Confirming diagnoses of acute pancreatitis with commonly available electronic data.

BACKGROUND: Recorded diagnoses of acute pancreatitis (AP) are often inaccurate resulting in limited utility for case identification in large data sources, especially where electronic medical records (EMR) are not available. Our objectives were to validate diagnoses of AP and to identify an algorithm using additional data to enhance the identification of AP cases in different data sources. METHODS: We randomly sampled 550 persons with an AP diagnosis from inpatient data or outpatient or emergency department diagnoses immediately preceding a hospitalization and 150 negative controls with a differential diagnosis (cholangitis or cholecystitis). We conducted an EMR review to confirm cases of AP and used logistic regression to develop EMR-based and claims-based algorithms to identify confirmed AP cases with variables typically available in electronic data sources. Algorithm performance was assessed using the C statistic, sensitivity, specificity, and positive and negative predictive value. RESULTS: Of the 550 patients with an AP diagnosis, 467 (84.9%) were confirmed cases. An AP diagnosis alone had high sensitivity (98.9%), modest specificity (63.6%), and a C statistic of 0.813. An EMR-based model using an AP diagnosis, body mass index ≥30 kg/m2 , a serum lipase >3 times upper limit of normal and diabetes attained a C-statistic of 0.914. A claims-based model attained a C-statistic of 0.892 using an AP diagnosis and dichotomous variables for whether a serum lipase test and/or an abdominal ultrasound was performed. CONCLUSIONS: Our simple algorithms increased the accuracy of identification of AP cases providing widespread applicability to epidemiological and drug safety studies.

Safety of Empagliflozin: An Individual Participant-Level Data Meta-Analysis from Four Large Trials.

INTRODUCTION: Empagliflozin is a sodium-glucose co-transporter-2 inhibitor used to treat type 2 diabetes (T2D) to improve glycemic control, reduce risk of cardiovascular death in patients with T2D, and treat patients with symptomatic chronic heart failure (HF) and chronic kidney disease (CKD). The safety profile of empagliflozin is well documented, although adverse events (AEs) remain of interest to clinicians. This study provides an up-to-date safety evaluation of empagliflozin. METHODS: Data were pooled from four long-term trials which included: patients with T2D and established cardiovascular disease (EMPA-REG OUTCOME), patients with HF, with/without diabetes (EMPEROR-Reduced and EMPEROR-Preserved), and patients with CKD, with/without diabetes (EMPA-KIDNEY). Since three of the four trials evaluated empagliflozin 10 mg, the meta-analysis was restricted to this dose. RESULTS: Total trial medication exposure was 19,727 patient-years for patients who received empagliflozin (n = 10,472) and 19,447 patient-years for placebo (n = 10,461). The percentages of patients with serious AEs, fatal AEs, and AEs leading to discontinuation were similar for both groups. The incidences of serious urinary tract infection and serious pyelonephritis or urosepsis were similar for both groups but higher for women taking empagliflozin versus placebo. Serious genital infections were not increased with empagliflozin versus placebo. There was a slight increase in ketoacidosis and serious volume depletion in patients who received empagliflozin versus placebo. The occurrence of serious acute kidney injury was lower with empagliflozin versus placebo. Empagliflozin was not associated with an increased incidence of severe hypoglycemia, bone fractures, or lower limb amputations. Empagliflozin is therefore considered safe in people without diabetes, the elderly, patients with very low estimated glomerular filtration rate, low body mass index, and HF. Safety is unaltered by blood pressure, concomitant medication for hypertension, HF, and immunosuppression. CONCLUSION: This meta-analysis of long-term safety data extends current knowledge and confirms the safety and tolerability of empagliflozin.

