Investigation of nosocomial SARS-CoV-2 transmission from two patients to healthcare workers identifies close contact but not airborne transmission events.

OBJECTIVE: To describe the pattern of transmission of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) during 2 nosocomial outbreaks of coronavirus disease 2019 (COVID-19) with regard to the possibility of airborne transmission. DESIGN: Contact investigations with active case finding were used to assess the pattern of spread from 2 COVID-19 index patients. SETTING: A community hospital and university medical center in the United States, in February and March, 2020, early in the COVID-19 pandemic. PATIENTS: Two index patients and 421 exposed healthcare workers. METHODS: Exposed healthcare workers (HCWs) were identified by analyzing the electronic medical record (EMR) and conducting active case finding in combination with structured interviews. Healthcare coworkers (HCWs) were tested for COVID-19 by obtaining oropharyngeal/nasopharyngeal specimens, and RT-PCR testing was used to detect SARS-CoV-2. RESULTS: Two separate index patients were admitted in February and March 2020, without initial suspicion for COVID-19 and without contact or droplet precautions in place; both patients underwent several aerosol-generating procedures in this context. In total, 421 HCWs were exposed in total, and the results of the case contact investigations identified 8 secondary infections in HCWs. In all 8 cases, the HCWs had close contact with the index patients without sufficient personal protective equipment. Importantly, despite multiple aerosol-generating procedures, there was no evidence of airborne transmission. CONCLUSION: These observations suggest that, at least in a healthcare setting, most SARS-CoV-2 transmission is likely to take place during close contact with infected patients through respiratory droplets, rather than by long-distance airborne transmission.

Effect of human very low-density lipoproteins on cardiotrophin-like cytokine factor 1 (CLCF1) activity.

The cytokines CLCF1 and CNTF are ligands for the CNTF receptor and the apolipoprotein E (ApoE) receptor sortilin. Both share structural similarities with the N-terminal domain of ApoE, known to bind CNTF. We therefore evaluated whether ApoE or ApoE-containing lipoproteins interact with CLCF1 and regulate its activity. We observed that CLCF1 forms complexes with the three major isoforms of ApoE in co-immunoprecipitation and proximity assays. FPLC analysis of mouse and human sera mixed with CLCF1 revealed that CLCF1 co-purifies with plasma lipoproteins. Studies with sera from ApoE-/- mice indicate that ApoE is not required for CLCF1-lipoprotein interactions. VLDL- and LDL-CLCF1 binding was confirmed using proximity and ligand blots assays. CLCF1-induced STAT3 phosphorylation was significantly reduced when the cytokine was complexed with VLDL. Physiological relevance of our findings was asserted in a mouse model of oxygen-induced retinopathy, where the beneficial anti-angiogenic properties of CLCF1 were abrogated when co-administrated with VLDL, indicating, that CLCF1 binds purified lipoproteins or lipoproteins in physiological fluids such as serum and behave as a "lipocytokine". Albeit it is clear that lipoproteins modulate CLCF1 activity, it remains to be determined whether lipoprotein binding directly contributes to its neurotrophic function and its roles in metabolic regulation.

Information leaflet and antibiotic prescribing strategies for acute lower respiratory tract infection: a randomized controlled trial.

CONTEXT: Acute lower respiratory tract infection is the most common condition treated in primary care. Many physicians still prescribe antibiotics; however, systematic reviews of the use of antibiotics are small and have diverse conclusions. OBJECTIVE: To estimate the effectiveness of 3 prescribing strategies and an information leaflet for acute lower respiratory tract infection. DESIGN, SETTING, AND PATIENTS: A randomized controlled trial conducted from August 18, 1998, to July 30, 2003, of 807 patients presenting in a primary care setting with acute uncomplicated lower respiratory tract infection. Patients were assigned to 1 of 6 groups by a factorial design: leaflet or no leaflet and 1 of 3 antibiotic groups (immediate antibiotics, no offer of antibiotics, and delayed antibiotics). INTERVENTION: Three strategies, immediate antibiotics (n = 262), a delayed antibiotic prescription (n = 272), and no offer of antibiotics (n = 273), were prescribed. Approximately half of each group received an information leaflet (129 for immediate antibiotics, 136 for delayed antibiotic prescription, and 140 for no antibiotics). MAIN OUTCOME MEASURES: Symptom duration and severity. RESULTS: A total of 562 patients (70%) returned complete diaries and 78 (10%) provided information about both symptom duration and severity. Cough rated at least "a slight problem" lasted a mean of 11.7 days (25% of patients had a cough lasting > or =17 days). An information leaflet had no effect on the main outcomes. Compared with no offer of antibiotics, other strategies did not alter cough duration (delayed, 0.75 days; 95% confidence intervals [CI], -0.37 to 1.88; immediate, 0.11 days; 95% CI, -1.01 to 1.24) or other primary outcomes. Compared with the immediate antibiotic group, slightly fewer patients in the delayed and control groups used antibiotics (96%, 20%, and 16%, respectively; P<.001), fewer patients were "very satisfied" (86%, 77%, and 72%, respectively; P = .005), and fewer patients believed in the effectiveness of antibiotics (75%, 40%, and 47%, respectively; P<.001). There were lower reattendances within a month with antibiotics (mean attendances for no antibiotics, 0.19; delayed, 0.12; and immediate, 0.11; P = .04) and higher attendance with a leaflet (mean attendances for no leaflet, 0.11; and leaflet, 0.17; P = .02). CONCLUSION: No offer or a delayed offer of antibiotics for acute uncomplicated lower respiratory tract infection is acceptable, associated with little difference in symptom resolution, and is likely to considerably reduce antibiotic use and beliefs in the effectiveness of antibiotics.

