Role of PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia

Patients with familial hypercholesterolemia (FH) are at high or very high risk for cardiovascular disease. Those with heterozygous FH (HeFH) often do not reach low-density lipoprotein cholesterol (LDL-C) targets with statin and ezetimibe therapy, and those with homozygous FH (HoFH) usually require additional lipid-modifying therapies. Drugs that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) offer a novel approach to reduce LDL-C. The monoclonal antibodies, alirocumab and evolocumab, given by subcutaneous injection every 2 or 4 weeks produce reductions in LDL-C of 50% to 60% in patients with HeFH, allowing many of them to achieve their LDL-C goals. Patients with HoFH show a reduced and more variable LDL-C response, which appears to depend on residual LDL receptor activity, and those with receptor-negative mutations may show no response. Inclisiran is a long-acting small interfering RNA therapeutic agent that inhibits the synthesis of PCSK9. Subcutaneous doses of 300 mg can reduce LDL-C by more than 50% for at least 6 months and the responses in HeFH and HoFH patients are similar to those achieved with monoclonal antibodies. These PCSK9 inhibitors are generally well tolerated and they provide a new opportunity for effective treatment for the majority of patients with FH.

Role of PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia

Patients with familial hypercholesterolemia (FH) are at high or very high risk for cardiovascular disease. Those with heterozygous FH (HeFH) often do not reach low-density lipoprotein cholesterol (LDL-C) targets with statin and ezetimibe therapy, and those with homozygous FH (HoFH) usually require additional lipid-modifying therapies. Drugs that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) offer a novel approach to reduce LDL-C. The monoclonal antibodies, alirocumab and evolocumab, given by subcutaneous injection every 2 or 4 weeks produce reductions in LDL-C of 50% to 60% in patients with HeFH, allowing many of them to achieve their LDL-C goals. Patients with HoFH show a reduced and more variable LDL-C response, which appears to depend on residual LDL receptor activity, and those with receptor-negative mutations may show no response. Inclisiran is a long-acting small interfering RNA therapeutic agent that inhibits the synthesis of PCSK9. Subcutaneous doses of 300 mg can reduce LDL-C by more than 50% for at least 6 months and the responses in HeFH and HoFH patients are similar to those achieved with monoclonal antibodies. These PCSK9 inhibitors are generally well tolerated and they provide a new opportunity for effective treatment for the majority of patients with FH.

Patient safety culture among medical students in Singapore and Hong Kong

<p><b>INTRODUCTION</b>Undergraduate education in medical schools plays an important role in promoting patient safety. Medical students from different backgrounds may have different perceptions and attitudes toward issues concerning safety. This study aimed to investigate whether patient safety cultures differed between students from two Asian countries, and if they did, to find out how they differed. This study also aimed to identify the educational needs of these students.</p><p><b>METHODS</b>A voluntary, cross-sectional and self-administered questionnaire survey was conducted on 259 students from two medical schools - one in Hong Kong and the other in Singapore. None of the students had received any formal teaching on patient safety. We used a validated survey instrument, the Attitudes to Patient Safety Questionnaire III (APSQ-III), which was designed specifically for students and covered nine key factors of patient safety culture.</p><p><b>RESULTS</b>Of the 259 students, 81 (31.3%) were from Hong Kong and 178 (68.7%) were from Singapore. The overall response rate was 66.4%. Significant differences between the two groups of students were found for two key factors - 'patient safety training', with Hong Kong students being more likely to report having received more of such training (p = 0.007); and 'error reporting confidence', which Singapore students reported having less of (p < 0.001). Both groups considered medical errors as inevitable, and that long working hours and professional incompetence were important causes of medical errors. The importance of patient involvement and team functioning were ranked relatively lower by the students.</p><p><b>CONCLUSION</b>Students from different countries with no prior teaching on patient safety may differ in their baseline patient safety cultures and educational needs. Our findings serve as a reference for future longitudinal studies on the effects of different teaching and healthcare development programmes.</p>

Two hundred endoscopic extraperitoneal inguinal hernioplasties: cost containment by reusable instruments / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To report our experience of 200 endoscopic totally extraperitoneal inguinal hernioplasties utilizing reusable instruments.</p><p><b>METHODS</b>Between August 1999 and June 2000, 200 endoscopic totally extraperitoneal hernioplasties were performed on 163 patients. The mean age of the study population was 63 years with a male to female ratio of 157:6. Perioperative details and postoperative outcomes were prospectively evaluated and analyzed.</p><p><b>RESULTS</b>A total of 196 (98%) endoscopic extraperitoneal inguinal hernioplasties were successfully performed. Conversion rates to transabdominal preperitoneal and open repairs were 1.5% (n = 3) and 0.5% (n = 1), respectively. There were no other intraoperative complications. Postoperative morbidity included retention of urine (n = 7), wound bruising (n = 2), atelectasis (n = 2) and gouty arthritis (n = 1). The mean visual analogue pain scores at rest were 2.3, 1.6 and 1.9 on postoperative days 0, 1 and 2, respectively. The mean length of hospital stay was 1.9 days. 113 patients (69%) returned to normal activities within one week. Of the 35 patients who experienced both open and laparoscopic repair, 80% expressed preference for endoscopic hernioplasty in the event of future recurrence.</p><p><b>CONCLUSIONS</b>Endoscopic extraperitoneal inguinal hernioplasty can be safely performed utilizing reusable trocars. Substantial reduction of operative cost could be achieved by the elimination of disposable instruments. Deficiencies of the reusable metallic trocar, namely peri-cannula air-leak and sliding movements of the trocar, can be overcome by purse-string suture of the fascial opening.</p>