Real-world experience with the all-oral, interferon-free regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir for the treatment of chronic hepatitis C virus infection in the German Hepatitis C Registry.

Real-world studies are relevant to complement clinical trials on novel antiviral therapies against chronic hepatitis C; however, clinical practice data are currently limited. This study investigated effectiveness and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r)±dasabuvir (DSV)±ribavirin (RBV) for treatment of HCV genotype (GT) 1 and GT4 infection in a large real-world cohort. The German Hepatitis C Registry is an observational cohort study prospectively collecting clinical practice data on direct-acting antiviral therapies. Patients with GT1/4 infection treated with OBV/PTV/r±DSV±RBV were analysed. Effectiveness was assessed by sustained virologic response in 558 patients who reached post-treatment week 12 (SVR12). Safety is reported in 1017 patients who initiated treatment. Of the patients, 892 (88%) had GT1 and 125 (12%) had GT4 infection. Prior treatment experience and cirrhosis were reported in 598 (59%) and 228 (22%) patients, respectively. Overall, SVR12 (mITT) was 96% (486/505) in GT1- and 100% (53/53) in GT4 patients. SVR12 rates were high across subgroups including patients with cirrhosis (95%, 123/129), patients with moderate to severe renal impairment (100%, 34/34), and subgroups excluded from registrational trials like patients ≥70 years (96%, 64/67) and failures to prior protease inhibitor treatment (96%, 46/48). Adverse events (AEs) and serious AEs were reported in 52% (525/1017) and 2% (21/1017) of patients, respectively, and led to treatment discontinuation in 1.5% (15/1017) of patients. OBV/PTV/r±DSV±RBV was effective and generally well tolerated for treatment of HCV infection in clinical practice.

Screening for autoantibodies in chronic hepatitis C patients has no effect on treatment initiation or outcome.

Autoantibodies in hepatitis C virus-infected patients may indicate autoimmune hepatitis or other immune-mediated diseases. This may impact safety and efficacy of interferon-based therapy of chronic hepatitis C. We investigated the association between a positive test result for a variety of autoantibodies and the initiation and efficacy of therapy for chronic hepatitis C. We analysed an observational cohort of 24 306 patients for an association between autoantibodies and treatment outcome. 8241 patients were tested simultaneously for antinuclear antibodies (ANA), liver kidney microsomal antibodies (LKM), smooth muscle antibodies (SMA) and antimitochondrial antibodies (AMA). Matched-pair analysis was performed matching one autoantibody-positive patient to three controls. Control patients had negative tests for all four antibodies. Analyses were performed for patients with a single positive autoantibody test and for patients with multiple positive autoantibody tests. A positive test result for ANA, LKM, SMA or AMA did not affect the physician's decision to initiate therapy with pegylated interferon and ribavirin. In addition, a positive test for one or multiple autoantibodies did not adversely affect sustained virologic response. There was no difference in fibrosis stage or alanine transaminase at baseline or during therapy irrespective of antibody status. Thyroid dysfunction was more frequent in patients with positive LKM antibodies (P = 0.004). Initiation of therapy for chronic hepatitis C and outcome were not affected by the presence of ANA, LKM, SMA or AMA. Routine testing of these autoantibodies seems not warranted. Determination of autoantibodies should be guided by individualized clinical decisions.

High-dose silibinin rescue treatment for HCV-infected patients showing suboptimal virologic response to standard combination therapy.

Incomplete suppression of hepatitis C virus (HCV) replication with persistence of minimal viremia (partial virologic response) leading to treatment failure can be observed in a significant proportion of HCV type 1-infected patients during antiviral therapy. Recently, high-dose intravenous silibinin has demonstrated strong antiviral activity against HCV. We were therefore interested in whether patients with partial virologic response can be rescued by the on-treatment addition of a short-term course of high-dose intravenous silibinin infusions. Twenty patients who failed to achieve a complete virologic response to different interferon-based regimens qualified for the rescue strategy and received 1400 mg/day silibinin infusions on two consecutive days. Complete viral suppression (below the limit of detection <6 IU/mL, TMA assay) could be induced in 13 of 20 patients within the first week after the short-term silibinin infusion, and all but one of them also remained HCV RNA negative during the subsequent follow-up period on continued peginterferon plus ribavirin treatment. In the remaining seven patients, no complete suppression could be achieved although four showed a significant HCV RNA reduction in response to silibinin. Silibinin infusions were generally well tolerated, and activation of abdominal peristalsis with nausea, diarrhoea and vomiting were the most prominent side effects. Of the twelve patients who exhibited a durable response to peginterferon and ribavirin treatment, three achieved an SVR, two achieved a week 12 SVR and four suffered a viral relapse. Three patients could not complete the assigned antiviral treatment with peginterferon alpha and ribavirin for nonvirological reasons. Short-term administration of high-dose intravenous silibinin might be an interesting approach to rescue patients with ongoing minimal residual viremia while on interferon-based therapy. These preliminary findings may stimulate further studies to evaluate more refined therapeutic strategies.