Formoterol delivered by Turbuhaler: in pediatric asthma.

Formoterol is an inhaled long-acting beta(2)-adrenoceptor agonist, with a rapid onset of action and a bronchodilator effect that lasts for at least 12 hours. As add-on therapy to anti-inflammatory medication (e.g. corticosteroids), formoterol 4.5 and 9 microg twice daily delivered by Turbuhaler for 3 months significantly improved lung function (change from baseline in forced expiratory volume in 1 second and/or peak expiratory flow) compared with placebo in randomised, double-blind trials in pediatric patients (aged 6-17 years). In addition, formoterol 9 microg twice daily for 12 weeks reduced the use of rescue medication compared with salmeterol 50 microg twice daily in a nonblind trial in pediatric patients (aged 7-16 years). Single-dose formoterol 4.5 or 9 microg delivered by Turbuhaler provided significant prophylaxis against exercise-induced bronchoconstriction compared with placebo, and demonstrated a longer duration of effect than terbutaline, in a randomized, double-blind, crossover trial in pediatric patients (aged 8-17 years). Formoterol delivered by Turbuhaler was well tolerated in pediatric patients, with respiratory infection being the most commonly reported adverse event.

Spotlight on ramipril in the prevention of cardiovascular outcomes.

UNLABELLED: Ramipril (Altace)Use of tradenames is for product identification purposes only and does not imply endorsement.), an angiotensin-converting enzyme (ACE) inhibitor, is a prodrug which is rapidly hydrolyzed after absorption to the active metabolite ramiprilat. Earlier trials have shown that ACE inhibitors, when given to patients with low ejection fractions, have reduced the relative risk of myocardial infarction (MI) and other ischemic events by 14-23%. Subsequently, the double-blind, randomized, placebo-controlled, multicenter Heart Outcomes Prevention Evaluation (HOPE) study has shown that, in patients who are not known to have low ejection fraction or heart failure but are at increased risk for developing cardiovascular events, ramipril reduced the incidence of stroke, MI and death due to cardiovascular disease. Results from the HOPE study, in which 9297 patients were randomized to receive either ramipril 10 mg/day or placebo for a mean of 4.5 years, indicate that ramipril reduced the relative risk of the composite outcome of MI, stroke and cardiovascular death by 22%. The incidence of the composite outcome was significantly lower in the ramipril group than in the placebo group (14.0% vs 17.8%). Patients who received ramipril, compared with placebo recipients, had a significantly decreased incidence of stroke, MI or death due to cardiovascular disease (3.4% vs 4.9%, 9.9% vs 12.3% and 6.1% vs 8.1%, respectively). The relative risk of death from any cause was reduced among patients who received ramipril. In addition, treatment with ramipril reduced as the incidence of revascularization procedures, and, among patients with diabetes mellitus, ramipril reduced the incidence of complications related to diabetes mellitus, including the development of overt nephropathy. Moreover, in patients without a previous diagnosis of diabetes mellitus, ramipril, compared with placebo, significantly reduced the development of diabetes mellitus. Furthermore, compared with patients receiving placebo, patients receiving ramipril had a reduced rate of progression of carotid artery wall thickness. CONCLUSION: Ramipril 10 mg/day can significantly reduce the incidence of MI, stroke or death from cardiovascular causes in patients aged > or =55 years who are at increased risk for the development of ischemic cardiovascular events due to a history of stroke, coronary artery disease (with controlled blood pressure), diabetes mellitus plus at least one other risk factor or peripheral vascular disease but no heart failure or low ejection fraction. Therefore, in addition to dietary and lifestyle modifications, ramipril should be an integral part of secondary prevention therapy in patients at increased risk for the development of cardiovascular events.

