A NOTCH4 missense mutation confers resistance to multiple sclerosis in Japanese

Background: The G allele of NOTCH4 rs422951 is protective against demyelinating disease in Japanese. Objectives: The purpose of this study was to assess the relation of the G allele to neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) and multiple sclerosis (MS) and the interaction between the G allele and HLA-DRB1 alleles, and to clarify any association of the G allele with clinical features. Methods: DNA sequencing was used to genotype 106 NMO/NMOSD patients, 118 MS patients and 152 healthy controls (HCs) for rs422951. Results: G allele frequency in MS patients, but not that in NMO/NMOSD patients, was lower than that in HCs (8.9% vs 21.7%, p<0.0001, odds ratio (OR)=0.35). HLA-DRB1*0405 was positively associated with MS (OR=2.22, pcorr=0.0380) while DRB1*0901 was negatively associated (OR=0.32, pcorr =0.0114). Logistic regression analyses revealed that, after adjusting for gender and either HLA-DRB1*0405 or DRB1*0901, rs422951 was associated with MS in the dominant model (OR=0.37, 95% confidence interval (CI)= 0.20–0.66, p=0.0012). Haplotype analyses identified two susceptible and three resistant haplotypes formed from rs422951 and either HLA-DRB1*0405 or DRB1*0901. There were no statistically significant differences in clinical features between G allele carriers and non-G allele carriers. Conclusion: This NOTCH4 missense mutation decreased the risk for developing MS in Japanese, but did not affect clinical features of those who had already developed the disease.

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Reduction of Surgical Site Infection Rates Associated With Active Surveillance

Infection Control and Hospital Epidemiology ◽

10.1086/509843 ◽

2006 ◽

Vol 27 (12) ◽

pp. 1347-1351 ◽

Cited By ~ 107

Author(s):

C. Brandt ◽

D. Sohr ◽

M. Behnke ◽

F. Daschner ◽

H. Rüden ◽

...

Keyword(s):

Logistic Regression ◽

Confidence Interval ◽

Surgical Site Infection ◽

Odds Ratio ◽

Surveillance System ◽

Operative Procedure ◽

Operative Procedures ◽

Site Infection ◽

Multiple Logistic Regression ◽

Regression Analyses

Objective.To evaluate whether surgical site infection (SSI) rates decrease in surgical departments as a result of performing active SSI surveillance.Design.Retrospective multiple logistic regression analyses.Setting.A group of 130 surgical departments of German hospitals participating in the Krankenhaus Infektions Surveillance System (KISS).Methods.Data for 19 categories of operative procedures performed between January 1997 and June 2004 were included (119,114 operations). Active SSI surveillance was performed according to National Nosocomial Infections Surveillance system (NNIS) methods and definitions. Departments' SSI rates were calculated individually for each year of surveillance and for each operative procedure category, taking into account when the individual departments had begun their surveillance activities. Multiple logistic regression analyses on a single operation basis were carried out with stepwise variable selection to predict outcomes for patients with SSI. The variables included were as follows: the department's year of participation, NNIS risk index variables, patients' age and sex, and the hospitals' structural characteristics, such as yearly operation frequency, number of beds, and academic status.Results.For 14 of 19 operative procedure categories analyzed, there was a tendency toward lower SSI rates that was associated with increasing duration of SSI surveillance. In multiple logistic regression analyses of pooled data for all operative procedures, the departments' participation in the surveillance system was a significant independent protective factor. Compared with the surveillance year 1, the SSI risk decreased in year 2 (odds ratio, 0.84; 95% confidence interval, 0.77-0.93) and in year 3 (odds ratio, 0.75; 95% confidence interval, 0.68-0.82), and there was no change in year 4.Conclusion.The SSI incidence was reduced by one quarter as a result of the surveillance-induced infection control efforts, which indicates the usefulness of a voluntary surveillance system.

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Serum IgG4 Levels at Diagnosis Can Predict Unfavorable Outcomes of Untreated Patients With IgG4-related Disease: A Japanese Single-Center Retrospective Study

10.21203/rs.3.rs-394250/v1 ◽

2021 ◽

Author(s):

Ichiro Mizushima ◽

Masahiro Konishi ◽

Hajime Sanada ◽

Kazuyuki Suzuki ◽

Akari Takeji ◽

...

