Green zoning: An effective policy tool to tackle the Covid-19 pandemic

Green zoning has emerged as a widely used policy response to tackle the Covid-19 pandemic. ‘Green zones’—areas where the virus is under control based on a uniform set of conditions—can progressively return to normal economic and social activity levels, and mobility between them is permitted. By contrast, stricter public health measures are in place in ‘red zones’, and mobility between red and green zones is restricted. France and Spain were among the first countries to introduce green zoning in April 2020. Subsequently, more and more countries followed suit and the European Commission advocated for the implementation of a European green zoning strategy, which has been supported by the EU member states. While there remain coordination problems, green zoning has proven to be an effective strategy for containing the spread of the virus and limiting its negative economic and social impact. This strategy should provide important lessons and prove useful in future outbreaks. Research in epidemiology indicates that thoroughly implemented and operationalised green zoning can prevent the spread of a transmittable disease that is poorly understood, highly virulent, and potentially highly lethal. Finally, there is strong evidence that green zoning can reduce economic and societal damage as it avoids worst-in-class measures.     

Antibody and memory B cell responses to the dengue virus NS1 antigen in individuals with varying severity of past infection

To further understand the role of NS1-specific antibodies (Abs) in disease pathogenesis, we compared neutralizing antibody levels (Nabs), NS1-Ab levels, IgG antibody subclass profiles and NS1-specific memory B-cell responses (Bmems) in individuals, with varying severity of past dengue. Nabs (Neut50 titres) were assessed using the Foci Reduction Neutralization Test (FRNT) and in-house ELISAs were used to assess NS1-Abs and NS1-Ab subclasses for all four DENV serotypes in individuals with past DF (n = 22), those with past DHF (n = 14) and seronegative (SN) individuals (n = 7). B-cell ELISpot assays were used to assess NS1-specific Bmem responses. 15/22 (68.18%) individuals with past DF and 9/14 (64.29%) individuals with past DHF had heterotypic infections. Neut50 titres were found to be significantly higher for DENV1 than DENV2 (p = 0.0006) and DENV4 (p = 0.0127), in those with past DHF, whereas there was no significant difference seen in titres for different DENV serotypes in those with past DF. Overall NS1-Ab to all serotypes and NS1-specific IgG1 responses for DENV1, 2 and 4 serotypes were significantly higher in those with past DHF than individuals with past DF. Those with past DHF also had higher IgG1 than IgG3 for DENV1 and DENV3, whereas no differences were seen in those with past DF. Over 50% of those with past DF or DHF had NS1-specific Bmem responses to >2 DENV serotypes. There was no difference in the frequency of Bmem responses to any of the DENV serotypes between individuals with past DF and DHF. Although the frequency of Bmem responses to DENV1 correlated with DENV1-specific NS1-Abs levels (Spearman r = 0.35, p = 0.02), there was no correlation with other DENV serotypes. We found that those with past DF had broadly cross-reactive Nabs, while those with past DHF had higher NS1-Ab responses possibly with a different functionality profile than those with past DF. Therefore, it would be important to further evaluate the functionality of NS1-specific antibody and Bmem responses to find out the type of antibody repertoire that is associated with protection against severe disease.     

Double β-lactam regimen compared to an aminoglycoside/β-lactam regimen as empiric antibiotic therapy for febrile granulocytopenic cancer patients

In a prospective, randomized trial, 205 febrile episodes in granulocytopenic cancer patients were treated with ceftazidime with or without tobramycin (C±T), both agents being administered only if the initial granulocyte count was below 200/l, or ceftazidime plus piperacillin (C+P). The overall response rate was 71% (39 of 60 for C±T and 45 of 58 for C+P). Logistic regression analyses documented no evidence of a significant difference between the two regimens in overall treatment effect after accounting for the linear effects of potentially important variables, such as infection type and granulocyte count. Although the response rates for the subgroup of patients with bacteremias was better with the C+P regimen (P=0.06), there was no difference in response for patients with bacteremia and profound (<100/gml) sustained granulocytopenia. The double -lactam combination demonstrated in vitro synergism in 73%; antagonism was not seen. Both regimens produced execllent serum bactericidal levels (C±T geometric mean peak 1:170; C+P peak 1:137) against gram-negative but not gram-positive pathogens (1:4; 1:7 respectively) that had caused bacteremia. Emergence of resistance and significant coagulopathy and/or bleeding did not occur during therapy. Antibiotic-related nephrotoxicity was noted in 7 of 95 trials in the C+P and in 6 of 89 trials in the C±T group (P=0.19). The incidence of secondary infections in patients with profound (<100/l) sustained granulocytopenia was lower in the C±T group (P=0.04). Alimentary canal anaerobic flora preservation with C±T, and suppression with C+P, was demonstrated. These results suggest that these regimens are of similar effectiveness and neigher is associated with major toxicity.     

Single-Dose Pharmacokinetics of Aztreonam in Healthy Volunteers and Renal Failure Patients

Summary

The pharmacokinetics of aztreonam were studied in 6 healthy male volunteers and 12 male patients with various degrees of chronic renal failure after intravenous bolus injection of 1g of the drug. Serum pharmacokinetics of aztreonam were described by an open, two-compartment kinetic model. The serum levels of aztreonam exceeded the reported minimum inhibitory concentration (MIC)₉₀ for Enterobacteriaceae for 8 hours and up to 24 hours, in healthy volunteers and renal failure patients, respectively. However, the serum levels of the drug exceeded the MIC₅₀ for Pseudomonas aeruginosa for only 4 hours and 12 hours in healthy volunteers and patients, respectively. The half-life of elimination (t 1/2/β) increased significantly (P < 0.001) from 1.8 ± 0.14 h in healthy volunteers and to 4.9 ± 1.1 h in patients with renal failure. The total serum clearance of aztreonam decreased significantly (P< 0.001) from 84.2 ± 7.8 ml/h/kg in healthy volunteers to 30.2 + 9.2 ml/h/kg in patients with renal failure. Á linear correlation (r = 0.971, P< 0.001) was found between creatinine clearance and the total serum clearance of aztreonam. The AUC_0–∞ increased significantly (P< 0.001) from 137.5 ± 12.2 μg/h/ml in healthy volunteers to 464 ± 114.5 μg/h/ml in patients with renal failure.     

Dutch guidelines for physiotherapy in patients with stress urinary incontinence: an update

Introduction and hypothesis

Stress urinary incontinence (SUI) is the most common form of incontinence impacting on quality of life (QOL) and is associated with high financial, social, and emotional costs. The purpose of this study was to provide an update existing Dutch evidence-based clinical practice guidelines (CPGs) for physiotherapy management of patients with stress urinary incontinence (SUI) in order to support physiotherapists in decision making and improving efficacy and uniformity of care.

Materials and methods

A computerized literature search of relevant databases was performed to search for information regarding etiology, prognosis, and physiotherapy assessment and management in patients with SUI. Where no evidence was available, recommendations were based on consensus. Clinical application of CPGs and feasibility were reviewed. The diagnostic process consists of systematic history taking and physical examination supported by reliable and valid assessment tools to determine physiological potential for recovery. Therapy is related to different problem categories. SUI treatment is generally based on pelvic floor muscle exercises combined with patient education and counseling. An important strategy is to reduce prevalent SUI by reducing influencing risk factors.

Results

Scientific evidence supporting assessment and management of SUI is strong.

Conclusions

The CPGs reflect the current state of knowledge of effective and tailor-made intervention in SUI patients.