[Epidemiology and clinical characteristics of patients with chronic hepatitis B (CHB) in Germany - results of a nationwide cross-sectional study]. / Epidemiologie und Klinik von Patienten mit chronischer Hepatitis B (CHB) in Deutschland - Ergebnisse einer bundesweiten Querschnittstudie.

BACKGROUND AND AIMS: Knowledge about the epidemiology, demography and social status of patients with replicative chronic hepatitis B (CHB) in Germany is still scarce. This cross-sectional study evaluated in patients with chronic hepatitis B infection, with a serum HBV-DNA concentration of at least 10,000 copies/mL (> 2000 IU/mL) at documentation visit, the epidemiology, socio-demographics, time of diagnosis, history of disease, prior therapies as well the therapeutic decision. METHODS: 74 German centres with predominately hepatologic focus, recorded in an online-survey the pseudonymised data of patients with chronic HBV-infection with a serum HBV-DNA-concentration of at least 10,000 copies/mL (n = 35). RESULTS: 65 % of the patients were male. The mean age was 40 ± 14 years. 63 % were immigrants (i. e., country of birth not being Germany). 37 % were HBeAg-positive. Mean ALT value 114 ± 183 IU/mL in males and 77 ± 176 IU/mL in females. ALT was above the upper limit of normal (ULN) in 59 % and 9 % of the patients were cirrhotic. The large immigrant groups, Turks (22 %), people from the former USSR (11 %) or from Southeast Asia (10 %) differed in terms of age, sex, HBeAg-status and clinical parameters clearly from each other as well as from German patients. 55 % of the patients from SE-Asia were female and overall considerably younger than German patients. 69 % of the patients with HBV-DNA > 10,000 copies/mL combined with ALT-levels above ULN, and 87 % with advanced fibrosis recieved antiviral treatment. CONCLUSIONS: This database currently contains the largest collection of epidemiological data of CHB patients in Germany. It therefore allows a representative overview on the disease in Germany. In Germany CHB epidemiology is triggered by migration from countries with higher CHB prevalence. However, the high proportion of patients coming from states of the former USSR is likely to be a historical peculiarity of Germany. The sometimes weak German language skills as well as the cultural specifics in the different immigrant groups are still a challenge for health-care providers. The high proportion of viraemic patients, already being treated, could indicate a suboptimal efficacy of the available therapeutic options at the time documentation.

Estimating the likelihood of sustained virological response in chronic hepatitis C therapy.

The likelihood of a sustained virological response (SVR) is the most important factor for physicians and patients in the decision to initiate and continue therapy for chronic hepatitis C (CHC) infection. This study identified predictive factors for SVR with peginterferon plus ribavirin (RBV) in patients with CHC treated under 'real-life' conditions. The study cohort consisted of patients from a large, retrospective German multicentre, observational study who had been treated with peginterferon alfa-2a plus RBV or peginterferon alfa-2b plus RBV between the years 2000 and 2007. To ensure comparability regarding peginterferon therapies, patients were analysed in pairs matched by several baseline variables. Univariate and multivariate logistic regression analyses were used to determine the effect of nonmatched baseline variables and treatment modality on SVR. Among 2378 patients (1189 matched pairs), SVR rates were 57.9% overall, 46.5% in HCV genotype 1/4-infected patients and 77.3% in genotype 2/3-infected patients. In multivariate logistic regression analysis, positive predictors of SVR were HCV genotype 2 infection, HCV genotype 3 infection, low baseline viral load and treatment with peginterferon alfa-2a. Negative predictors of SVR were higher age (≥40 years), elevated baseline gamma-glutamyl transpeptidase (GGT) and low baseline platelet count (<150,000/µL). Among patients treated with peginterferon plus RBV in routine clinical practice, genotype, baseline viral load, age, GGT level and platelet levels all predict the likelihood of treatment success. In patients matched by baseline characteristics, treatment with peginterferon alfa-2a may be a positive predictor of SVR when compared to peginterferon alfa-2b.

