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Economic evaluations in the hip arthroplasty literature: lessons to be learned.

Readers are increasingly encountering articles dealing with health economic evaluations that compare various surgical strategies, leaving orthopaedists with the challenge of determining which program is cost-efficient and truly pertains to their setting. This study carries out a systematic review of the literature to appraise the quality, quantity, and type of economic evaluation as it pertains to the hip arthroplasty literature. To identify all relevant articles, we conducted a comprehensive computerized bibliographic search of Medline from 1966 to 1996. This search produced 1,611 abstracts that were screened. Studies that were incorporated met the following inclusion criteria: i) formal economic analysis, ii) an intervention specific to hip arthroplasty, and iii) the perspective of the study was evident (ie, patient, provider, society). These studies were appraised with regards to methodologic soundness based on 8 established economic principles. Only 68 articles from the 138 retrieved met the study criteria. Only 2 of the 68 articles met all 8 criteria of a comprehensive economic evaluation. The hip arthroplasty literature is deficient in methodologically sound economic evaluations. Several guidelines are introduced to aid orthopaedists in appraising the various economic studies, and recommendations are made to improve the quality of these studies in the orthopaedic literature. We suggest that the generation of such information should rank high on the priority list of the orthopaedic profession, granting agencies, and governments.

Arthroplasty, Replacement, Hip↗

Medical evaluation of nephrolithiasis.

A careful and individualized evaluation of risk factors is a fundamental part of the management of patients with urinary tract stone disease. Identification and correction of important abnormalities provide the basis for designing an efficient and rational treatment program, aiming at an arrest or at least reduction of recurrent stone formation. It is beyond doubt that appropriate therapeutic steps in this regard are of great benefit for the patient. It needs to be emphasized, however, that no success will be obtained unless the patient is willing and able to follow the ensuing dietary recommendations and medical advice.

Calcium Oxalate↗

Discovering Neural Nets with Low Kolmogorov Complexity and High Generalization Capability.

Many neural net learning algorithms aim at finding "simple" nets to explain training data. The expectation is that the "simpler" the networks, the better the generalization on test data (--> Occam's razor). Previous implementations, however, use measures for "simplicity" that lack the power, universality and elegance of those based on Kolmogorov complexity and Solomonoff's algorithmic probability. Likewise, most previous approaches (especially those of the "Bayesian" kind) suffer from the problem of choosing appropriate priors. This paper addresses both issues. It first reviews some basic concepts of algorithmic complexity theory relevant to machine learing, and how the Solomonoff-Levin distribution (or universal prior) deals with the prior problem. The universal prior leads to a probabilistic method for finding "algorithmically simple" problem solutions with high generalization capability. The method is based on Levin complexity (a time-bounded generalization of Kolmogorov complexity) and inspired by Levin's optimal universal search algorithm. For a given problem, solution candidates are computed by efficient "self-sizing" programs that influence their own runtime and storage size. The probabilistic search algorithm finds the "good" programs (the ones quickly computing algorithmically probable solutions fitting the training data). Simulations focus on the task of discovering "algorithmically simple" neural networks with low Kolmogorov complexity and high generalization capability. It is demonstrated that the method, at least with certain toy problems where it is computationally feasible, can lead to generalization results unmatchable by previous neural network algorithms. Much remains to be done, however, to make large scale applications and "incremental learning" feasible. Copyright 1997 Elsevier Science Ltd.

Journal Article↗

A computer adaptive testing approach for assessing physical functioning in children and adolescents.

