and this information should be incorporated into the decision-making process. For first-line treatment, clarithromycin triple therapy should be confined to patients with no previous history of macrolide exposure who reside in areas where clarithromycin resistance amongst H. pylori isolates is known to be low. Most patients will be better served by first-line treatment with bismuth quadruple therapy or concomitant therapy consisting of a PPI, clarithromycin, amoxicillin, and metronidazole. When first-line therapy fails, a salvage regimen should avoid antibiotics that were previously used. If a patient received a first-line treatment containing clarithromycin, bismuth quadruple therapy or levofloxacin salvage regimens are the preferred treatment options. If a patient received first-line bismuth quadruple therapy, clarithromycin or levofloxacin-containing salvage regimens are the preferred treatment options. Details regarding the drugs, doses and durations of the recommended and suggested first-line and salvage regimens can be found in the guideline.

BACKGROUND: Communication problems in health care may arise as a result of healthcare providers focusing on diseases and their management, rather than people, their lives and their health problems. Patient-centred approaches to care delivery in the patient encounter are increasingly advocated by consumers and clinicians and incorporated into training for healthcare providers. However, the impact of these interventions directly on clinical encounters and indirectly on patient satisfaction, healthcare behaviour and health status has not been adequately evaluated. OBJECTIVES: To assess the effects of interventions for healthcare providers that aim to promote patient-centred care (PCC) approaches in clinical consultations. SEARCH METHODS: For this update, we searched: MEDLINE (OvidSP), EMBASE (OvidSP), PsycINFO (OvidSP), and CINAHL (EbscoHOST) from January 2000 to June 2010. The earlier version of this review searched MEDLINE (1966 to December 1999), EMBASE (1985 to December 1999), PsycLIT (1987 to December 1999), CINAHL (1982 to December 1999) and HEALTH STAR (1975 to December 1999). We searched the bibliographies of studies assessed for inclusion and contacted study authors to identify other relevant studies. Any study authors who were contacted for further information on their studies were also asked if they were aware of any other published or ongoing studies that would meet our inclusion criteria. SELECTION CRITERIA: In the original review, study designs included randomized controlled trials, controlled clinical trials, controlled before and after studies, and interrupted time series studies of interventions for healthcare providers that promote patient-centred care in clinical consultations. In the present update, we were able to limit the studies to randomized controlled trials, thus limiting the likelihood of sampling error. This is especially important because the providers who volunteer for studies of PCC methods are likely to be different from the general population of providers. Patient-centred care was defined as a philosophy of care that encourages: (a) shared control of the consultation, decisions about interventions or management of the health problems with the patient, and/or (b) a focus in the consultation on the patient as a whole person who has individual preferences situated within social contexts (in contrast to a focus in the consultation on a body part or disease). Within our definition, shared treatment decision-making was a sufficient indicator of PCC. The participants were healthcare providers, including those in training. DATA COLLECTION AND ANALYSIS: We classified interventions by whether they focused only on training providers or on training providers and patients, with and without condition-specific educational materials. We grouped outcome data from the studies to evaluate both direct effects on patient encounters (consultation process variables) and effects on patient outcomes (satisfaction, healthcare behaviour change, health status). We pooled results of RCTs using standardized mean difference (SMD) and relative risks (RR) applying a fixed-effect model. MAIN RESULTS: Forty-three randomized trials met the inclusion criteria, of which 29 are new in this update. In most of the studies, training interventions were directed at primary care physicians (general practitioners, internists, paediatricians or family doctors) or nurses practising in community or hospital outpatient settings. Some studies trained specialists. Patients were predominantly adults with general medical problems, though two studies included children with asthma. Descriptive and pooled analyses showed generally positive effects on consultation processes on a range of measures relating to clarifying patients' concerns and beliefs; communicating about treatment options; levels of empathy; and patients' perception of providers' attentiveness to them and their concerns as well as their diseases. A new finding for this update is that short-term training (less than 10 hours) is as successful as longer training.The analyses showed mixed results on satisfaction, behaviour and health status. Studies using complex interventions that focused on providers and patients with condition-specific materials generally showed benefit in health behaviour and satisfaction, as well as consultation processes, with mixed effects on health status. Pooled analysis of the fewer than half of included studies with adequate data suggests moderate beneficial effects from interventions on the consultation process; and mixed effects on behaviour and patient satisfaction, with small positive effects on health status. Risk of bias varied across studies. Studies that focused only on provider behaviour frequently did not collect data on patient outcomes, limiting the conclusions that can be drawn about the relative effect of intervention focus on providers compared with providers and patients. AUTHORS' CONCLUSIONS: Interventions to promote patient-centred care within clinical consultations are effective across studies in transferring patient-centred skills to providers. However the effects on patient satisfaction, health behaviour and health status are mixed. There is some indication that complex interventions directed at providers and patients that include condition-specific educational materials have beneficial effects on health behaviour and health status, outcomes not assessed in studies reviewed previously. The latter conclusion is tentative at this time and requires more data. The heterogeneity of outcomes, and the use of single item consultation and health behaviour measures limit the strength of the conclusions.