Efficacy and tolerability of peginterferon alfa-2a or alfa-2b plus ribavirin in the daily routine treatment of patients with chronic hepatitis C in Germany: the PRACTICE study.

In randomized clinical trials, treatment with peginterferon plus ribavirin (RBV) results in a sustained virological response (SVR) in around half of hepatitis C virus genotype 1-infected and 80% of genotype 2/3-infected individuals. This study aimed to evaluate efficacy and tolerability of peginterferon alfa-2a plus RBV compared with peginterferon alfa-2b plus RBV for the treatment of chronic hepatitis C in routine clinical practice. The intent-to-treat cohort consisted of 3414 patients treated with either peginterferon alfa-2a plus RBV (Group A) or peginterferon alfa-2b plus RBV (Group B) in 23 centres participating in the large, multicentre, observational PRACTICE study. Collected data included baseline characteristics, treatment regimen, RBV dose and outcome. Rates of early virological response, end of treatment response and SVR were 76.6%, 75.7% and 52.9% in Group A, and 70.2%, 65.6% and 50.5% in Group B, respectively. In patients matched by baseline parameters, 59.9% of patients in Group A and 55.9% in Group B achieved an SVR (P < or = 0.051). In genotype 1-infected patients matched by baseline parameters and cumulative RBV dose, SVR rates were 49.6% and 43.7% for Group A and Group B, respectively (P < or = 0.047); when matched by baseline parameters and RBV starting dose, SVR rates were 49.9% and 44.6%, respectively (P = 0.068). Overall, 21.8% of group A and 29.6% of group B patients discontinued treatment (P < or = 0.0001). The efficacy and tolerability of peginterferon plus RBV in this large cohort of patients treated in routine daily practice was similar to that in randomized clinical trials. In matched pairs analyses, more patients achieved an SVR with peginterferon alfa-2a compared with peginterferon alfa-2b.

Severe intraventricular hemorrhage and withdrawal of support in preterm infants.

OBJECTIVE: The objective of the study was to determine whether withdrawal of support in severe 'intraventricular hemorrhage' (IVH), that is, IVH grade 3 and periventricular hemorrhagic infarction (PVHI), has decreased after publication of studies that show improved prognosis and to examine cranial ultrasonograms, including PVHI territories defined by Bassan. STUDY DESIGN: Retrospective cohort of preterm infants from 23 0/7 to 28 6/7 weeks' gestation in 1993 to 2013. RESULTS: Among the 1755 infants, 1494 had no bleed, germinal matrix hemorrhage (GMH) or IVH grade 2, 137 had grade 3 IVH and 124 had PVHI. The odds of withdrawal of support, adjusted for severity of GMH-IVH and baseline variables, did not decrease after publications showing better prognosis. Among 82 patients who died with PVHI, 76 had life support withdrawn, including 34 without another contributing cause of death. The median number of PVHI territories involved was three. CONCLUSION: Withdrawal of support adjusted for severity of GMH-IVH did not significantly change after publications showing better prognosis.

Mortality among infants with evolving bronchopulmonary dysplasia increases with major surgery and with pulmonary hypertension.

OBJECTIVE: To assess whether mortality in patients with evolving bronchopulmonary dysplasia (BPD, defined as ⩾28 days of oxygen exposure with lung disease) is independently associated with pulmonary arterial hypertension (PAH) and surgery. STUDY DESIGN: Single institution retrospective birth cohort of preterm infants with gestational age (GA) 230/7 to 366/7 weeks, and evolving BPD delivered between 2001 and 2014. Surgery was classified as minor or major using published criteria. Mortality was analyzed by stepwise logistic regression analysis. RESULTS: Among 577 patients with evolving BPD, 33 (6%) died prior to discharge. Mortality decreased with GA (adjusted odds ratio (aOR): 0.69; 95% confidence interval (CI): 0.55, 0.87), birth weight Z-score (aOR: 0.69, 95% CI: 0.47, 0.996) and increased with PAH (aOR: 30, 95% CI: 2.1, 415), major surgery (aOR; 2.8, 95% CI: 1.3, 6.3), and PAH and surgery (aOR: 10.3, 95% CI: 2.5, 42.1). CONCLUSION: Among preterm patients with evolving BPD, PAH and surgery are independently associated with mortality.

