Oral apremilast in the treatment of active psoriatic arthritis: results of a multicenter, randomized, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and safety of apremilast, a novel, orally available small molecule that specifically targets phosphodiesterase 4, in the treatment of active psoriatic arthritis (PsA). METHODS: This phase II, multicenter, randomized, double-blind, placebo-controlled study included the following: a 12-week treatment phase, with patients receiving placebo, apremilast 20 mg twice per day, or apremilast 40 mg once per day; a 12-week treatment-extension phase, with patients in the placebo group re-randomized to receive apremilast; and a 4-week observational phase after treatment cessation. The primary end point was the proportion of patients achieving the American College of Rheumatology criteria for 20% improvement (ACR20) at week 12. Safety assessments included adverse events (AEs), physical examinations, vital signs, laboratory parameters, and electrocardiograms. RESULTS: Of the 204 patients with PsA who were randomized to a treatment group, 165 completed the treatment phase. At the end of the treatment phase (week 12), 43.5% of patients receiving apremilast 20 mg twice per day (P < 0.001) and 35.8% of those receiving 40 mg once per day (P = 0.002) achieved an ACR20 response, compared with 11.8% of those receiving placebo. At the end of the treatment-extension phase (week 24), >40% of patients in each group (patients receiving apremilast 20 mg twice per day, patients receiving apremilast 40 mg once per day, and patients in the placebo group re-randomized to receive apremilast) achieved the ACR20 level of improvement. Most patients in the treatment phase (84.3%) and treatment-extension phase (68.3%) reported ≥ 1 AE. Diarrhea, headache, nausea, fatigue, and nasopharyngitis were reported most frequently; most events were mild or moderate. No clinically relevant laboratory or electrocardiographic abnormalities were reported. CONCLUSION: Treatment with apremilast at a dosage of 20 mg twice per day or 40 mg once per day demonstrated efficacy in comparison with placebo and was generally well tolerated in patients with active PsA. The balance of efficacy, tolerability, and safety supports further study of apremilast in PsA.

A clinicopathological study on management of diabetic foot ulcer in tertiary care centre.

INTRODUCTION: Diabetes is a disease in which the body's ability to produce or respond to the hormone insulin is impaired, resulting in abnormal metabolism of carbohydrates and elevated levels of glucose in the blood. India being the Diabetes Capital of the World has a Prevalence of 65.1 million suffering from DM of the Entire Indian Population being 1.33 billion of Worlds 6 billion people. This states that almost half of the Indian Population will sometime in their life be detected with Diabetes Almost 15-20 % of the population suffering from Diabetes are seen to have Diabetic Foot Ulcer at least once in their lifetime. It is also been noted that 10-15 % of patients suffering from Diabetic Foot Ulcer require Expert Management or Multi Disciplinary Approach. Diabetic foot ulcers have many pathogenic mechanisms, These risk factors are as follows: gender (male), duration of diabetes longer than 10 years, advanced age of patients, high Body Mass Index and other co-morbidities such as retinopathy, diabetic peripheral neuropathy, peripheral vascular disease, high glycated haemoglobin level (HbA1C), foot deformity, high plantar pressure, infections and inappropriate foot selfcare habits. Rough estimates are at about 1,00,000 lower limbs are amputated in India every year, of which at least seventy-five percent are neuropathic feet with secondary infections and are potentially preventable.

Transdermal fentanyl improves pain control and functionality in patients with osteoarthritis: an open-label Canadian trial.

Current treatment guidelines advocate opioids for arthritis when standard analgesics produce inadequate relief. Efficacy, adverse effects (AEs), dosing regimens, physician expertise and patient preference influence treatment selection. This study assessed transdermal fentanyl (TDF) as a treatment option for osteoarthritis (OA) patients. This prospective, Canadian open-label, 8-week trial assessed the efficacy and safety of TDF in patients with OA of hip or knee with moderate-to-severe target joint pain inadequately controlled using weak opioids. TDF was initiated at 25 mcg/h and titrated to optimal pain control. Rescue acetaminophen 500 mg was allowed (maximum 4 g/day). The main endpoint was improvement in pain control assessment rating (five rating categories); pain intensity (0-10 numerical scale), functionality (WOMAC-OA Index), health-related quality of life (SF-36 Health Survey) and global impression were also evaluated. Eighty-one patients (61% female, mean age 60 years) were enrolled; 62 were evaluable. All had failed on previous weak opioid therapy, primarily codeine or codeine combinations. At treatment end, 65% rated pain control as improved (Pain Control Assessment rating change >or=1 category; p<0.0001); mean change in pain intensity was a reduction of greater than 2 (p<0.0001); almost 50% were maintained on TDF 25 mcg/h with less than 1.3 g/day of rescue acetaminophen. At 1 month and end of treatment, changes in the SF-36 physical global scale and individual sub-scores for the pain index and role-physical scales were highly significant (p<0.0001). Improvement in functionality was noted at 1 month and at end of treatment with significant reductions in total WOMAC score, individual pain, stiffness and physical function sub-scores (p<0.0001). AEs causing discontinuation (n=32) included nausea, dizziness and vomiting. Most treatment-related AEs were mild to moderate in intensity. TDF improved pain control, functionality and health-related quality of life in these patients. The findings support current recommendations for use of opioids such as TDF as a treatment option for a sub-population of patients with OA pain.