A randomized, multicentre, open-label, phase II study compared temozolomide (TMZ), an oral second-generation alkylating agent, and procarbazine (PCB) in 225 patients with glioblastoma multiforme at first relapse. Primary objectives were to determine progression-free survival (PFS) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment. Secondary objectives were to assess overall survival and health-related quality of life (HRQL). TMZ was given orally at 200 mg/m(2)/day or 150 mg/m(2)/day (prior chemotherapy) for 5 days, repeated every 28 days. PCB was given orally at 150 mg/m(2)/day or 125 mg/m(2)/day (prior chemotherapy) for 28 days, repeated every 56 days. HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 [+3]) and the Brain Cancer Module 20 (BCM20). The 6-month PFS rate for patients who received TMZ was 21%, which met the protocol objective. The 6-month PFS rate for those who received PCB was 8% (P = 0.008, for the comparison). Overall PFS significantly improved with TMZ, with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group (P = 0.0063). The 6-month overall survival rate for TMZ patients was 60% vs. 44% for PCB patients (P = 0.019). Freedom from disease progression was associated with maintenance of HRQL, regardless of treatment received. TMZ had an acceptable safety profile; most adverse events were mild or moderate in severity.

BACKGROUND: The National Surgical Quality Improvement Project (NSQIP) has reduced morbidity rates in Veterans Affairs Hospitals. As the NSQIP methods move to private-sector hospitals, funding responsibilities will shift to the medical center. The objective of the current study was to calculate hospital costs associated with postoperative complications, because reducing morbidity may offset the costs of using the NSQIP. STUDY DESIGN: Patient data were obtained from a single private-sector center involved in the NSQIP from 2001 to 2002 (n=1,008). Cost data were derived from the hospital's internal cost-accounting database (TSI; Transitions Systems Inc). Total hospital costs associated with both minor complications and major complications were calculated. Multiple linear regression was used to determine the cost of each type of complication after adjusting for patient characteristics. RESULTS: Rates of minor complications (6.3%, 64 events) and major complications (6.6%, 67 events) were similar. Median hospital costs were lowest for patients without complications (4,487 dollars) compared with those with minor (14,094 dollars) and major complications (28,356 dollars) (p<0.001). After adjusting for differences in patient characteristics, major complications were associated with an increase of 11,626 dollars (95% CI, 9,419 dollars to 13,832 dollars; p<0.001). Minor complications were not associated with increased costs in the adjusted analysis. CONCLUSIONS: Given the substantial costs associated with major postoperative complications, reducing morbidity may provide sufficient cost savings to offset the resources needed to participate in the private-sector expansion of the NSQIP.

Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson’s disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy. Medulloblastoma is the most common malignant brain tumour in children; having assembled over 1,000 samples the authors report that somatic copy number aberrations are common in medulloblastoma, in particular a tandem duplication of SNCAIP, a gene associated with Parkinson’s disease, which is restricted to subgroup 4α, and translocations of PVT1, which are restricted to Group 3. Medulloblastoma is the most common malignant brain tumour in children. Four papers published in the 2 August 2012 issue of Nature use whole-genome and other sequencing techniques to produce a detailed picture of the genetics and genomics of this condition. Notable findings include the identification of recurrent mutations in genes not previously implicated in medulloblastoma, with significant genetic differences associated with the four biologically distinct subgroups and clinical outcomes in each. Potential avenues for therapy are suggested by the identification of targetable somatic copy-number alterations, including recurrent events targeting TGFβ signalling in Group 3, and NF-κB signalling in Group 4 medulloblastomas.

BACKGROUND: Surgeons frequently struggle to determine patient suitability for liver transplantation. Objective and comprehensive measures of overall burden of disease, such as sarcopenia, could inform clinicians and help avoid futile transplantations. STUDY DESIGN: The cross-sectional area of the psoas muscle was measured on CT scans of 163 liver transplant recipients. After controlling for donor and recipient characteristics using Cox regression models, we described the relationship between psoas area and post-transplantation mortality. RESULTS: Psoas area correlated poorly with Model for End-Stage Liver Disease score and serum albumin. Cox regression revealed a strong association between psoas area and post-transplantation mortality (hazard ratio = 3.7/1,000 mm(2) decrease in psoas area; p < 0.0001). When stratified into quartiles based on psoas area (holding donor and recipient characteristics constant), 1-year survival ranged from 49.7% for the quartile with the smallest psoas area to 87.0% for the quartile with the largest. Survival at 3 years among these groups was 26.4% and 77.2%, respectively. The impact of psoas area on survival exceeded that of all other covariates in these models. CONCLUSIONS: Central sarcopenia strongly correlates with mortality after liver transplantation. Such objective measures of patient frailty, such as sarcopenia, can inform clinical decision making and, potentially, allocation policy. Additional work is needed develop valid and clinically relevant measures of sarcopenia and frailty in liver transplantation.

Pancreatic cysts are very common with the majority incidentally identified. There are several types of pancreatic cysts; some types can contain cancer or have malignant potential, whereas others are benign. However, even the types of cysts with malignant potential rarely progress to cancer. At the present time, the only viable treatment for pancreatic cysts is surgical excision, which is associated with a high morbidity and occasional mortality. The small risk of malignant transformation, the high risks of surgical treatment, and the lack of high-quality prospective studies have led to contradictory recommendations for their immediate management and for their surveillance. This guideline will provide a practical approach to pancreatic cyst management and recommendations for cyst surveillance for the general gastroenterologist.