The purpose of this article is to demonstrate: (1) the accuracy and (2) the reduction in amount of time and effort in assessing physical functioning (self-care and mobility domains) of children and adolescents using computer-adaptive testing (CAT). A CAT algorithm selects questions directly tailored to the child's ability level, based on previous responses. Using a CAT algorithm, a simulation study was used to determine the number of items necessary to approximate the score of a full-length assessment. We built simulated CAT (5-, 10-, 15-, and 20-item versions) for self-care and mobility domains and tested their accuracy in a normative sample (n=373; 190 males, 183 females; mean age 6y 11mo [SD 4y 2m], range 4mo to 14y 11mo) and a sample of children and adolescents with Pompe disease (n=26; 21 males, 5 females; mean age 6y 1mo [SD 3y 10mo], range 5mo to 14y 10mo). Results indicated that comparable score estimates (based on computer simulations) to the full-length tests can be achieved in a 20-item CAT version for all age ranges and for normative and clinical samples. No more than 13 to 16% of the items in the full-length tests were needed for any one administration. These results support further consideration of using CAT programs for accurate and efficient clinical assessments of physical functioning.

Activities of Daily Living↗

Tin speciation in the femtogram range in open ocean seawater by gas chromatography/inductively coupled plasma mass spectrometry using a shield torch at normal plasma conditions.

A sensitive method for the determination of ultratrace organotin species in seawater is described. The merits and demerits of derivatization methods using Grignard reagent or sodium tetraethylborate (NaBEt4) were evaluated in terms of derivatization efficiency, applicability to the programmed temperature vaporization (PTV) method, and procedural blanks. The sensitivity of the gas chromatography/inductively coupled plasma mass spectrometry (GC/ICPMS) was improved by more than 100-fold by operating the shield torch at normal plasma conditions, compared with that obtained without using it. The absolute detection limit as tin reached subfemtogram (fg) levels. Furthermore, the detection limit in terms of relative concentration was improved 100-fold by using the PTV method, which enabled the injection of a large sample volume of as much as 100 microL without loss of analyte. When the organotin species in seawater were extracted into hexane with a preconcentration factor of 1000 after ethylation with NaBEt4 and a 100 microL aliquot of the extract was injected into the GC, the instrumental detection limit in relative concentration reached 0.01 pg/L in original seawater. Sources of contamination of organotin species during the sample preparation were examined, and a purification method of NaBEt4 was developed. Finally, the method was successfully applied to open ocean seawater samples containing organotin species at the level of 1-100 pg/L.

Borates↗

Microwave-assisted Acid decomposition of animal- and plant-derived samples for element analysis.

A single microwave-assisted acid-decomposition procedure is proposed for sample preparation of plant- and bovine-derived materials prior to multielement determination by inductively coupled plasma-optical emission spectrometry (ICP-OES). The procedure involved sample grinding in a cryogenic mill to reduce particle sizes and increase the surface area for acid attack, followed by decomposition under high pressure and temperature. A single heating program was employed and efficiently destroyed most of the organic matrix by using small volumes of nitric acid and hydrogen peroxide. Accuracy of the elemental analysis was indicated by the good agreement between certified and found values of elements in plant and animal samples at 95% confidence level. The sample preparation procedure was fast and reproducible, and proved to be efficient for elemental analysis in agricultural and food-related samples by a sensitive multielement technique such as ICP-OES.

Animals↗

5'-Homoneplanocin A inhibits hepatitis B and hepatitis C.

As an outgrowth of our program to develop an efficient synthesis of 5'-homoneplanocin A, its antiviral potential was explored beyond that already in the literature. From that, this compound was found to have meaningful activity toward hepatitis B and hepatitis C, which represents an example of one agent effective toward both viruses. These data and an improved preparation of 5'-homoneplanocin A are reported.

Adenosine↗

Hybrid-hybrid matrix structural refinement of a DNA three-way junction from 3D NOESY-NOESY.

Homonuclear 3D NOESY-NOESY has shown great promise for the structural refinement of large biomolecules. A computationally efficient hybrid-hybrid relaxation matrix refinement methodology, using 3D NOESY-NOESY data, was used to refine the structure of a DNA three-way junction having two unpaired bases at the branch point of the junction. The NMR data and the relaxation matrix refinement confirm that the DNA three-way junction exists in a folded conformation with two of the helical stems stacked upon each other. The third unstacked stem extends away from the junction, forming an acute angle (approximately 60 degrees) with the stacked stems. The two unpaired bases are stacked upon each other and are exposed to the solvent. Helical parameters for the bases in all three strands show slight deviations from typical values expected for right-handed B-form DNA. Inter-nucleotide imino-imino NOEs between the bases at the branch point of the junction show that the junction region is well defined. The helical stems show mobility (+/- 20 degrees) indicating dynamic processes around the junction region. The unstacked helical stem adjacent to the unpaired bases shows greater mobility compared to the other two stems. The results from this study indicate that the 3D hybrid-hybrid matrix MORASS refinement methodology, by combining the spectral dispersion of 3D NOESY-NOESY and the computational efficiency of 2D refinement programs, provides an accurate and robust means for structure determination of large biomolecules. Our results also indicate that the 3D MORASS method gives higher quality structures compared to the 2D complete relaxation matrix refinement method.