Efficacy and tolerability of valdecoxib in treating the signs and symptoms of severe rheumatoid arthritis: a 12-week, multicenter, randomized, double-blind, placebo-controlled study.

OBJECTIVE: This study compared the efficacy and tolerability of the cyclooxygenase-2-selective inhibitor valdecoxib with the nonselective NSAID naproxen and with placebo in treating severe rheumatoid arthritis (RA). METHODS: This 12-week, multicenter, randomized, double-blind, placebo-controlled study compared the efficacy and tolerability of valdecoxib 10 mg QD (n = 170) or naproxen 500 mg BID (n = 167) with placebo (n = 171) in treating the signs and symptoms of severe RA. Study patients were aged >or=18 years and were diagnosed as having RA for >or=6 months that was stable due to a treatment regimen. Severe RA was defined as a physician's and patient's global assessment of disease activity of fair, poor, or very poor at baseline; >or=6 tender or painful joints; >or=3 swollen joints; >or=45 minutes of morning stiffness; a visual analog scale pain rating of >or=40 mm; or increases since baseline in these measures. Efficacy outcome measures included the percentage of patients achieving an American College of Rheumatology Responder Index 20% (ACR-20) at weeks 1, 6 and 12. Adverse events (AEs) were graded by the investigator as mild, moderate, or severe at weeks 1, 6, and 12. RESULTS: Of the 508 patients randomized, 340 completed the study. The study groups were comparable for age, ethnic origin, weight, height, and concomitant medications, but the naproxen group had significantly more men (29% [49/167]) than the valdecoxib (18% [31/170]) and placebo (16% [27/171]) groups. The percentage of patients achieving an ACR-20 response was significantly greater in the valdecoxib and naproxen treatment groups (58.8% [100/170] and 60.8% [101/166], respectively) than in the placebo group (39.6% [67/169]) at week 12 (both, P < 0.001). The percentage of patients achieving an ACR-20 response was significantly greater in the naproxen group than in the placebo group at both week 1 (53.6% [89/166] vs 37.9% [64/169]; P = 0.003) and week 6 (64.5% [107/166] vs 46.7% [79/169]; P = 0.001), and in the valdecoxib group compared with placebo at week 1 (52.9% [90/170]; P = 0.008) but not at week 6. Patients in the valdecoxib and naproxen groups had significantly improved efficacy compared with placebo in most of the other secondary assessments of inflammation, pain, and function. The incidence of AEs was similar in all groups (valdecoxib, 54.1% [92/170]; naproxen, 55.4% [92/166]; and placebo, 52.9% [90/170]). CONCLUSION: Valdecoxib 10 mg QD administered over 12 weeks was significantly better than placebo and similar to naproxen 500 mg BID in treating the signs and symptoms of severe RA in these patients.

A comparison of the analgesic efficacy of Tramadol Contramid OAD versus placebo in patients with pain due to osteoarthritis.

One thousand twenty-eight (1,028) patients with pain due to osteoarthritis (OA) of the knee were enrolled in this multicenter, randomized, double-blind, parallel study designed to assess the analgesic efficacy and safety of Tramadol Contramid OAD compared to placebo. An open-label phase was followed by a double-blind phase, in which a total of 646 patients were randomized to double-blind treatment with placebo or Tramadol Contramid OAD. Patients were titrated to their optimal dose (200mg or 300 mg), which was maintained for 12 weeks. An absolute mean reduction of 3.0+/-2.1 on a Pain Intensity Numerical Rating Scale (PI-NRS) was noted in the Tramadol Contramid OAD treatment group. The difference between active and placebo groups regarding this absolute mean reduction was statistically significant (P<0.001) throughout the study. The responder analysis demonstrated that a significantly greater percentage of patients in the active treatment arm achieved a reduction of >or=1 and >or=2 points on the PI-NRS score by the end of the study (P=0.035). A significantly greater percentage of respondents in the Tramadol Contramid OAD group indicated improvement on both the Patient and Physician Global Impressions of Change (P=0.0002). Both the 200mg and 300 mg doses contributed to the overall superiority of Tramadol Contramid OAD. The most frequent adverse events were consistent with the known side effects of tramadol and were generally mild to moderate in intensity. These results confirm that Tramadol Contramid OAD given once daily is an efficacious and safe treatment for pain due to OA.

