Efficacy and tolerability of alosetron for the treatment of irritable bowel syndrome in women and men: a meta-analysis of eight randomized, placebo-controlled, 12-week trials

BACKGROUND: Stimulated 5-hydroxytryptamine-3 (5-HT(3)) receptors promote intestinal motility, secretion, and sensation, effects that are related to the known pathophysiology of irritable bowel syndrome (IBS). A previous meta-analysis of 6 randomized controlled trials of the 5-HT(3)-receptor antagonist alosetron found that this agent was associated with global improvement in symptoms, pain, and discomfort in patients with IBS. OBJECTIVE: This was a meta-analysis of randomized, placebo-controlled trials that evaluated the efficacy and tolerability of alosetron for the management of IBS. It updated and expanded on the previous meta-analysis. METHODS: PubMed, EMBASE, SCOPUS, Web of Science, and the cochrane central Register of controlled Trials were searched from 1966 through September 2007 for placebo-controlled trials that examined the efficacy and tolerability of alosetron in the management of IBS. The search terms were alosetron, 5-HT, irritable bowel, functional bowel diseases, and irritable colon. No language restriction was applied. The data were analyzed in terms of 2 main outcomes: global improvement in IBS symptoms and adequate relief of IBS pain and discomfort. RESULTS: Eight multicenter, randomized, placebo-controlled, 12-week clinical trials met the criteria for inclusion in the meta-analysis. The studies included 4,170 patients with IBS (80% female) who were randomized to receive either alosetron or placebo. All patients met the Rome criteria for IBS, and all subtypes of IBS were represented. Most patients had diarrhea-predominant IBS; only 2.6% of patients had constipation-predominant IBS. In the 3 trials included in the analysis of global improvement in symptoms, alosetron was significantly more effective than placebo (relative risk [RR] = 1.60; 95% CI, 1.44-1.76; P <0.001). In the 6 trials included in the analysis of adequate relief of IBS pain and discomfort, there was also a significant difference in favor of alosetron (RR = 1.31; 95% CI, 1.20-1.43; P < 0.001). Analysis of adequate relief of IBS pain and discomfort by sex also indicated significant differences between alosetron and placebo in both sexes (female: RR = 1.34 [95% cI, 1.21-1.48]; male: RR = 1.23 [95% CI, 1.02-1.47]). The analysis of tolerability, which was based on data from 7 studies, found a significant difference between alosetron and placebo (RR = 1.19; 95% cI, 1.07-1.31; P<0.001). The only adverse events that occurred with a significantly higher incidence in those treated with alosetron compared with placebo were constipation in 8 trials (RR = 4.35; 95% CI, 3.01-6.26; P < 0.001) and abdominal pain and discomfort in 5 trials (RR = 1.96; 95% CI, 1.46-2.64; P < 0.001). In the alosetron group, there were 4 cases of ischemic colitis (0.16%) and 2 cases of serious complications of constipation (0.08%); neither of these was reported in the placebo group. Alosetron was not associated with any deaths. CONCLUSIONS: Alosetron was effective in these men and women with IBS. constipation was the most frequently reported adverse event associated with alosetron therapy. Ischemic colitis and serious complications of constipation were reported in a small number of patients treated with alosetron.     

Familial association in adults with functional gastrointestinal disorders

OBJECTIVE: To evaluate the association between functional gastrointestinal (GI) symptoms and a family history of abdominal pain or bowel problems. SUBJECTS AND METHODS: A valid self-report questionnaire that records GI symptoms and spouse's and first-degree relatives' history of abdominal pain or bowel troubles and includes the psychosomatic symptom checklist (a measure of somatization) was mailed to an age- and sex-stratified random sample of Olmsted County, Minnesota, residents aged 30 to 64 years. A logistic regression model that adjusted for age, sex, and somatic symptom score was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of a positive family history for each functional GI disorder. RESULTS: Six hundred forty-three (72%) of 892 eligible subjects returned the survey. Reporting a first-degree relative with abdominal pain or bowel problems was significantly associated with reporting of irritable bowel syndrome (OR, 2.3; 95% CI, 1.3-3.9) and dyspepsia (OR, 1.8; 95% CI, 1.05-3.0) but not constipation, diarrhea, or gastroesophageal reflux. The reporting of a spouse with abdominal pain or bowel problems was not associated with any of these disorders. CONCLUSIONS: A history of abdominal pain or bowel troubles in first-degree relatives was significantly associated with irritable bowel syndrome and dyspepsia. Whether the familial associations represent similar exposures in a shared environment, heightened familial awareness of GI symptoms (reporting bias), or genetic factors remains to be determined.     

