Outcomes of changing immunosuppressive therapy after treatment failure in patients with noninfectious uveitis.

PURPOSE: To evaluate the outcomes of changing immunosuppressive therapy for noninfectious uveitis after failure. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with noninfectious uveitis managed at 2 tertiary uveitis clinics in the United Kingdom and Australia. METHODS: Participants with a history of using immunosuppressive therapy were identified in clinics, and notes were reviewed by doctors trained in uveitis therapy. Each treatment episode/course (starting or changing a therapy) was identified, and demographic details, clinical characteristics, drug used (second-line immunosuppressive agent [ISA] or biologicals), and drug doses were obtained. MAIN OUTCOME MEASURES: For each treatment episode, the reasons for changing therapy, corticosteroid-sparing effects, and control of inflammation were determined. RESULTS: A total of 147 patients were identified who underwent 309 different treatment episodes. Fifty-five percent of patients eventually required a change in treatment after their first treatment episode/course. Forty-five episodes involved switching from one ISA to another, with 50% to 100% of these patients achieving "success" (prednisolone ≤10 mg and sustained control) with the new ISA. A combination of ISAs were used in 53 episodes, with "success" being achieved in 50% to 71% of these patients. Biological agents were used in 45 episodes, the most common one being infliximab, which achieved success in 80% of patients. CONCLUSIONS: Our data suggest that control of inflammation can be achieved after switching or combining ISAs.

Discharge readiness after minor gynaecological surgeries comparing dexmedetomidine and ketamine premedication in bispectral index (BIS) guided propofol-based anaesthesia.

BACKGROUND AND AIMS: Dexmedetomidine and ketamine are commonly used pre-medicants to propofol. Previous literature shows a delay in recovery with their use without any clarity on discharge. This study was planned to find out whether adding these premedicants to Bispectral index (BIS) guided propofol anaesthesia led to delayed discharge in minor gynaecological surgeries. METHODS: Totally, 120 adult females belonging to American Society of Anesthesiologists (ASA) physical status I and II undergoing minor gynaecological surgeries under general anaesthesia were randomly allocated to receive 1 µg/kg dexmedetomidine (Group D), 0.5 mg/kg ketamine (Group K) and normal saline (Group P) as premedication. Propofol 1% was used for induction and maintenance of anaesthesia keeping BIS between 55 and 70. After the procedure, patients were assessed primarily for discharge readiness using Modified Post Anaesthesia Discharge Scoring System (MPADSS).The secondary outcomes were Modified Aldrete Score (MAS), total dose of propofol used and haemodynamics. RESULTS: The percentage of patients ready for discharge were 22.5%, 30% and 15%at 1 hour in group D, K and P, respectively (p = 0.275). Median MAS was 5, 4 and 6 respectively for group D, K and P immediately post-surgery (p = 0.000). The mean dose of propofol used was 69.75 ± 12.56 mg in group D and 135.25 ± 9.2 mg in group P (p = 0.001). There were significant haemodynamic variations in group D (16.4% fall in heart rate at 5 minutes and 24.18% fall in mean arterial pressure at 15 minutes). CONCLUSION: Premedication with dexmedetomidine and ketamine in propofol anaesthesia does not delay discharge. However, stable haemodynamics and good analgesia with ketamine make it a better option.

The Latest Drugs in Development That Reduce Intraocular Pressure in Ocular Hypertension and Glaucoma.

Glaucoma causes irreversible vision loss, with elevated intraocular pressure (IOP) being the only known modifiable risk factor. There are a variety of medical and interventional options for lowering IOP; however, despite these treatments, glaucoma continues to be a leading cause of visual impairment. Further research continues to strive for treatment options with improved side effect profiles, additional IOP-lowering effects, and ease of use. This review provides a brief summary of current IOP-lowering therapies and then outlines pipeline ocular hypotensive agents, their mechanisms of action, benefits, and side effect profiles. Advancements are seen within currently used eye drop classes such as prostaglandin analogues, Rho kinase inhibitors and nitric oxide donors, whilst there are also new drug classes, such as tyrosine protein kinase activators. Most developing drugs are topical drop formulations, with a number already having entered Phase III trials. Alternative drug delivery methods are also in development and will be briefly discussed. Pharmacological and drug delivery developments continue to provide glaucoma patients and clinicians with new options and the promise of better outcomes, particularly in terms of improved tolerance and reduced frequency of dosing.

Testosterone Increases the Expression and Phosphorylation of AMP Kinase α in Men With Hypogonadism and Type 2 Diabetes.