Incidence and Management of Infusion Reactions to Infliximab in a Prospective Real-world Community Registry.

OBJECTIVE: Infliximab (IFX) is a therapeutic monoclonal antibody targeting tumor necrosis factor-α indicated in the treatment of chronic inflammatory diseases. IFX is administered by intravenous infusion and may be associated with different types of infusion reactions. METHODS: RemiTRAC Infusion (NCT00723905) is a Canadian observational registry in which patients receiving IFX are followed prospectively to document premedication use, adverse events, infusion reactions, and the management of infusion reactions. The primary endpoint was to assess factors associated with infusion reactions. RESULTS: There were 1632 patients enrolled and 24,852 infusions recorded. Most patients (63.1%) were treated for rheumatologic conditions such as rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis. Of the 1632 patients, 201 (12.3%) reported at least 1 infusion reaction. Three hundred twenty-two infusions were associated with an infusion reaction (1.3%), and most were mild to moderate in severity (95%). The most common infusion reactions were pruritus (19.9%), flushing (9.9%), or dyspnea (6.2%). Multivariate analysis showed that antihistamines premedication, number of previous infusion reactions, and female sex were significantly associated with an increased incidence of infusion reactions (p < 0.0011). The use of any concomitant immunosuppressant or corticosteroids did not influence the incidence of infusion reactions. Antihistamine premedication was associated with an increased incidence of infusion reactions (OR 1.58, p = 0.0007). CONCLUSION: This registry shows that in community-based infusion clinics, infusion reactions to IFX are uncommon and mild to moderate in nature. Antihistamines, intravenous steroids, and acetaminophen are widely used as preventative premedication, although this study showed an absence of benefit with their use.

Use of corticosteroids in patients with rheumatoid arthritis treated with infliximab: treatment implications based on a real-world Canadian population.

OBJECTIVE: To describe the rate of concomitant oral corticosteroid use at antitumour necrosis factor (TNF) initiation and at disease remission, and to assess its effect on incidence of infection and sustainability of remission among patients with rheumatoid arthritis (RA) treated with infliximab in Canadian routine care. METHODS: Biological naïve patients with RA followed in the Biologic Treatment Registry Across Canada (BioTRAC) were included. The time-dependent association between corticosteroid dose (no use, ≤5 mg/day, >5 mg/day) and the incidence of first infection, while considering possible confounders, remission sustainability and the incidence of subsequent infections were assessed with Cox regression. RESULTS: 838 patients were included; mean (SD) baseline age and disease duration were 55.6 (13.5) and 10.5 (9.8) years, respectively. After a mean (SD) of 51.3 (43.6) months, the total incidence of adverse events (AEs) and infections were 110.2 and 19.6 per 100 person-years (PY), respectively. In multivariate analysis, the HR (95% CI) for acquiring an infection was 2.48 (1.24 to 4.98) with >5 mg/day of corticosteroids versus no corticosteroids. Similarly, ≤5 mg/day of corticosteroids was associated with increased hazard for infection (2.12 (0.97 to 4.66)). Despite DAS28 (disease activity score 28) or Clinical Disease Activity Index (CDAI) remission, corticosteroids were continued in 16.4% and 16.7% of cases, respectively. Continued corticosteroid treatment was not associated with sustainability of remission (HRDAS28 (95% CI) 1.40 (0.95 to 2.06); HRCDAI 1.19 (0.75 to 1.88)), however, it had a significant impact on development of infection (HRDAS28 (95% CI) 1.78 (1.00 to 3.19); HRCDAI 2.38 (1.14 to 4.99)). CONCLUSIONS: Oral corticosteroid treatment was associated with increased risk of development of infection without impacting sustainability of remission. These results support the notion that corticosteroids should be used concomitantly with anti-TNF for the shortest period possible to achieve remission, and then tapered. TRIAL REGISTRATION NUMBER: NCT00741793.

A rare instance of retrosternal goitre presenting with obstructive sleep apnoea in a middle-aged person.

