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PubMed2005

International staging system for multiple myeloma.

PURPOSE: There is a need for a simple, reliable staging system for multiple myeloma that can be applied internationally for patient classification and stratification. PATIENTS AND METHODS: Clinical and laboratory data were gathered on 10,750 previously untreated symptomatic myeloma patients from 17 institutions, including sites in North America, Europe, and Asia. Potential prognostic factors were evaluated by univariate and multivariate techniques. Three modeling approaches were then explored to develop a staging system including two nontree and one tree survival assessment methodologies. RESULTS: Serum beta2-microglobulin (Sbeta2M), serum albumin, platelet count, serum creatinine, and age emerged as powerful predictors of survival and were then used in the tree analysis approach. A combination of Sbeta2M and serum albumin provided the simplest, most powerful and reproducible three-stage classification. This new International Staging System (ISS) was validated in the remaining patients and consists of the following stages: stage I, Sbeta2M less than 3.5 mg/L plus serum albumin > or = 3.5 g/dL (median survival, 62 months); stage II, neither stage I nor III (median survival, 44 months); and stage III, Sbeta2M > or = 5.5 mg/L (median survival, 29 months). The ISS system was further validated by demonstrating effectiveness in patients in North America, Europe, and Asia; in patients less than and > or = 65 years of age; in patients with standard therapy or autotransplantation; and in comparison with the Durie/Salmon staging system. CONCLUSION) The new ISS is simple, based on easy to use variables (Sbeta2M and serum albumin), and recommended for early adoption and widespread use.

Age Factors↗

PubMed1995

Prognostic relevance of a histologic classification system applied in bone marrow biopsies from patients with multiple myeloma: a histopathological evaluation of biopsies from 153 untreated patients.

A total of 153 diagnostic bone marrow biopsies from patients with advanced stages of multiple myeloma corresponding to stages II and III according to the Durie/Salmon classification were evaluated prior to any treatment in a prospective therapy trial of the German Myeloma Treatment Group. Histologic sections were analyzed according to a pre-defined system of criteria microscopically by 2 observers, determining three criteria: 1) grading by histopathology, regarding the cytologic differentiation of neoplastic cells and quantifying the percentage of plasmacytic, pleomorphic, and plasmablastic myeloma cells distributed within the sections; 2) the volume of infiltration; and 3) the pattern of neoplastic growth. Furthermore, four other criteria, namely hematopoiesis, fiber increase, osteomalacia, and micro-osteo-lesions, were evaluated. A cluster analysis using the three histological criteria revealed three groups of patients with significantly different survival times based on histological criteria only; the three criteria were mentioned above. It is concluded from these results that bone marrow biopsies, when evaluated histologically by grading and staging according to the three criteria, provide most valuable prognostic parameters in myeloma patients.

Bone Marrow↗

PubMed2003

Burning mouth syndrome. A retrospective analysis of clinical characteristics and treatment outcomes.

Burning mouth syndrome is a condition characterized by burning sensations of the oral cavity in the absence of physical abnormalities of the mucosa or a detectable underlying medical disorder. It is a multifactorial disorder with unclear etiology, affecting predominatly middle-aged women. Multiple approaches to treatment have been described in the literature, with few controlled clinical trials regarding their efficacy. The objectives of this retrospective study were to: 1. determine the epidemiologic characteristics of BMS patients referred to an oral medicine practice; 2. determine if BMS classification correlates with response to treatment; 3. determine the efficacy of a variety of known therapies for BMS. A database was constructed from the charts of 150 consecutive patients diagnosed with BMS; and these charts were reviewed. Patients were classified according to previously published criteria for BMS. Presumed etiologies were grouped into depression/anxiety-associated; hematinic deficiencies, including iron, folate and vitamin B complex; oral habits: and idiopathic BMS. Treatment approaches were divided into seven categories: soft desensitizing appliance; tricyclic antidepressants (TCA); benzodiazepines (BZD); topical analgesics; hematinic supplements; habit awareness counseling; and multi-modal therapy (combining two or more of the above). Improvement was recorded using a zero to 100% VAS scale and classified as no relief (0%); mild (0-40%); meaningful/moderate (41-80%); and profound relief (81-100%). Burning mouth syndrome without any identifiable cause (idiopathic) was diagnosed in 33 patients (46.6%). Patients were followed up at one month (4 weeks) after the initial visit. Nine patients (12.7%) reported profound relief; 17 patients (23.9%) reported meaningful relief; 39 patients (54.9%) reported mild relief. This retrospective review showed no significant correlation between classification of BMS and response to therapy. The most effective treatment modalities were habit awareness, followed by TCAs.