Children with chronic pain: impact of sex and age on long-term outcomes

The present study examined the long-term pain and disability outcomes of a pediatric chronic pain clinic cohort and evaluated whether these outcomes differed by age and sex. Patients were interviewed a mean of 3 years after their last appointment at a pediatric pain clinic. The cohort comprised 95 females and 48 males, aged 5-23 years when interviewed. Of the cohort, 62.2% (67 females, 22 males) reported continuing pain. Females were significantly more likely than males to report continuing pain (OR=2.9, 95% CI=1.4-5.8, p=.005), use of health care (OR=5.1, 95% CI=1.4-18.5, p=.01), medication (OR=4.7, 95% CI=1.3-16.9, p=.02) and non-drug methods of pain control (OR=3.4, 95% CI=1.3-9.2, p=.02). For patients whose pain had associated psychosocial factors, females (76.4%) were significantly more likely than males (21.4%) to report continuing pain (OR=13.8, 95% CI=3.3-58.4, p=.005). Finally, among patients still experiencing pain, the frequency of pain episodes increased significantly with age (OR=1.3, 95% CI=1.0-1.5, p=.02). Results indicate that chronic pain persists for many children despite treatment at specialized clinics. Females may be at higher risk for continuing pain and report greater use of health care, medication, and non-drug methods of pain control.     

Clinical Characteristics of Diabetic vs Nondiabetic Patients Who "Rule-in" for Acute Myocardial Infarction

OBJECTIVE: To compare the clinical characteristics of diabetic vs nondiabetic patients who present to the ED with acute myocardial infarction (AMI). METHODS: This was a prospective, observational study at a suburban, university hospital ED of patients presenting to the ED during study hours between December 1993 and October 1996 with typical and atypical symptoms consistent with cardiac ischemia. Diabetic and nondiabetic patients with AMI were compared. Demographic, historical, and clinical data were recorded by trained research assistants using a standardized, closed-question, data collection instrument. Final discharge diagnosis of AMI was assigned by WHO criteria. Continuous variables were analyzed by t-tests. Clinical variables were analyzed by chi-square tests. All tests were two-tailed with alpha preset at 0.05. RESULTS: There were 216 patients with AMI during the study period; 51 of these patients (24%) were diabetic. For diabetic vs nondiabetic patients with AMI, there was no significant difference in age (64.0 +/- 13 vs 60.0 +/- 14 years, p = 0.13), female gender (37% vs 26%, p = 0.13), and time to presentation from symptom onset (192 +/- 238 vs 251 +/- 456 minutes, p = 0.41). Hypertension was the only cardiac risk factor significantly more prevalent in diabetic vs nondiabetic patients with AMI (77% vs 50%, OR = 1.54, 95% CI = 1.24 to 1.91, p = 0.001), though elevated cholesterol (48% vs 33%, OR = 1.47, 95% CI = 1.02 to 2.12, p = 0.06) tended to be more prevalent in the diabetic group. There was no statistically significant difference between the two groups in terms of the frequency of chest pain (OR = 1.04, 95% CI = 0.95 to 1.14, p = 0.30), associated symptoms, and diagnostic ECGs (OR = 1.16, 95% CI = 0.76 to 1.79, p = 0.53). CONCLUSION: Diabetic patients with AMI may have similar symptoms upon presentation as do nondiabetic patients with AMI. Of the cardiac risk factors, hypertension is more prevalent in diabetic vs nondiabetic patients with AMI.     

Lesser evaluated determinants of fistula formation in children with hypospadias

Determinants of fistula formation, some of them not previously evaluated, were studied in 30 consecutive children admitted for hypospadias repair to our centre. All children were screened for any urinary or local infections. Vicryl and catgut were used alternately for reconstruction of the neo-urethra. Per urethral drainage was employed in all patients. The presence of unfavourable local anatomical factors, the surgeon's satisfaction at the end of the procedure and duration of surgery were noted. The patients were followed up for any urethrocutaneous fistula. Unsatisfactory surgery (chi-square = 6.53, p = 0.01), unfavourable anatomical factors (chi-square = 10.80, p = 0.001) and local infection (chi-square = 5.66, p = 0.017) had a strong association with fistula formation, whereas urine leakage and a history of previous surgery had only a marginal association. On application of stepwise binary logistic regression, unfavourable local anatomical factors (OR [95% CI]: 13.19 [1.20-143.50]) and urine leakage (OR [95% CI]: 14.35 [1.20-171.45]) emerge as strong risk factors for urethrocutaneous fistula, and local infection (OR [95% CI]: 8.70 (0.93-81.01]) as a moderate risk factor.     