INTRODUCTION: In endemic goitre areas, 20% of the population over 70 will have retrosternal goitre.(12) Obstructive sleep apnoea (OSA) occurs when there are repeated episodes of complete or partial blockage of the upper airway during sleep. PRESENTATION OF CASE: A 55-year-old man was being treated for obstructive sleep apnoea, came with stridor worsening over the 2 and was advised CPAP ventilation. In our institution, he was diagnosed to have goitre with retrosternal extension with no hypo/hyperthyroidism. He was an obese (BMI - 30Kg/m(2)) male with a short, broad neck and clinically no obvious swelling in the neck. He had stridor, with positive Kocher's test as well as Pemberton's sign. His TFT's were normal and CT scan revealed widening of superior mediastinum. Patient was pre-medicated with low dose (0.1µg) fentanyl, and induced with inhalational anaesthesia (sevoflourane). Endotracheal intubation was done using 6 no. ET tube, without muscle relaxation, and the thyroid was removed through a conventional Kocher's incision. Thyroid was enlarged 25cm by 10cm in retrosternal position. Postoperatively, pt was reversed and shifted to ICU, was monitored for the next 24hours. He was extubated uneventfully the next morning. Patient had a good post-op recovery and was discharged on the 7th post-op day. DISCUSSION: Terms such as retrosternal, substernal, intrathoracic, or mediastinal have been used to describe a goitre that extends beyond the thoracic inlet. However, there is a lack of consensus regarding the exact definition of a retrosternal goitre (RSG).(1) The majority of patients present with shortness of breath or asthma like symptoms (68.8%), as was the case in the studied patient. Other modes of presentation include neck mass (75%), hoarseness of voice (37.5%), dysphagia (31.3%), stridor/wheezing (19%), or SVC obstruction. Upper airway obstruction due to thyroid gland has been reported up to 31%(2) and difficulty in intubation has been reported in 11%.(3) Central airway obstruction produces symptoms of dyspnoea, stridor, or obstructive pneumonia and is often misdiagnosed as asthma.(4) The CT scan was the most useful tool showing the nature and extent of the lesion in the reported case. In a recent publication, the CT scan was considered the gold-standard preoperative radiological investigation.(5) Surgery is the only effective treatment for retrosternal goitres. In most cases, suppressive therapy with thyroxine is ineffective in reducing the size of multinodular goitres;(7,8) radio-iodine therapy is both generally ineffective in large goitres(8) and may induce acute inflammation and swelling of the gland with the potential for airway obstruction. The operation of choice is usually a total thyroidectomy. Only around 2% of patients undergoing thyroidectomy for retrosternal goitre will require surgical access other than a standard collar incision (either manubriotomy, sternotomy or thoracotomy).(9) CONCLUSION: Despite all the advances in investigative modalities, retrosternal goitre still exists in 20% of patients over 70 years in endemic regions. It has to be recognised that it can be a cause of obstructive sleep apnoea. Early detection and prompt management goes a long way in decreasing the morbidity and mortality in patients with RSG.

Modified Technique of Mesh Hepatorrhaphy for Management of Juxtahepatic Venous Injury in a Case of Blunt Liver Trauma: A Case Report.

The liver is the most frequently injured organ in cases of blunt abdominal trauma. Injuries to the caudate lobe are rarely isolated and usually associated with retrohepatic caval injury or hepatic vein injury. The management of the associated vascular injuries is usually difficult owing to the short courses of the hepatic veins and the difficulty in obtaining proximal and distal control of the suprarenal and suprahepatic inferior vena cava - hence the frequency of perihepatic packing in the management of caudate lobe and hepatic venous injuries. We present here a rare case of the failure of perihepatic packing to effectively control hemorrhage from blunt injury to the caudate lobe and retrohepatic vena cava. A case of blunt abdominal trauma with injury to the caudate lobe and retrohepatic venous injury was initially managed with perihepatic packing. The patient developed hemorrhage 48 h after pack removal, which was then successfully managed with mesh hepatorrhaphy of the caudate lobe.

Filarial granuloma of the testicular tunic mimicking a testicular neoplasm: a case report.

INTRODUCTION: Any firm or solid intratesticular mass on examination and/or any hypoechoic area within the tunica albuginea on imaging is markedly suspicious for testicular cancer. Filarial involvement of the testicular tunic has not been reported previously. CASE PRESENTATION: A 32-year-old man presented with a history of noticing a swelling in his right testicle for a period of 1 month which had become painful over the 10 days before presentation. Pre-operative imaging failed to shed light on the nature of the lesions (malignant or benign). The diagnostic dilemma was explained to the patient and informed consent was obtained for an orchiectomy. The patient underwent a high inguinal orchiectomy. The histopathology revealed a filarial granuloma of the testicular tunic. CONCLUSION: While it is generally regarded that any testicular swelling, especially in a young person, should be treated as a malignancy unless proven otherwise, it is important to remember that infectious diseases such as filariasis and tuberculosis may mimic neoplasms. Careful consideration of these diagnoses must be given when dealing with testicular swellings especially in areas where the prevalence of these diseases is high.

Comparison of APACHE II and Imrie Scoring Systems in predicting the severity of Acute Pancreatitis.

There has been an increasing amount of work worldwide in search for tests not only to be able to absolutely diagnose acute pancreatitis, but more importantly to prognosticate patients at admission. While the tests are still within the realm of research laboratories and involve complex computing and analytical methods, we believed that the already widely practiced methods of scoring needed to be verified in the Indian context. And, hence, the study.