Adult↗

PubMed2004

Immunohistochemical analysis of cyclin D1 and p53 in multiple myeloma: relationship to proliferative activity and prognostic significance.

Conflicting data are reported on the clinical significance of cyclin D1 deregulation in multiple myeloma. The aim of this study was to evaluate the incidence and prognostic significance of cyclin D1 expression and p53 mutations in multiple myeloma, as well as the relationship of their expression with selected clinical data, histological features, and proliferative activity of myeloma cells. We analyzed bone marrow biopsy specimens obtained from 59 patients with newly diagnosed multiple myeloma. Expression of cyclin D1 and p53 was analyzed using standard immunohistochemical method of B5-fixed and routinely processed paraffin-embedded bone marrow specimens. Cyclin D1 was overexpressed in 14/59 (27%) and p53 in 5/59 (8.5%) specimens. There was no significant correlation between cyclin D1 overexpression and age, gender, clinical stage (Durie-Salmon classification), extent of osteolytic lesions, type of monoclonal protein, hemoglobin concentration, platelet count, serum concentration of creatinine, calcium, C-reactive protein, and beta2-microglobulin. No association was observed between the expression of cyclin D1 and the extent of bone marrow infiltration, histological grade, proliferative activity index (measured with Ki-67 immunoreactivity) and response to therapy. No significant difference was observed regarding overall survival between cyclin D1 positive and cyclin D1 negative patients (29 vs 36 mo, p = 0.76). Results of this study did not revealed prognostic significance of cyclin D1 overexpression in multiple myeloma. Mutations of p53 gene are rare events in myeloma, suggesting their limited role in the pathogenesis of the disease.

Adult↗

PubMed2004

Non-sequential structure-based alignments reveal topology-independent core packing arrangements in proteins.

MOTIVATION: Proteins of the same class often share a secondary structure packing arrangement but differ in how the secondary structure units are ordered in the sequence. We find that proteins that share a common core also share local sequence-structure similarities, and these can be exploited to align structures with different topologies. In this study, segments from a library of local sequence-structure alignments were assembled hierarchically, enforcing the compactness and conserved inter-residue contacts but not sequential ordering. Previous structure-based alignment methods often ignore sequence similarity, local structural equivalence and compactness. RESULTS: The new program, SCALI (Structural Core ALIgnment), can efficiently find conserved packing arrangements, even if they are non-sequentially ordered in space. SCALI alignments conserve remote sequence similarity and contain fewer alignment errors. Clustering of our pairwise non-sequential alignments shows that recurrent packing arrangements exist in topologically different structures. For example, the three-layer sandwich domain architecture may be divided into four structural subclasses based on internal packing arrangements. These subclasses represent an intermediate level of structure classification, more general than topology, but more specific than architecture as defined in CATH. A strategy is presented for developing a set of predictive hidden Markov models based on multiple SCALI alignments.

Algorithms↗

PubMed2004

The promise of a DNA taxonomy.

Not only is the number of described species a very small proportion of the estimated extant number of taxa, but it also appears that all concepts of the extent and boundaries of 'species' fail in many cases. Using conserved molecular sequences it is possible to define and diagnose molecular operational taxonomic units (MOTU) that have a similar extent to traditional 'species'. Use of a MOTU system not only allows the rapid and effective identification of most taxa, including those not encountered before, but also allows investigation of the evolution of patterns of diversity. A MOTU approach is not without problems, particularly in the area of deciding what level of molecular difference defines a biologically relevant taxon, but has many benefits. Molecular data are extremely well suited to re-analysis and meta-analysis, and data from multiple independent studies can be readily collated and investigated by using new parameters and assumptions. Previous molecular taxonomic efforts have focused narrowly. Advances in high-throughput sequencing methodologies, however, place the idea of a universal, multi-locus molecular barcoding system in the realm of the possible.

Base Sequence↗

PubMed2000

The effects of self-movement, observation, and imagination on mu rhythms and readiness potentials (RP's): toward a brain-computer interface (BCI).