Empagliflozin is used in adults with type 2 diabetes mellitus (T2D) to improve blood glucose control and in people with T2D and established cardiovascular disease to reduce the risk of death from cardiovascular disease. Also, it is used to treat people with chronic heart failure or chronic kidney disease. Although many clinical trials have shown the effectiveness and safety of empagliflozin, the evaluation of adverse events (AEs) remains of interest. This study further examined the safety of empagliflozin by analyzing four large, long-term clinical trials. These trials included over 20,900 patients with T2D and established cardiovascular disease, patients with heart failure, and patients with chronic kidney disease. Adverse events of interest were pooled and analyzed. Results show the risk of the investigated AEs was similar whether patients had received empagliflozin or placebo. The risk of urinary tract infections, including those that spread to the kidneys, was higher for women taking empagliflozin versus placebo. Ketoacidosis was rare but more frequent in patients taking empagliflozin. A reduction in blood volume was slightly more frequent in people taking empagliflozin versus placebo. The risk of kidney injury was reduced in patients taking empagliflozin versus placebo. The risk of genital infections, hypoglycemia, bone fractures, or lower limb amputations was not increased with empagliflozin. No new safety concerns were raised, including in people who were elderly, had kidney disease, low body weight, T2D, or heart failure. This analysis is consistent with current knowledge of empagliflozin safety in a broad range of patients.

Primary intracranial melanoma, amelanotic variant: Case report.

Primary brain melanoma is a very rare tumour (only 0.07% of primary CNS neoplasms) which usually shows with abundant melanin content; whereas hypo/melanotic variants have been scarcely described. We introduce the case of a female patient with headache, left brachial paresis and frontallobar syndrome. The MRI image showed a right frontal mass with homogeneous contrast uptake. As treatment, a complete surgical resection was performed. Pathology was diagnostic for melanoma, with very low melanin content and a high proliferative index. A thorough extension study was performed to rule out an extracranial primary origin. Due to several intercurrent complications, the patient evolved unfavorably, not being able to receive further treatment. The amelanotic variant of primary intracranial malignant melanomas has not been described in detail previously. We will review the literature, focusing on the particularities of management and diagnosis of this clinical entity.

1.34-µm Nd:YVO4 laser mode-locked by SHG-lens formation in periodically-poled stoichiometric lithium tantalate.

Self-starting, steady-state χ((2))-lens mode-locking of a 1.34-µm diode-pumped Nd:YVO(4) laser using intracavity second harmonic generation in PPMgSLT is demonstrated. Pulses as short as 3.6 ps with an average output power of ~1 W are obtained at a repetition rate of 120 MHz.

Passive mode-locking of a diode-pumped Nd:YVO(4) laser by intracavity SHG in PPKTP.

Experimental results on passive mode-locking of a Nd:YVO(4) laser using intracavity frequency doubling in periodically poled KTP (PPKTP) crystal are reported. Both, negative cascaded chi((2)) lensing and frequency doubling nonlinear mirror (FDNLM) are exploited for the laser mode-locking. The FDNLM based on intensity dependent reflection in the laser cavity ensures self-starting and self-sustaining mode-locking while the cascaded chi((2)) lens process contributes to substantial pulse shortening. This hybrid technique enables generation of stable trains of pulses at high-average output power with several picoseconds pulse width. The pulse repetition rate of the laser is 117 MHz with average output power ranging from 0.5 to 3.1 W and pulse duration from 2.9 to 5.2 ps.

High-power picosecond Nd:GdVO4 laser mode locked by SHG in periodically poled stoichiometric lithium tantalate.

Periodically poled stoichiometric lithium-tantalate is used for mode locking of a diode-pumped Nd:GdVO(4) laser by intracavity second-harmonic generation. Stable and self-starting operation is observed achieving average output powers of up to 5 W at a pulse-repetition rate of 107 MHz. The obtained pulse durations range from 6.5 ps at maximum output power down to 3.2 ps at 1.4 W.

