Follow-up of patients with urinary tract infections discharged from the emergency department: a mixed methods study.

OBJECTIVES: To evaluate the quality of culture follow-up after emergency department (ED) discharge in patients with urinary tract infections (UTIs). METHODS: This convergent mixed methods study included an observational cohort study and a qualitative interview study in UTI patients discharged from the ED of a Dutch university hospital. The primary outcomes of the observational study were the proportion of patients requiring adjustment of antibiotic therapy after culture review, and the proportion of patients in whom these adjustments were made. Logistic regression identified factors associated with these outcomes. Interviews assessed patient experiences and transcripts were analysed using inductive thematic content analysis. Integration of the results informed recommendations for high-quality follow-up. RESULTS: Out of 455 patients, 285 (63%) required culture-based treatment adjustments. In most patients, no adjustments were made (239/285, 84%). De-escalation was most frequently omitted (98%), followed by discontinuation of antibiotics (92%). A mean of 7.1 (SD  3.8) antibiotic days per patient could have been avoided in 103 patients. Patients with diabetes were less likely to require adjustments (aOR   0.50, 95%-CI  0.29-0.85). Patients with moderate or severe renal impairment (aOR  4.1, 95%-CI  1.45-11.33; aOR  4.2, 95%-CI   1.50-11.94) or recurrent UTIs (aOR  5.0, 95%-CI  2.27-11.18) were more likely to have received necessary adjustments. Twelve interviews also revealed varying degrees of follow-up. Three themes were identified: 'information and communication', 'coordination and accessibility of care' and 'individual needs and preferences'. Recommendations for high-quality follow-up advocate a person centred approach. CONCLUSIONS: This study highlights the importance of urine culture follow-up after ED discharge, mainly to reduce unnecessary antibiotic treatment, promote de-escalation and improve patient experience.

Nephrotoxicity of concomitant piperacillin/tazobactam and teicoplanin compared with monotherapy.

OBJECTIVES: Piperacillin/tazobactam combined with vancomycin has been associated with a decline in renal function when compared with monotherapy. Teicoplanin is a glycopeptide similar to vancomycin. We investigated whether piperacillin/tazobactam combined with teicoplanin is associated with a decline in renal function as well. METHODS: We conducted a single-centre retrospective cohort study with data from our electronic health records from 9 August 2013 to 15 November 2019, including all adult patients that received either piperacillin/tazobactam, teicoplanin or piperacillin/tazobactam + teicoplanin. The incidence of acute kidney injury (AKI) at 48-72 h served as the primary outcome, whereas change in serum creatinine served as a secondary outcome. RESULTS: Of the 4202 included patients, 3188 (75.9%) received piperacillin/tazobactam, 791 (18.8%) received teicoplanin and 223 (5.3%) received piperacillin/tazobactam + teicoplanin. The incidence of AKI at 48-72 h after commencement of antibiotic therapy was 5.4% for piperacillin/tazobactam, 3.4% for teicoplanin and 11.7% for piperacillin/tazobactam + teicoplanin (P < 0.001). However, mean serum creatinine at 48-72 h was slightly higher in the piperacillin/tazobactam + teicoplanin group therapy compared with baseline [+1.61% (95% CI -2.25 to 5.70)], indicating a slight decrease in renal function, and decreased for piperacillin/tazobactam [-1.98% (95% CI -2.73 to -1.22)] and teicoplanin [-8.01% (95% CI -9.54 to -6.45)]. After correcting for significant confounders in a multivariate linear regression analysis, these patterns remained. CONCLUSIONS: Our study suggests that piperacillin/tazobactam + teicoplanin is associated with a higher prevalence of AKI compared with monotherapy. However, as the overall decline in renal function with piperacillin/tazobactam + teicoplanin is very small, its clinical relevance is likely limited. Therefore, piperacillin/tazobactam + teicoplanin can probably be safely combined.

How to measure quantitative antibiotic use in order to support antimicrobial stewardship in acute care hospitals: a retrospective observational study.

