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PubMed2006

Parametric and nonparametric population methods: their comparative performance in analysing a clinical dataset and two Monte Carlo simulation studies.

BACKGROUND AND OBJECTIVES: This study examined parametric and nonparametric population modelling methods in three different analyses. The first analysis was of a real, although small, clinical dataset from 17 patients receiving intramuscular amikacin. The second analysis was of a Monte Carlo simulation study in which the populations ranged from 25 to 800 subjects, the model parameter distributions were Gaussian and all the simulated parameter values of the subjects were exactly known prior to the analysis. The third analysis was again of a Monte Carlo study in which the exactly known population sample consisted of a unimodal Gaussian distribution for the apparent volume of distribution (V(d)), but a bimodal distribution for the elimination rate constant (k(e)), simulating rapid and slow eliminators of a drug. METHODS: For the clinical dataset, the parametric iterative two-stage Bayesian (IT2B) approach, with the first-order conditional estimation (FOCE) approximation calculation of the conditional likelihoods, was used together with the nonparametric expectation-maximisation (NPEM) and nonparametric adaptive grid (NPAG) approaches, both of which use exact computations of the likelihood. For the first Monte Carlo simulation study, these programs were also used. A one-compartment model with unimodal Gaussian parameters V(d) and k(e) was employed, with a simulated intravenous bolus dose and two simulated serum concentrations per subject. In addition, a newer parametric expectation-maximisation (PEM) program with a Faure low discrepancy computation of the conditional likelihoods, as well as nonlinear mixed-effects modelling software (NONMEM), both the first-order (FO) and the FOCE versions, were used. For the second Monte Carlo study, a one-compartment model with an intravenous bolus dose was again used, with five simulated serum samples obtained from early to late after dosing. A unimodal distribution for V(d) and a bimodal distribution for k(e) were chosen to simulate two subpopulations of 'fast' and 'slow' metabolisers of a drug. NPEM results were compared with that of a unimodal parametric joint density having the true population parameter means and covariance. RESULTS: For the clinical dataset, the interindividual parameter percent coefficients of variation (CV%) were smallest with IT2B, suggesting less diversity in the population parameter distributions. However, the exact likelihood of the results was also smaller with IT2B, and was 14 logs greater with NPEM and NPAG, both of which found a greater and more likely diversity in the population studied. For the first Monte Carlo dataset, NPAG and PEM, both using accurate likelihood computations, showed statistical consistency. Consistency means that the more subjects studied, the closer the estimated parameter values approach the true values. NONMEM FOCE and NONMEM FO, as well as the IT2B FOCE methods, do not have this guarantee. Results obtained by IT2B FOCE, for example, often strayed visibly away from the true values as more subjects were studied. Furthermore, with respect to statistical efficiency (precision of parameter estimates), NPAG and PEM had good efficiency and precise parameter estimates, while precision suffered with NONMEM FOCE and IT2B FOCE, and severely so with NONMEM FO. For the second Monte Carlo dataset, NPEM closely approximated the true bimodal population joint density, while an exact parametric representation of an assumed joint unimodal density having the true population means, standard deviations and correlation gave a totally different picture. CONCLUSIONS: The smaller population interindividual CV% estimates with IT2B on the clinical dataset are probably the result of assuming Gaussian parameter distributions and/or of using the FOCE approximation. NPEM and NPAG, having no constraints on the shape of the population parameter distributions, and which compute the likelihood exactly and estimate parameter values with greater precision, detected the more likely greater diversity in the parameter values in the population studied. In the first Monte Carlo study, NPAG and PEM had more precise parameter estimates than either IT2B FOCE or NONMEM FOCE, as well as much more precise estimates than NONMEM FO. In the second Monte Carlo study, NPEM easily detected the bimodal parameter distribution at this initial step without requiring any further information. Population modelling methods using exact or accurate computations have more precise parameter estimation, better stochastic convergence properties and are, very importantly, statistically consistent. Nonparametric methods are better than parametric methods at analysing populations having unanticipated non-Gaussian or multimodal parameter distributions.

Aged↗
PubMed2006

Assessing the predictive validity and efficacy of a multimodal training programme for laparoscopic radical prostatectomy (LRP).