The Association Between Emergency Department Crowding and Adverse Cardiovascular Outcomes in Patients with Chest Pain

Objectives: While emergency department (ED) crowding is a worldwide problem, few studies have demonstrated associations between crowding and outcomes. The authors examined whether ED crowding was associated with adverse cardiovascular outcomes in patients with chest pain syndromes (chest pain or related complaints of possible cardiac origin). Methods: A retrospective analysis was performed for patients ≥30 years of age with chest pain syndrome admitted to a tertiary care academic hospital from 1999 through 2006. The authors compared rates of inpatient adverse outcomes from ED triage to hospital discharge, defined as delayed acute myocardial infarction (AMI), heart failure, hypotension, dysrhythmias, and cardiac arrest, which occurred after ED arrival using five separate crowding measures. Results: Among 4,574 patients, 251 (4%) patients developed adverse outcomes after ED arrival; 803 (18%) had documented acute coronary syndrome (ACS), and of those, 273 (34%) had AMI. Compared to less crowded times, ACS patients experienced more adverse outcomes at the highest waiting room census (odds ratio [OR] = 3.7, 95% confidence interval [CI] = 1.3 to 11.0) and patient-hours (OR = 5.2, 95% CI = 2.0 to 13.6) and trended toward more adverse outcomes during time of high ED occupancy (OR = 3.1, 95% CI = 1.0 to 9.3). Adverse outcomes were not significantly more frequent during times with the highest number of admitted patients (OR = 1.6, 95% CI = 0.6 to 4.1) or the highest trailing mean length of stay (LOS) for admitted patients transferred to inpatient beds within 6 hours (OR = 1.5, 95% CI = 0.5 to 4.0). Patients with non-ACS chest pain experienced more adverse outcomes during the highest waiting room census (OR = 3.5, 95% CI = 1.4 to 8.4) and patient-hours (OR = 4.3, 95% CI = 2.6 to 7.3), but not occupancy (OR = 1.8, 95% CI = 0.9 to 3.3), number of admitted patients (OR = 0.6, 95% CI 0.4 to 1.1), or trailing LOS for admitted patients (OR = 1.2, 95% CI = 0.6 to 2.0). Conclusions: There was an association between some measures of ED crowding and a higher risk of adverse cardiovascular outcomes in patients with both ACS-related and non–ACS-related chest pain syndrome.     

Critical illness polyneuropathy: risk factors and clinical consequences. A cohort study in septic patients

OBJECTIVE: To determine risk factors and clinical consequences of critical illness polyneuropathy (CIP) evaluated by the impact on duration of mechanical ventilation, length of stay and mortality. DESIGN: Inception cohort study. SETTING: Intensive care unit of a tertiary hospital. PATIENTS: Septic patients with multiple organ dysfunction syndrome requiring mechanical ventilation and without previous history of polyneuropathy. INTERVENTIONS: Patients underwent two scheduled electrophysiologic studies (EPS): on the 10th and 21st days after the onset of mechanical ventilation. RESULTS: Eighty-two patients were enrolled, although nine of them were not analyzed. Forty-six of the 73 patients presented CIP on the first EPS and 4 other subjects were diagnosed with CIP on the second evaluation. The APACHE II scores of patients with and without CIP were similar on admission and on the day of the first EPS. However, days of mechanical ventilation [32.3 (21.1) versus 18.5 (5.8); p=0.002], length of ICU and hospital stay in patients discharged alive from the ICU as well as in-hospital mortality were greater in patients with CIP (42/50, 84% versus 13/23, 56.5%; p=0.01). After multivariate analysis, independent risk factors were hyperosmolality [odds ratio (OR) 4.8; 95% confidence intervals (95% CI) 1.05-24.38; p=0.046], parenteral nutrition (OR 5.11; 95% CI 1.14-22.88; p=0.02), use of neuromuscular blocking agents (OR 16.32; 95% CI 1.34-199; p=0.0008) and neurologic failure (GCS below 10) (OR 24.02; 95% CI 3.68-156.7; p<0.001), while patients with renal replacement therapy had a lower risk for CIP development (OR 0.02; 95% CI 0.05-0.15; p<0.001). By multivariate analysis, CIP (OR 7.11; 95% CI 1.54-32.75; p<0.007), age over 60 years (OR 9.07; 95% CI 2.02-40.68; p<0.002) and the worst renal SOFA (OR 2.18; 95% CI 1.27-3.74; p<0.002) were independent predictors of in-hospital mortality. CONCLUSIONS: CIP is associated with increased duration of mechanical ventilation and in-hospital mortality. Hyperosmolality, parenteral nutrition, non-depolarizing neuromuscular blockers and neurologic failure can favor CIP development.     

Pain in pediatric oncology--children's and parents' perspectives.