A cornerstone of antimicrobial stewardship programs (ASPs) is monitoring quantitative antibiotic use. Frequently used metrics are defined daily dose (DDD) and days of therapy (DOT). The purpose of this study was (1) to explore for the hospital setting the possibilities of quantitative data retrieval on the level of medical specialty and (2) to describe factors affecting the usability and interpretation of these quantitative metrics. We performed a retrospective observational study, measuring overall systemic antibiotic use at specialty level over a 1-year period, from December 1st 2014 to December 1st 2015, in one university and 13 non-university hospitals in the Netherlands. We distinguished surgical and non-surgical adult specialties. The association between DDDs, calculated from aggregated dispensing data, and DOTs, calculated from patient-level prescription data, was explored descriptively and related to organizational factors, data sources (prescription versus dispensing data), data registration, and data extraction. Twelve hospitals were able to extract dispensing data (DDD), three of which on the level of medical specialty; 13 hospitals were able to extract prescription data (DOT), 11 of which by medical specialty. A large variation in quantitative antibiotic use was found between hospitals and the correlation between DDDs and DOTs at specialty level was low. Differences between hospitals related to organizational factors, data sources, data registration, and data extraction procedures likely contributed to the variation in quantitative use and the low correlation between DDDs and DOTs. The differences in healthcare organization, data sources, data registration, and data extraction procedures contributed to the variation in reported quantitative use between hospitals. Uniform registration and extraction procedures are necessary for appropriate measurement and interpretation and benchmarking of quantitative antibiotic use.

A survey on antimicrobial stewardship prerequisites, objectives and improvement strategies: systematic development and nationwide assessment in Dutch acute care hospitals.

Background: Stewardship guidelines define three essential building blocks for successful hospital antimicrobial stewardship programmes (ASPs): stewardship prerequisites, stewardship objectives and improvement strategies. Objectives: We systematically developed a survey, based on these building blocks, to evaluate the current state of antimicrobial stewardship in hospitals. We tested this survey in 64 Dutch acute care hospitals. Methods: We performed a literature review on surveys of antimicrobial stewardship. After extraction and categorization of survey questions, five experts merged and rephrased questions during a consensus meeting. After a pilot study, the survey was sent to 80 Dutch hospitals. Results: The final survey consisted of 46 questions, categorized into hospital characteristics, stewardship prerequisites, stewardship objectives and stewardship strategies. The response rate was 80% (n = 64). Ninety-four percent of hospitals had established an antimicrobial stewardship team, consisting of at least one hospital pharmacist and one clinical microbiologist. An infectious diseases specialist was present in 68% of the teams. Nine percent had dedicated IT support. Forty-one percent of the teams were financially supported, with a median of 0.6 full-time equivalents (FTE; 0.1-1.8). The majority of hospitals performed monitoring of restricted antibiotic agents (91%), dose optimization (65%), bedside consultation (56%) and intravenous-to-oral switch (53%). Fifty-eight percent of the hospitals provided education to residents and 28% to specialists. Conclusions: The survey provides information on the progress that is being made in hospitals regarding the three building blocks of a successful ASP, and provides clear aims to strengthen ASPs. Ultimately, these data will be related to national data on antibiotic consumption and resistance.

Pharmacokinetics of caspofungin in ICU patients.

OBJECTIVES: Caspofungin is used for treatment of invasive fungal infections. As the pharmacokinetics (PK) of antimicrobial agents in critically ill patients can be highly variable, we set out to explore caspofungin PK in ICU patients. METHODS: ICU patients receiving caspofungin were eligible. Patients received a loading dose of 70 mg followed by 50 mg daily (70 mg if body weight >80 kg); they were evaluable upon completion of the first PK curve at day 3. Additionally, daily trough samples were taken and a second PK curve was recorded at day 7. PK analysis was performed using a standard two-stage approach. RESULTS: Twenty-one patients were evaluable. Median (range) age and body weight were 71 (45-80) years and 75 (50-99) kg. PK sampling on day 3 (n = 21) resulted in the following median (IQR) parameters: AUC0-24 88.7 (72.2-97.5) mg·h/L; Cmin 2.15 (1.40-2.48) mg/L; Cmax 7.51 (6.05-8.17) mg/L; V 7.72 (6.12-9.01) L; and CL 0.57 (0.54-0.77) L/h. PK sampling on day 7 (n = 13) resulted in AUC0-24 107.2 (90.4-125.3) mg·h/L, Cmin 2.55 (1.82-3.08) mg/L, Cmax 8.65 (7.16-9.34) mg/L, V 7.03 (5.51-7.73) L and CL 0.54 (0.44-0.60) L/h. We did not identify any covariates significantly affecting caspofungin PK in ICU patients (e.g. body weight, albumin, liver function). Caspofungin was well tolerated and no unexpected side effects were observed. CONCLUSIONS: Caspofungin PK in ICU patients showed limited intraindividual and moderate interindividual variability, and caspofungin was well tolerated. A standard two-stage approach did not reveal significant covariates. Our study showed similar caspofungin PK parameters in ICU patients compared with non-critically ill patients.