Do currently recommended Bayley-III cutoffs overestimate motor impairment in infants born <27 weeks gestation?

OBJECTIVE: To determine whether a Bayley-III motor composite score of 85 may overestimate moderate-severe motor impairment by analyzing Bayley-III motor components and developing cut-point scores for each. STUDY DESIGN: Retrospective study of 1183 children born <27 weeks gestation at NICHD Neonatal Research Network centers and evaluated at 18-22 months corrected age. Gross Motor Function Classification System determined gross motor impairment. Statistical analyses included linear and logistic regression and sensitivity/specificity. RESULTS: Bayley-III motor composite scores were strong indicators of gross/fine motor impairment. A motor composite cut-point of 73 markedly improved the specificity for identifying gross and/or fine motor impairment (94% compared with a specificity of 76% for the proposed new cut-point of 85). A Fine Motor Scaled Score <3 differentiated mild from moderate-severe fine motor impairment. CONCLUSIONS: This study indicates that a Bayley-III motor composite score of 85 may overestimate impairment. Further studies are needed employing term controls and longer follow-up.

Neurodevelopmental outcomes after hypothermia therapy in the era of Bayley-III.

OBJECTIVE: Bayley-III scales are currently used to evaluate outcomes of term infants following hypothermia therapy, while all before reported outcomes in this population have used Bayley-II. Our objectives were to determine the incidence of abnormal neurodevelopmental outcomes using Bayley III and the predictive value of Magnetic resonance imaging (MRI) in infants who received systemic hypothermia. STUDY DESIGN: We conducted a prospective cohort study of inborn infants who underwent hypothermia for moderate/severe neonatal encephalopathy from October 2005-November 2011. RESULT: Eighty newborns underwent hypothermia (incidence of 1/1000). Of the survivors, 89% had Bayley-III performed around 24 months of age. An abnormal outcome using Bayley-III <85 occurred in 50%, while Bayley III <70 occurred in 13%. MRI predicted Bayley III<85 with sensitivity of 73%, specificity of 84%, positive-predictive value of 84% and negative-predictive value of 74%. CONCLUSION: A Bayley-III 85 cutoff identifies a disability rate of 50%, and MRI was predictive of abnormal outcomes. Findings can be useful for counseling of families and planning of future studies using Bayley III.

Venous thromboembolism during hip plaster cast immobilisation: review of the literature.

INTRODUCTION: There is a paucity of data regarding the risk of deep vein thrombosis during hip plaster cast immobilisation. The purpose of this article was to review the available evidence regarding the incidence of symptomatic venous thromboembolism (VTE) during hip plaster cast immobilisation. METHODS AND MATERIALS: All papers describing hip plaster cast immobilisation published in the English literature retrieved from PubMed, EMBASE and the Cochrane database were reviewed. Articles regarding children, hip dysplasia, congenital hip dislocation and Legg-Calvé-Perthes were excluded. A total of three papers were available for analysis. We also describe a case of pulmonary embolism during hip cast immobilisation. RESULTS: The overall incidence of symptomatic VTE during hip plaster cast immobilisation was 0% in 343 patients. The incidence of symptomatic VTE in hip cast brace was 2.3% (range 0-3%). DISCUSSION: Our systematic review of the literature showed a paucity of data regarding the incidence of VTE during hip plaster cast immobilisation. We describe the first case of pulmonary embolism during hip plaster cast immobilisation. We recommend that patients who are fitted with a hip plaster cast should be routinely screened for additional risk factors. When risk factors are present, patients should be considered for pharmacological thromboprophylaxis.

High-resolution laser spectroscopy on the negative osmium ion.

We have applied a combination of laser excitation and electric-field detachment to negative atomic ions for the first time, resulting in an enhancement of the excited-state detection efficiency for spectroscopy by at least 2 orders of magnitude. Applying the new method, a measurement of the bound-bound electric-dipole transition frequency in (192)Os- was performed using collinear spectroscopy with a narrow-bandwidth cw laser. The transition frequency was found to be 257.831 190(35) THz [wavelength 1162.747 06(16) nm, wave number 8600.3227(12) cm(-1)], in agreement with the only prior measurement, but with more than 100-fold higher precision.