Pooled Safety and Tolerability Analysis of Empagliflozin in Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: The aim of this analysis was to characterize the safety and tolerability of empagliflozin in patients with type 2 diabetes mellitus (T2DM) who were randomized to empagliflozin (10/25 mg) or placebo in clinical trials. METHODS: Pooled data from 20 trials were analyzed for patients with T2DM treated with empagliflozin 10 mg (n = 4858), empagliflozin 25 mg (n = 5057), or placebo (n = 4904). The dataset comprised 15 randomized phase I-III trials, an extension trial and dose escalation studies. Adverse events (AEs) were assessed descriptively in participants who took ≥ 1 dose of study drug. AE incidence rates per 100 patient-years were calculated to adjust for differences in drug exposure between trials. RESULTS: Total exposure was 16,480 and 7857 patient-years in the pooled empagliflozin 10/25 mg and placebo groups, respectively. The incidence of any AEs, AEs leading to treatment discontinuation, severe AEs, and serious AEs was similar across groups. The frequency of serious AEs requiring hospitalization was 18.6% for the empagliflozin 10/25 mg group and 21.3% for the placebo group. The empagliflozin 10/25 mg group was not associated with a higher rate of confirmed hypoglycemia versus placebo, except in patients co-administered insulin and/or a sulfonylurea (31.5% vs. 30.2%, respectively). The incidence of events consistent with urinary tract infections (UTI) was also similar for the empagliflozin 10/25 mg group versus placebo (9.27 vs. 9.70/100 patient-years, respectively). History of UTI was identified as a risk factor for UTI during treatment. Events consistent with genital infections occurred more frequently with empagliflozin 10/25 mg than placebo (3.54 vs. 0.95/100 patient-years, respectively). The frequency of AEs consistent with volume depletion was similar across groups, but higher with empagliflozin 10/25 mg than placebo in patients aged 75 to < 85 years and those on loop diuretics at baseline. CONCLUSION: This comprehensive analysis confirms that both empagliflozin 10 mg and 25 mg are well tolerated in patients with T2DM, reinforcing the established clinical safety profile of empagliflozin.

Empagliflozin is approved to treat adults with type 2 diabetes mellitus (T2DM) insufficiently controlled by diet and exercise. It lowers blood glucose levels by inhibiting sodium-glucose co-transporter-2 (SGLT2), a protein involved in glucose reabsorption by the kidneys. By blocking SGLT2, glucose is removed in urine instead of being reabsorbed into the bloodstream. Numerous clinical studies have shown the effectiveness and safety of empagliflozin, but recent reports of two types of serious side effects [fractures and lower limb amputations (LLAs)] associated with another drug in the class, canagliflozin, has triggered a review of the risk associated with taking SGLT2 inhibitors. To examine the safety and tolerability of empagliflozin we pooled data from 20 clinical trials involving over 15,000 patients with T2DM who received either empagliflozin or placebo (control). We found that the risk of side effects was similar whether patients received empagliflozin or placebo. This included side effects that led to treatment being stopped as well as severe and serious side effects, including fractures and LLAs. Empagliflozin was not associated with a higher rate of hypoglycemia (low blood sugar) versus placebo, except in patients also treated with insulin and/or a sulfonylurea (31.5% vs. 30.2%, respectively). The risk of urinary tract infections was also similar for empagliflozin versus placebo (9.27 vs. 9.70/100 patient-years, respectively). However, genital infections, as anticipated, occurred more frequently in patients treated with empagliflozin than placebo (3.54 vs. 0.95/100 patient-years, respectively). Overall, this analysis confirms the results of previous studies showing that empagliflozin is well tolerated in patients with T2DM.

Safety and effectiveness of empagliflozin in Japanese patients with type 2 diabetes: interim analysis from a post-marketing surveillance study.

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are effective treatments for type 2 diabetes mellitus (T2DM). We present the interim findings of an ongoing post-marketing surveillance (PMS) study in Japanese patients with T2DM receiving empagliflozin.Research design and methods: This 3-year, prospective, observational, multicenter PMS evaluated the safety and effectiveness of empagliflozin in Japanese clinical practice. Patients with T2DM who had not been treated with empagliflozin before enrollment were eligible. Assessments, including the primary endpoint of incidence of adverse drug reactions (ADRs), were based on electronic case report forms (eCRF).Results: Of 8,180 registered patients from 1,103 sites, 7,618 patients had an eCRF including a follow-up visit and were treated (mean age, 58.8 years; 10.5% aged ≥75 years; 63.2% male; mean HbA1c, 8.01%; 41.8% with HbA1c ≥8.0%; 24.8% and 61.8% with at least mild hepatic and renal impairment, respectively). Mean treatment duration was 98.4 weeks; 644 (8.5%) patients had ≥1 ADR, including 8.5% of patients aged ≥75 years. Hypoglycemia, urinary tract infection, genital infections, volume depletion, diabetic ketoacidosis, and lower limb amputation occurred in 0.28%, 0.62%, 0.53%, 0.33%, 0%, and 0.03% of patients, respectively.Conclusions: The reported ADRs were consistent with the known safety profile of empagliflozin.Trial registration: ClinicalTrials.gov identifier: NCT02489942.