Base Pairing↗

Assessing administrative costs of mental health and substance abuse services.

Increasing competition in the market for mental health and substance abuse MHSA services and the potential to realize significant administrative savings have created an imperative to monitor, evaluate, and control spending on administrative functions. This paper develops a generic model that evaluates spending on administrative personnel by a group of providers. The precision of the model is demonstrated by examining a set of data assembled from five MHSA service providers. The model examines a differential cost construction derived from inter-facility comparisons of administrative expenses. After controlling for the scale of operations, the results enable MHSA programs to control the efficiency of administrative personnel and related rates of compensation. The results indicate that the efficiency of using the administrative complement and the scale of operations represent the lion's share of the total differential cost. The analysis also indicates that a modest improvement in the use of administrative personnel results in substantial cost savings, an increase in the net cash flow derived from operations, an improvement in the fiscal performance of the provider, and a decline in opportunity costs that assume the form of foregone direct patient care.

Cost Control↗

Self-ligating brackets and treatment efficiency.

A number of laboratory studies have shown very low levels of archwire friction for self-ligating brackets when compared to conventional ligation methods. However, justifiable reservations have been expressed as to the in vivo relevance of these findings. This study was designed to compare treatment efficiency with conventional fully programmed brackets and Damon SL self-ligating brackets. Thirty consecutively finished cases treated by the author with Damon SL brackets were compared with 30 matched cases treated by the author with conventional brackets. Parallel studies quantified the incidence of technical problems with Damon SL brackets and with conventional ligatures and also the chairside time required for ligation/slide closure and ligature removal/slide opening with these two bracket types. The Damon SL cases required an average of four fewer months and four fewer visits to be treated to an equivalent level of occlusal regularity as measured by the PAR scores.

Journal Article↗

Drug target validation and identification of secondary drug target effects using DNA microarrays.

We describe here a method for drug target validation and identification of secondary drug target effects based on genome-wide gene expression patterns. The method is demonstrated by several experiments, including treatment of yeast mutant strains defective in calcineurin, immunophilins or other genes with the immunosuppressants cyclosporin A or FK506. Presence or absence of the characteristic drug 'signature' pattern of altered gene expression in drug-treated cells with a mutation in the gene encoding a putative target established whether that target was required to generate the drug signature. Drug dependent effects were seen in 'targetless' cells, showing that FK506 affects additional pathways independent of calcineurin and the immunophilins. The described method permits the direct confirmation of drug targets and recognition of drug-dependent changes in gene expression that are modulated through pathways distinct from the drug's intended target. Such a method may prove useful in improving the efficiency of drug development programs.

Calcineurin↗

Tumor necrosis factor-alpha- and IL-4-independent development of Langerhans cell-like dendritic cells from M-CSF-conditioned precursors.

GM-CSF and transforming growth factor beta (TGFbeta ) are required for the generation of Langerhans cells (LC), members of the dendritic cell (DC) family. Tumor necrosis factor alpha (TNFalpha) and IL-4 can enhance LC differentiation from human monocytes or CD34(+) progenitors. Here, we show that M-CSF-cultured DC precursors derived from CD34(+) progenitors resemble dermal CD14(+) cells and readily convert to LC-like DC in GM-CSF/TGFbeta. The cells express Langerin, CD1a, and CCR6, migrate in response to CCR6 ligand CCL20, and contain Birbeck granules. TNFalpha and IL-4, added separately or together, have an inhibitory effect on LC differentiation. Cells differentiated in the presence of IL-4 and TNFalpha express low levels of CCR7. This suggests that M-CSF-conditioned DC precursors retain the capacity to efficiently undergo a differentiation program, giving rise to LC-like DC solely through the effect of GM-CSF and TGFbeta.