Management of infected pancreatic necrosis in the intensive care unit: a narrative review.

BACKGROUND: Severe acute pancreatitis is marked by organ failure and (peri)pancreatic necrosis with local complications such as infected necrosis. Infection of these necrotic collections together with organ failure remain the major causes of admission to an intensive care unit (ICU) in acute pancreatitis. Appropriate treatment of infected necrosis is essential to reduce morbidity and mortality. Overall knowledge of the treatment options within a multidisciplinary team-with special attention to the appropriate use of antimicrobial therapy and invasive treatment techniques for source control-is essential in the treatment of this complex disease. OBJECTIVES: To address the current state of microbiological diagnosis, antimicrobial treatment, and source control for infected pancreatic necrosis in the ICU. SOURCES: A literature search was performed using the Medline and Cochrane libraries for articles subsequent to 2003 using the keywords: infected necrosis, pancreatitis, intensive care medicine, treatment, diagnosis and antibiotic(s). CONTENT: This narrative review provides an overview of key elements of diagnosis and treatment of infected pancreatic necrosis in the ICU. IMPLICATIONS: In pancreatic necrosis it is essential to continuously (re)evaluate the indication for antimicrobial treatment and invasive source control. Invasive diagnostics (e.g. through fine-needle aspiration, FNA), preferably prior to the start of broad-spectrum antimicrobial therapy, is advocated. Antimicrobial stewardship principles apply: paying attention to altered pharmacokinetics in the critically ill, de-escalation of broad-spectrum therapy once cultures become available, and early withdrawal of antibiotics once source control has been established. This is important to prevent the development of antimicrobial resistance, especially in a group of patients who may require repeated courses of antibiotics during the prolonged course of their illness.

Nationwide survey of hospital antibiotic stewardship programs in France.

OBJECTIVE: We aimed to evaluate the current state of antibiotic stewardship (ABS) in French public and private acute care hospitals. METHODS: We conducted a cross-sectional online questionnaire survey. The selection of participating hospitals was performed through a stratified random sampling procedure among all French public and private hospitals with acute care beds. RESULTS: 97/215 (45%) hospitals participated. A formal ABS program was implemented in 84% (80/95) of hospitals. A person officially in charge of this program (i.e., ABS program leader) was present in almost all participating hospitals (99%, 95/96) and s/he coordinated a multidisciplinary ABS team in 42% (40/96) of cases. The median time spent on ABS activities was 1.7, 1.6, and 0.8hours/week/100 acute care beds for infectious disease (ID) specialists, pharmacists, and microbiologists respectively; 27% (7/26) of ID specialists/other clinicians, 58% (15/26) of pharmacists, and 80% (16/20) of microbiologists received no salary support for the stewardship activities conducted as part of the team. Local guidelines (94%, 88/94), electronic medical records (85%, 80/94), and an antibiotic restriction policy (92%, 82/89) were implemented in almost all hospitals. Reports on antibiotic consumption and local resistance rates were available in 100% (91/91) and 84% (76/91) of hospitals, respectively. CONCLUSION: Despite the existence of national requirements, hospital ABS programs are not fully implemented in France, mainly because of inadequate institutional support and funding.

