Acute hypoglycemia and risk of cardiac arrhythmias in insulin-treated type 2 diabetes and controls.

OBJECTIVE: Hypoglycemia is associated with an increased risk of cardiovascular disease including cardiac arrhythmias. We investigated the effect of hypoglycemia in the setting of acute glycemic fluctuations on cardiac rhythm and cardiac repolarization in insulin-treated patients with type 2 diabetes compared with matched controls without diabetes. DESIGN: A non-randomized, mechanistic intervention study. METHODS: Insulin-treated patients with type 2 diabetes (n = 21, age (mean ± s.d.): 62.8 ± 6.5 years, BMI: 29.0 ± 4.2 kg/m2, HbA1c: 6.8 ± 0.5% (51.0 ± 5.4 mmol/mol)) and matched controls (n = 21, age: 62.2 ± 8.3 years, BMI 29.2 ± 3.5 kg/m2, HbA1c: 5.3 ± 0.3% (34.3 ± 3.3 mmol/mol)) underwent a sequential hyperglycemic and hypoglycemic clamp with three steady-states of plasma glucose: (i) fasting plasma glucose, (ii) hyperglycemia (fasting plasma glucose +10 mmol/L) and (iii) hyperinsulinemic hypoglycemia (plasma glucose < 3.0 mmol/L). Participants underwent continuous ECG monitoring and blood samples for counterregulatory hormones and plasma potassium were obtained. RESULTS: Both groups experienced progressively increasing heart rate corrected QT (Fridericia's formula) interval prolongations during hypoglycemia ((∆mean (95% CI): 31 ms (16, 45) and 39 ms (24, 53) in the group of patients with type 2 diabetes and controls, respectively) with similar increases from baseline at the end of the hypoglycemic phase (P = 0.43). The incidence of ventricular premature beats increased significantly in both groups during hypoglycemia (P = 0.033 and P < 0.0001, respectively). One patient with type 2 diabetes developed atrial fibrillation during recovery from hypoglycemia. CONCLUSIONS: In insulin-treated patients with type 2 diabetes and controls without diabetes, hypoglycemia causes clinically significant and similar increases in cardiac repolarization that might increase vulnerability for serious cardiac arrhythmias and sudden cardiac death.

Whole exome sequencing of distant relatives in multiplex families implicates rare variants in candidate genes for oral clefts.

A dozen genes/regions have been confirmed as genetic risk factors for oral clefts in human association and linkage studies, and animal models argue even more genes may be involved. Genomic sequencing studies should identify specific causal variants and may reveal additional genes as influencing risk to oral clefts, which have a complex and heterogeneous etiology. We conducted a whole exome sequencing (WES) study to search for potentially causal variants using affected relatives drawn from multiplex cleft families. Two or three affected second, third, and higher degree relatives from 55 multiplex families were sequenced. We examined rare single nucleotide variants (SNVs) shared by affected relatives in 348 recognized candidate genes. Exact probabilities that affected relatives would share these rare variants were calculated, given pedigree structures, and corrected for the number of variants tested. Five novel and potentially damaging SNVs shared by affected distant relatives were found and confirmed by Sanger sequencing. One damaging SNV in CDH1, shared by three affected second cousins from a single family, attained statistical significance (P = 0.02 after correcting for multiple tests). Family-based designs such as the one used in this WES study offer important advantages for identifying genes likely to be causing complex and heterogeneous disorders.

Association of admission hematocrit with 6-month and 1-year mortality in intensive care unit patients.

BACKGROUND: This study examined the association of hematocrit (Hct) levels measured upon intensive care unit (ICU) admission and red blood cell transfusions to long-term (1-year or 180-day) mortality for both surgical and medical patients. STUDY DESIGN AND METHODS: Administrative and laboratory data were collected retrospectively on 2393 consecutive medical and surgical male patients admitted to the ICU between 2003 and 2009. We stratified patients based on their median Hct level during the first 24 hours of their ICU stay (Hct < 25.0%, 25% ≤ Hct < 30%, 30% ≤ Hct < 39%, and 39.0% and higher). An extended Cox regression analysis was conducted to identify the time period after ICU admission (0 to <180, 180 to 365 days) when low Hct (<25.0) was most strongly associated with mortality. The unadjusted and adjusted relationship between admission Hct level, receipt of a transfusion, and 180-day mortality was assessed using Cox proportional hazards regression modeling. RESULTS: Patients with an Hct level of less than 25% who were not transfused had the worst mortality risk overall (hazard ratio [HR], 6.26; 95% confidence interval [CI], 3.05-12.85; p < 0.001) during the 6 months after ICU admission than patients with a Hct level of 39.0% or more who were not transfused. Within the subgroup of patients with a Hct level of less than 25% only, receipt of a transfusion was associated with a significant reduction in the risk of mortality (HR, 0.40; 95% CI, 0.19-0.85; p = 0.017). CONCLUSION: Anemia of a Hct level of less than 25% upon admission to the ICU, in the absence of a transfusion, is associated with long-term mortality. Our study suggests that there may be Hct levels below which the transfusion risk-to-benefit imbalance reverses.

Differential relationships between continuity of care practices, engagement in continuing care, and abstinence among subgroups of patients with substance use and psychiatric disorders.

OBJECTIVE: We examined whether patient subgroups with differing substance use disorders (SUDs) and psychiatric severity levels varied on engagement in continuing care and abstinence outcomes, the association of continuity of care practices to engagement, and the association of engagement to abstinence. METHOD: Staff in 28 Veterans Affairs SUD treatment programs used the Addiction Severity Index to assess 865 (98% male) patients' alcohol, other drug, and psychiatric problems at treatment entry. At discharge, staff supplied data on patients' treatment, motivation, and continuity of care practices. Administrative data assessed continuing care engagement. Six months after discharge, 673 patients completed a self-reported Addiction Severity Index. The sample comprised four SUD subgroups (abstinent from alcohol and other drugs, used alcohol only, used other drugs only, used alcohol and other drugs) and two psychiatric severity subgroups (high and moderate to low). RESULTS: Patients receiving more continuity of care services engaged in continuing care longer. This association was weaker for the high psychiatric severity subgroup than for the moderate-to-low psychiatric severity subgroup. Engagement in continuing care was the most important predictor of abstinence overall. The positive association between engagement in continuing care and abstinence was strongest for the SUD subgroup using both alcohol and other drugs. This group had the lowest likelihood of abstinence if they engaged in little or no continuing care but showed the greatest increase in abstinence with longer continuing care engagement. CONCLUSIONS: Subgroups' differential responsiveness to continuity of care services and engagement highlights the crucial importance of continuing care interventions to improve abstinence outcomes for certain subgroups of patients who use both alcohol and other drugs.

[Biometric analysis of the unstable shoulder]. / Biometrische Analyse des instabilen Schultergelenkes.

An osteometry of instable glenohumeral-joints was done by computerized tomography. In comparison of type and direction of the instability, a marked retroversion of the glenoid was found in posterior luxation, not only in the instable, but also in the contralateral side. There seems no statistical prove of an influence by a changed radius or width of the humerus-head nor by a reduced retrotorsion of the humerus. Posttraumatic disorders like HILL-SACHS-lesions or BANKART-lesions are more easily detected by computerized tomography than by conventional radiography.