There is a lack of valid epidemiological data on malignancy-associated pain in modern pediatric oncology. Pediatric oncology patients (self-assessment) and their parents from 28 hospitals were questioned using age-adapted, structured interviews and validated pain assessment tools. Pain intensity was measured by the NRS and Bieri faces scale. We conducted 363 interviews with patients and their parents, and 46 with the parents alone (if patients <2.5 years). Pain was reported at the time of the interview or within the last 24 h, 7 d, or 4 weeks in 15%, 28%, 50% and 58% of cases, respectively. The proportion of patients suffering severe to maximal pain (NRS>3; Bieri>2) increased significantly (p=0.001, chi2 test). The median pain intensity for the most severe pain episode within the last 4 weeks was 6.7 (NRS 0-10). Adverse effects of anti-tumor therapy were the most frequent cause of pain. Multivariate analyses depicted general physical condition either "severely reduced" (ASA status 3) (OR 4.0, 95% CI 1.1-14.7, p=0.037) or "moderately reduced" (ASA status 2) (OR 1.8, 95% CI 1.1-2.9, p=0.018), "in-patient status" (OR 1.8, 95% CI 1.2-2.9, p=0.010), and "co-morbidity present" (OR 3.5, 95% CI 1.1-10.7, p=0.030) as risk factors for severe to maximal pain. General anesthesia was the only factor significantly (OR 0.14, 95% CI 0.05-0.39, p<0.01) associated with a reduction in the proportion of patients suffering severe to maximal pain during bone marrow aspiration. Our data emphasize both the importance of in-house acute pain control and the need for general anesthesia during painful procedures in pediatric oncology.     

术后慢性疼痛患病率调查及危险因素分析

目的:探讨术后慢性疼痛(chronic postsurgical pain, CPSP)的患病率和相关危险因素。方法:纳入2019年2月在复旦大学附属中山医院接受非急诊手术治疗的376例患者,于术后3个月电话随访术后慢性疼痛情况并使用医院焦虑抑郁量表(hospital anxiety and depression scale, HADS)评估患者的心理状态。对存在术后慢性疼痛者采用数字评分法(numerical rating scale, NRS)和神经病理性疼痛量表(Douleur Neuropathique 4 questions, DN4)评估疼痛的强度、性质。采用多因素logistic回归确定术后慢性疼痛的独立危险因素。结果:20.7%(78/376)患者发生术后慢性疼痛,其中中重度疼痛占16.7%(13/376)。腹部手术(OR=3.148,95%CI 1.047～9.467)、术前非手术区域的慢性疼痛史(OR=6.852,95%CI 3.246～14.464)、手术时间大于3 h(OR=2.803,95%CI 1.089～7.217)是术后慢性疼痛的独立危险因素。结论:术后慢性疼痛的患病率为20.7%,其中1/6为中重度疼痛;腹部手术、术前非手术区域的慢性疼痛史和手术时间长是术后慢性疼痛的预警因素。     

Depression predicts disability in long-term chronic pain patients

Purpose : Investigators have examined factors that predict treatment outcome and disability status in chronic pain patients, including psychopathology and personality characteristics with equivocal results. The purpose of this study was to evaluate the usefulness of personality characteristics, depression, and personality disorders in predicting disability status in pain patients with long-term follow-up. The setting was a rehabilitation hospital in Southern Sweden. Method : Subjects were 184 pain patients (mean age=43.4 (10.8) years; 72.8% female) who had no more than 365 sick leave days (Mean sick leave days=132.7 (128.2)) prior to the baseline personality and psychiatric evaluation. The baseline evaluation consisted of a psychiatric interview that included the administration of the Structured Clinical Interview for DSM-IV Screen Questionnaire (SCID-II), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Karolinska Scales of Personality (KSP). Disability status was assessed by insurance record review a minimum of two-and-a-half years after baseline evaluation. Results : Multivariate logistic regression suggests that age (OR=1.09, 95% CI=1.02-1.18; p =0.013), number of sick leave days prior to evaluation (OR=1.01, 95% CI=1.01-1.02; p =0.018), and baseline diagnosis of depression significantly predicted subsequent disability status (OR=7.04, 95% CI=1.15-42.93; p =0.034). Baseline personality traits and the diagnosis of a personality disorder were not useful predictors of disability status in our sample. Conclusions : These data suggest that depression, but not personality disorders characteristics, was an important disability predictor in chronic pain patients with extended follow-up.     

A questionnaire-based survey on the etiopathogenesis of chronic constipation during a medical check-up in Japan

The study group of the Japanese Society of Gastroenterology released evidence-based clinical practice guidelines for chronic constipation (CC) in 2017, and irritable bowel syndrome (IBS) was treated as one of the causes of CC. We examined the differences in characteristics between IBS and non-IBS subjects with CC who underwent a medical check-up in Japan. A total of 10,658 subjects participated in this study, and we focused on 467 subjects who fulfilled the diagnostic criteria of CC using a questionnaire survey. The number of IBS subjects was 21, and they had sleep disorders, were more symptomatic (e.g., abdominal pain, abdominal bloating/distension, feeling stressed, annoyance, lack of motivation, fatigue upon waking, and feeling depressed), and had more episodes of sensation of incomplete evacuation and anorectal obstruction/blockage during defecation than non-IBS subjects. Furthermore, stool frequency of IBS subjects was significantly different from non-IBS subjects. Multivariate ordinal logistic regression analysis revealed that the factors associated with a higher stool frequency were IBS [odds ratio (OR), 2.46; 95% confidence interval (CI), 1.00–6.05; p = 0.049], male sex (OR, 1.97; 95% CI, 1.20–3.23; p = 0.007), and regular exercise (OR, 1.80; 95% CI, 1.05–3.07; p = 0.033). These findings suggest that IBS has unique characteristics in subjects with CC.     