Comparison of antimicrobial stewardship programmes in acute-care hospitals in four European countries: A cross-sectional survey.

Antimicrobial stewardship programmes (ASPs) are designed to improve antibiotic use. A survey was systematically developed to assess ASP prerequisites, objectives and improvement strategies in hospitals. This study assessed the current state of ASPs in acute-care hospitals throughout Europe. A survey containing 46 questions was disseminated to acute-care hospitals: all Dutch (n = 80) and Slovenian (n = 29), 215 French (25%, random stratified sampling) and 62 Italian (49% of hospitals with an infectious diseases department, convenience sampling) acute-care hospitals, for a Europe-wide assessment. Response rates for the Netherlands (Nl), Slovenia (Slo), France (Fr) and Italy (It) were 80%, 86%, 45% and 66%. There was variation between countries in the prerequisites met and the objectives and improvement strategies chosen. A formal ASP was present mainly in the Netherlands (90%) and France (84%) compared with Slovenia (60%) and Italy (60%). Presence of an antimicrobial stewardship (AMS) team ranged from 42% (Fr) to 94% (Nl). Salary support for AMS teams was provided in 68% (Fr), 51% (Nl), 33% (Slo) and 12% (It) of surveyed hospitals. Quantity of antibiotic use was monitored in the majority of hospitals, ranging from 72% (Nl) to 100% (Slo and Fr) of acute-care hospitals. Participating countries varied substantially in the use of 'prospective monitoring and advice' as a strategy to improve AMS objectives. ASP prerequisites, objectives and improvement activities vary considerably across Europe, with room for improvement. Stimulating appropriate system prerequisites throughout Europe, e.g. by introducing staffing standards and financial support for ASPs, seems a first priority.

Development of quality indicators for the antibiotic treatment of complicated urinary tract infections: a first step to measure and improve care.

BACKGROUND: Appropriateness of antibiotic treatment of urinary tract infection (UTI) is important. The aim of this study was to develop a set of valid, reliable, and applicable indicators to assess the quality of antibiotic use in the treatment of hospitalized patients with complicated UTI. METHODS: A multidisciplinary panel of 13 experts reviewed and prioritized recommendations extracted from a recently developed evidence-based national guideline for the treatment of complicated UTI. The content validity was assessed in 2 consecutive rounds with an in-between discussion meeting. Next, we tested the feasibility, interobserver reliability, opportunity for improvement, and case-mix stability of the potential indicators for a data set of 341 inpatients and outpatients with complicated UTIs who were treated at the urology or internal medicine departments at 4 hospitals. RESULTS: The panel selected and prioritized 13 indicators. Four and 9 indicators were performed satisfactorily in the urology and internal medicine departments, as follows: performance of urine culture, prescription of treatment in accordance with guidelines, tailoring of treatment on the basis of culture results, and a switch to oral treatment when possible in the urology and internal medicine departments; and selective use of fluoroquinolones, administration of treatment for at least 10 days, prescription of treatment for men in accordance with guidelines, replacement of catheters in patients with UTI, and adaptation of the dosage on the basis of renal function in the internal medicine department. CONCLUSION: A systemic evidence- and consensus-based approach was used to develop a set of valid quality indicators. Tests of the applicability of these indicators in practice in different settings is essential before they are used in quality-improvement strategies.

QTc prolongation during erythromycin used as prokinetic agent in ICU patients.

BACKGROUND: High-dose erythromycin used as antibiotic prolongs QTc interval. Low-dose erythromycin is frequently used as a prokinetic agent, especially in patients in the intensive care unit (ICU). It is unknown whether low-dose erythromycin affects cardiac repolarisation and puts patients at risk for torsades de pointes. METHODS: In this prospective study, we included ICU patients treated with erythromycin as prokinetic in a dose of 200 mg twice a day. An ECG was performed before, 15 min and 24 hours after the start of erythromycin. Cardiac repolarisation was assessed by rate-corrected analysis of the QT interval (QTc) on the ECG by two independent investigators. Starting or stopping other possibly QTc prolonging drugs during the study period was an exclusion criterion. Wilcoxon signed-rank test and Friedman's test were used for statistical analysis to assess prolongation of QTc. Primary outcome was defined by the prolongation of QTc after 15 min and 24 hours. RESULTS: 51 patients were eligible for this study. In these patients, QTc increased significantly from 430 ms at baseline to 439 ms (p=0.03) after 15 min and 444 ms (p=0.01) after 24 hours. After 15 min and 24 hours, the upper limit of 95% CI for prolongation of QTc was well above 10 ms. No QTc-related arrhythmias were seen. CONCLUSIONS: During treatment with erythromycin in a dose of 200 mg twice a day. QTc prolonged mildly but significantly. Sequential ECG registration should be performed when low-dose erythromycin is prescribed, especially in the presence of other risk factor for QTc prolongation.