[Epidemiology of chronic hepatitis C in Germany--an analysis of 10,326 patients in hepatitis centres and outpatient units]. / Epidemiologie der chronischen Hepatitis C in Deutschland--Eine Analyse von 10,326 Hepatitis-C-Virus-Infizierten aus Schwerpunktpraxen und -ambulanzen.

Little is known about the epidemiology of chronic hepatitis C (CHC) in Germany and especially about the importance of transmission, duration of infection, genotypes, symptoms and quality of life of the patients. The current study prospectively evaluates epidemiological and clinical data of patients infected with the hepatitis C virus (HCV). Using online data entry, various characteristics of 10,326 untreated patients with CHC were documented from March 2003 until May 2006 in 352 centres all over Germany. Mean age of patients was 43.4 years. Patients infected by i.v. drug abuse were considerably younger (36.5 years) than the remaining patients (49.2 years). As indicated by their native language, 64.4% of the patients came from Germany and 19.2% from Russia. 61.7% were infected with genotype 1 and 34.9% with genotype 2 or 3. 45.5% of the patients had been infected by i.v. drug abuse. In at least 5.4% of the patients liver cirrhosis had been proved by biopsy. 63.5% of the patients felt an impairment of quality of life caused by CHC. In many patients infected with hepatitis C socio-economic issues are existent. This is reflected, i.e., in very high rates of unemployment in special subpopulations. Coinfections with hepatitis B and HIV occurred in 1.5% and 4.7%, respectively. Nearly 80% of patients were managed near their homes. The data of the 10 326 patients represent about 2% of all German patients with CHC. This database is up to now the largest of its kind and gives a representative insight into the epidemiological situation of CHC in Germany.

Characterization and application of a thermostable primary transport system: cytochrome-C oxidase from Bacillus stearothermophilus.

Cytochrome-c oxidase from Bacillus stearothermophilus has been purified to homogeneity by detergent extraction followed by DEAE-cellulose, hydroxyapatite- and gel-filtration chromatography. The enzyme is a typical cytochrome-aa3-type oxidase which binds carbon monoxide and is sensitive to classical oxidase inhibitors like cyanide and azide. The purified enzyme is composed of three different subunits (57, 37 and 22 kDa). The subunit with intermediate molecular mass contains a covalently attached heme-c moiety. The enzyme appeared to be extremely thermostable (inactivation temperature = 81 degrees C). Highest turnover rates of the reconstituted enzyme were obtained with Saccharomyces cerevisiae cytochrome c or reduced forms of non-physiological electron donors like N,N,N',N'-tetramethyl-p-phenylenediamine and phenazine methosulphate. The reconstituted enzyme can generate a proton-motive force consisting of a high membrane potential and trans-membrane pH gradient. The high electro-motive force of the enzyme (delta p = -180 to -200 mV) indicates that this enzyme functions as a high-capacity electrogenic proton pump. Liposomes containing the purified thermostable and thermoactive cytochrome-c oxidase were fused with membranes from the fermentative bacterium Clostridium acetobutylicum. In the hybrid system a high proton-motive force can be generated upon oxidation of reduced N,N,N',N'-tetramethyl-p-phenylenediamine by the incorporated oxidase which subsequently can be used to drive secondary transport of amino acids. This demonstrates the applicability of the cytochrome-c oxidase to study solute transport in membranes of fermentative bacteria.

Sodium ion-dependent amino acid transport in membrane vesicles of Bacillus stearothermophilus.