OBJECTIVES: To assess the predictive validity (ability to correlate to real-life environment) and efficacy of a training programme for laparoscopic radical prostatectomy (LRP), based on a structured and progressive pelvitrainer component with hands-on clinical training in the operating room (OR). METHODS: Prospective data on 500 LRP cases were analysed with 80 excluded due to incomplete records. The operation was divided into multiple steps. Times for these steps were compared among 11 surgeons with different laparoscopic expertise (first-, second-, and third-generation surgeons in order of decreasing experience) and correlated to times for specific exercises on the pelvitrainer that simulated particular steps. Perioperative parameters were also evaluated among the three groups. RESULTS: Pelvitrainer times achieved by trainees (third-generation surgeons) did not differ significantly with times for corresponding steps of LRP. There was also no significant difference for total OR time between the second- and third-generation surgeons (205 and 207 min, respectively; p>0.05) although the time for the first-generation surgeons was faster than both (176 min). Short-term quality indicators for first, second, and third generations included transfusion rates (2.3%, 2.4%, and 2.6%, respectively), positive margin rates (20.3%, 21.5%, and 23.0%) and complications, which did not differ significantly among the generations although the first-generation surgeons had the lowest rates. CONCLUSIONS: A carefully designed training programme that incorporates both pelvitrainer and mentor-based operative training is essential for the effective and safe transfer of skills and knowledge required to learn LRP.

Adult↗
PubMed1994

Endoscopically defined treatment strategies in patients with locally advanced esophageal cancer.

Sixty-five consecutive, locally advanced esophageal cancer patients were treated by the West Side Medical Center Esophageal Service at the Cook County and University of Illinois hospitals. Each patient was prospectively evaluated with multiple endoscopies including esophagogastroduodenoscopy, bronchoscopy, nasopharyngoscopy, and laryngoscopy. Twenty-four patients (37%) had endoscopic findings that significantly altered therapeutic regimens. Patients identified as having an obvious or impending esophageal fistula or poor performance status were treated in a palliative fashion. Forty (61.5%) patients were considered candidates for treatment with multimodal therapy which included radiation, chemotherapy, and surgery. There was a response rate of 82.5% and a 1-year disease-free survival of 88.9% which was statistically significant when compared to the other patient treatment groups. These data illustrate the necessity of multiple endoscopic evaluation of locally advanced esophageal cancer patients for stratification into appropriate treatment groups. Aggressive treatment afforded selected patients excellent relief of presenting symptomatology, as well as an improved, more acceptable, disease-free survival.

Adenocarcinoma↗
PubMed1997

Prospective evaluation of local excision for small rectal cancers.

OBJECTIVE: Most data on local excisions for rectal cancer are based on retrospective studies. We review the results of a prospective registry of patients eligible for local excision of rectal cancer using a transanal, transsphincteric, or transcoccygeal technique combined with multimodality therapy for lesions penetrating the muscularis propria (T2) or perirectal fat (T3). METHODS: Patients with lesions less than 4 cm in diameter and less than 10 cm from the dentate line, with no evidence of distant metastases or invasion into the perirectal fat, were eligible for local excision. Patients with invasion into the muscularis propria (T2) or greater (T3) received adjuvant chemoradiation therapy. RESULTS: Forty-eight patients have been followed prospectively. Average age is 63 years. Thirty-three patients underwent a transanal excision. Fifteen patients underwent either a transsphincteric or technique excision. There was no perioperative mortality. Pathology revealed 1 Tis, 21 T1, 21 T2, and 5 T3 cancers. Mean follow-up is 40.5 months. Cancer-related overall mortality was 4 percent. Overall local or distant recurrence rate was 8 percent (4/48). Recurrence appeared to be related to presence of a positive margin or aggressive histology (lymphatic invasion). Local recurrences were treated with salvage therapy. CONCLUSION: Local excision can be used selectively for small rectal cancers, with minimum morbidity. Recurrence rates are low (8 percent). Patients with either a positive margin or lymphatic invasion need to be considered for further therapy, including abdominoperineal resection, even with T1 lesions. Adjuvant chemoradiation appears to be a benefit for all T2 or T3 cancers.

Adenocarcinoma↗
PubMed2005

Multivariate analysis of risk factors for wound infection in head and neck squamous cell carcinoma surgery with opening of mucosa. Study of 260 surgical procedures.

