Real life experience on the use of Remdesivir in patients admitted to COVID-19 in two referral Italian hospital: a propensity score matched analysis.

Remdesivir (RDV) was the first Food and Drug Administration (FDA)-approved medication for COVID-19, with discordant data on efficacy in reducing mortality risk and disease progression. In the context of a dynamic and rapidly changing pandemic landscape, the utilization of real-world evidence is of utmost importance. The objective of this study is to evaluate the impact of RDV on patients who have been admitted to two university referral hospitals in Italy due to COVID-19. All patients older than 18 years and hospitalized at two different universities (Bari and Palermo) were enrolled in this study. To minimize the effect of potential confounders, we used propensity score matching with one case (Remdesivir) and one control that never experienced this kind of intervention during hospitalization. Mortality was the primary outcome of our investigation, and it was recorded using death certificates and/or medical records. Severe COVID-19 was defined as admission to the intensive care unit or a qSOFAscore ≥ 2 or CURB65scores ≥ 3. After using propensity score matching, 365 patients taking Remdesivir and 365 controls were included. No significant differences emerged between the two groups in terms of mean age and percentage of females, while patients taking Remdesivir were less frequently active smokers (p < 0.0001). Moreover, the patients taking Remdesivir were less frequently vaccinated against COVID-19. All the other clinical, radiological, and pharmacological parameters were balanced between the two groups. The use of Remdesivir in our cohort was associated with a significantly lower risk of mortality during the follow-up period (HR 0.56; 95% CI 0.37-0.86; p = 0.007). Moreover, RDV was associated with a significantly lower incidence of non-invasive ventilation (OR 0.27; 95% CI 0.20-0.36). Furthermore, in the 365 patients taking Remdesivir, we observed two cases of mild renal failure requiring a reduction in the dosage of Remdesivir and two cases in which the physicians decided to interrupt Remdesivir for bradycardia and for QT elongation. Our study suggests that the use of Remdesivir in hospitalized COVID-19 patients is a safe therapy associated with improved clinical outcomes, including halving of mortality and with a reduction of around 75% of the risk of invasive ventilation. In a constantly changing COVID-19 scenario, ongoing research is necessary to tailor treatment decisions based on the latest scientific evidence and optimize patient outcomes.

Physician density: will we ever close the gap?

OBJECTIVE: Physician density is a crucial element of a well-functioning health system. Previous research has investigated factors affecting country-level physician supply. To date, however, no evidence has been provided about the patterns of convergence in physician density among countries. This paper thus tested club convergence in physician density in 204 countries worldwide from 1990 to 2019. A nonlinear time-varying factor model was adopted to identify potential clubs, wherein groups of countries tend to converge towards the same level of physician density. Our primary purpose was to document the potential long-lasting disparity in future global physician distribution. RESULTS: Despite physician density increasing in all regions globally from 1990 to 2019, we found no evidence in favor of the hypothesis of global convergence. Conversely, the clustering algorithm successfully identified three main patterns (i.e., three final clubs). With few exceptions, the results indicated an uneven physician distribution between the majority of North and Sub-Saharan African countries (where physician density would remain well below the estimated threshold of at least 70% of the Universal Health Coverage Services Index) and the rest of the world. These findings support the WHO's global strategy to reverse the chronic under-investment in human resources for health.

Mortality Attributable to Bloodstream Infections Caused by Different Carbapenem-Resistant Gram-Negative Bacilli: Results From a Nationwide Study in Italy (ALARICO Network).

BACKGROUND: Our aim was to analyze mortality attributable to carbapenem-resistant (CR) gram-negative bacilli (GNB) in patients with bloodstream infections (BSIs). METHODS: Prospective multicentric study including patients with GNB-BSI from 19 Italian hospitals (June 2018-January 2020). Patients were followed-up to 30 days. Primary outcomes were 30-day mortality and attributable mortality. Attributable mortality was calculated in the following groups: Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales, metallo-ß-lactamases (MBL)-producing Enterobacterales, CR-Pseudomonas aeruginosa (CRPA), CR-Acinetobacter baumannii (CRAB). A multivariable analysis with hospital fixed-effect was built to identify factors associated with 30-day mortality. Adjusted OR (aORs) were reported. Attributable mortality was calculated according to the DRIVE-AB Consortium. RESULTS: Overall, 1276 patients with monomicrobial GNB BSI were included: 723/1276 (56.7%) carbapenem-susceptible (CS)-GNB, 304/1276 (23.8%) KPC-, 77/1276 (6%) MBL-producing CRE, 61/1276 (4.8%) CRPA, and 111/1276 (8.7%) CRAB BSI. Thirty-day mortality in patients with CS-GNB BSI was 13.7% compared to 26.6%, 36.4%, 32.8% and 43.2% in patients with BSI by KPC-CRE, MBL-CRE, CRPA and CRAB, respectively (P < .001). On multivariable analysis, age, ward of hospitalization, SOFA score, and Charlson Index were factors associated with 30-day mortality, while urinary source of infection and early appropriate therapy resulted protective factors. Compared to CS-GNB, MBL-producing CRE (aOR 5.86, 95% CI 2.72-12.76), CRPA (aOR 1.99, 95% CI 1.48-5.95) and CRAB (aOR 2.65, 95% CI 1.52-4.61) were significantly associated with 30-day mortality. Attributable mortality rates were 5% for KPC-, 35% for MBL, 19% for CRPA, and 16% for CRAB. CONCLUSIONS: In patients with BSIs, carbapenem-resistance is associated with an excess of mortality, with MBL-producing CRE carrying the highest risk of death.