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Confidence Interval ◽

Clinical Features ◽

Logistic Regression Analysis ◽

Odds Ratio ◽

Laboratory Data ◽

Single Center ◽

Igg4 Related Disease ◽

Serum Igg4

Abstract Background The outcomes of patients with IgG4-RD who are not treated are unclear. This study aimed to clarify these outcomes and identify the factors related to them. Methods We retrospectively evaluated various clinical features including laboratory data and involved organs at diagnosis in 107 patients with IgG4-RD, who were followed up for more than 6 months, at a single center in Japan. We compared the clinical features of the 27 untreated patients with those of the 80 patients treated with glucocorticoid. The patient outcomes were investigated, and logistic regression analysis was performed to identify factors related to them. Results The patients comprised 73 men and 34 women (median age 67 years). The untreated patients had significantly lower IgG4-RD responder index (9 vs 12) and fewer affected organs (1 vs 3) than did those treated with glucocorticoid. Of these 27 patients, 8 experienced deterioration of IgG4-RD after the diagnosis. In the age- and sex-adjusted logistic regression analysis, serum IgG4 elevation (per 100 mg/dL, odds ratio 1.194, 95% confidence interval 1.017–1.402) was the only significant factor related to disease deterioration in untreated patients with IgG4-RD, whereas not serum IgG4 levels (per 100 mg/dL, odds ratio 0.995, 95% confidence interval 0.921–1.075) but history of allergy (OR 3.134, 95% confidence interval 1.094–8.977, P = 0.033) related to deterioration in patients who underwent treatment. Conclusions Serum IgG4 levels may be a useful predictor of unfavorable outcomes in untreated patients with IgG4-RD, who tend to have fewer affected organs and lower IgG4-RD responder index.

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Association Analysis of COQ2 Variant in Dementia and Essential Tremor

Parkinson s Disease ◽

10.1155/2015/926280 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4

Author(s):

Yin Xia Chao ◽

Ebonne Yu Lin Ng ◽

Huihua Li ◽

Kandiah Nagaendran ◽

Yuen Yih ◽

...

Keyword(s):

Logistic Regression ◽

Confidence Interval ◽

Multiple System Atrophy ◽

Essential Tremor ◽

Association Analysis ◽

Odds Ratio ◽

Healthy Controls ◽

Age And Gender ◽

And Gender

Objective. COQ2 mutations have been reported in Japanese multiple system atrophy (MSA) patients. We examined the role of COQ2 in patients with dementia and essential tremor (ET), two common neurodegenerative conditions.Materials & Methods. A total of 2064 subjects, including 560 patients with dementia, 466 patients with ET, and 1038 healthy controls, were included. Genotyping for the COQ2 V393A (T>C) was carried out. Odds ratio (OR) adjusted by age and gender, together with 95% confidence interval (CI), was reported by means of logistic regression.Results. The frequency of the polymorphic variant V393A heterozygous (T/C) was 2.7% in dementia, 1.1% in ET, and 2.5% in controls (OR = 0.70, 95% confidence interval is 0.29–1.72 for dementia, and OR = 0.47, 95% confidence interval is 0.17–1.31,p=0.1217for ET). There was no significant association between V393A variant with dementia and ET.Conclusion. There was no significant association between V393A variant with dementia and ET. COQ2 gene is unlikely to play a significant role in patients with dementia or ET in our population.

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Smoking as a risk factor for multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458512470862 ◽

2012 ◽

Vol 19 (8) ◽

pp. 1022-1027 ◽

Cited By ~ 34

Author(s):

Jonatan Salzer ◽

Göran Hallmans ◽

Maria Nyström ◽

Hans Stenlund ◽

Göran Wadell ◽

...