The goal of this prospective study was to determine risk factors for wound infections (WI) for patients with head and neck cancer who had undergone surgical procedures with opening of upper aerodigestive tract mucosa in multimodal therapeutic approaches. Two hundred and sixty consecutive surgical procedures were studied at Oscar Lambret Cancer Center over a 36-month period. Twenty-five variables were recorded for each patient. Statistical evaluation used chi2 test analysis (categorical data) and Mann-Whitney test (continuous variables). Multivariate analysis was performed with logistic regression model. The overall rate of WI was 45% (117/260). Univariate analysis indicated that five variables were significantly related to the likelihood of WI: male sex (p = 0.03), previous chemotherapy (p = 0.009), duration of previous hospital stay (p = 0.013), hypopharyngeal location (p = 0.003), post-laryngectomy tracheostoma (p < 0.001). Multivariate analysis identified only one major risk factor for WI: post-laryngectomy tracheostoma (Odd Ratio 1.9 [95% CI 1.3-3]; 33% versus 64%; p = 0.001). Despite antibiotic prophylaxis, WI occurrence is high. This study identified one major risk factor, post-laryngectomy tracheostomy. Long-term curative antibiotherapy must be evaluated in cancer head and neck surgery requiring post-laryngectomy tracheostoma.

Adult↗
PubMed2006

Model-based imaging.

The concept of model-based imaging provides a possibility of integration of both structural and functional information obtained by imaging and nonimaging sources of diagnostically relevant information. Merging information of different origin and nature in a simulated computer patient-specific three-dimensional (3-D) model is important for multimodal imaging approaches to medical diagnostics. The work of F. L. Lizzi on life-like imaging done nearly 20 years ago was the first successful attempt of patient-specific 3-D computer modeling using conventional ultrasonography data. He demonstrated the applications of such 3-D models, which incorporated acoustic, optical and thermal properties of imaged tissue, in physiologic studies, in planning and monitoring ultrasonic hyperthermia and ablation. However, numerous obstacles hinder the wide use of the model-based imaging concept. Using the example of model-based imaging of prostate, the advantages and limitation on the applicability of the concept are discussed. Attempts of implementing the model-based imaging concept in the mechanical imaging technology--imaging with the use of measurements of stress pattern on the surface of tissue--are described. It is shown that composing a patient-specific 3-D model requires well-defined and carefully validated algorithms for translating features of the object assessed by an imaging modality into the quantitative anatomic and histopathologic parameters.

Algorithms↗
PubMed2002

Multimodal protocol influence on stroke and neurocognitive deficit prevention after ascending/arch aortic operations.

BACKGROUND: Various techniques are used for brain protection during aortic surgery. Rather than evaluate each factor separately, we evaluated the early outcome of a multimodal protocol (mannitol, thiopental, MgSO4, lidocaine, CO2 field flooding, Leukoguard filter, head ice packing, electroencephalographic arrest at 20 degrees C, alpha-stat, increasing right subclavian artery cannulation, and antegrade/retrograde brain perfusion) for brain protection. METHODS: Prospectively collected data were analyzed on 403 ascending or arch aortic operations including 199 (49%) arch replacements conducted between July 25, 1991, and September 25, 2001. The mean age was 61.6 years (range 22 to 91 years); 48 (12%) had Marfan syndrome; 141 (35%) had dissection; 134 (33%) had composite grafts inserted; and 138 (34%) had concurrent coronary bypasses performed. RESULTS: Stroke occurred in 2.0% (8/403) (3 permanent, 5 transient), clinical neurocognitive deficits in 2.5% (10/403) either by testing or patient complaint 2 to 3 weeks after surgery, and 98% (395/403) were 30-day survivors. Univariate predictors of stroke, neurocognitive decline, or death were the following: for stroke, aorta symptom severity grade (1 to 4) (p = 0.001), pump time (p = 0.001), arrest time (p = 0.001), macroscopic atheroma (p = 0.041), concurrent descending/thoracoabdominal aneurysm (p = 0.036), and highest blood rewarming temperature (p = 0.043); for neurocognitive decline, degree of cooling (p = 0.046), pump time (p = 0.001), cooling time (p = 0.001), day extubated (p = 0.042), and antegrade brain perfusion (p = 0.004); for death, pump time (p = 0.001) and clamp time (p = 0.011). The multivariable independent predictors of stroke, neurocognitive decline, or death were the following: for stroke, aorta symptoms grade (p = 0.025), peripheral vascular disease (p = 0.043), and pump time (p = 0.015); neurocognitive decline, preoperative New York Heart Association dyspnea class (p = 0.022), pump time (p = 0.05), arrest time (p = 0.06), day extubated (p = 0.042), and antegrade perfusion (p = 0.023); and for death, pump time (p = 0.018). CONCLUSIONS: Pump time continues to be the most important predictor of adverse events. The benefit of antegrade or retrograde perfusion remains unproven, partly because of the low event rate (< 2.5%) but may be beneficial for prolonged circulatory arrest. Embolic material either from macroscopic atheroma, descending or thoracoabdominal aneurysms, or associated with peripheral vascular disease, increases the risk of stroke. Preoperative symptoms influence outcome.