BACKGROUND: The management of degenerative spondylolisthesis associated with spinal stenosis remains controversial. Surgery is widely used and has recently been shown to be more effective than nonoperative treatment when the results were followed over two years. Questions remain regarding the long-term effects of surgical treatment compared with those of nonoperative treatment. METHODS: Surgical candidates from thirteen centers with symptoms of at least twelve weeks' duration as well as confirmatory imaging showing degenerative spondylolisthesis with spinal stenosis were offered enrollment in a randomized cohort or observational cohort. Treatment consisted of standard decompressive laminectomy (with or without fusion) or usual nonoperative care. Primary outcome measures were the Short Form-36 (SF-36) bodily pain and physical function scores and the modified Oswestry Disability Index at six weeks, three months, six months, and yearly up to four years. RESULTS: In the randomized cohort (304 patients enrolled), 66% of those randomized to receive surgery received it by four years whereas 54% of those randomized to receive nonoperative care received surgery by four years. In the observational cohort (303 patients enrolled), 97% of those who chose surgery received it whereas 33% of those who chose nonoperative care eventually received surgery. The intent-to-treat analysis of the randomized cohort, which was limited by nonadherence to the assigned treatment, showed no significant differences in treatment outcomes between the operative and nonoperative groups at three or four years. An as-treated analysis combining the randomized and observational cohorts that adjusted for potential confounders demonstrated that the clinically relevant advantages of surgery that had been previously reported through two years were maintained at four years, with treatment effects of 15.3 (95% confidence interval, 11 to 19.7) for bodily pain, 18.9 (95% confidence interval, 14.8 to 23) for physical function, and -14.3 (95% confidence interval, -17.5 to -11.1) for the Oswestry Disability Index. Early advantages (at two years) of surgical treatment in terms of the secondary measures of bothersomeness of back and leg symptoms, overall satisfaction with current symptoms, and self-rated progress were also maintained at four years. CONCLUSIONS: Compared with patients who are treated nonoperatively, patients in whom degenerative spondylolisthesis and associated spinal stenosis are treated surgically maintain substantially greater pain relief and improvement in function for four years.

BACKGROUND: Patients with chronic hepatitis C virus (HCV) infection who have not had a response to therapy with peginterferon and ribavirin may benefit from the addition of multiple direct-acting antiviral agents to their treatment regimen. METHODS: This open-label, phase 2a study included an exploratory cohort of 21 patients with chronic HCV genotype 1 infection who had not had a response to previous therapy (i.e., had not had ≥2 log(10) decline in HCV RNA after ≥12 weeks of treatment with peginterferon and ribavirin). We randomly assigned patients to receive the NS5A replication complex inhibitor daclatasvir (60 mg once daily) and the NS3 protease inhibitor asunaprevir (600 mg twice daily) alone (group A, 11 patients) or in combination with peginterferon alfa-2a and ribavirin (group B, 10 patients) for 24 weeks. The primary end point was the percentage of patients with a sustained virologic response 12 weeks after the end of the treatment period. RESULTS: A total of 4 patients in group A (36%; 2 of 9 with HCV genotype 1a and 2 of 2 with genotype 1b) had a sustained virologic response at 12 weeks after treatment and also at 24 weeks after treatment.. Six patients (all with HCV genotype 1a) had viral breakthrough while receiving therapy, and resistance mutations to both antiviral agents were found in all cases; 1 patient had a viral response at the end of treatment but had a relapse after the treatment period. All 10 patients in group B had a sustained virologic response at 12 weeks after treatment, and 9 had a sustained virologic response at 24 weeks after treatment. Diarrhea was the most common adverse event in both groups. Six patients had transient elevations of alanine aminotransferase levels to more than 3 times the upper limit of the normal range. CONCLUSIONS: This preliminary study involving patients with HCV genotype 1 infection who had not had a response to prior therapy showed that a sustained virologic response can be achieved with two direct-acting antiviral agents only. In addition, a high rate of sustained virologic response was achieved when the two direct-acting antiviral agents were combined with peginterferon alfa-2a and ribavirin. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT01012895.).

In this study, the effects of procedure type, timing, and other clinical variables on complication rates in mastectomy reconstruction were prospectively evaluated. Using a prospective cohort design, women undergoing first-time, immediate or delayed breast reconstruction were recruited from 12 centers and 23 plastic surgeons. Complication data for expander/implant, pedicle transverse rectus abdominis musculocutaneous (TRAM) flap, and free TRAM flap procedures were evaluated 2 years after surgery in 326 patients. For each patient, the total number of complications was recorded and the complication data were dichotomized in two ways: (1) total complications and (2) major complications (those requiring reoperation, rehospitalization, or nonperioperative intravenous antibiotic treatment). The effects of procedure type, timing, radiotherapy, chemotherapy, age, smoking, and body mass index on complication rates were analyzed using logistic regression. Immediate reconstructions had significantly higher total as well as major complication rates, compared with delayed procedures (p = 0.011 and 0.005, respectively). Furthermore, higher body mass indexes were associated with significantly higher total and major complication rates (p = 0.005 and p < 0.001, respectively). No significant effects on complication rates were noted for procedure type or for the other independent variables, although there was evidence of trends for higher total and major complication rates in implant patients who received radiotherapy and a trend for higher major complication rates in TRAM flap patients who received chemotherapy. It was concluded that (1) immediate reconstructions were associated with significantly higher complication rates than delayed procedures, and (2) procedure type had no significant effect on complication rates.