Current movement-based brain-computer interfaces (BCI's) utilize spontaneous electroencephalogram (EEG) rhythms associated with movement, such as the mu rhythm, or responses time-locked to movements that are averaged across multiple trials, such as the readiness potential (RP), as control signals. In one study, we report that the mu rhythm is not only modulated by the expression of self-generated movement but also by the observation and imagination of movement. In another study, we show that simultaneous self-generated multiple limb movements exhibit properties distinct from those of single limb movements. Identification and classification of these signals with pattern recognition techniques provides the basis for the development of a practical BCI.

Adult↗

PubMed2026

TFAM organizes DNA into compact higher order structures.

TFAM (Transcription Factor A, Mitochondrial) is an essential human protein that plays two key roles in mitochondrial DNA (mtDNA) homeostasis. TFAM acts as a transcription factor that specifically binds to promoter regions, but it is also solely responsible for organizing mtDNA into nucleoids by nonspecifically covering the entire genome. Many studies have addressed TFAM in transcription regulation, but its role as a genome organizing entity is not well characterized. The current understanding of how TFAM compacts DNA into nucleoids is based on crystal structures of a TFAM monomer bound to short fragments of DNA (22-28 bp). However, this does not adequately reflect the biological role of TFAM in organizing the nucleoid where multiple TFAM molecules oligomerize on the 16.5 kb genome to form the nucleoid. Here, we present a biochemical and structural analysis of TFAM oligomerization on longer DNA. Our results show that TFAM compacts longer segments of DNA into higher order complexes that are homogenous yet exhibit continuous conformational dynamics.

Major classification: Biological sciences↗

PubMed2006

MultiSeq: unifying sequence and structure data for evolutionary analysis.

BACKGROUND: Since the publication of the first draft of the human genome in 2000, bioinformatic data have been accumulating at an overwhelming pace. Currently, more than 3 million sequences and 35 thousand structures of proteins and nucleic acids are available in public databases. Finding correlations in and between these data to answer critical research questions is extremely challenging. This problem needs to be approached from several directions: information science to organize and search the data; information visualization to assist in recognizing correlations; mathematics to formulate statistical inferences; and biology to analyze chemical and physical properties in terms of sequence and structure changes. RESULTS: Here we present MultiSeq, a unified bioinformatics analysis environment that allows one to organize, display, align and analyze both sequence and structure data for proteins and nucleic acids. While special emphasis is placed on analyzing the data within the framework of evolutionary biology, the environment is also flexible enough to accommodate other usage patterns. The evolutionary approach is supported by the use of predefined metadata, adherence to standard ontological mappings, and the ability for the user to adjust these classifications using an electronic notebook. MultiSeq contains a new algorithm to generate complete evolutionary profiles that represent the topology of the molecular phylogenetic tree of a homologous group of distantly related proteins. The method, based on the multidimensional QR factorization of multiple sequence and structure alignments, removes redundancy from the alignments and orders the protein sequences by increasing linear dependence, resulting in the identification of a minimal basis set of sequences that spans the evolutionary space of the homologous group of proteins. CONCLUSION: MultiSeq is a major extension of the Multiple Alignment tool that is provided as part of VMD, a structural visualization program for analyzing molecular dynamics simulations. Both are freely distributed by the NIH Resource for Macromolecular Modeling and Bioinformatics and MultiSeq is included with VMD starting with version 1.8.5. The MultiSeq website has details on how to download and use the software: http://www.scs.uiuc.edu/~schulten/multiseq/

Algorithms↗

PubMed2004

Presence and HRCT quantification of bronchiectasis in coal workers.