Management of community-acquired pneumonia in adults: 2016 guideline update from the Dutch Working Party on Antibiotic Policy (SWAB) and Dutch Association of Chest Physicians (NVALT).

The Dutch Working Party on Antibiotic Policy in collaboration with the Dutch Association of Chest Physicians, the Dutch Society for Intensive Care and the Dutch College of General Practitioners have updated their evidence-based guidelines on the diagnosis and treatment of community-acquired pneumonia (CAP) in adults who present to the hospital. This 2016 update focuses on new data on the aetiological and radiological diagnosis of CAP, severity classification methods, initial antibiotic treatment in patients with severe CAP and the role of adjunctive corticosteroids. Other parts overlap with the 2011 guideline. Apart from the Q fever outbreak in the Netherlands (2007-2010) no other shifts in the most common causative agents of CAP or in their resistance patterns were observed in the last five years. Low-dose CT scanning may ultimately replace the conventional chest X-ray; however, at present, there is insufficient evidence to advocate the use of CT scanning as the new standard in patients evaluated for CAP. A pneumococcal urine antigen test is now recommended for all patients presenting with severe CAP; a positive test result can help streamline therapy once clinical stability has been reached and no other pathogens have been detected. Coverage for atypical microorganisms is no longer recommended in empirical treatment of severe CAP in the non-intensive care setting. For these patients (with CURB-65 score >2 or Pneumonia Severity Index score of 5) empirical therapy with a 2nd/3rd generation cephalosporin is recommended, because of the relatively high incidence of Gram-negative bacteria, and to a lesser extent S. aureus. Corticosteroids are not recommended as adjunctive therapy for CAP.

Changes in membrane lipid composition of human erythrocytes after dietary supplementation of (n-3) polyunsaturated fatty acids. Maintenance of membrane fluidity.

The effect of dietary (n-3) polyunsaturated fatty acids on erythrocyte membrane lipid composition, fluidity, and flexibility was studied in seven healthy subjects. An eight weeks daily supplementation of 3 g of the (n-3) fatty acids eicosapentaenoic and docosahexaenoic acid resulted in an increased unsaturation of erythrocyte phosphatidylcholine (PC) and phosphatidylethanolamine (PE). This change was accompanied by a slight decrease in PC and PE content (P less than 0.05) and an increase in sphingomyelin content (P less than 0.01). The erythrocyte membrane fluidity, measured with electron spin resonance of intact erythrocytes and with fluorescence polarization of erythrocyte ghosts did not change. No change was seen in the viscosity of erythrocyte suspensions of haematocrit = 0.80, measured at various shear rates. The supplementation caused a 42% decrease in plasma triacylglycerol levels. We suggest that the change in the erythrocyte membrane fatty acid composition induced by the dietary supplementation of (n-3) fatty acids might be counteracted by a change in the phospholipid class distribution, resulting in overall maintenance of membrane fluidity.

Quality of antibiotic use for lower respiratory tract infections at hospitals: (how) can we measure it?