OBJECTIVES: To evaluate the extent to which intensive care units participating in the initial Keystone ICU project sustained reductions in rates of catheter related bloodstream infections. Design Collaborative cohort study to implement and evaluate interventions to improve patients' safety. SETTING: Intensive care units predominantly in Michigan, USA. INTERVENTION: Conceptual model aimed at improving clinicians' use of five evidence based recommendations to reduce rates of catheter related bloodstream infections rates, with measurement and feedback of infection rates. During the sustainability period, intensive care unit teams were instructed to integrate this intervention into staff orientation, collect monthly data from hospital infection control staff, and report infection rates to appropriate stakeholders. MAIN OUTCOME MEASURES: Quarterly rate of catheter related bloodstream infections per 1000 catheter days during the sustainability period (19-36 months after implementation of the intervention). RESULTS: Ninety (87%) of the original 103 intensive care units participated, reporting 1532 intensive care unit months of data and 300 310 catheter days during the sustainability period. The mean and median rates of catheter related bloodstream infection decreased from 7.7 and 2.7 (interquartile range 0.6-4.8) at baseline to 1.3 and 0 (0-2.4) at 16-18 months and to 1.1 and 0 (0.0-1.2) at 34-36 months post-implementation. Multilevel regression analysis showed that incidence rate ratios decreased from 0.68 (95% confidence interval 0.53 to 0.88) at 0-3 months to 0.38 (0.26 to 0.56) at 16-18 months and 0.34 (0.24-0.48) at 34-36 months post-implementation. During the sustainability period, the mean bloodstream infection rate did not significantly change from the initial 18 month post-implementation period (-1%, 95% confidence interval -9% to 7%). CONCLUSIONS: The reduced rates of catheter related bloodstream infection achieved in the initial 18 month post-implementation period were sustained for an additional 18 months as participating intensive care units integrated the intervention into practice. Broad use of this intervention with achievement of similar results could substantially reduce the morbidity and costs associated with catheter related bloodstream infections.