PURPOSE: The purpose of this study was to evaluate the presence of bronchiectasis in coal workers with or without coal worker pneumoconiosis (CWP) and to assess the extent of bronchiectasis, severity of bronchial wall dilatation and thickening by high resolution computed tomography (HRCT). MATERIALS AND METHODS: The retrospective study consisted of HRCT archieves of 93 coal workers. The coal workers with previous diagnosis of COPD (six), asthma (one) and tuberculosis (three) were excluded. Five coal workers with progressive massive fibrosis were not included into the study. The resulting patient group consisted of 78 patients (43 CWP; 35 non-CWP). Pneumoconiosis profusions of CWP workers were between p0/1 and p2/2 according to ILO 1980 chest X-ray classification. HRCT examinations of all subjects were evaluated for the presence, extent, dilatation and thickness of bronchiectasis. Analysis of extent, dilatation and thickness were performed according to established criteria. RESULTS: The diagnosis of bronchiectasis was put on 19 of 43 CWP (44.1%) and 7 of 35 non-CWP workers (20.0%). There were statistically significant differences between bronchiectasis positive and negative coal workers with CWP concerning age and exposure duration (P = 0.012 and 0.009, respectively). Then, multiple logistic regression analysis was performed to define exact risk factors. Exposure duration was only found to be related with presence of bronchiectasis [(odds ratio) OR = 1.494, 95% confidence interval 1.168-1.912]. CONCLUSIONS: The data from the present study shows that bronchiectasis is frequent and severe in CWP workers than without. Bronchiectasis is influenced by coal dust exposure. Thus, coal dust protection measures must be controlled efficiently to prevent bronchiectasis in coal workers.

Adult↗

PubMed2001

Quantitative classification of life-style types in predaceous phytoseiid mites.

Classification of species into different functional groups based on biological criteria has been a difficult problem in ecology. The difficulty mainly arises because natural classification patterns are not necessarily mutually exclusive. The more group characteristics overlap, the more difficult it is to identify the membership of a species in the overlapping portions of any two groups. In this paper, we present an application of discriminant analysis by creating classification models from life history and morphological data for two specialist and two generalist life-styles type of predaceous phytoseiid mites. Two stages can be distinguished in our method: life-style group membership assignment and trait variable evaluation. We use a Bayesian framework to create a classifier system to locate or assign species within a mixture of trait distributions. The method assumes that a mixture of trait distributions can represent the multiple dimensions of biological data. The mixture is most evident near the boundaries between groups. Because of the complexity of analytical solution, an iterative method is used to estimate the unknown means, variances, and mixing proportion between groups. We also developed a criterion based on information theory to evaluate model performance with different combinations of input variables and different hypotheses. We present a working example of our proposed methods. We apply these methods to the problem of selecting key species for inoculative release and for classical introductions of biological pest control agents.

Animals↗

PubMed1998

Changing HIV infection rates and risk in an African-American community cohort.

This longitudinal study of a homogeneously urban African-American community cohort drawn from the metropolitan New York area (USA) analyzed three-year change in HIV-1 antibody prevalence and self-reported risk practices separately for men and women. Specifically, risk practices reported on personal interviews and results from blood sero-assay in 1989-1990 were compared to similar interview reports of risk practices and HIV assay from saliva samples in 1993. Results showed: (1) women's infection rates increased more than men's, resulting in a male to female infection ratio of 1.5:1; (2) heterosexual transmission accounted for most of women's new infection; (3) in multivariate analysis, multiple partners was a significant heterosexual risk indicator for both men and women, increasing infection odds five-fold; and (4) buying sex also increased heterosexual men's infection odds approximately five-fold. Results document increasing rates of African-American HIV infection linked largely to heterosexual exposure risk, that the African-American male-female infection ratio resembles the global rather than North American one, and also the utility of an expanded classification of heterosexual exposure risk.

Adult↗

PubMed1997

Risk indicators of low back pain among workers in Japan. Association of familial and physical factors with low back pain.

STUDY DESIGN: A questionnaire was given to 3,042 Japanese workers at a factory in 1992. It surveyed age, gender, weight, height, job classification, and work environment, as well as the perceived causes, onset age, and characteristics of low back pain. Family history of low back pain among first-degree relatives and perception of physical condition also were assessed. OBJECTIVES: To investigate the risk indicators of low back pain in Japanese workers with various kinds of job classifications in a manufacturing company. SUMMARY OF BACKGROUND DATA: Risk indicators of low back pain in Japanese patients have not been fully investigated in previous studies. METHODS: Prevalence rates and characteristics of low back pain were examined among 3,042 factory workers (2,517 men and 525 woman) with jobs with varying physical demands. In the analysis of risk indicators of low back pain, the odds ratios and 95% confidence intervals were computed. In addition, a multiple logistic analysis was performed to evaluate risk indicators of low back pain. RESULTS: Point and lifetime prevalence of low back pain were correlated with the physical demands of the job. The perceived cause found to be most associated with low back pain were lifting in workers with jobs requiring moderate to heavy work and sports activity in sedentary workers. Family history of low back pain in parents, siblings, and children was a risk indicator of low back pain. The average age of the first attack of low back pain in workers with a family history of it in their parents was significantly younger than that in workers with no family history in a multiple logistic analysis in male workers, the physical work demands, age, and family history of low back pain in their parents were risk indicators; however, obesity was not a risk indicator. Physical and mental conditions of workers also were associated with low back pain. CONCLUSIONS: The physical job demands show a clear association with the point and lifetime prevalence of low back pain, and improvements in work conditions may decrease low back symptoms among workers. It is likely that a family history of low back pain and physical and mental conditions of workers also should be considered in the management of low back pain.