Amino acid transport in membrane vesicles of Bacillus stearothermophilus was studied. A relatively high concentration of sodium ions is needed for uptake of L-alanine (Kt = 1.0 mM) and L-leucine (Kt = 0.4 mM). In contrast, the Na(+)-H(+)-L-glutamate transport system has a high affinity for sodium ions (Kt less than 5.5 microM). Lithium ions, but no other cations tested, can replace sodium ions in neutral amino acid transport. The stimulatory effect of monensin on the steady-state accumulation level of these amino acids and the absence of transport in the presence of nonactin indicate that these amino acids are translocated by a Na+ symport mechanism. This is confirmed by the observation that an artificial delta psi and delta mu Na+/F but not a delta pH can act as a driving force for uptake. The transport system for L-alanine is rather specific. L-Serine, but not L-glycine or other amino acids tested, was found to be a competitive inhibitor of L-alanine uptake. On the other hand, the transport carrier for L-leucine also translocates the amino acids L-isoleucine and L-valine. The initial rates of L-glutamate and L-alanine uptake are strongly dependent on the medium pH. The uptake rates of both amino acids are highest at low external pH (5.5 to 6.0) and decline with increasing pH. The pH allosterically affects the L-glutamate and L-alanine transport systems. The maximal rate of L-glutamate uptake (Vmax) is independent of the external pH between pH 5.5 and 8.5, whereas the affinity constant (Kt) increases with increasing pH. A specific transport system for the basic amino acids L-lysine and L-arginine in the membrane vesicles has also been observed. Transport of these amino acids occurs most likely by a uniport mechanism.

Non-invasive evaluation of activity in inflammatory bowel disease by power Doppler sonography.

BACKGROUND: To study the vascularization in the diseased bowel wall by power Doppler sonography in patients with inflammatory bowel disease. PATIENTS AND METHODS: The diseased bowel wall was investigated in 99 patients with inflammatory bowel disease (60 patients with Crohn's disease and 39 patients with ulcerative colitis) either with active disease or in remission by B-mode and power Doppler sonography. Disease activity was determined by clinical indices. Twenty healthy age and sex matched individuals served as controls. RESULTS: Bowel wall was thickened in active Crohn's disease (mean 7 mm, range 4-14) and ulcerative colitis (mean 5 mm, range 2-15) as compared to healthy controls (mean 2 mm, range 1-3), p < 0.001. In contrast to healthy controls blood vessels were detected in the bowel wall in 100 % of patients with active Crohn's disease and 91 % with active ulcerative colitis. Vascularization was significant decreased in patients with quiescent versus active disease in ulcerative colitis (p < 0.05), while in Crohn's disease there was no significance between active and remission phase. CONCLUSIONS: Thickened and hypervascularized bowel wall are characteristic findings in inflammatory bowel disease. A combination of B-mode and power Doppler sonography offers an additional noninvasive procedure for the determination of activity in patients with inflammatory bowel disease.

Comprehensive follow-up care and life-threatening illnesses among high-risk infants: A randomized controlled trial.

CONTEXT: Inner-city high-risk infants often receive limited and fragmented care, a problem that may increase serious illness. OBJECTIVE: To assess whether access to comprehensive care in a follow-up clinic is cost-effective in reducing life-threatening illnesses among high-risk, inner-city infants. DESIGN: Randomized controlled trial. SETTING AND PARTICIPANTS: A total of 887 very-low-birth-weight infants born in a Texas county hospital between January 1988 and March 1996 and followed up in a children's hospital clinic. One hundred four infants who became ineligible or died after randomization but before nursery discharge were excluded from the analysis. INTERVENTIONS: Infants were randomly assigned to receive routine follow-up care (well-baby care and care for chronic illnesses; n = 441) or comprehensive care (which included the components of routine care plus care for acute illnesses, with 24-hour access to a primary caregiver; n = 446). MAIN OUTCOME MEASURES: Life-threatening illnesses (ie, causing death or hospital admission for pediatric intensive care) occurring between nursery discharge and age 1 year, assessed by blinded evaluators from inpatient charts and state Medicaid and vital statistics records; and hospital costs (estimated from department-specific cost-to-charge ratios). RESULTS: Comprehensive care resulted in a mean of 3.1 more clinic visits and 6.7 more telephone conversations with clinic staff (P<.001 for both). One-year outcomes were unknown for fewer comprehensive-care infants than routine-care infants (9 vs 28; P =.001). Identified deaths were similar (11 in comprehensive care vs 13 in routine care; P =.68). The comprehensive-care group had 48% fewer life-threatening illnesses (33 vs 63; P<.001), 57% fewer intensive care admissions (23 vs 53; P =.003), and 42% fewer intensive care days (254 vs 440; P =.003). Comprehensive care did not increase the mean estimated cost per infant for all care ($6265 with comprehensive care and $9913 with routine care). CONCLUSION: Comprehensive follow-up care by experienced caregivers can be highly effective in reducing life-threatening illness without increasing costs among high-risk inner-city infants. JAMA. 2000;284:2070-2076.