An estimated 350 million persons worldwide and 1.25 million in the United States are infected with hepatitis B virus (HBV). Hepatitis B carriers are at risk for development of cirrhosis and hepatocellular carcinoma (HCC). The natural history of chronic HBV infection is variable. Persons with chronic HBV infection need lifelong monitoring to determine if and when intervention with antiviral therapy is needed and to observe for serious sequelae. These guidelines were developed under the auspices of, and approved by, the Practice Guidelines Committee of the American Association for the Study of Liver Diseases. The original guidelines were published in HEPATOLOGY 2001;34:1225–1241.1 In light of recent progress, particularly in the treatment of chronic hepatitis B, these guidelines were updated in September of 2003. A complete version of the updated guidelines, including a review of recently published literature, can be found at the AASLD web site, www.aasld.org. Following is a summary of the updated recommendations for treatment of chronic hepatitis B. The recommendations were graded as I (randomized controlled trials), II-1 (controlled trials without randomization), II-2 (cohort or case-control analytic studies), II-3 (multiple time series, dramatic uncontrolled experiments), and III (opinions of respected authorities, descriptive epidemiology). HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HBeAg, hepatitis B e antigen; ALT, alanine aminotransferase; IFN-α, interferon alfa; HBsAg, hepatitis B surface antigen. In a controlled trial that involved 286 children aged 2 to 17 years, randomized to lamivudine (3 mg/kg/d up to 100 mg/d) or placebo, hepatitis B e antigen (HBeAg) seroconversion was observed in 22% lamivudine-treated children versus 13% placebo controls (P = .06), while HBeAg loss was observed in 26% and 15%, respectively (P = 0.03).2 HBeAg seroconversion rate was higher among children with elevated alanine aminotransferase (ALT) levels. Lamivudine-resistant mutation was detected in 19% of treated children during the 1-year period. Among patients who experienced HBeAg seroconversion during lamivudine treatment, the durability of response after cessation of therapy has ranged from 38% to 77%.3-5 The 3-year cumulative relapse rate varied from 36% to 54%, with most of the relapses occurring during the first year posttreatment. The risk of developing lamivudine resistance increases with the duration of therapy. In a study from Asia, genotypic resistance increased from 14% in year 1 to 38%, 49%, 66%, and 69% after 2, 3, 4, and 5 years, respectively, of treatment.6 Long-term follow-up studies showed that over time, the initial benefit is negated in patients with lamivudine-resistant mutants. In one study that compared liver histology in 63 patients prior to and after 3 years of lamivudine treatment, necroinflammatory scores were improved in 77% and worsened in 5% of patients without lamivudine-resistant mutants, but improved in only 45% and worsened in 14% of those with lamivudine-resistant mutants.7 For patients with confirmed lamivudine-resistance, the options include continuing lamivudine treatment as long as benefit to the patient (based on clinical assessment, ALT, and HBV DNA levels) is maintained; discontinuing treatment and monitoring for hepatitis flares; or switching to other antiviral agents such as adefovir, which are effective in suppressing lamivudine-resistant HBV. Two recent reports from Asia suggest that discontinuation of lamivudine in patients with resistant mutants is not associated with increased frequency of hepatitis flares or decompensation, compared with those who continued to receive lamivudine.8, 9 Thus, stopping lamivudine is a reasonable option for immunocompetent patients without cirrhosis, as long as they are closely monitored; but patients with underlying cirrhosis or immunosuppression should be switched to adefovir before stopping lamivudine. Adefovir dipivoxil is an orally bioavailable prodrug of adefovir, a nucleotide analog of adenosine monophosphate that inhibits both HBV reverse transcriptase and DNA polymerase activity. Adefovir has been shown to be effective in suppressing not only wild-type HBV but also lamivudine-resistant HBV mutants. In a randomized trial of 515 patients with HBeAg-positive chronic hepatitis B treated with 30-mg or 10-mg doses of adefovir or placebo for 48 weeks, a significantly higher proportion of adefovir-treated patients had histologic response, HBeAg loss, normalization of ALT levels, and reduction of HBV DNA, compared with those who received placebo (all P < .001).10 HBeAg seroconversion was observed in 12% of the adefovir and 6% of the placebo groups (P = .049). In a trial of 184 patients with HBeAg-negative chronic hepatitis B who were randomized to receive adefovir 10 mg or placebo for 48 weeks, histologic response, normalization of ALT, and undetectable serum HBV DNA by polymerase chain reaction assay were observed significantly more frequently in the treatment group (all P < .001).11 During year 2, the proportion of patients with undetectable serum HBV DNA and normal ALT levels increased from 46% at week 48 to 51% at week 96 among those who continued treatment, and decreased from 59% to 3% among those in whom therapy was stopped.12 In a compassionate-use study involving 128 patients with decompensated cirrhosis and 196 patients with recurrent hepatitis B after liver transplant, with lamivudine resistance, addition of adefovir was associated with a 3–4 log10 reduction in serum HBV DNA levels, which was sustained throughout the course of treatment.13 Virologic response was accompanied by stable or decreased ALT and Child-Pugh score. A pilot study in 58 patients with compensated chronic hepatitis B and lamivudine resistance found that adefovir alone had similar efficacy as combination treatment of lamivudine and adefovir in suppressing replication of lamivudine-resistant HBV.14 Adefovir has not been evaluated in children. Nephrotoxiciy (increase in serum creatinine by ≥0.5 mg/dL above baseline values on two consecutive occasions) was observed in 8% of patients who received adefovir 30 mg for 1 year and in none of the patients with compensated liver disease who received adefovir 10 mg for 1 year. However, nephrotoxicity has been reported in 2.5% of patients with compensated liver disease who received 2 years of adefovir 10 mg, and in 12% of transplant recipients and 28% of patients with decompensated cirrhosis who received 1 year of adefovir 10 mg.13, 15 The recommended dose of adefovir for adults with normal renal function is 10 mg daily orally. Dosing interval should be increased in patients with renal insufficiency. The optimal duration of adefovir treatment is unclear. Data on the durability of HBeAg seroconversion after adefovir is discontinued have not been presented. Preliminary data indicate that patients with HBeAg negative chronic hepatitis will require long-term treatment as most patients will relapse when adefovir is withdrawn after 1 year.14 Based on experience with lamivudine, consideration should be given to treating patients in whom HBeAg seroconversion has occurred for an additional 3 to 6 months after HBeAg seroconversion is confirmed (two occasions at least 2 months apart) to reduce post-treatment relapse. Long-term treatment will also be required for patients with lamivudine-resistant mutants, particularly those with decompensated cirrhosis or recurrent hepatitis B posttransplant. A major advantage of adefovir is the lack of resistance after the first year of therapy, but drug-resistant mutation, asparagine to threonine (rtN236T), downstream of the YMDD motif, has been reported in 2 of 79 (2.5%) patients with HBeAg-negative chronic hepatitis B during the second year of therapy.16In vitro studies confirmed that this mutation confers resistance to adefovir, but the resistant mutant appears to be susceptible to lamivudine and entecavir. Reactivation of HBV replication with hepatitis flares and rarely hepatic decompensation have been reported to occur in 20% to 50% of hepatitis B carriers undergoing immunosuppressive or cancer chemotherapies, especially when corticosteroids are included.17, 18 Administration of lamivudine has been reported to reduce the frequency and severity of the hepatitis flares, and to improve survival compared to historical controls.17, 19 HBeAg-positive patients with elevated ALT levels and compensated liver disease should be observed for 3 to 6 months for spontaneous seroconversion from HBeAg to HBe antibody prior to initiation of treatment (III). Patients who meet the criteria for chronic hepatitis B (serum HBV DNA >105 copies/mL and persistent or intermittent elevation in aminotransferase levels) should be evaluated further with a liver biopsy (III). Patients in the inactive hepatitis B surface antigen (HBsAg) carrier state should be monitored with periodic liver chemistries every 6 to 12 months, as liver disease may become active even after many years of quiescence (III). Patients with HBeAg-positive chronic hepatitis B: A. ALT greater than 2 times normal, or moderate/severe hepatitis on biopsy. These patients should be considered for treatment. Treatment should be delayed for 3 to 6 months in persons with compensated liver disease to determine whether spontaneous HBeAg seroconversion occurs. Treatment may result in virologic, biochemical, and histologic response (I) and also appear to improve clinical outcome (II-3). Treatment may be initiated with IFN-α, lamivudine or adefovir as the 3 treatments have similar efficacy. B. ALT persistently normal or minimally elevated (<2 times normal). These patients should not be initiated on treatment (I). Liver biopsy may be considered in patients with fluctuating or minimally elevated ALT levels and treatment initiated if there is moderate or severe necroinflammation. C. Children with elevated ALT greater than 2 times normal. These patients should be considered for treatment if ALT levels remain elevated at this level for longer than 6 months (I). Both IFN-α and lamivudine are approved treatments for children with chronic hepatitis B. Patients with HBeAg-negative chronic hepatitis B (serum HBV DNA >105 copies/mL, elevated ALT >2 times normal or moderate/severe hepatitis on biopsy) should be considered for treatment (I). Treatment may be initiated with IFN-α, lamivudine, or adefovir (I for adefovir and II-1 for IFNα and lamivudine). In view of the need for long-term treatment, IFNα or adefovir is preferred. Patients who failed to respond to prior IFN-α therapy may be retreated with lamivudine or adefovir if they fulfill the criteria listed above (I). Persons who develop breakthrough infection while on lamivudine should be treated with adefovir if there is worsening of liver disease, if they had decompensated cirrhosis or recurrent hepatitis B after liver transplant, or if they require concomitant immunosuppressive therapy (II-2). Patients with compensated cirrhosis are best treated with lamivudine or adefovir because of the risk of hepatic decompensation associated with IFN-α related flares of hepatitis. Patients with decompensated cirrhosis should be considered for lamivudine treatment (III-3). Adefovir may be used as an alternative to lamivudine, although it has not been evaluated as a primary treatment in these patients. If adefovir is used, close monitoring of renal function with testing of blood urea nitrogen and creatinine every 1 to 3 months should be performed. Treatment should be coordinated with transplant centers. IFN-α should not be used in patients with decompensated cirrhosis (II-3). For patients with an inactive HBsAg carrier state, antiviral treatment is not indicated. IFN-α is administered as subcutaneous injections. The recommended IFN-α dose for adults is 5 million units (MU) daily or 10 MU thrice weekly (I). The recommended IFN-α dose for children is 6 MU/m2thrice weekly with a maximum of 10 MU (I). The recommended treatment duration for HBeAg-positive chronic hepatitis B is 16 weeks (I). The recommended treatment duration for HBeAg-negative chronic hepatitis B is 12 months (II-3). Lamivudine is administered orally. The recommended lamivudine dose for adults with normal renal function and no HIV coinfection is 100 mg daily (I). The recommended lamivudine dose for children is 3 mg/kg/d with a maximum of 100 mg/d (I). The recommended treatment duration for HBeAg-positive chronic hepatitis B is a minimum of 1 year (I). Patients in whom HBeAg seroconversion has occurred should be maintained on treatment for 3 to 6 months after HBeAg seroconversion is confirmed (two occasions at least 2 months apart) to reduce posttreatment relapse. Treatment may be continued in patients who have not developed HBeAg seroconversion. Treatment may be continued in patients who have breakthrough infection due to lamivudine-resistant mutants as long as benefit to the patient (based on clinical assessment, ALT level, and HBV DNA level) is maintained. The recommended treatment duration for HBeAg-negative chronic hepatitis B is longer than 1 year, but the optimal duration has not been established (II-3). The recommended dose of lamivudine for persons coinfected with HIV is 150 mg twice daily, along with other antiretroviral medications (I). Adefovir is administered orally. The recommended adefovir dose for adults with normal renal function is 10 mg daily (I). The recommended treatment duration for HBeAg-positive chronic hepatitis B is a minimum of 1 year. The benefits versus risks of longer duration of treatment are unknown (I). The recommended treatment duration for HBeAg-negative chronic hepatitis B is longer than 1 year. Longer duration of treatment is likely necessary for sustained response, but the optimal duration of treatment and the benefits versus risks of longer duration of treatment remain to be determined (I). The recommended treatment duration for patients with lamivudine-resistant mutants has not been determined. Long-term treatment is required particularly for patients with decompensated cirrhosis or allograft infection. For patients with compensated liver disease, there appears to be no advantage to continuing lamivudine therapy in patients switched to adefovir but an overlap period of 2–3 months is advisable to minimize the risk of hepatitis flares during the transition (III). HBsAg testing should be performed in persons who have high risk of HBV infection, prior to initiation of chemotherapy or immunosuppressive therapy (III). Prophylactic antiviral therapy with lamivudine is recommended for HBV carriers at the onset of cancer chemotherapy or of a finite course of immunosuppressive therapy, and maintained for 6 months after completion of chemotherapy or immunosuppressive therapy (III). This guideline was approved by the American Association for the Study of Liver Diseases (AASLD) and represents the position of the Association. It was produced in collaboration with the AASLD Practice Guidelines Committee. Members of the AASLD Practice Guidelines Committee included: K. Rajender Reddy, M.D. (Chair), Bruce R. Bacon, M.D., David E. Bernstein, M.D., Thomas D. Boyer, M.D., Henry C. Bodenheimer, M.D., Robert L. Carithers, M.D., Gary L. Davis, M.D., James E. Everhart, M.D., Thomas W. Faust, M.D., Stuart C. Gordon, M.D., Elizabeth Hospenheide, R.N., B.S.N., F. Blaine Hollinger, M.D., Donald M. Jensen, M.D., Maureen Jonas, M.D., Jacob Korula, M.D., Michael R. Lucey, M.D., Timothy M. McCashland, M.D., Jan M. Novak, M.D., Melissa Palmer, M.D., F. Fred Poordad, M.D., Robert Reindollar, M.D., Eve A. Roberts, M.D., Thomas Shaw-Stiffel, M.D., Margaret C. Shuhart, M.D., James R. Spivey, M.D., Brent A. Tetri, M.D., and Zobair M. Younossi, M.D.