Safety and Tolerability of Empagliflozin in Patients with Type 2 Diabetes: Pooled Analysis of Phase I-III Clinical Trials.

INTRODUCTION: We characterized the safety and tolerability of empagliflozin in patients with type 2 diabetes (T2DM) randomized 1:1:1 to placebo, empagliflozin 10 mg, or empagliflozin 25 mg in clinical trials. METHODS: Pooled data were analyzed from patients with T2DM treated with placebo (N = 4203), empagliflozin 10 mg (N = 4221), or empagliflozin 25 mg (N = 4196) in 15 randomized phase I-III trials plus four extension studies. Adverse events (AEs) were assessed descriptively in participants who took at least one dose of study drug. AE incidence rates per 100 patient-years were calculated to adjust for differences in drug exposure between trials. RESULTS: Total exposure was 7369, 7782, and 7754 patient-years in the placebo, empagliflozin 10 mg, and 25 mg groups, respectively. The incidence of any AEs, severe AEs, serious AEs, and AEs leading to discontinuation was no higher in participants treated with empagliflozin vs. placebo. Empagliflozin was not associated with an increased risk of hypoglycemia vs. placebo, except in participants on background sulfonylurea. The incidence of events consistent with urinary tract infection was similar across treatment groups (8.7-9.5/100 patient-years). Events consistent with genital infection occurred more frequently in participants treated with empagliflozin 10 and 25 mg (3.5 and 3.4/100 patient-years, respectively) than placebo (0.9/100 patient-years). The incidence of AEs consistent with volume depletion was similar across treatment groups (1.7-1.9/100 patient-years) but was higher with empagliflozin 10 mg and 25 mg vs. placebo in participants aged 75 years or older (3.2 and 3.0 vs. 2.3/100 patient-years, respectively). The rates of bone fractures, cancer events, renal AEs, venous thromboembolic events, hepatic injury, acute pancreatitis, lower limb amputations, and diabetic ketoacidosis were similar across treatment groups. CONCLUSION: This analysis of pooled safety data based on more than 15,000 patient-years' exposure supports a favorable benefit-risk profile of empagliflozin in patients with T2DM. FUNDING: Boehringer Ingelheim Pharma GmbH.

Variante amelanótica en melanoma cerebral primario: a propósito de un caso / Primary intracranial melanoma, amelanotic variant: Case report

El melanoma cerebral primario es un tumor muy infrecuente (0,07% de las neoplasias primarias del SNC). Generalmente muestra un abundante contenido en melanina, y solo en contadas ocasiones se han descrito variantes hipoamelanóticas. Presentamos el caso de una paciente con clínica de cefalea, paresia braquial izquierda y síndrome lobar frontal. La RM mostró una masa frontal derecha con captación homogénea de contraste. Como tratamiento, se realizó una resección quirúrgica completa. El estudio anatomopatológico fue diagnóstico para melanoma, con muy escaso contenido en melanina y alto índice proliferativo. Se realizó un estudio de extensión exhaustivo para descartar otra localización primaria. Debido a varias complicaciones intercurrentes, la paciente evolucionó desfavorablemente, sin llegar a recibir otros tratamientos. La variante amelanótica de los melanomas cerebrales primarios no ha sido descrita con detalle previamente. Repasamos la literatura al respecto y discutimos los detalles de manejo y diagnóstico de esta entidad clínica (AU)

Primary brain melanoma is a very rare tumour (only 0.07% of primary CNS neoplasms) which usually shows with abundant melanin content; whereas hypo/melanotic variants have been scarcely described. We introduce the case of a female patient with headache, left brachial paresis and frontal lobar syndrome. The MRI image showed a right frontal mass with homogeneous contrast uptake. As treatment, a complete surgical resection was performed. Pathology was diagnostic for melanoma, with very low melanin content and a high proliferative index. A thorough extension study was performed to rule out an extracranial primary origin. Due to several intercurrent complications, the patient evolved unfavorably, not being able to receive further treatment. The amelanotic variant of primary intracranial malignant melanomas has not been described in detail previously. We will review the literature, focusing on the particularities of management and diagnosis of this clinical entity (AU)