Impact of a Multistep Bundles Intervention in the Management and Outcome of Gram-Negative Bloodstream Infections: A Single-Center "Proof-of-Concept" Study.

Background: This is a "proof-of-concept" study aiming to evaluate the impact of a multistep bundles intervention in the management and outcomes of patients with gram-negative bloodstream infections (GN-BSIs). Methods: This was a single-center, quasi-experimental design study. In the pre-phase (January 2019 to May 2020), patients were retrospectively enrolled. During the post-phase (June 2020 to September 2021), all patients were prospectively enrolled in a nonmandatory 3-step bundles intervention arm including (i) step 1: imaging to detect deep foci of infection, follow-up blood cultures and procalcitonin monitoring; (ii) step 2: early targeted antibiotic treatment and surgical source control; (iii) step 3: discontinuation of antibiotics within 7-10 days in case of uncomplicated BSI. Patients were followed up to 28 days from BSI onset. The primary outcome was 28-day mortality. Results: A total of 271 patients were enrolled: 127 and 144 in the pre- vs post-phase, respectively. Full application of step 1 (67% vs 42%; P < .001), step 2 (83% vs 72%; P = .031), and step 3 (54% vs 2%; P < .001) increased in the post-phase. Overall, the intervention reduced 28-day mortality (22% vs 35%, respectively; P = .016) and the median duration of total (11 vs 15 days; P < .001) and targeted (8 vs 12 days; P = .001) antibiotic therapy. Finally, the multivariate Cox regression confirmed the independent protective effect of adherence to step 1 (adjusted hazard ratio [aHR], 0.36; 95% CI, 0.20-0.63) and step 2 (aHR, 0.48; 95% CI, 0.29-0.81) on risk of 28-day mortality. Conclusions: Clinical management and outcomes of patients with GN-BSIs may be improved by providing a pre-established multistep bundles intervention.

Loa loa in the Vitreous Cavity of the Eye: A Case Report and State of Art.

Loa loa is a filarial nematode responsible for loiasis, endemic to West-Central Africa south of the Sahara and transmitted by flies. This study reports a case of L. loa in the vitreous cavity of the eye of a young patient, along with an in-depth literature review. A 22-year-old woman from Cameroon who migrated from Cameroon to Italy was referred to the Emergency Ophthalmology Department at Policlinico di Bari in July 2021 with the presence of a moving parasite in the subconjunctiva of the left eye. A recent onset of a papular lesion on the dorsal surface of the right wrist and a nodular lesion in the scapular region were detected. L. loa filariasis was diagnosed based on anamnestic data, clinical and paraclinical signs, and a parasitological test confirming the presence of microfilariae in two blood samples collected in the morning of two different days. Because of the unavailability of diethylcarbamazine (DEC), albendazole (ALB) 200 mg twice daily was administered for 21 days. A mild exacerbation of pruritus occurred during treatment, but resolved with the use of an antihistamine. A single dose of 12 mg ivermectin was prescribed at the end of the treatment with albendazole. Unlike other endemic parasite infections, L. loa is not included in the Global Program to Eliminate Lymphatic Filariasis, because it is not mentioned in the WHO and CDC list of neglected tropical diseases. This can result in an overall risk of lack of attention and studies on loiasis, with lack of data on global burden of the disease.

Testing Club Convergence in Female Smoking Prevalence.