BACKGROUND: Traditionally, distal radial fractures in the elderly have been treated nonoperatively with casting. However, since the introduction of the volar locking plating system in 2000, there has been an interest in the use of more aggressive treatment methods. The purpose of the present study was to assess changing trends in the treatment of distal radial fractures in elderly patients in the United States. METHODS: We evaluated a 5% sample of Medicare data from 1996 to 1997 and a 20% sample from 1998 to 2005. Information on four treatment methods (closed treatment, percutaneous pin fixation, internal fixation, and external fixation) was extracted from the dataset. Other available data were diagnosis, physician specialty, and patient age, sex, and race. We calculated frequencies and rates to compare the utilization of different treatments over time. RESULTS: Over the ten-year time period examined, the rate of internal fixation of distal radial fractures in the elderly increased fivefold, from 3% in 1996 to 16% in 2005. Closed treatment, however, remained the predominant method (used for 82% of the fractures in 1996 and 70% in 2005). Fractures in patients with an age of eighty-five years or more were significantly more likely to be treated in a closed fashion (p < 0.0001). There was a large variation among physician specialties with regard to the fixation methods that were used. Orthopaedic surgeons were significantly more likely to use closed treatment than hand surgeons were, whereas hand surgeons were significantly more likely to use internal fixation than orthopaedic surgeons were. CONCLUSIONS: Since 2000, although the majority of distal radial fractures are still treated nonoperatively, there has been an increase in the use of internal fixation and a concurrent decrease in the rate of closed treatment of distal radial fractures in the elderly in the United States.