CONTEXT: Adenosine 5'-monophosphate-activated protein kinase-α (AMPKα) is a mediator of exercise-induced glucose uptake in skeletal muscle. OBJECTIVE: We evaluated whether AMPKα expression and phosphorylation are reduced in skeletal muscle and adipose tissue of patients with hypogonadotropic hypogonadism (HH), and whether testosterone replacement therapy results in restoration of the expression and phosphorylation of AMPKα. DESIGN: This is a secondary analysis of a previously completed trial that showed an insulin-sensitizing effect of testosterone therapy in men with type 2 diabetes and HH. SETTING: Clinical research center at university. PATIENTS: Thirty-two men with HH and 32 eugonadal men were compared at baseline. INTERVENTIONS: Men with HH were treated with intramuscular injections of testosterone or placebo every 2 weeks for 22 weeks. Quadriceps muscle biopsies and subcutaneous abdominal fat biopsies were obtained before and after 4-hour euglycemic hyperinsulinemic clamp, prior to and after testosterone or placebo therapy. OUTCOME MEASURES AND RESULTS: mRNA expression of AMPKα in hypogonadal men was lower by 37% in adipose tissue and 29% in skeletal muscle, respectively, compared with levels in eugonadal men, while phosphorylated AMPKα was lower by 22% and 28%, respectively. Following testosterone replacement, the expression of AMPKα did not alter in the fasting state but increased markedly by 41% and 46% in adipose tissue and muscle, respectively, after the clamp. In contrast, phosphorylated AMPKα increased by 69% in muscle after testosterone therapy but did not change following the clamp. CONCLUSIONS: Testosterone modulates the expression of AMPKα and phosphorylated AMPKα. These effects may contribute to the improved insulin sensitivity following testosterone therapy.

Acute effects of insulin on skeletal muscle growth and differentiation genes in men with type 2 diabetes.

AIMS: Insulin has anabolic effects on skeletal muscle. However, there is limited understanding of the molecular mechanisms underlying this effect in humans. We evaluated whether the skeletal muscle expression of satellite cell activator fibroblast growth factor 2 (FGF2) and muscle growth and differentiation factors are modulated acutely by insulin during euglycemic-hyperinsulinemic clamp (EHC). DESIGN AND METHODS: This is a secondary investigation and analysis of samples obtained from a previously completed trial investigating the effect of testosterone replacement in males with hypogonadotropic hypogonadism and type 2 diabetes. Twenty men with type 2 diabetes underwent quadriceps muscle biopsies before and after 4 h of EHC. RESULTS: The infusion of insulin during EHC raised the expression of myogenic growth factors, myogenin (by 72 ± 20%) and myogenin differentiation protein (MyoD; by 81 ± 22%). Insulin reduced the expression of muscle hypertrophy suppressor, myogenic regulatory factor 4 (MRF4) by 34 ± 14%. In addition, there was an increase in expression of FGF receptor 2, but not FGF2, following EHC. The expression of myostatin did not change. CONCLUSIONS: Insulin has an acute potent effect on expression of genes that can stimulate muscle differentiation and growth.

Severe Symptomatic Hypocalcemia from HIV Related Hypoparathyroidism.

We report the case of a 54-year-old Caucasian female who presented with a two-year history of persistent hypocalcemia requiring multiple hospitalizations. Her medical history was significant for HIV diagnosed four years ago. She denied any history of prior neck surgery or radiation. Her vital signs were stable with an unremarkable physical exam. Pertinent medications included calcium carbonate, vitamin D3, calcitriol, efavirenz, emtricitabine, tenofovir disoproxil, hydrochlorothiazide, and inhaled budesonide/formoterol. Laboratory testing showed total calcium of 5.7 mg/dL (normal range: 8.4-10.2 mg/dL), ionized calcium of 2.7 mg/dL (normal range: 4.5-5.5 mg/dL), serum phosphate of 6.3 mg/dL (normal range: 2.7-4.5 mg/dL), and intact PTH of 7.6 pg/mL (normal range: 15-65 pg/mL). She was diagnosed with primary hypoparathyroidism. Anti-calcium-sensing receptor antibodies and NALP5 antibodies were tested and found to be negative. During subsequent clinic visits, doses of calcium supplements and calcitriol were titrated. Last corrected serum calcium level was 9.18 mg/dL. She was subsequently lost to follow-up. This case gives insight into severe symptomatic hypocalcemia from primary hypoparathyroidism attributed to HIV infection. We suggest that calcium levels should be closely monitored in patients with HIV infection.

Elevated Intraocular Pressure in Patients Undergoing Penetrating Keratoplasty and Descemet Stripping Endothelial Keratoplasty.