Adult↗

PubMed2003

Reporting of the incidence of hospitalised injuries: numerator issues.

OBJECTIVES: To examine and discuss the implications on the incidence of hospitalised injuries of selecting cases from principal diagnosis field only compared with considering all diagnosis fields, the inclusion compared with the exclusion of medical injuries, and the impact of identifying multiple admissions. METHODS: Analysis of data from the 1999-2000 New South Wales Inpatient Statistics Collection, Australia, including an internal linkage of the same dataset. RESULTS: Approximately 27.5% of records with a non-injury primary diagnosis include a nature of injury diagnosis in a subsequent diagnostic field. This figure increased to more than half (53%) of discharges for medical injuries. The internal linkage showed that 6.5% of discharges were repeat admissions for the same International Classification of Diseases, 10th revision (ICD-10) injury code and that 13.8% were repeat admissions for any ICD-10 injury code. The proportions of repeat admissions varied according to the type and the mechanism of injury. CONCLUSIONS: Selecting hospitalised injury cases from the principal diagnosis alone would underestimate medical injury cases as well as other injuries occurring in hospital. Repeat admissions should always be considered particularly in the case of thermal injuries, self harm, and medical injuries. Due to the limitations of data linkage, alternative methods need to be developed to identify repeat admissions. Other areas in which further research would be beneficial to a more uniform reporting of injury hospitalisations include better identification of injuries occurring in hospital, a review of ICD-10 injury codes, and the development an ICD-10 based severity measure which can be readily used with hospital discharge data.

Adolescent↗

PubMed1999

Artificial neural networks improve the prediction of mortality in intracerebral hemorrhage.

BACKGROUND: Artificial neural network (ANN) analysis methods have led to more sensitive diagnosis of myocardial infarction and improved prediction of mortality in breast cancer, prostate cancer, and trauma patients. Prognostic studies have identified early clinical and radiographic predictors of mortality after intracerebral hemorrhage (ICH). To date, published models have not achieved the accuracy necessary for use in making decisions to limit medical interventions. We recently reported a logistic regression model that correctly classified 79% of patients who died and 90% of patients who survived. In an attempt to improve prediction of mortality we computed an ANN model with the same data. OBJECTIVE: To determine whether an ANN analysis would provide a more accurate prediction of mortality after ICH when compared with multiple logistic regression models computed using the same data. METHODS: Analyses were conducted on data collected prospectively on 81 patients with supratentorial ICH. Multiple logistic regression was used to predict hospital mortality, then an ANN analysis was applied to the same data set. Input variables were age, gender, race, hydrocephalus, mean arterial pressure, pulse pressure, Glasgow Coma Scale score, intraventricular hemorrhage, hydrocephalus, hematoma size, hematoma location (ganglionic, thalamic, or lobar), cisternal effacement, pineal shift, history of hypertension, history of diabetes, and age. RESULTS: The ANN model correctly classified all patients (100%) as alive or dead compared with 85% correct classification for the logistic regression model. A second ANN verification model was equally accurate. The ANN was superior to the logistic regression model on all objective measures of fit. CONCLUSIONS: ANN analysis more effectively uses information for prediction of mortality in this sample of patients with ICH. A well-validated ANN may have a role in the clinical management of ICH.

Adolescent↗

PubMed1990

Predictors of blood pressure and hypertension in Tecumseh, Michigan.