Birkmeyer, John D. MD, FACS; Dimick, Justin B. MD; Birkmeyer, Nancy J.O. PhD Author Information

PURPOSE: To test the hypothesis-given the increasing emphasis on quantitative computed tomographic (CT) phenotypes of chronic obstructive pulmonary disease (COPD)-that a relationship exists between COPD exacerbation frequency and quantitative CT measures of emphysema and airway disease. MATERIALS AND METHODS: This research protocol was approved by the institutional review board of each participating institution, and all participants provided written informed consent. One thousand two subjects who were enrolled in the COPDGene Study and met the GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria for COPD with quantitative CT analysis were included. Total lung emphysema percentage was measured by using the attenuation mask technique with a -950-HU threshold. An automated program measured the mean wall thickness and mean wall area percentage in six segmental bronchi. The frequency of COPD exacerbation in the prior year was determined by using a questionnaire. Statistical analysis was performed to examine the relationship of exacerbation frequency with lung function and quantitative CT measurements. RESULTS: In a multivariate analysis adjusted for lung function, bronchial wall thickness and total lung emphysema percentage were associated with COPD exacerbation frequency. Each 1-mm increase in bronchial wall thickness was associated with a 1.84-fold increase in annual exacerbation rate (P = .004). For patients with 35% or greater total emphysema, each 5% increase in emphysema was associated with a 1.18-fold increase in this rate (P = .047). CONCLUSION: Greater lung emphysema and airway wall thickness were associated with COPD exacerbations, independent of the severity of airflow obstruction. Quantitative CT can help identify subgroups of patients with COPD who experience exacerbations for targeted research and therapy development for individual phenotypes.

Despite years of advising patients to alter their dietary and supplementary fiber intake, the evidence surrounding the use of fiber for functional bowel disease is limited. This paper outlines the organization of fiber types and highlights the importance of assessing the fermentation characteristics of each fiber type when choosing a suitable strategy for patients. Fiber undergoes partial or total fermentation in the distal small bowel and colon leading to the production of short-chain fatty acids and gas, thereby affecting gastrointestinal function and sensation. When fiber is recommended for functional bowel disease, use of a soluble supplement such as ispaghula/psyllium is best supported by the available evidence. Even when used judiciously, fiber can exacerbate abdominal distension, flatulence, constipation, and diarrhea.