Transdermal ethinylestradiol/norelgestromin: a review of its use in hormonal contraception.

UNLABELLED: Ethinylestradiol 20 microg/day plus norelgestromin 150 microg/day have been formulated into a transdermal patch for hormonal contraception. The predominant mechanism of action for transdermal ethinylestradiol/norelgestromin (Ortho Evra, Evra) is inhibition of ovulation by suppression of gonadotropins. It suppresses follicular development, induces changes to the endometrium that reduce the probability of implantation, and increases the viscosity of cervical mucus, which may prevent sperm penetration into the uterus. Two large randomized, nonblind efficacy studies demonstrated that transdermal ethinylestradiol/norelgestromin was as efficacious in preventing pregnancy as oral triphasic ethinylestradiol/levonorgestrel or oral ethinylestradiol/desogestrel. A large, noncomparative study also showed transdermal ethinylestradiol/norelgestromin to have good contraceptive efficacy. Moreover, in the two comparative trials, women using transdermal ethinylestradiol/norelgestromin had higher rates of perfect compliance than women using oral contraception. Age did not affect the rate of perfect compliance in women using the transdermal ethinylestradiol/norelgestromin patch, whereas the rate of compliance reduced with younger age in oral contraceptive users. Pooled results from three efficacy studies found that 1.8% of patches were replaced as a result of complete detachment and 2.9% because of partial detachment. Physical exercise, water immersion, and living in a humid climate did not affect patch adhesion. Transdermal ethinylestradiol/norelgestromin was generally well tolerated in clinical trials. The most common menstrual disturbances were breakthrough bleeding/spotting and dysmenorrhea. The incidence of discontinuation of treatment because of an adverse event was < or = 3.2%, with the most common reason being application-site reactions. CONCLUSIONS: Transdermal ethinylestradiol/norelgestromin offers a well tolerated, effective, reversible, and easy-to-use method of hormonal contraception with an increased likelihood of compliance relative to oral contraceptives.

Olmesartan medoxomil.

Olmesartan medoxomil is a nonpeptide angiotensin II receptor antagonist which selectively and competitively inhibits the type 1 angiotensin II receptor without affecting other receptors regulating the cardiovascular system. In well designed randomised trials, olmesartan medoxomil was significantly more effective than placebo, and at dosages of 10 to 20 mg/day was at least as effective as atenolol 50 to 100 mg/day in reducing diastolic blood pressure (DBP). At dosages of 5 to 20 mg/day, olmesartan medoxomil was more effective than captopril 12.5 to 50mg twice daily at lowering seated DBP in patients with mild to moderate hypertension in a dose titration study. Reductions in seated DBP were greater with olmesartan medoxomil 10 to 20 mg/day than losartan 50 to 100 mg/day. Olmesartan medoxomil at 20 mg/day was more effective in lowering seated DBP than losartan 50 mg/day, valsartan 80 mg/day or irbesartan 150 mg/day, and was more efficacious than losartan 50 mg/day or valsartan 80 mg/day at reducing 24-hour ambulatory systolic blood pressure. Olmesartan medoxomil has shown no clinically important pharmacokinetic interactions with digoxin, warfarin or antacid (aluminium magnesium hydroxide). Adverse events were infrequent in clinical studies of olmesartan medoxomil and were similar to those attributed to placebo. With olmesartan medoxomil, the frequency of dizziness was higher than with placebo but similar to that occurring with losartan, valsartan and irbesartan.

Ramipril: a review of its use in the prevention of cardiovascular outcomes.