BACKGROUND: To assess and improve the quality of antibiotic use in patients with community-acquired pneumonia (CAP) and acute exacerbation of chronic bronchitis or chronic obstructive pulmonary disease (AECB), a valid set of quality indicators is required. This set should also be applicable in practice. METHODS: Guidelines and literature were reviewed to derive potential indicators for quality of antibiotic use in treating hospitalized patients with lower respiratory tract infection (LRTI). To assess the evidence base of each indicator, a literature review was performed. Grade A recommendations were considered valid. For grade B-D recommendations, an expert panel performed a consensus procedure on the indicator's relevance to patient health, reduction of antimicrobial resistance, and cost containment. To test applicability in practice, feasibility, opportunity for improvement, reliability, and case-mix stability were determined for a data set of 899 hospitalized patients with LRTI. RESULTS: None of the potential indicators from guidelines and literature were supported by grade A evidence. Nineteen indicators were selected by consensus procedure (12 indicators for CAP and 7 indicators for AECB). Lack of feasibility and of opportunity for improvement led to the exclusion of 4 indicators. A final set of 15 indicators was defined (9 indicators for CAP and 6 indicators for AECB). CONCLUSIONS: A valid set of quality indicators for antibiotic use in hospitalized patients with LRTI was developed by combining evidence and expert opinion in a carefully planned procedure. Subjecting indicators to an applicability test is essential before using them in quality-improvement projects. In our demonstration setting, 4 of the 19 indicators were inapplicable in practice.

Antibiotic control measures in Dutch secondary care hospitals.

Control measures for the use of antibiotics are essential because of the potential harmful consequences of side effects. Various methods have been developed to help curb undesirable antibiotic prescription. We performed a survey in Dutch secondary care hospitals (response rate 73%) to make an inventory of these measures and elucidate possible shortcomings. Almost every hospital was using an antibiotic formulary (97%), sometimes supported by extra restrictions in antibiotic choice (55%). Local practice guidelines (95%) were commonly present, but effective implementation, for example using intranet applications, could be improved (21%). National guidelines had received little attention in the composition process of local guidelines (19%). Other measures such as educational programmes for specialists (11%) and feedback on antibiotic prescription (52%) remained largely underused, although their effective implementation may optimise antibiotic prescription in hospitals.

Revised SWAB guidelines for antimicrobial therapy of community-acquired pneumonia.

The Dutch Working Party on Antibiotic Policy (SWAB) develops evidence-based guidelines, aimed at optimalisation of antibiotic use and limitation of the spread of antimicrobial resistance. A revision of the SWAB guideline for the treatment of community-acquired pneumonia (CAP), published in 1998, was considered necessary because of changes in resistance patterns and new insights into the epidemiology, diagnostics and treatment of CAP. In contrast to the former version, this guideline is transmural and has been drawn up according to the recommendations for evidence-based guideline development by a multidisciplinary committee consisting of experts from all relevant professional societies. The 'severity of disease' exhibited by the patient with pneumonia on admission is considered important for the choice of the optimum empirical treatment strategy. Severely ill patients are treated empirically with a drug directed against multiple potential pathogens, including Legionella spp. Classification according to 'severity of disease' can be accomplished with a validated scoring system (Pneumonia Severity Index or CURB-65 score) or pragmatically, based on the site of treatment: an outpatient setting, a clinical ward or an intensive care unit. The Legionella urine antigen test plays an important role in decisions on the choice of initial antibiotic treatment.

[Suicidal and aggressive thoughts as a result of taking a Hypericum preparation (St. John's wort)]. / Suïcidale en agressieve gedachten bij gebruik van hypericumpreparaat (sint-janskruid).

A 51-year-old woman presented at the internal medical outpatients' clinic complaining of fatigue. She had been having frightening suicidal and homicidal thoughts for about 9 months prior to coming to the clinic. Physical examination and extensive laboratory examination revealed no abnormalities. She had been taking vitamin C and a herbal extract of St. John's wort. She was asked to stop taking this herbal extract and her suicidal and homicidal thoughts disappeared within about 3 weeks. She then recalled having used the preparation for some time 3 years earlier, which had given her similar psychiatric symptoms. At that time these symptoms had also disappeared after discontinuation of the preparation. This case illustrates that it is very important to ask about the use of non-regular medication during history taking.

[Optimizing the antibiotics policy in The Netherlands. VIII. Revised SWAB guidelines for antimicrobial therapy in adults with community-acquired pneumonia]. / Optimaliseren van het antibioticabeleid in Nederland. VIII. Herziene SWAB-richtlijnen voor antimicrobiële therapie bij thuis opgelopen pneumonie.