Depression predicts disability in long-term chronic pain patients

PURPOSE: Investigators have examined factors that predict treatment outcome and disability status in chronic pain patients, including psychopathology and personality characteristics with equivocal results. The purpose of this study was to evaluate the usefulness of personality characteristics, depression, and personality disorders in predicting disability status in pain patients with long-term follow-up. The setting was a rehabilitation hospital in Southern Sweden. METHOD: Subjects were 184 pain patients (mean age = 43.4 (10.8) years; 72.8% female) who had no more than 365 sick leave days (Mean sick leave days = 132.7 (128.2)) prior to the baseline personality and psychiatric evaluation. The baseline evaluation consisted of a psychiatric interview that included the administration of the Structured Clinical Interview for DSM-IV Screen Questionnaire (SCID-II), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Karolinska Scales of Personality (KSP). Disability status was assessed by insurance record review a minimum of two-and-a-half years after baseline evaluation. RESULTS: Multivariate logistic regression suggests that age (OR = 1.09, 95% CI = 1.02-1.18; p = 0.013), number of sick leave days prior to evaluation (OR= 1.01, 95% CI= 1.01-1.02; p = 0.018), and baseline diagnosis of depression significantly predicted subsequent disability status (OR = 7.04, 95% CI = 1.15-42.93; p = 0.034). Baseline personality traits and the diagnosis of a personality disorder were not useful predictors of disability status in our sample. CONCLUSIONS: These data suggest that depression, but not personality disorders characteristics, was an important disability predictor in chronic pain patients with extended follow-up.     

Abdominal obesity and insulin resistance in patients with type 2 diabetes in a Swedish community. Skaraborg hypertension and diabetes project

OBJECTIVE: To explore the association between abdominal obesity and insulin resistance in patients with type 2 diabetes. DESIGN: A cross-sectional observational study. SETTING: Primary care in Skara, Sweden. SUBJECTS: A total of 198 men and 186 women with type 2 diabetes who consecutively completed an annual check-up in 1992-1993. MAIN OUTCOME MEASURES: Abdominal obesity was defined according to criteria for the metabolic syndrome using the waist circumference (WC): > 102 cm for men and > 88 cm for women. Insulin resistance was estimated using the Homeostasis Model Assessment (HOMA), and was dichotomized by the 75th percentile (IR). RESULTS: Abdominal obesity was found in 66 men (33%), and in 106 women (57%). Pearson's correlation coefficients between components of the metabolic syndrome and IR were statistically significant for WC, waist-hip ratio, serum triglycerides, and HDL cholesterol, and were higher for WC (0.40) than for waist-hip ratio (0.23) in both genders (p < 0.001). The association between WC and IR was challenged by successively entering other components of the metabolic syndrome into the model in a logistic regression. In the final model, adjusting for differences in age, systolic blood pressure, HbA1c, serum triglycerides, HDL cholesterol, and microalbuminuria, the association remained statistically significant both in men (OR 8.6, 95% CI 3.0-25.2, p < 0.001), and in women (OR 5.6, 95% CI 1.7-18.1, p = 0.004). CONCLUSIONS: WC provides a feasible measure for insulin resistance in the vast majority of subjects with type 2 diabetes. It is convenient and less expensive than direct means and could be used as a proxy for insulin resistance in population studies.     

The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: A randomised,double-blind,placebo-controlled phenotype-stratified study

In neuropathic pain it has been suggested that pain phenotype based on putative pain mechanisms may predict response to treatment. This was a randomised, double-blind, placebo-controlled, and phenotype-stratified study with 2 6-week treatment periods of oxcarbazepine (1800-2400 mg) and placebo. The primary efficacy measure was change in median pain intensity between baseline and the last week of treatment measured on an 11-point numeric rating scale, and the primary objective was to compare the effect of oxcarbazepine in patients with and without the irritable nociceptor phenotype as defined by hypersensitivity and preserved small nerve fibre function determined by detailed quantitative sensory testing. Ninety-seven patients with peripheral neuropathic pain due to polyneuropathy, surgical or traumatic nerve injury, or postherpetic neuralgia were randomised. The intention-to-treat population comprised 83 patients: 31 with the irritable and 52 with the nonirritable nociceptor phenotype. In the total sample, oxcarbazepine relieved pain of 0.7 points (on a numeric rating scale 0-10; 95% confidence interval [CI] 0.4-1.4) more than placebo (P = 0.015) and there was a significant interaction between treatment and phenotype of 0.7 (95% CI 0.01-1.4, P = 0.047). The number needed to treat to obtain one patient with more than 50% pain relief was 6.9 (95% CI 4.2-22) in the total sample, 3.9 (95% CI 2.3-12) in the irritable, and 13 (95% CI 5.3-∞) in the nonirritable nociceptor phenotype. In conclusion, oxcarbazepine is more efficacious for relief of peripheral neuropathic pain in patients with the irritable vs the nonirritable nociceptor phenotype.     