Antigens, CD↗

Direct early intervention with stuttering: some preliminary data.

Many clinicians recognize a need for direct intervention with cases of early stuttering. However, this recognition is not supported by adequate empirical information about how such cases should be managed. One possibility is that early stuttering might be controllable by parent-administered, operant, verbal stimulation procedures. The purpose of this paper is to present preliminary data that depict the results of such an intervention procedure with four cases of early stuttering. Speech measures were gathered in a variety of speaking situations, within and beyond the clinic, over a 2-month pretreatment period and a 9-month posttreatment period. Results showed that the 4 subjects achieved reductions in stuttering comparable to those reported for adult treatment programs. However, the present results were obtained in far fewer clinical hours than normally needed in the treatment for older subjects. The treatment times in the present study also compare favorably to those published in other reports of operant intervention procedures with children. These findings suggest that cases of early stuttering might be managed effectively by parents, with limited expenditure of clinical time. Findings are discussed in terms of their implications for the development of early intervention programs that are more efficient and effective than existing intervention procedures for older clients.

Child, Preschool↗

First-trimester Down's syndrome screening using nuchal translucency: a prospective study in patients undergoing chorionic villus sampling.

The value of the measurement of nuchal translucency thickness for predicting fetal Down's syndrome and other aneuploidies was prospectively evaluated at 8-15 weeks of gestation in 1819 consecutive pregnancies scheduled for karyotyping by chorionic villus sampling. In 43 cases, a chromosomal unbalanced aberration was found. Two teams of ultrasonologists who examined patients attending either National Health Service (Series 1) or private practice clinics (Series 2) were involved in the study. The same type of ultrasound machine and standardized approach were used in both study groups. In those cases in which the maximum subcutaneous thickness of the translucency was 3 mm or greater, the incidence of chromosomal aberration was 18.6% compared to 1.7% in the cases in which this was below 3 mm. The sensitivity, specificity and relative risk for all aneuploidies were 30%, 96% and 10.83, respectively, and no difference was found between trisomy 21 and other types of aneuploidy. The sensitivity and specificity and relative risk were significantly higher at 9-10 weeks than between 11 and 15 weeks. The results were concordant in the two series; however, the overall values for sensitivity (20% vs. 39%), specificity (94% vs. 98%) and relative risk (4.13 vs. 24.20) were clearly higher in the group of private patients. The results obtained confirm the potential application of the measurement of nuchal translucency thickness for fetal aneuploidy screening before the end of the first trimester and suggest that a multiplicity of individual, structural and organizational factors may interact and play a crucial role in determining the actual efficiency of ultrasound screening programs.

Adult↗

Successful storage of RBCs for 9 weeks in a new additive solution.

BACKGROUND: This study explored the effect of storing packed RBCs suspended in 200 mL of an alkaline, hypotonic, experimental additive solution (EAS 61). STUDY DESIGN AND METHODS: Packed RBC units prepared from RBCs collected from healthy donors in CPD were stored for 8 (n = 10) and 9 (n = 10) weeks under blood bank conditions after the addition of 200 mL of EAS 61 (adenine, 2 mM:; dextrose, 110 mM:; mannitol, 55 mM:; NaCl, 26 mM:; Na(2)HPO(4), 12 mM:). Standard methods were used for in vitro assays. The 24-hour in vivo autologous recoveries were measured with (51)Cr. RESULTS: Mean +/- SD recoveries at 8 and 9 weeks were 81 +/- 7 and 77 +/- 7 percent. After 9 weeks, the ATP of the RBCs was 81 percent of the initial value, hemolysis was 0.35 percent, supernatant potassium was 46 mEq per L, and the morphologic index was 94.1. CONCLUSION: Packed RBCs suspended in 200 mL of EAS 61 can be stored satisfactorily for 9 weeks. Longer RBC storage should reduce outdating, increase availability of transfusions in remote locations, and improve the efficiency of autologous donor programs.