PURPOSE: Our aim was to compare changes in intraocular pressure (IOP) and management of glaucoma in patients undergoing either penetrating keratoplasty (PK) or Descemet stripping endothelial keratoplasty (DSEK). METHOD: A retrospective review of all patients who underwent primary corneal transplantation at Sydney Eye Hospital (Sydney, Australia) from January 2008 to December 2010 was performed. Eyes with comparable indications and either primary PK or DSEK with 12 months of follow-up were included. Data on IOP and antiglaucoma management postoperatively were collected. An IOP elevation of ≥30% from baseline or an absolute IOP of >24 at 1 year postoperatively was significant. RESULTS: Sixty-one eyes from 61 patients met the inclusion criteria. Comparable eyes had undergone either PK (n=28, 46%) or DSEK (n=33, 54%). In patients without prior glaucoma (n=39), 29% of those in the PK group and 28% in the DSEK group required a change in therapy to control IOP (P=0.970). If there was prior glaucoma (n=22), the PK group required a change in 71% of patients compared with the DSEK group, 63% (P=0.665). In both groups of patients, PK and DSEK, elevation of IOP of at least 30% from baseline to 1 year was seen in 39% (P=0.993) regardless of glaucoma status. CONCLUSIONS: Elevation of IOP is a serious consequence of both PK and DSEK, even despite maximal medical therapy in certain cases. DSEK has an equivalent incidence of IOP elevation to PK in comparable patients. Careful monitoring of IOP and appropriate therapy should be instituted to prevent progression to glaucoma.

Road Map for Opioid Management in the Inpatient Setting: A Structured Approach to Opioid Selection and Titration.

INTRODUCTION: Effective pain management is a major challenge of medicine as patients with acute and chronic pain conditions require careful evaluation and treatment. Despite required pain management education in postgraduate training, effective pain management is often not achieved in the hospital setting. For example, the Accreditation Council for Graduate Medical Education in 2007 required internal medicine residencies to include instruction on pain management. However, studies have demonstrated a lack of pain management knowledge in trainees in pediatrics, neurology, internal medicine, and family practice. This includes a lack of basic skills in pain assessment, knowledge of narcotic pain medication pharmacology, and management of patients with pain at the end of life. METHODS: We developed the Road Map for Opioid Management in the Inpatient Setting as an instructional method via a PowerPoint-based slide show to guide clinicians on the thought process for opioid selection and titration. We include opioid conversion cards, additional resources, questions for self-efficacy and knowledge pre- or postassessment, and a posttest. Our educational intervention was successful. RESULTS: After initial training, over 60% of learners (i.e., residents, fellows, and other health care professionals) felt confident or extremely confident in each of the following: choosing an opioid for patients with renal failure, determining when to dilute naloxone for opioid reversal, converting fentanyl patch to fentanyl drip, and determining which pain scale to use for nonverbal patients with dementia. DISCUSSION: Our instructional program is an organized and effective tool to provide education for opioid management to clinicians.

Insulin Resistance and Inflammation in Hypogonadotropic Hypogonadism and Their Reduction After Testosterone Replacement in Men With Type 2 Diabetes.

OBJECTIVE: One-third of men with type 2 diabetes have hypogonadotropic hypogonadism (HH). We conducted a randomized placebo-controlled trial to evaluate the effect of testosterone replacement on insulin resistance in men with type 2 diabetes and HH. RESEARCH DESIGN AND METHODS: A total of 94 men with type 2 diabetes were recruited into the study; 50 men were eugonadal, while 44 men had HH. Insulin sensitivity was calculated from the glucose infusion rate (GIR) during hyperinsulinemic-euglycemic clamp. Lean body mass and fat mass were measured by DEXA and MRI. Subcutaneous fat samples were taken to assess insulin signaling genes. Men with HH were randomized to receive intramuscular testosterone (250 mg) or placebo (1 mL saline) every 2 weeks for 24 weeks. RESULTS: Men with HH had higher subcutaneous and visceral fat mass than eugonadal men. GIR was 36% lower in men with HH. GIR increased by 32% after 24 weeks of testosterone therapy but did not change after placebo (P = 0.03 for comparison). There was a decrease in subcutaneous fat mass (-3.3 kg) and increase in lean mass (3.4 kg) after testosterone treatment (P < 0.01) compared with placebo. Visceral and hepatic fat did not change. The expression of insulin signaling genes (IR-ß, IRS-1, AKT-2, and GLUT4) in adipose tissue was significantly lower in men with HH and was upregulated after testosterone treatment. Testosterone treatment also caused a significant fall in circulating concentrations of free fatty acids, C-reactive protein, interleukin-1ß, tumor necrosis factor-α, and leptin (P < 0.05 for all). CONCLUSIONS: Testosterone treatment in men with type 2 diabetes and HH increases insulin sensitivity, increases lean mass, and decreases subcutaneous fat.