Keyword(s):

Multiple Sclerosis ◽

Logistic Regression ◽

Risk Factor ◽

Confidence Interval ◽

Tobacco Use ◽

Odds Ratio ◽

Disease Onset ◽

Recall Bias ◽

Blood Samples ◽

Increased Risk

Background: Smoking has been associated with an increased risk for multiple sclerosis, but no studies have measured levels of the nicotine metabolite cotinine in prospectively collected samples to assess exposure. Objective: To investigate the effects of laboratory defined tobacco use on the risk for multiple sclerosis using prospectively collected biobank blood samples. Methods: Levels of cotinine were measured in n=192 cases, and n=384 matched controls, using an immunoassay. The risk for multiple sclerosis was estimated using matched logistic regression. Results: Elevated cotinine levels (≥10 ng/ml) were associated with a significantly increased risk for multiple sclerosis, (odds ratio, OR 1.5, 95% confidence interval, CI 1.0–2.1). This association was only present in young individuals (below median age at blood sampling, <26.4 years), (OR 2.2, 95% CI 1.3–3.8). Conclusions: This study confirms that smoking is a risk factor for multiple sclerosis. It has the advantage of using analyses of cotinine levels in samples that were collected several years before disease onset, thus excluding any risk for recall bias and minimising the risk for reversed causation. Our results also suggest that the smoking related immunological events that contribute to the development of multiple sclerosis occur early in life.

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Serum IgG4 levels at diagnosis can predict unfavorable outcomes of untreated patients with IgG4-related disease

Scientific Reports ◽

10.1038/s41598-021-92814-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ichiro Mizushima ◽

Masahiro Konishi ◽

Hajime Sanada ◽

Kazuyuki Suzuki ◽

Akari Takeji ◽

...

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Confidence Interval ◽

Clinical Features ◽

Logistic Regression Analysis ◽

Odds Ratio ◽

Laboratory Data ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4

AbstractThe outcomes of patients with immunoglobulin G4 (IgG4)-related disease (IgG4-RD) who are not treated are unclear. This study aimed to clarify these outcomes and identify the factors related to them. We retrospectively evaluated various clinical features including laboratory data and involved organs at diagnosis in 107 patients with IgG4-RD, who were followed up for more than 6 months, at a single center in Japan. We compared the clinical features of the 27 untreated patients with those of the 80 patients treated with glucocorticoid. The patient outcomes were investigated, and logistic regression analysis was performed to identify factors related to them. The patients comprised 73 men and 34 women (median age 67 years). The untreated patients had significantly lower IgG4-RD responder index (9 vs. 12) and fewer affected organs (1 vs. 3) than did those treated with glucocorticoid. Of these 27 patients, 8 experienced deterioration of IgG4-RD after the diagnosis. In the age- and sex-adjusted logistic regression analysis, serum IgG4 elevation (per 100 mg/dL, odds ratio 1.194, 95% confidence interval 1.017–1.402) was the only significant factor related to disease deterioration in untreated patients with IgG4-RD, whereas not serum IgG4 levels (per 100 mg/dL, odds ratio 0.995, 95% confidence interval 0.921–1.075) but history of allergy (OR 3.134, 95% confidence interval 1.094–8.977, P = 0.033) related to deterioration in patients who underwent treatment. Serum IgG4 levels may be a useful predictor of unfavorable outcomes in untreated patients with IgG4-RD, who tend to have fewer affected organs and lower IgG4-RD responder index.

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Impact of digitally acquired peer diagnostic input on diagnostic confidence in outpatient cases: A pragmatic randomized trial

Journal of the American Medical Informatics Association ◽

10.1093/jamia/ocaa278 ◽

2020 ◽

Author(s):

Elaine C Khoong ◽

Valy Fontil ◽

Natalie A Rivadeneira ◽

Mekhala Hoskote ◽

Shantanu Nundy ◽

...