The Dutch Working Party on Antibiotic Policy (SWAB) has revised the 1998 guideline for community-acquired pneumonia (CAP) in light of changing resistance patterns for common pathogens and new developments in epidemiology, diagnostic testing and treatment strategies. The current guideline is applicable to both primary and inpatient care, and has been developed by delegates of all professional organisations involved in the treatment of CAP, following recommendations for evidence-based guideline development. Assessment of a patient's 'severity of illness' at presentation is considered important when choosing an optimal empirical antibiotic regimen for CAP. Severely-ill patients should be treated with antibiotics covering the most important expected pathogens, including Legionella. Assessment of the severity of illness may be facilitated by the use of validated scoring systems like the pneumonia severity index and the 'confusion, urea, respiratory-rate, blood-pressure, 65-years-of-age' (CURB-65) score. Patients can also be stratified based on their location during treatment: in the community, a normal ward or an intensive-care unit. Legionella urine antigen testing is considered an important tool in the process of deciding on an optimal antibiotic regimen for CAP. Empirical therapy should be replaced with pathogen-directed therapy if the causative agent is identified.

Hypocholesterolemic effect of dietary soy protein versus casein in rhesus monkeys (Macaca mulatta).

Ten mature female rhesus monkeys were alternately fed semipurified diets containing casein or soy protein for periods of 13 to 17 wk. Each diet was fed for two periods. When the animals were changed from the commercial diet to the semipurified diet containing soy protein, a significant elevation in serum cholesterol occurred. The serum cholesterol levels gradually increased further, when the soy protein in the diet was replaced by casein. However, when subsequently the casein in the diet was replaced by soy protein, a significant decrease in serum cholesterol levels was observed. Finally, when the animals were changed back to the casein diet, a significant increase in serum cholesterol again occurred. Changes in serum cholesterol due to modulations in the type of protein in the diet were reflected mainly by changes in low-density lipoprotein cholesterol. Thus, the results of this study clearly show that the type of protein in the diet markedly affects serum cholesterol levels not only in experimental animals such as the rabbit, as is well known, but also in the rhesus monkey, which is more akin to man.

Simvastatin (MK-733): a potent cholesterol synthesis inhibitor in heterozygous familial hypercholesterolaemia.

Simvastatin (MK-733), a new inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, was administered to 38 patients with heterozygous familial hypercholesterolaemia for 24 weeks. A dose of 40 mg per day produced a mean reduction in low density lipoprotein cholesterol of 43-45% and in triglycerides of 21-31%. Mean high density lipoprotein cholesterol increased significantly by 10-13%. There were no major differences in response whether the drug was taken in one or two doses. MK-733 was tolerated well. Adverse effects were infrequent and limited to slight increases of alanine aminotransferase, creatine phosphokinase and bilirubin. This drug appears to be a potent inhibitor of cholesterol synthesis and has produced the largest therapeutic response as monotherapy in patients with familial hypercholesterolaemia.

Serum lipid levels in growth hormone-deficient men.

To evaluate the impact of growth hormone deficiency (GHD) on lipid metabolism, serum lipid and apolipoprotein concentrations were measured in 64 GHD adult males (mean age, 27.1 +/- 4.7 years). Results were compared with those obtained from an age- and sex-matched control group. Total cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein (apo) B levels were significantly higher in GHD patients (P < .001). In 14 patients (23%), total cholesterol concentration exceeded the 95th percentile for healthy adults. Total and LDL cholesterol were inversely related to plasma insulin-like growth factor-I (IGF-I). Apo B also tended to be negatively correlated with IGF-I; however, statistical significance was not reached (P = .054). High-density lipoprotein (HDL) cholesterol and plasma triglyceride concentrations were within normal limits, whereas apo A-1 and A-2 levels were only slightly different from normal. We conclude that GHD in adulthood is associated with mild hypercholesterolemia due to an increased LDL cholesterol level. An inverse relationship was established between LDL cholesterol concentration and GH secretory status.