Adult↗
PubMed2001

Improved prognosis following peritonectomy procedures and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from appendiceal carcinoma.

AIMS: The prognosis of patients with peritoneal carcinomatosis from gastrointestinal malignancies is poor. The aim of this study was to analyse the results of multimodality treatment for peritoneal carcinomatosis of appendiceal carcinoma. PATIENTS AND METHODS: From 07/95 to 01/00, 17 patients (13 males, 4 female, median age 58 years) underwent peritonectomy procedures in combination with intraperitoneal hyperthermic chemotherapy. Surgical, pathological and survival data were analysed retrospectively. RESULTS: All patients had undergone previous surgical treatment and one patient had received chemotherapy. In all patients peritonectomy procedures, as described by Sugarbaker, were performed with the aim of achieving a macroscopically complete cytoreduction (range 2-6, median 4 procedures per patient). Following resection, open hyperthermic intraperitoneal chemotherapy with cisplatin was performed. Eleven patients had postoperative complications (predominantly "non-surgical") and two patients died postoperatively. The 4-year survival rate was 75%. Complete cytoreducion had a statistically significant positive influence on long-term survival. CONCLUSIONS: In selected patients (WHO status 0/1, minimal residual disease, no distant metastases, complete cytoreduction), the prognosis for patients with peritoneal carcinomatosis of appendiceal origin can be improved by peritonectomy procedures and hyperthermic intraperitoneal chemotherapy. Postoperative morbidity may be increased due to "non-surgical" complications.

Adult↗
PubMed2000

Accurate alignment of functional EPI data to anatomical MRI using a physics-based distortion model.

Mapping of functional magnetic resonance imaging (fMRI) to conventional anatomical MRI is a valuable step in the interpretation of fMRI activations. One of the main limits on the accuracy of this alignment arises from differences in the geometric distortion induced by magnetic field inhomogeneity. This paper describes an approach to the registration of echo planar image (EPI) data to conventional anatomical images which takes into account this difference in geometric distortion. We make use of an additional spin echo EPI image and use the known signal conservation in spin echo distortion to derive a specialized multimodality nonrigid registration algorithm. We also examine a plausible modification using log-intensity evaluation of the criterion to provide increased sensitivity in areas of low EPI signal. A phantom-based imaging experiment is used to evaluate the behavior of the different criteria, comparing nonrigid displacement estimates to those provided by a imagnetic field mapping acquisition. The algorithm is then applied to a range of nine brain imaging studies illustrating global and local improvement in the anatomical alignment and localization of fMRI activations.

Algorithms↗
PubMed2006

Blastemal expression of type I insulin-like growth factor receptor in Wilms' tumors is driven by increased copy number and correlates with relapse.

Most Wilms' tumors are of low stage, favorable histology, and have a high likelihood of cure with current multimodal therapy. Despite this, there remains a group of patients whose tumors recur for whom intensive salvage regimens result in survival of only 50%. Fitting a Cox proportional hazards model to microarray-based comparative genomic hybridization (aCGH) data on 68 Wilms' tumor samples, we identified a significant correlation between increased copy number at chromosome 15q26.3 insulin-like growth factor I receptor (IGFIR) and tumor relapse (adjusted P = 0.014). Wilms' tumors (13%) exhibited a low-level gain corresponding to three to four copies of the gene by aCGH analysis, 9 of 10 of which exhibited high IGFIR mRNA levels. Although IGFIR protein expression was restricted to the epithelial cells of fetal kidney and Wilms' tumors in most cases, 12% of tumors were also found to express IGFIR in the blastemal compartment. Blastemal IGFIR protein expression was associated with an increased copy number and a shorter relapse-free survival time (P = 0.027, log-rank test). In addition to the membrane localization, IGFIR was localized to the perinuclear region of the blastemal cells in 6% of Wilms' tumors. These data provide evidence that an increase in IGFIR gene copy number results in aberrant expression in the blastemal compartment of some Wilms' tumors and is associated with an adverse outcome in these patients. These findings suggest the possibility of use of targeted agents in the therapy of these children.