Keyword(s):

Logistic Regression ◽

Randomized Trial ◽

Odds Ratio ◽

Primary Outcome ◽

Mixed Effects ◽

Regression Analyses ◽

Diagnostic Confidence ◽

Diagnostic Uncertainty ◽

Intervention Impact ◽

High Uncertainty

Abstract Objective The study sought to evaluate if peer input on outpatient cases impacted diagnostic confidence. Materials and Methods This randomized trial of a peer input intervention occurred among 28 clinicians with case-level randomization. Encounters with diagnostic uncertainty were entered onto a digital platform to collect input from ≥5 clinicians. The primary outcome was diagnostic confidence. We used mixed-effects logistic regression analyses to assess for intervention impact on diagnostic confidence. Results Among the 509 cases (255 control; 254 intervention), the intervention did not impact confidence (odds ratio [OR], 1.46; 95% confidence interval [CI], 0.999-2.12), but after adjusting for clinician and case traits, the intervention was associated with higher confidence (OR, 1.53; 95% CI, 1.01-2.32). The intervention impact was greater in cases with high uncertainty (OR, 3.23; 95% CI, 1.09- 9.52). Conclusions Peer input increased diagnostic confidence primarily in high-uncertainty cases, consistent with findings that clinicians desire input primarily in cases with continued uncertainty.

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Prediction of Hospital Mortality Rates by Admission Laboratory Tests

Clinical Chemistry ◽

10.1373/clinchem.2005.059030 ◽

2006 ◽

Vol 52 (2) ◽

pp. 325-328 ◽

Cited By ~ 53

Author(s):

Paul Froom ◽

Zvi Shimoni

Keyword(s):

Internal Medicine ◽

Logistic Regression ◽

Confidence Interval ◽

Regression Model ◽

Odds Ratio ◽

Laboratory Tests ◽

Logistic Regression Model ◽

Complete Blood Count ◽

Laboratory Data ◽

Regional Hospital

Abstract Background: The aim of this study was to explore whether electronically retrieved laboratory data can predict mortality in internal medicine departments in a regional hospital. Methods: All 10 308 patients hospitalized in internal medicine departments over a 1-year period were included in the cohort. Nearly all patients had a complete blood count and basic clinical chemistries on admission. We used logistic regression analysis to predict the 573 deaths (5.6%), including all variables that added significantly to the model. Results: Eight laboratory variables and age significantly and independently contributed to a logistic regression model (area under the ROC curve, 88.7%). The odds ratio for the final model per quartile of risk was 6.44 (95% confidence interval, 5.42–7.64), whereas for age alone, the odds ratio per quartile was 2.01 (95% confidence interval, 1.84–2.19). Conclusions: A logistic regression model including only age and electronically retrieved laboratory data highly predicted mortality in internal medicine departments in a regional hospital, suggesting that age and routine admission laboratory tests might be used to ensure a fair comparison when using mortality monitoring for hospital quality control.

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T cell response to two immunodominant proteolipid protein (PLP) peptides in multiple sclerosis patients and healthy controls

Multiple Sclerosis Journal ◽

10.1177/135245859600100503 ◽

1996 ◽

Vol 1 (5) ◽

pp. 270-278 ◽

Cited By ~ 26

Author(s):

CM Pelfrey ◽

LR Tranquill ◽

AB Vogt ◽

HF McFarland

Keyword(s):

Multiple Sclerosis ◽

T Cell ◽

Demyelinating Disease ◽

T Cell Responses ◽

Proteolipid Protein ◽

T Cell Response ◽

Healthy Controls ◽

Cell Responses ◽

Hla Binding ◽

Multiple Sclerosis Patients

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system in which autoimmune T lymphocytes reacting with myelin antigens are believed to play a pathogenic role. Since HLA binding is involved in the selection of T cell responses, we have examined PLP peptide binding to HLA DR2, an HLA allele frequently found in MS patients. Both PLP 40–60 and PLP 89–106 show significant, high affinity binding to HLA DR2. We then tested whether responses to PLP peptides 40–60 and 89–106 are elevated in multiple sclerosis patients compared to matched controls. We also analysed T cell responses to MBP 87–106, which is considered to be the immunodominant region of MBP in humans. Here we demonstrate heterogenous T cell responses to PLP 40–60, PLP 89–106 and MBP 87–106 in both MS patients and controls. The overall number of TCL and the HLA restriction of those TCL did not vary significantly in the two groups. PLP 40–60 specific cytolytic TCL were increased in MS patients, whereas healthy controls had increased percentages of cytolytic TCL responding to PLP 89–106 and MBP 87–106. Although the data presented here shows heterogenous responses in T cell numbers, differences in numbers and specificity of cytolytic cells could be involved in the pathogenesis of autoimmune demyelinating disease.