Failed extubation in a tertiary-level hospital intensive care unit,Pretoria, South Africa

Background A prospective cohort study sought to measure the incidence and outcomes of failed extubation in Dr George Mukhari Academic Hospital intensive care unit (ICU), as well as to identify possible factors associated with failed extubation. Methods Data were collected over a 6-month period from 1 July 2015 to 31 December 2015. Pre-intubation parameters recorded on the data collection sheet included secretions, Glasgow Coma Scale (GCS), fluid balance, Tobin index, partial pressure of carbon dioxide (pCO₂ ), partial pressure of oxygen (PaO₂ ), comorbidities and weaning method. Results A total of 242 patients were enrolled over the 6-month study period. Of the 242 patients, 86 were excluded owing to pre-set exclusion criteria (death before extubation; tracheostomy before extubation; re-intubation >72 hours post extubation). An extubation failure rate of 16.7% (n=26) was observed. The incidence of ventilator-associated pneumonia in the failed extubation group was 19.23%, whereas death was recorded in 42.31% of patients who failed extubation. The average length of ICU stay in the reintubated group was 11.58 days, and 4.04 days for successfully extubated patients. Only low GCS had a statistically significant impact on failed extubation: p=0.0025; odds ratio (OR) for low v. normal 5.13 (95% confidence interval (CI) 1.78 - 14.79). Other predictor variables measured did not reach statistical significance. Weaning method: p=0.3737, OR for No T-piece v. T-piece 1.65 (95% CI 0.547 - 4.976); comorbidities: p=0.5914, OR for two or more comorbidities v. no comorbidities 2.079 (95% CI 0.246 - 17.539), no comorbidities v. single comorbidity 0.802 (95% CI 0.211 - 3.043); fluid balance: p=0.6625, OR for negative v. positive fluid balance 0.571 (95% CI 0.170 - 1.916), OR for neutral v. positive fluid balance <0.001 (95% CI <0.001 - >999.999); pCO₂ : p=0.7510, OR for high v. normal pCO₂ 1.344 (95% CI 0.346 - 5.213), OR for low v. normal pCO₂ 1.515 (95% CI 0.501 - 4.576); PaO₂ : p=0.4405, OR for high v. normal 1.156 (95% CI 0.382 - 3.494); OR for low v. normal PaO₂ 2.638 (95% CI 0.553 - 12.587); Tobin index (Fischer’s exact test): p=0.7476. Conclusion Low pre-extubation GCS is a predictor of failed extubation. Contributions of the study The study is a prospective observational study conducted in a high-volume referral hospital. It adds valuable scientific information to a growing body of data on the topic of extubation failure. It further reinforces the importance of extubation failure and the requirement for due diligence to be paid before a patient is extubated.     

Inhibitor kappaB-alpha haplotype GTC is associated with susceptibility to acute respiratory distress syndrome in Caucasians

OBJECTIVE: The nuclear factor (NF)-kappaB regulates inflammatory responses and plays important roles in the pathogenesis of acute respiratory distress syndrome (ARDS). Inhibitor kappaB-alpha (NFKBIA) inhibits NF-kappaB and controls its activities. The objective was to determine whether polymorphisms in NFKBIA gene would be associated with ARDS development. DESIGN: Prospective cohort of adults with clinical risk factors for ARDS. SETTING: Hospital system. PATIENTS: Patients were 1,210 critically ill Caucasian patients meeting study criteria for a defined risk factor for ARDS who were enrolled and prospectively followed for 60 days; 382 had ARDS, and 828 were controls. INTERVENTIONS: Genetic polymorphisms in the NFKBIA promoter (-881A/G, -826C/T, -297C/T) were determined using TaqMan techniques. MEASUREMENTS AND MAIN RESULTS: The three polymorphisms were in Hardy-Weinberg equilibrium. No individual genotype was significantly associated with ARDS development. In contrast, haplotypes of NFKBIA were globally associated with ARDS development (p = .02, degree of freedom = 2). The frequency of haplotype GTC (-881G/-826T/-297C) was significantly higher among ARDS patients (7.4%) than that among controls (5.2%) (p = .03). Crude analysis showed that the haplotype GTC was significantly associated with higher risks of ARDS in the whole cohort compared with the common haplotype ACC (-881A/-826C/-297C) (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.03-2.09; p = .03), especially among male subjects (OR, 1.90; 95% CI, 1.20-2.97; p < .01). After adjustment for covariates, the haplotype GTC remained significantly associated with increased risk of ARDS in the whole cohort (OR, 1.66; 95% CI, 1.09-2.53; p = .02), particularly among male patients (OR, 1.98; 95% CI, 1.16-3.40; p = .02) and among subjects with direct pulmonary injury (OR, 1.75; 95% CI, 1.04-2.95; p = .04). CONCLUSIONS: The haplotype GTC of NFKBIA gene is associated with higher risk of ARDS in Caucasians, particularly in male patients and in patients with direct lung injury.     