UNLABELLED: Ramipril, an angiotensin-converting enzyme (ACE) inhibitor, is a prodrug which is rapidly hydrolysed after absorption to the active metabolite ramiprilat. Earlier trials have shown that ACE inhibitors, when given to patients with low ejection fractions, have reduced the relative risk of myocardial infarction (MI) and other ischaemic events by 14 to 23%. Subsequently, the double-blind, randomised, placebo-controlled, multicentre Heart Outcomes Prevention Evaluation (HOPE) study has shown that, in patients who are not known to have low ejection fraction or heart failure but are at increased risk for developing cardiovascular events, ramipril reduced the incidence of stroke, MI and death due to cardiovascular disease. Results from the HOPE study, in which 9297 patients were randomised to receive either ramipril 10 mg/day or placebo for a mean of 4.5 years, indicate that ramipril reduced the relative risk of the composite outcome of MI, stroke and cardiovascular death by 22%. The incidence of the composite outcome was significantly lower in the ramipril group than in the placebo group (14.0 vs 17.8%). Patients who received ramipril, compared with placebo recipients, had a significantly decreased incidence of stroke, MI or death due to cardiovascular disease (3.4 vs 4.9%, 9.9 vs 12.3% and 6.1 vs 8.1%, respectively). The relative risk of death from any cause was reduced among patients who received ramipril. In addition, treatment with ramipril reduced as the incidence of revascularisation procedures, and, among patients with diabetes mellitus, ramipril reduced the incidence of complications related to diabetes mellitus, including the development of overt nephropathy. Moreover, in patients without a previous diagnosis of diabetes mellitus, ramipril, compared with placebo, significantly reduced the development of diabetes mellitus. Furthermore, compared with patients receiving placebo, patients receiving ramipril had a reduced rate of progression of carotid artery wall thickness. CONCLUSION: Ramipril 10 mg/day can significantly reduce the incidence of MI, stroke or death from cardiovascular causes in patients aged > or =55 years who are at increased risk for the development of ischaemic cardiovascular events due to a history of stroke, coronary artery disease (with controlled blood pressure), diabetes mellitus plus at least one other risk factor or peripheral vascular disease but no heart failure or low ejection fraction. Therefore, in addition to dietary and lifestyle modifications, ramipril should be an integral part of secondary prevention therapy in patients at increased risk for the development of cardiovascular events.

Clindamycin/benzoyl peroxide gel: a review of its use in the management of acne.

UNLABELLED: Clindamycin/benzoyl peroxide gel has demonstrated clinical efficacy in the treatment of acne vulgaris through both antibacterial and anti-inflammatory means. Benzoyl peroxide may exert its antibacterial activity by the interaction of oxidized intermediates with elements of bacterial cells. Clindamycin inhibits bacterial protein synthesis by binding to the 50S ribosomal subunits causing inhibition of peptide-bond formation. Benzoyl peroxide decreases inflammatory damage by inhibiting the release of reactive oxygen species from polymorphonuclear leukocytes (PMNs) through the killing of PMNs. Clindamycin suppresses the complement-derived chemotaxis of polymorphonuclear leukocytes in vitro, thereby reducing the potential for inflammation. Several well designed clinical trials have demonstrated that twice-daily application of clindamycin 1%/benzoyl peroxide 5% gel for 10 to 16 weeks was more effective in reducing the number of inflammatory lesions than benzoyl peroxide 5%, clindamycin 1% or vehicle in patients with mild to moderately severe acne. Two studies also showed clindamycin/benzoyl peroxide to be more effective than benzoyl peroxide, clindamycin or vehicle in reducing total lesions, and one study showed clindamycin/benzoyl peroxide to be significantly more efficacious than clindamycin or vehicle in reducing the number of noninflammatory lesions. Moreover, in two trials, physician-rated mean global improvement scores, as well as patient-rated scores in one of those trials, were significantly greater in the clindamycin/benzoyl peroxide group than in the benzoyl peroxide, clindamycin or vehicle groups. In another study, clindamycin/benzoyl peroxide was as efficacious as benzoyl peroxide/erythromycin in the reduction of inflammatory and noninflammatory lesions and in raising mean global improvement scores, but was significantly more effective than benzoyl peroxide in the reduction of inflammatory lesions and in increasing both physician- and patient-assessed global improvement scores. Clindamycin/benzoyl peroxide gel applied twice daily was well tolerated in clinical trials in patients with acne, and has a tolerability profile similar to that of benzoyl peroxide alone. The most common adverse events were dry skin, peeling, erythema and rash; however, adverse event-caused treatment discontinuation rates for patients using clindamycin/benzoyl peroxide were low, ranging from 0 to 0.8%. CONCLUSIONS: Clindamycin/benzoyl peroxide gel has demonstrated efficacy and good overall tolerability in several well designed clinical studies in the topical treatment of patients with mild to moderately severe acne vulgaris. Clindamycin/benzoyl peroxide was more effective than benzoyl peroxide, clindamycin or vehicle, and similar in efficacy to benzoyl peroxide/erythromycin in the reduction of inflammatory lesions and in raising physician- and patient-assessed mean global improvement scores. It may be useful in treating patients with acne caused by resistant strains of Propionibacterium acnes. Clindamycin/benzoyl peroxide gel is an effective topical agent in the treatment of patients with mild to moderately severe acne. It is a suitable alternative for patients who are currently using topical antibacterials either alone or in conjunction with other topical anti-acne agents or systemic antibacterials.