BACKGROUND Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. OBJECTIVES In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. METHODS ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3–74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2–111.0 mg/dL). RESULTS In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [Cl]: 0.52–0.90) and 1.11 (95% Cl: 0.83–1.49), with treatment-lipoprotein(a) interaction on MACE ( P interaction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% Cl: 0.72–0.92) and 0.89 (95% Cl: 0.75–1.06), with P interaction = 0.43. CONCLUSIONS In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402 )

Surface plays a crucial role in biological interactions. Surface treatments have been applied to metallic biomaterials in order to improve their wear properties, corrosion resistance, and biocompatibility. A systematic review was performed on studies investigating the effects of implant surface treatments on biocompatibility. We searched the literature using PubMed, electronic databases from 1990 to 2009. Key words such as implant surface topography, surface roughness, surface treatment, surface characteristics, and surface coatings were used. The search was restricted to English language articles published from 1990 to December 2009. Additionally, a manual search in the major dental implant journals was performed. When considering studies, clinical studies were preferred followed by histological human studies, animal studies, and in vitro studies. A total of 115 articles were selected after elimination: clinical studies, 24; human histomorphometric studies, 11; animal histomorphometric studies, 46; in vitro studies, 34. The following observations were made in this review: · The focus has shifted from surface roughness to surface chemistry and a combination of chemical manipulations on the porous structure. More investigations are done regarding surface coatings. · Bone response to almost all the surface treatments was favorable. · Future trend is focused on the development of osteogenic implant surfaces. Limitation of this study is that we tried to give a broader overview related to implant surface treatments. It does not give any conclusion regarding the best biocompatible implant surface treatment investigated till date. Unfortunately, the eventually selected studies were too heterogeneous for inference of data.

This report demonstrates the clinical use of a modified, truly anatomic, root analogue zirconia implant for immediate replacement of a right mandibular first premolar. A 22-year-old female patient with chronic apical periodontitis of the right mandibular first premolar was referred and the tooth was carefully extracted. A truly anatomical, root identical, roughened zirconia implant modified by macro-retentions was manufactured and placed into the extraction socket by tapping 3 days later. After 4 months a composite crown was cemented in place. No complications occurred during the healing period. A good functional and aesthetic result was achieved with minimal bone resorption and soft tissue recession at 18 months follow-up. This report describes the successful clinical use of an immediate, single stage, truly anatomical root-analogue zirconia implant for replacement of a single rooted tooth. Significant modifications such as macro-retentions yielded primary stability and excellent osseointegration. This novel approach is minimally invasive, respects the underlying anatomy and aids socket prevention. In addition the procedure saves time and cost, has good patient acceptance as there is no need for osteotomy, sinus lift or bone augmentation.

Pseudoaneurysms of the branches of the external carotid artery as a result of trauma are rare in oral and maxillofacial surgery practice. The most affected branches are the superficial temporal artery, internal maxillary artery and distal part of facial artery, usually where they pass over the bone. Very few cases of facial artery pseudoaneurysms of proximal parts (from external carotid artery up to the lower border of the mandible) are reported in the literature. We present a review of literature for management of late post-traumatic pseudoaneurysmal cyst and a case report involving proximal part of facial artery in the submandibular region following open reduction and rigid fixation of the condylar fracture in a 25-year-old male. To our knowledge this is the fourth reported case of proximal facial artery pseudoaneurysm.

Diabetes mellitus was considered a fatal malady until the discovery, extraction and commercial availability of insulins. Numerous other classes of drugs ranging from sulfonylureas to sodium‐glucose co‐transporter‐2 inhibitors were then marketed. However, with the prevalence of diabetes mellitus increasing every year, many more drugs and therapies are under investigation. This review article aimed to summarize the significant developments in the pharmacotherapy of diabetes mellitus and outline the progress made by the recent advances, 100 years since insulins were first extracted successfully. Insulin analogues and insulin delivery pumps have further improved glycaemic control in diabetes mellitus. Cardiovascular and renal outcome trials have changed the landscape of diabetology, with some of these drugs also efficacious in nondiabetics. Newer drug delivery systems are being evaluated to improve the efficacy and reduce the dosing frequency and adverse effects of antidiabetics. Some newer drugs with novel mechanisms of action targeting type 1 and type 2 diabetes have also shown promise in recent clinical trials. These drugs include dual glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide 1‐agonists, glucokinase activators, anti‐CD3 monoclonal antibodies and glimins. Their efficacy needs to be evaluated in larger studies.

Aims:To study anti-ulcer effect of Amlodipine and compared it with ranitidine in indomethacin, alcohol and pyloric ligation-induced gastric ulcers in wistar rats.Materials and Methods:Gastric ulcers were induced in Wistar albino rats by oral administration of indomethacin (200 mg/kg), alcohol (80%, 1 ml/100 gm) and by pyloric ligation. Antiulcer activity of amlodipine (0.5 mg/kg, i.p.) was observed either alone or in combination with ranitidine (15 mg/kg, i.p.), on ulcer index, gastric pH and gastric volume. Statistical analysis was done by ANOVA and unpaired one tailed ‘t‘ test. P<0.05 was considered statistically significant.Results:Amlodipine produced significant (P<0.05) decrease in ulcer index and gastric pH as compared to control. It also produced significant (P<0.05) increase in gastric volume as compared to ranitidine. The anti-ulcer effects of ranitidine were significantly higher than that of amlodipine. Combination of amlodipine and ranitidine did not show significant increase in anti-ulcer activity as compared with ranitidine alone.Conclusions:Amlodipine produced significant anti-ulcer effects in all 3 experimental models. Amlodipine increased the volume of gastric secretions as compared to ranitidine.

Background: Many adverse drug reactions (ADRs), interactions and specific toxicities are known once drug is exposed to a larger population. Spontaneous reporting adverse events (AEs) are fundamental to a robust pharmacovigilance (PhV). Increasing physician awareness about the pharmacovigilance and ADR reporting can significantly contribute the safety of medicines. Objective of the study was to assess the knowledge, attitude and practices related to PhV among medical professionals at a tertiary care teaching hospital.Methods: Postgraduate students (PGs) and medical teachers at a Medical College and tertiary care hospital were evaluated for their knowledge, attitude and practice of pharmacovigilance with the help of a structured questionnaire. Suggestions for improving the effectiveness of the pharmacovigilance practices were also sought.Results: One-hundred and fifty doctors [91 (60.7%) PGs and 59 (39.3%) medical teachers] participated. Overall, 48.7% were males. 96% believed that PhV is important in medical practice but only 79.3% knew the definition of pharmacovigilance. Only 24.7% were aware of the existing nationwide pharmacovigilance program whereas the international collaborating center was known to 26% of the participants. 96% believed that it is the duty of a treating physician to report an ADR while 36.7% felt that ADR reporting should be the responsibility of a separate team. Surprisingly, 54% felt that financial aid should be provided for ADR reporting. 42.7% have not reported any ADR whilst only 16% have reported more than 10 ADRs in their career. To create an ADR database (79.3%) was the common expectation from the PhV center. 98.7% suggested continued medical education (CME) and trainings to improve the effectiveness of PhV in Indian setting.Conclusions: Regardless of a fair attitude towards PhV, the practice of ADR reporting is poor probably because of lack of sufficient knowledge about PhV. Motivating the physicians through CMEs and trainings so as to improve and strengthen the pharmacovigilance practices is the current need in India.

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