Clinical differentiation between acute renal infarction and acute ureteral stone in the emergency department: A single-center retrospective case-control study

BackgroundFew studies have compared renal infarction (RI) and ureteral stone (US), so there is insufficient evidence for emergency clinicians (ECs) to quickly suspect RI during the first assessment. Therefore, we compared the initial clinical presentation and laboratory findings of these diseases in the emergency department (ED) to determine a factor that may indicate RI.MethodsThis single-center retrospective case-control study included 42 patients with acute RI and 210 with US who visited the ED from 2014 to 2020. Medical record data from first ED arrival were investigated, and clinical presentations, blood and urine test results obtained in the ED were compared and analyzed using logistic regression analysis.ResultsECs never suspected the initial diagnosis of RI as RI. The most common initial diagnosis was US (40.5%). Among patients with US, 150 patients (71.4%) were suspected of having US (p < 0.001). Abdominal pain (61.9%) was the most common chief complaint in the RI group, and flank pain (73.8%) was the most common in the US group (p < 0.001). 27 factors showed significant differences between the groups. Among those, age ≥ 70 years (odds ratio [OR]: 311.2, 95% confidence interval [CI]: 2.0–47,833.1), history of A-fib (OR: 149872.8, 95% CI: 289.4–7.8E+07), fever ≥37.5 °C (OR: 297.3, 95% CI: 3.3–27,117.8), Cl⁻ ≤ 103 mEq/L (OR: 9.0, 95% CI: 1.0–80.1), albumin ≤4.3 g/dL (OR: 26.6, 95% CI: 2.1–330.3), LDH ≥500 IU/L (OR: 17.9, 95% CI: 1.8–182.5), and CRP ≥0.23 mg/dL (OR: 7.5, 95% CI: 1.1–52.3) showed significantly high ORs, whereas urine RBCs (OR: 0, 95% CI: 0–0.02) showed a low OR (p < 0.05). The regression model showed good calibration (chi-square: 6.531, p = 0.588) and good discrimination (area under the curve = 0.9913).ConclusionsWhen differentiating acute RI from US in the ED, age ≥ 70 years, history of A-fib, fever ≥37.5 °C, LDH ≥500 IU/L, Cl⁻ ≤ 103 mEq/L, albumin ≤4.3 g/dL, CRP ≥0.23 mg/dL and negative urine RBC result suggest the possibility of RI.     

Antiphospholipid, anti-beta 2-glycoprotein-I and anti-oxidized-low-density-lipoprotein antibodies in antiphospholipid syndrome

Antiphospholipid antibodies (aPL), anti-beta 2-glycoprotein I (anti-beta 2-GPI) and anti-oxidized-low-density lipoprotein (LDL) antibodies are all implicated in the pathogenesis of antiphospholipid syndrome. To investigate whether different autoantibodies or combinations thereof produced distinct effects related to their antigenic specificities, we examined the frequencies of antiphospholipid syndrome (APS)-related features in the presence of different antibodies [aPL, beta 2-GPI, anti-oxidized low density lipoprotein (LDL)] in 125 patients with APS. Median follow-up was 72 months: 58 patients were diagnosed as primary APS and 67 as APS plus systemic lupus erythematosus (SLE). Anticardiolipin antibodies (aCL), anti-beta 2-GPI and anti-oxidized LDL antibodies were determined by ELISA; lupus anticoagulant (LA) by standard coagulometric methods. Univariate analysis showed that patients positive for anti-beta 2-GPI had a higher risk of recurrent thrombotic events (OR = 3.64, 95% CI, p = 0.01) and pregnancy loss (OR = 2.99, 95% CI, p = 0.004). Patients positive for anti-oxidized LDL antibodies had a 2.24-fold increase in the risk of arterial thrombosis (2.24, 95% CI, p = 0.03) and lower risk of thrombocytopenia (OR = 0.41 95% CI, p = 0.04). Patients positive for aCL antibodies had a higher risk of pregnancy loss (OR = 4.62 95% CI, p = 0.001). When these data were tested by multivariate logistic regression, the association between anti-beta 2-GPI and pregnancy loss and the negative association between anti-oxidized LDL antibodies and thrombocytopenia disappeared.     

