The economic impact of cytomegalovirus infection after liver transplantation

BACKGROUND: We studied the economic impact of cytomegalovirus (CMV) disease and its effective reduction with antiviral prophylaxis in liver transplant recipients. METHOD: Analysis of institutional charge data accumulated during a prospective, randomized, controlled trial comparing oral acyclovir 800 mg four times daily for 120 days (ACV) and intravenous ganciclovir 5 mg/kg every 12 h for 14 days followed by ACV for 106 days (GCV) was performed. RESULTS: Liver transplant recipients who developed CMV disease had significantly higher charges (median: $148,300) than those who developed asymptomatic CMV infection ($119,600) or experienced no CMV infection ($114,100) (P<0.01). A multiple linear regression analysis indicated that CMV disease is associated with a 49% increase in charges, independent of other factors influencing increased hospitalization charges. In CMV-seronegative patients who received a CMV-seropositive donor organ, GCV prophylaxis was associated with a significant reduction in charges, as compared to ACV prophylaxis ($113,900 vs. $153,300, respectively; P=0.02). CONCLUSIONS: CMV disease is an independent risk factor for increased resource utilization associated with liver transplantation. The use of an effective prophylactic antiviral regimen provides savings in health care resources, particularly in patients at high risk for developing CMV disease.     

Innovation Experiences from Africa-Led Drug Discovery at the Holistic Drug Discovery and Development (H3D) Centre

As the so-called “next frontier” in global economic terms, Africa’s disease burden continues to choke and cripple economic growth across the continent. The highest burden is attributable to malaria and tuberculosis (TB), which also remain among the deadliest infectious diseases affecting mankind the world over (Malaria, 627,000 deaths; TB, 1.5 million deaths, in 2020). In achieving self-determination with respect to the health needs of all who live on the continent, Africa must align with global north efforts and be a source of health innovation. This will in part require the creation of an ecosystem of innovative pharmaceutical R&D and expanding it across the continent by scaling up through sustained performance and excellence. To this end, the Holistic Drug Discovery and Development (H3D) Centre at University of Cape Town in South Africa has risen to this challenge. Here, we highlight the innovation experiences gained at H3D, covering the advances made in our quest to contribute to a global pipeline of therapeutic interventions against malaria and TB. We discuss selected chemical series starting from their identification, structure–activity relationships, mode of action, safety, proof-of-concept studies, and lessons learned.     

Preclinical and first‐in‐human phase I studies of KW‐2450, an oral tyrosine kinase inhibitor with insulin‐like growth factor receptor‐1/insulin receptor selectivity

Numerous solid tumors overexpress or have excessively activated insulin‐like growth factor receptor‐1 (IGF‐1R). We summarize preclinical studies and the first‐in‐human study of KW‐2450, an oral tyrosine kinase inhibitor with IGF‐1R and insulin receptor (IR) inhibitory activity. Preclinical activity of KW‐2450 was evaluated in various in vitro and in vivo models. It was then evaluated in a phase I clinical trial in 13 patients with advanced solid tumors (NCT00921336). In vitro, KW‐2450 inhibited human IGF‐1R and IR kinases (IC₅₀ 7.39 and 5.64 nmol/L, respectively) and the growth of various human malignant cell lines. KW‐2450 40 mg/kg showed modest growth inhibitory activity and inhibited IGF‐1‐induced signal transduction in the murine HT‐29/GFP colon carcinoma xenograft model. The maximum tolerated dose of KW‐2450 was 37.5 mg once daily continuously; dose‐limiting toxicity occurred in two of six patients at 50 mg/day (both grade 3 hyperglycemia) and in one of seven patients at 37.5 mg/day (grade 3 rash). Four of 10 evaluable patients showed stable disease. Single‐agent KW‐2450 was associated with modest antitumor activity in heavily pretreated patients with solid tumors and is being further investigated in combination therapy with lapatinib/letrozole in patients with human epidermal growth factor receptor 2‐postive metastatic breast cancer.     

Peripancreatic Fat Invasion Is an Independent Predictor of Poor Outcome Following Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma

Background  

Following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC), identification of peripancreatic fat tumor invasion promotes a tumor to stage T3. We sought to understand better the impact of histological peripancreatic fat invasion on prognosis and site of recurrence in a cohort of patients with PDAC.     

Stapled diverticulectomy for solitary caecal diverticulitis

Caecal diverticulitis is an uncommon phenomenon in western countries. The clinical diagnosis is often difficult as it mimics other acute abdominal conditions like appendicitis, colitis or neoplasia. Diagnosis is often made at operation. Operative strategy has been controversial and there is no broad consensus emerging. We report the case of a 71-year-old woman, known to have chronic obstructive pulmonary disease, who presented acutely with right iliac fossa pain. A clinical diagnosis of appendicitis was made. At laparoscopy, a solitary, inflamed, gangrenous caecal diverticulum was found. A laparoscopic stapled diverticulectomy was performed. The patient made a steady post-operative recovery. Histology confirmed diverticulitis. We conclude that stapled diverticulectomy for solitary caecal diverticulitis is a safe and effective surgical strategy when confronted with this scenario.     

The Quacks of John Hunter's Time

The basic parameters underlying evaluation of body weight have been stature and weight; however, body weight is too gross a reference base for physiologic parameters or definitive clinical evaluation. Except in the grossly obese or very lean subjects, it is impossible to assess the amount of body fat from scale weight alone.

Although anthropometric measurements of both circumferences and diameters have long been utilized in quantitatively assessing body build, they have not been too meaningful. Now, a revitalized anthropometric procedure with a measuring tape and an anthropometer is available for this purpose. The author describes the technic involved and its interpretation in male and female subjects.     

静心电针法治疗围绝经期综合征临床研究

目的:观察静心电针法治疗围绝经期综合征的临床疗效。方法:将符合标准的围绝经期患者60例随机分为治疗组(30例)和对照组(30例)。治疗组给予静心电针法治疗,对照组给予克龄蒙治疗,均治疗3个周期。分别于治疗前、治疗1个月、治疗3个月(即治疗结束)、治疗后3个月及治疗后6个月进行随访,采用改良的Kupperman指数(KI)进行症状评分,并于治疗前、治疗结束各检测1次血清雌二醇(E2)、卵泡刺激素(FSH)、黄体生成激素(LH)。结果:治疗组和对照组的总有效率比较差异无统计学意义(90.00%vs.93.33%,P>0.05)。2组KI评分,治疗后各时间点与治疗前比较差异均有统计学意义(P<0.01),2组之间各时间点差异无统计学意义(P>0.05),2组在治疗期间,KI均有下降,当治疗结束后3个月与6个月时,KI评分稍有上升,对照组上升稍多,但2组之间差异无统计学意义(P>0.05)。2组治疗后,性激素水平均得到改善(P<0.01),但2组之间差异无统计学意义(P>0.05)。结论:静心电针法治疗围绝经期综合征,安全、疗效好,值得推广应用。