Addition of Liraglutide to Insulin in Patients With Type 1 Diabetes: A Randomized Placebo-Controlled Clinical Trial of 12 Weeks.

OBJECTIVE: To investigate whether addition of three different doses of liraglutide to insulin in patients with type 1 diabetes (T1D) results in significant reduction in glycemia, body weight, and insulin dose. RESEARCH DESIGN AND METHODS: We randomized 72 patients (placebo = 18, liraglutide = 54) with T1D to receive placebo and 0.6, 1.2, and 1.8 mg liraglutide daily for 12 weeks. RESULTS: In the 1.2-mg and 1.8-mg groups, the mean weekly reduction in average blood glucose was -0.55 ± 0.11 mmol/L (10 ± 2 mg/dL) and -0.55 ± 0.05 mmol/L (10 ± 1 mg/dL), respectively (P < 0.0001), while it remained unchanged in the 0.6-mg and placebo groups. In the 1.2-mg group, HbA1c fell significantly (-0.78 ± 15%, -8.5 ± 1.6 mmol/mol, P < 0.01), while it did not in the 1.8-mg group (-0.42 ± 0.15%, -4.6 ± 1.6 mmol/mol, P = 0.39) and 0.6-mg group (-0.26 ± 0.17%, -2.8 ± 1.9 mmol/mol, P = 0.81) vs. the placebo group (-0.3 ± 0.15%, -3.3 ± 1.6 mmol/mol). Glycemic variability was reduced by 5 ± 1% (P < 0.01) in the 1.2-mg group only. Total daily insulin dose fell significantly only in the 1.2-mg and 1.8-mg groups (P < 0.05). There was a 5 ± 1 kg weight loss in the two higher-dose groups (P < 0.05) and by 2.7 ± 0.6 kg (P < 0.01) in the 0.6-mg group vs. none in the placebo group. In the 1.2- and 1.8-mg groups, postprandial plasma glucagon concentration fell by 72 ± 12% and 47 ± 12%, respectively (P < 0.05). Liraglutide led to higher gastrointestinal adverse events (P < 0.05) and ≤1% increases (not significant) in percent time spent in hypoglycemia (<55 mg/dL, 3.05 mmol/L). CONCLUSIONS: Addition of 1.2 mg and 1.8 mg liraglutide to insulin over a 12-week period in overweight and obese patients with T1D results in modest reductions of weekly mean glucose levels with significant weight loss, small insulin dose reductions, and frequent gastrointestinal side effects. These findings do not justify the use of liraglutide in all patients with T1D.

A Prospective Randomized Study Comparing Non-absorbable Polypropylene (Prolene®) and Delayed Absorbable Polyglactin 910 (Vicryl®) Suture Material in Mass Closure of Vertical Laparotomy Wounds.

Wound dehiscence is a postoperative complication encountered following abdominal surgery. A prospective randomized study was conducted to compare the incidence of wound dehiscence with a delayed absorbable and a nonabsorbable suture material in the mass closure of vertical laparotomy wounds. In one group, 100 patients were analyzed after closure with Prolene®, and in another group, 100 patients were analyzed after closure with Vicryl®. The incision was closed by continuous far and near suture technique using polypropylene (Prolene) suture in one group and a synthetic delayed absorbable polyglactin 910 (Vicryl) suture in the other group. There was significant difference in the incidence of wound dehiscence between the two groups: 6 % with Prolene and 17 % with Vicryl, (χ (2) = 5.944, 1 DF, P value = 0.0148). The overall incidence of wound dehiscence was 11.5 % in this study. The incidence of wound dehiscence in both the study groups was higher than expected as compared to previous literature. There was a significant difference between the two suture materials. In our study, Prolene is a better suture material for closure of vertical laparotomy wounds.

Pneumobilia After Penetrating Trauma Abdominal Wall with no Injury to the Biliary Tree- A Case Report.

Pneumobilia denotes an abnormal connection between the gastrointestinal and the biliary tracts. In the absence of surgically created anastomosis between the bowel and the bile duct, the common causes for pneumobilia are gallstone obstruction, endoscopic interventions or emphysematous cholecystitis. We present the case of a young male with traumatic pneumobilia with gastric perforation and a tear in the mesentery of the small gut following penetrating trauma in the form of stab in the abdomen.