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Corticosteroid injection for coccydynia

Bone & Joint Open ◽

10.1302/2633-1462.111.bjo-2020-0146 ◽

2020 ◽

Vol 1 (11) ◽

pp. 709-714

Author(s):

Vilhjalmur Finsen ◽

Ante M. Kalstad ◽

Rainer G. Knobloch

Keyword(s):

Logistic Regression ◽

Confidence Interval ◽

Odds Ratio ◽

Corticosteroid Injection ◽

Term Efficacy ◽

Early Success ◽

Cortisone Injection ◽

Short And Long Term ◽

Regression Tests

Aims We aimed to establish the short- and long-term efficacy of corticosteroid injection for coccydynia, and to determine if betamethasone or triamcinolone has the best effect. Methods During 2009 to 2016, we treated 277 patients with chronic coccydynia with either one 6 mg betamethasone or one 20 mg triamcinolone cortisone injection. A susequent injection was given to 62 (26%) of the patients. All were reviewed three to four months after injection, and 241 replied to a questionnaire a mean of 36 months (12 to 88) after the last injection. No pain at the early review was considered early success. When the patient had not been subsequently operated on, and indicated on the questionnaire that they were either well or much better, it was considered a long-term success. Results At the three- to four-month review, 22 (9%) reported that they had no pain. The long-term success of one injection was 15% and rose to 29% after a second injection. Logistic regression tests showed that both early success (odds ratio (OR) 5.5, 95% confidence interval (CI) 2.1 to 14.4; p = 0.001) and late success (OR 3.7, 95% CI 1.7 to 8.3; p = 0.001) was greater with triamcinolone than with betamethasone. Late success was greater for patients with symptoms for less than 12 months (OR 3.0, 95% CI 1.4 to 6.7; p = 0.006). We saw no complications of the injections. Conclusion We conclude that the effect of corticosteroid injection for coccygodynia is moderate, possibly because we used modest doses of the drugs. Even so, they seem worthwhile as they are easily and quickly performed, and complications are rare. If the choice is between injections of betamethasone or triamcinolone, the latter should be selected. Cite this article: Bone Joint Open 2020;1-11:709–714.

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Multiple sclerosis relapse risk in the postoperative period: Effects of invasive surgery and anesthesia

Multiple Sclerosis Journal ◽

10.1177/1352458519860304 ◽

2019 ◽

Vol 26 (11) ◽

pp. 1437-1440

Author(s):

Lindsey B De Lott ◽

Samantha Zerafa ◽

Kerby Shedden ◽

Galit Levi Dunietz ◽

Michelle Earley ◽

...

Keyword(s):

Multiple Sclerosis ◽

Logistic Regression ◽

Medical Records ◽

Odds Ratio ◽

Conditional Logistic Regression ◽

Unadjusted Odds Ratio ◽

Relapse Risk ◽

Multiple Sclerosis Relapse ◽

Period Effects ◽

Tertiary Center

Background: Postoperative multiple sclerosis (MS) relapses are a concern among patients and providers. Objective: To determine whether MS relapse risk is higher postoperatively. Methods: Data were extracted from medical records of MS patients undergoing surgery at a tertiary center (2000–2016). Conditional logistic regression estimated within-patient unadjusted and age-adjusted odds of postoperative versus preoperative relapse. Results: Among 281 patients and 609 surgeries, 12 postoperative relapses were identified. The odds of postoperative versus preoperative relapse in unadjusted (odds ratio (OR) = 0.56, 95% confidence interval (CI) = 0.18–1.79; p = 0.33) or age-adjusted models (OR = 0.66, 95% CI = 0.20–2.16; p = 0.49) were not increased. Conclusions: Surgery/anesthesia exposure did not increase postoperative relapse risk. These findings require confirmation in larger studies.

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