Adult↗

Successful storage of RBCs for 10 weeks in a new additive solution.

BACKGROUND: The effect of storing packed RBCs suspended in 300 mL of an alkaline, experimental additive solution (EAS 64) was explored. STUDY DESIGN AND METHODS: RBC units prepared from blood collected from healthy donors into CPD were WBC reduced and stored for 10 weeks under blood bank conditions after the addition of 300 mL of EAS 64 (adenine, 2 mM:; dextrose, 50 mM:; mannitol, 20 mM:; NaCl, 75 mM:; Na(2)HPO(4), 9 mM:). For comparison, non-WBC-reduced units from the same donors were stored in a different additive solution (AS-1, Baxter Healthcare) for 6 weeks. Standard methods were used for the in vitro assays. The 24-hour in vivo recoveries were measured by using (51)Cr- and (99m)Tc-labeled RBCs. RESULTS: Mean recovery in the EAS 64 units after 10 weeks was 84 +/- 8 percent, the same as in the AS-1 units stored for 6 weeks. For EAS 64 and AS-1 units, respectively, the ATP of the RBCs was 85 percent and 64 percent of the initial value, hemolysis was 0.43 percent and 0.63 percent, supernatant potassium was 24 mEq per L and 44 mEq per L, and the morphologic index was 98 and 71. CONCLUSION: RBCs suspended in 300 mL of EAS 64 can be stored satisfactorily for 10 weeks. Longer RBC storage should reduce outdating, increase availability of transfusions in remote locations, and improve the efficiency of autologous donor programs.

Adenosine Triphosphate↗

The epidemiology of tuberculosis in San Francisco. A population-based study using conventional and molecular methods.

BACKGROUND: The epidemiology of tuberculosis in urban populations is changing. Combining conventional epidemiologic techniques with DNA fingerprinting of Mycobacterium tuberculosis can improve the understanding of how tuberculosis is transmitted. METHODS: We used restriction-fragment-length polymorphism (RFLP) analysis to study M. tuberculosis isolates from all patients reported to the tuberculosis registry in San Francisco during 1991 and 1992. These results were interpreted along with clinical, demographic, and epidemiologic data. Patients infected with the same strains were identified according to their RFLP patterns, and patients with identical patterns were grouped in clusters. Risk factors for being in a cluster were analyzed. RESULTS: Of 473 patients studied, 191 appeared to have active tuberculosis as a result of recent infection. Tracing of patients' contacts with the use of conventional methods identified links among only 10 percent of these patients. DNA fingerprinting, however, identified 44 clusters, 20 of which consisted of only 2 persons and the largest of which consisted of 30 persons. In patients under 60 years of age, Hispanic ethnicity (odds ratio, 3.3; P = 0.02), black race (odds ratio, 2.3; P = 0.02), birth in the United States (odds ratio, 5.8; P < 0.001), and a diagnosis of the acquired immunodeficiency syndrome (odds ratio, 1.8; P = 0.04) were independently associated with being in a cluster. Further study of patients in clusters confirmed that poorly compliant patients with infectious tuberculosis have a substantial adverse effect on the control of this disease. CONCLUSIONS: Despite an efficient tuberculosis-control program, nearly a third of new cases of tuberculosis in San Francisco are the result of recent infection. Few of these instances of transmission are identified by conventional contact tracing.

AIDS-Related Opportunistic Infections↗

To HITH or not to HITH: making a decision about establishing hospital in the home.

Hospital in the home is increasingly being considered as an alternative for the provision of acute care. This article provides an overview of Hospital in the Home in Australia, discussing some of the issues that should be considered when determining whether to establish or fund hospital in the home programs such as whether efficiency is increased, care is improved and whether patients perceive more choice. These issues are discussed in the context of a transparent funding strategy that is aimed at achieving predefined goals and objectives.

Australia↗