Cell Nucleus↗
PubMed2002

Imaging databases and neuroscience.

Brain atlases are equivalent to neuroimage databases provided an appropriate coordinate system to enable multisubject comparisons, along with comprehensive descriptions of the data, are included. Warping tools, visualization, and statistical analyses that accommodate the various neuroimaging modalities can be used to integrate diverse data and form comprehensive maps describing a particular subpopulation's brain structure and function. By linking task performance and genetic information to brain morphology, complex interrelations between genotype, phenotype, and behavior can be established. Several examples of these multimodal, multisubject atlases, including those that are dynamic, are presented.

Animals↗
PubMed2006

Lateralization of the human mirror neuron system.

A cortical network consisting of the inferior frontal, rostral inferior parietal, and posterior superior temporal cortices has been implicated in representing actions in the primate brain and is critical to imitation in humans. This neural circuitry may be an evolutionary precursor of neural systems associated with language. However, language is predominantly lateralized to the left hemisphere, whereas the degree of lateralization of the imitation circuitry in humans is unclear. We conducted a functional magnetic resonance imaging study of imitation of finger movements with lateralized stimuli and responses. During imitation, activity in the inferior frontal and rostral inferior parietal cortex, although fairly bilateral, was stronger in the hemisphere ipsilateral to the visual stimulus and response hand. This ipsilateral pattern is at variance with the typical contralateral activity of primary visual and motor areas. Reliably increased signal in the right superior temporal sulcus (STS) was observed for both left-sided and right-sided imitation tasks, although subthreshold activity was also observed in the left STS. Overall, the data indicate that visual and motor components of the human mirror system are not left-lateralized. The left hemisphere superiority for language, then, must be have been favored by other types of language precursors, perhaps auditory or multimodal action representations.

Adolescent↗
PubMed1976

Spontaneous regression of neuroblastoma.

Case of spontaneous regression of neuroblastoma continue to occur in the present multimodal therapy era at institutions where physicians are prepared to withhold treatment on certain patients with residual primary or metastatic disease. From a survey of the 22 member institutions of Children's Cancer Study Group, seven hospitals submitted data on 24 neuroblastoma patients whose disease underwent regression after minimal, unusual, or no treatment. An analysis of these patients and of 33 patients form two large series in the literature shows that the majority of patients are infants with Stage II or Stage IVS disease. The spontaneous regression usually consists of complete disappearance of the disease, but in some neuroblastomas, maturation to ganglioneuroma takes place. The various factors that may influence regression are discussed.

Age Factors↗
PubMed2000

Pleuropulmonary blastoma: management and prognosis of 11 cases.

BACKGROUND: Pleuropulmonary blastoma (PPB) is a rare and aggressive malignant tumor that affects children and adults. This neoplasm is histologically characterized by primitive blastema and a malignant mesenchymal stroma that often demonstrates multidirectional differentiation. Despite the introduction of multimodal therapy, the prognosis of patients with PPB remains poor. METHODS: In the current study the authors reported on PPB cases from a national retrospective search performed in 18 Italian Associations for Pediatric Hematology and Oncology centers. Clinical data, surgical notes, pathologic findings, and summaries of chemotherapy and radiotherapy were obtained from reports and correlated with outcome by standard statistical methods. RESULTS: The series included 11 patients (7 boys and 4 girls) with a median age of 32 months. Respiratory distress was the most common clinical symptom. In three patients the PPB developed from other primary dysplastic diseases: cystic adenomatoid malformation in one case and congenital lung cysts in the other two cases. Five patients experienced disease recurrences (local recurrence in three patients and distant metastasis in two patients, within the central nervous system and an intraocular location, respectively). Patients with a type 2 histologic pattern and/or pleural involvement were found to have a worse outcome compared with patients without such features. Event free survival at 2 years from the time of diagnosis was 45% for all patients. Overall survival at 2 years was 72% for all patients. CONCLUSIONS: PPB is an aggressive neoplasm of early childhood and to the authors' knowledge no adequate therapy has been defined to date for patients with PPB. After making the diagnosis, the main goal of therapy should be radical surgery, even in patients with microscopic residual disease. Because the response to chemotherapy is poor, the authors' experience suggests that chemotherapy should be given with local radiotherapy in the majority of patients.