Correlates of present blood pressure status are analyzed in 576 subjects (271 males, average age 32 years) in Tecumseh, Michigan. In addition to the current values, anthropometric and blood pressure data are available when the subjects were, on average, 6.9 and 22.2 years of age. Data on 351 fathers and 368 mothers when they were, on average, 32 years old are also available. Moderate, but significant correlations were found between present and past blood pressure and between past weight or skinfold thickness and the present blood pressure. These correlations were much weaker for childhood values than for values at age 22. When multiple regression techniques were used with blood pressure values at age 22 and parental values as independent variables, 40% of the present systolic blood pressure variance could be explained. Prediction of present hypertension status (blood pressure greater than 140 and/or 90 mm Hg) was evaluated by discriminant analysis. Three variables (weight at age 22, systolic blood pressure at age 22, and father's diastolic blood pressure) entered the model and accurately predicted the present blood pressure classification in 89% of the sample. When current blood pressure status was assessed with respect to previous blood pressure classification (upper 20%), family background, and overweight, a gradient of risk for hypertension was found. On the low end of risk was high childhood pressure (risk 19.1% versus 12.1% in the overall population). The highest risk occurred for those with high pressure and overweight at 22 years who also had a family background of high blood pressure (44% versus 12.1%). The prediction of hypertension from young adulthood to the early fourth decade of life is feasible and permits delineation of populations targeted for primary prevention.

Adult↗

PubMed2006

Gamma knife surgery for metastatic brain tumors from renal cell carcinoma.

OBJECT: The authors evaluated the results of Gamma Knife surgery (GKS) for the treatment of metastatic brain tumors from renal cell carcinoma (RCC). METHODS: The authors conducted a retrospective review of the clinical characteristics and treatment outcomes in 69 patients with metastatic brain tumors from RCC who underwent GKS at the authors' institution. Fifty-one patients were men, and 18 were women. The mean patient age was 64.2 years (range 45-85 years). The 69 patients underwent a total of 104 GKS procedures for treatment of 314 tumors. Eighteen patients received repeated GKS. Follow-up magnetic resonance (MR) imaging was used at a mean of 7.1 months after GKS to evaluate the change in 132 tumors after treatment. The mean prescription dose at the tumor margin was 21.8 Gy. The tumor growth control rate was 82.6%. Tumor volume and the delivered peripheral dose were significantly correlated with tumor growth control on univariate and multivariate analyses. Sixty (45.5%) of the 132 tumors assessed with MR imaging were associated with apparent peritumoral edema at the time of GKS. After treatment, peritumoral edema disappeared in 27 tumors, decreased in 13, was unchanged in 16, and progressed in four. Newly developed peritumoral edema after GKS was rare. The delivered peripheral dose was significantly correlated with control of peritumoral edema. The overall median survival time after GKS was 9.5 months. In this study, 34 patients died of systemic disease and 10 died of progressive brain metastases. Multivariate analysis showed that the number of lesions at the first GKS, the Karnofsky Performance Scale score at the first GKS, the recursive partitioning analysis classification, and the interval from diagnosis of RCC to brain metastasis were significantly correlated with survival time. CONCLUSIONS: Gamma Knife surgery is effective for metastatic brain tumors from RCC. The disappearance rate of tumors is relatively low, but growth control is high. The delivered dose to the tumor margin is significantly correlated with the control of peritumoral edema. Gamma Knife surgery should be used as the initial treatment modality, if possible, even in patients with multiple metastases. Repeated GKS is recommended for newly developed brain metastases because of the low sensitivity of RCC to conventional radiation therapy.

Aged↗

PubMed2000

Nocturia.

PURPOSE: We review the current state of knowledge of nocturia and present algorithms for diagnosis, classification and treatment. MATERIALS AND METHODS: We reviewed the recent literature on nocturia, and state-of-the-art methods of diagnosis, classification and treatment. RESULTS: Nocturia, which is among the most bothersome of all urological symptoms, has heretofore been poorly classified and understood. Multiple factors may result in nocturia, including pathological conditions, such as cardiovascular disease, diabetes mellitus, lower urinary tract obstruction, anxiety or primary sleep disorders, and behavioral and environmental factors. Nocturia may be attributed to nocturnal polyuria (nocturnal urine overproduction) and/or diminished nocturnal bladder capacity. Distinction between these conditions is made by a simple arithmetic analysis of a 24-hour voiding diary. CONCLUSIONS: Nocturia has been poorly studied, and its etiology and pathogenesis have been classified only recently. We present a scheme for diagnosis and care of patients suffering from loss of sleep due to nocturnal voiding.

Algorithms↗