Thrombocytopenia in patients in the medical intensive care unit: bleeding prevalence,transfusion requirements,and outcome

OBJECTIVE: To determine prevalence, risk factors, and outcome of thrombocytopenia in medical intensive care patients. DESIGN: Prospective observational study. SETTING: The 12-bed medical intensive care unit of a university hospital. PATIENTS: All consecutively admitted patients with normal platelet count at admission and an intensive care unit stay of >48 hrs during a 13-month period (n = 145). MEASUREMENTS AND MAIN RESULTS: The prevalence of intensive care unit-acquired thrombocytopenia (platelet count, <150.0/nL) was 64 of 145 patients (44%). Intensive care unit mortality was 31% in thrombocytopenic patients and 16% in nonthrombocytopenic patients (p =.03). Mortality was higher in patients with a nadir platelet count of <100.0/nL (p <.001) and in patients with a drop in platelet count of >/=30% (p <.001). In nonsurvivors, the decrease in platelet count was greater (p <.001), the nadir platelet count lower (p <.001), and the duration of thrombocytopenia longer (p =.008) than in survivors. A logistic regression analysis identified septic shock (odds ratio [OR], 3.65; 95% confidence interval [CI], 1.40-9.52), a higher Acute Physiology and Chronic Health Evaluation II Score at admission (OR, 1.06 for 1 point; 95% CI, 1.01-1.12), and a drop in platelet count exceeding 30% (OR, 3.73; 95% CI, 1.24-11.21), but not thrombocytopenia, as independent risk factors for intensive care unit death. Correction of thrombocytopenia was associated with reduced mortality (OR, 0.002; 95% CI, 0-0.08). Major bleeding prevalence and transfusion requirements were significantly higher with thrombocytopenia. Nadir platelet count was the only independent risk factor for bleeding (OR, 4.1 for every 100.0/nL; 95% CI, 1.9-8.8). Independently associated with thrombocytopenia were disseminated intravascular coagulation (OR, 14.94; 95% CI, 3.92-57.00), cardiopulmonary resuscitation as an admission category (OR, 5.17; 95% CI, 1.42-18.85), and a higher Sequential Organ Failure Assessment score (OR, 1.20 for a 1 point change; 95% CI, 1.02-1.40). CONCLUSIONS: Thrombocytopenia is common in medical intensive care unit patients. Thrombocytopenic patients have a higher prevalence of bleeding and greater transfusion requirements. A drop in platelet counts of > or = 30%, but not thrombocytopenia per se, is independently associated with intensive care unit death. Serial measurements of platelet counts are important and readily available markers for monitoring the patient's condition. Any drop in platelet count requires urgent clarification. Disseminated intravascular coagulation, signs of organ failure at admission, and cardiopulmonary resuscitation are predictors of intensive care unit-acquired thrombocytopenia.     

Symptom predictors of acute coronary syndromes in younger and older patients

BACKGROUND: Symptoms, a key element in the patient's decision to seek care, are critical to appropriate triage, and influence decisions to pursue further evaluation and initiation of treatment. Although many studies have described symptoms associated with acute coronary syndromes (ACS), few, if any, have examined symptom predictors of ACS and whether they differ by patients' age. OBJECTIVES: To explore symptom predictors of ACS in younger (< 70 years) and older (> or = 70 years) patients. To test the hypothesis that typical symptoms are predictive of ACS in younger patients, but are less predictive in older patients. METHOD: Secondary analysis of observational data gathered on 531 patients presenting to the emergency department of a regional cardiac referral center in New England with symptoms suggestive of ACS. RESULTS: Bivariate analyses revealed no symptoms significantly (p < .01) associated with ACS in older patients. In younger patients presence of chest symptoms and the total number of typical symptoms reported were significantly (p < .01) associated with ACS. After adjustment for age and gender, typical symptoms that were positive predictors of ACS in younger patients included chest symptoms (OR 2.37, 95% CI 1.32-4.27, p = .004) and arm pain (OR 1.78, 95% CI 1.03-3.09, p = .040). Additionally, the total number of typical symptoms reported (OR 1.68, 95% CI 1.31-2.15, p < .001) was a positive predictor of ACS in younger patients. The atypical symptom of fatigue (OR 2.52, 95% CI 1.10-5.81, p = .029) was a significant positive predictor of ACS, whereas dizziness/faintness (OR .50, 95% CI .26-.91, p = .024) was a significant negative predictor of ACS in younger patients. Logistic regression analysis using the entire sample revealed an interaction between age and number of typical symptoms indicating that younger patients had a 36% greater odds for ACS for each additional typical symptom present compared with older patients (OR 1.36, 95% CI 1.02-1.83, p = .038 for interaction between age and number of typical symptoms reported). The model with the interaction between age and chest symptoms revealed a borderline association (p = .10 for the interaction between age and chest symptoms), with younger patients being more likely than older patients to report chest symptoms. CONCLUSIONS: Typical symptoms are predictive of ACS in younger patients and less predictive in older patients.