Child↗
PubMedDate not supplied

[Communication interventions: windows of opportunity].

OBJECTIVE: An understanding of how verbal and non verbal language develops and how it is related to social behavior is essential in order to devise effective interventions for children with disorders of communication. We review the literature on interventions for children with communication disorders from the perspective of the clinical neurologist emphasizing both therapeutic and pharmacological interventions. FINDINGS: Our knowledge on effective interventions in children with disorders of communications is limited due to the heterogeneity of the population and the lack of well controlled studies. There is some limited data suggesting that therapeutic interventions for children with language impairments are most effective if all forms of communication are emphasized. Interventions should be adapted to the age of presentation and associated clinical findings of the child. CONCLUSIONS: A multimodal intervention approach is essential to maximize the potential of children with communication disorders. The role of medication in interventions for children with disorders of communication is limited to the treatment of associated symptoms that may interfere with the ability of a child to receive non pharmacological therapeutic interventions.

Brain↗
PubMed1983

Recent studies on intestinal vagal afferent innervation. Functional implications.

Data obtained during recent years have completely changed our understanding of the organization and function of visceral sensitivity. The digestive tract--and especially the small intestine--provides a very good example of this evolution. Classically, it was believed that the sensory innervation of the gut is supplied by both the vagus and the splanchnic nerves. The vagus nerves play the major role in the sensory innervation of the first part of the intestine (all layers of the bowel, except mesentery). These vagal sensory fibers are mostly nonmedullated and generally originate from free endings. Microelectrophysiological techniques have disclosed the existence of a great variety of receptors: mechanoreceptors, chemoreceptors, thermoreceptors and osmoreceptors in the intestinal area. Some receptors like glucoreceptors, are specific receptors since they do not respond to any stimuli other than glucose. Others, like osmosensitive receptors, behave as non-specific or multimodal receptors. The mechanism by which an identical structure (free ending) induces various sorts of signals (mechanical, thermal, chemical etc.) is not yet known, but several hypotheses have been proposed. The discovery of a varied and complex mass of information obtained from studies of the gut finally corroborates the behavioural and clinical data which suggest that the intestinal sensory innervation plays an important role in physiological regulation. Now it is possible to distinguish 3 main kinds of mechanisms involved according to whether they concern digestive motility, homeostasis or alimentary behaviour.

Afferent Pathways↗
PubMed2004

Strategies to improve immunization rates and well-child care in a disadvantaged population: a cluster randomized controlled trial.

OBJECTIVE: To measure the effect of a multimodal intervention on well-child care visit (WCV) and immunization rates in an inner-city population. DESIGN: Cluster randomized controlled trial. SETTING AND PARTICIPANTS: One-year cohort of 2843 infants born at a hospital in an integrated inner-city health care system. INTERVENTIONS: Eleven clinics were randomly allocated to 1 of 3 study arms: WCV intervention (n = 3), immunization intervention (n = 4), and controls (n = 4). Interventions to improve immunization and WCV rates included both patient-based and clinic-based activities. MAIN OUTCOME MEASURES: Up-to-date status with childhood immunizations and WCVs by age 12 months (primary) and health care utilization and charges (secondary). RESULTS: Compared with the control arm, the WCV and immunization arms had 5% to 6% higher immunization rates and 7% to 8% higher WCV rates. In multivariate analyses that accounted for the clustered nature of the data, the number of immunizations received was greater in the WCV arm than in controls. However, neither the WCV nor the immunization intervention increased WCV or immunization up-to-date rates. The WCV arm had slightly higher health care charges. Neither intervention affected emergency, urgent care or inpatient utilization. CONCLUSIONS: This multimodal intervention produced a small increase in the number of childhood immunizations delivered. However, patient- and clinic-based methods did not lead to significant increases in WCV or immunization up-to-date rates after controlling for other factors. Methods found in some settings to increase immunization up-to-date rates may not be as effective in a population of inner-city socioeconomically disadvantaged children.

Child Health Services↗