BACKGROUND: The Venous Thromboembolism Prevention Study (VTEPS) Network is a consortium of 5 tertiary referral centers established to examine venous thromboembolism (VTE) in plastic surgery patients. We report our midterm analyses of the study's control group to evaluate the incidence of VTE in patients who receive no chemoprophylaxis, and validate the Caprini Risk Assessment Model (RAM) in plastic surgery patients. STUDY DESIGN: Medical record review was performed at VTEPS centers for all eligible plastic surgery patients between March 2006 and June 2009. Inclusion criteria were Caprini score ≥3, surgery under general anesthesia, and postoperative hospital admission. Patients who received chemoprophylaxis were excluded. Dependent variables included symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) within the first 60 postoperative days and time to DVT or PE. RESULTS: We identified 1,126 historic control patients. The overall VTE incidence was 1.69%. Approximately 1 in 9 (11.3%) patients with Caprini score >8 had a VTE event. Patients with Caprini score >8 were significantly more likely to develop VTE when compared with patients with Caprini score of 3 to 4 (odds ratio [OR] 20.9, p < 0.001), 5 to 6 (OR 9.9, p < 0.001), or 7 to 8 (OR 4.6, p = 0.015). Among patients with Caprini score 7 to 8 or Caprini score >8, VTE risk was not limited to the immediate postoperative period (postoperative days 1-14). In these high-risk patients, more than 50% of VTE events were diagnosed in the late (days 15-60) postoperative period. CONCLUSIONS: The Caprini RAM effectively risk-stratifies plastic and reconstructive surgery patients for VTE risk. Among patients with Caprini score >8, 11.3% have a postoperative VTE when chemoprophylaxis is not provided. In higher risk patients, there was no evidence that VTE risk is limited to the immediate postoperative period.

BACKGROUND: Patients with scleroderma may have abnormal motility of the small intestine, with pseudoobstruction and bacterial overgrowth. Standard stimulatory agents are often ineffective in such patients. Because the somatostatin analogue octreotide evokes intestinal motor activity in normal subjects, we hypothesized that it might increase motility in patients with scleroderma. METHODS: We studied the effects of octreotide on intestinal motility and plasma motilin concentrations in five fasting patients with scleroderma who had bacterial overgrowth and in six fasting normal subjects. The motor effects of octreotide were correlated with its effects on abdominal symptoms and bacterial overgrowth as determined by the level of breath hydrogen excretion. RESULTS: In the normal subjects, octreotide (10 micrograms subcutaneously) increased the mean (+/- SD) frequency of intestinal migrating complexes, which reflect intestinal motility, from 1.5 +/- 1.0 to 4.1 +/- 1.1 every three hours. In the patients with scleroderma, who had no spontaneous migrating complexes, octreotide (100 micrograms) induced 3.6 +/- 2.3 complexes every three hours. These complexes propagated at the same velocity and had two-thirds the amplitude of the spontaneous complexes in normal subjects. Plasma motilin concentrations, which were higher in the patients with scleroderma (229 +/- 74 pmol per liter) than in the normal subjects (112 +/- 37 pmol per liter), were inhibited by octreotide, suggesting that intestinal activity evoked by octreotide is independent of motilin. Treatment of the patients with scleroderma with octreotide (50 micrograms every evening) for three weeks reduced breath hydrogen excretion while they were fasting from 25 +/- 5 to 4 +/- 2 ppm (P = 0.001) and breath hydrogen excretion after they ingested 50 g of glucose from 46 +/- 24 to 8 +/- 7 ppm (P = 0.015); these reductions were accompanied by a significant decrease in nausea, bloating, and abdominal pain and by less frequent emesis. CONCLUSIONS: Octreotide stimulates intestinal motility in normal subjects and in patients with scleroderma. In such patients, the short-term administration of octreotide reduces bacterial overgrowth and improves abdominal symptoms. This agent may be useful for the treatment of intestinal dysmotility in patients with scleroderma.

BACKGROUND: Mycophenolate Mofetil (MMF) has been shown to significantly decrease the number of acute rejection episodes in renal transplant recipients during the 1st year. A beneficial effect of MMF on long-term graft survival has been more difficult to demonstrate. This beneficial effect has not been detected, despite the impact of acute rejection on the development of chronic allograft nephropathy and experimental evidence that MMF may have a salutary effect on chronic allograft nephropathy independent of that of rejection. METHODS: Data on 66,774 renal transplant recipients from the U.S. renal transplant scientific registry were analyzed. Patients who received a solitary renal transplant between October 1, 1988 and June 30, 1997 were studied. The Cox proportional hazard regression was used to estimate relevant risk factors. Kaplan-Meier analysis was performed for censored graft survival. RESULTS: MMF decreased the relative risk for development of chronic allograft failure (CAF) by 27% (risk ratio [RR] 0.73, P<0.001). This effect was independent of its outcome on acute rejection. Censored graft survival using MMF versus azathioprine was significantly improved by Kaplan-Meier analysis at 4 years (85.61% v. 81.9%). The effect of an acute rejection episode on the risk of developing CAF seems to be increasing over time (RR=1.9, 1988-91; RR=2.9, 1992-94; RR=3.7, 1995-97). CONCLUSION: MMF therapy decreases the risk of developing CAF. This improvement is only partly caused by the decrease in the incidence of acute rejection observed with MMF; but, is also caused by an effect independent of acute rejection.