In this paper, we applied the concept of convergence to examine the evolution of smoking prevalence among women in 191 countries worldwide from 1990 to 2019. First, the non-linear time-varying factor model proposed by Phillips and Sul was adopted to identify potential clusters (clubs), wherein groups of countries converge to similar female smoking rates. Second, an ordered logit regression model was used to assess the impact of cigarette affordability on the probability of falling within a given cluster. The hypothesis of global convergence was rejected. However, the clustering algorithm successfully identified five and nine clubs, within countries with increasing and decreasing smoking prevalence, respectively. A higher relative income-price ratio (i.e., lower cigarette affordability) increased the likelihood of belonging to a club of countries with a low prevalence of female tobacco smoking.

Does the Prevalence of Obesity Affect the Demand for Soft Drinks? Evidence from Cross-Country Panel Data.

The impact of soft drinks on obesity has been widely investigated during the last decades. Conversely, the role of obesity as a factor influencing the demand for soft drinks remains largely unexplored. However, understanding potential changes in the demand for soft drinks, as a result of changes in the spread of obesity, may be useful to better design a comprehensive strategy to curb soft drink consumption. In this paper, we aim to answer the following research question: Does the prevalence of obesity affect the demand for soft drinks? For this purpose, we collected data in a sample of 97 countries worldwide for the period 2005-2019. To deal with problems of reverse causality, an instrumental variable approach and a two-stage least squares method were used to estimate the impact of the age-standardized obesity rate on the market demand for soft drinks. After controlling for several demographic and socio-economic confounding factors, we found that a one percent increase in the prevalence of obesity increases the consumption of soft drinks and carbonated soft drinks by about 2.37 and 1.11 L per person/year, respectively. Our findings corroborate the idea that the development of an obesogenic food environment is a self-sustaining process, in which obesity and unhealthy lifestyles reinforce each other, and further support the need for an integrated approach to curb soft drink consumption by combining sugar taxes with bans, regulations, and nutrition education programs.

Is the development of obesogenic food environments a self-reinforcing process? Evidence from soft drink consumption.

BACKGROUND: Understanding how the development of obesogenic food environments and the consumption of ultra-processed foods and beverages influence each other can help policymakers to identify effective ways to curb the current obesity epidemic. This paper was designed to investigate whether, and to what extent, the consumption of soft drinks and the prevalence of obesity are linked through feedback effects. METHODS: An ecological study design and a simultaneous equation model were used to investigate the existence of a vicious cycle between the consumption of soft drinks and the prevalence of obesity. The analysis was based on a longitudinal dataset covering per capita sales of soft drinks, the age-standardised prevalence rate of obesity and several demographic and socio-economic control variables in a sample of 98 countries worldwide for the period 2005-2019. RESULTS: Using a Two-Stage Least Squares (2SLS) regression model with fixed effects, we documented a self-reinforcing process that links consumption and obesity. Changes in the spread of obesity were associated with changes in soft drink consumption: a one-unit increase in the age-adjusted prevalence rate of obesity increased consumption by about 2.39 l per person per year. Similarly, as the consumption of soft drinks rose, so did the prevalence of obesity: the age-adjusted rate of obesity increased by 0.07% for every additional litre consumed per capita. Computing the impact multipliers, we found that the outcome of a one-unit decrease in the average price of soft drinks was twofold: a) the prevalence of obesity increased by around 0.17%; and b) consumption increased by around 2.40 l per person, the sum of the increase directly caused by the price reduction (2 l) and the increase due to the interplay between consumption and obesity (0.4 l). CONCLUSIONS: This study has identified a feedback loop between unhealthy habits (i.e. the consumption of soft drinks) and health outcomes (i.e. the prevalence of obesity). This interplay amplifies the impact of any exogenous changes in the determinants of consumption and obesity. These feedback effects should be considered and exploited in planning effective strategies to tackle the burden of obesity and the global epidemic of non-​communicable diseases.

Infection caused by Sporothrix schenckii: an autochthonous case in Bari, Southern Italy.

An autochthonous case of lymphocutaneous sporotrichosis caused by Sporothrix schenckii is reported. The patient developed skin lesions localized along the lymphatics that appeared after he suffered an injury while collecting wicker canes in marshy water. The fungus was identified as Sporothrix schenckii by MALDI-TOF and sequencing. Phylogenetic analysis was also performed. Low MIC values were detected for all tested echinocandins and azoles except for fluconazole. The patient was treated with itraconazole without significant improvement. A regression of lesions was observed after 3 months of therapy with voriconazole. Few cases of sporotrichosis have been reported in Europe. However, several cases of sporotrichosis have been described in Italy. The incidence of sporotrichosis in Italy may be underestimated and microbiologists, and clinicians must be aware of this fungal infection.

Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing Enterobacterales Infections: A Multicenter Nationwide Clinical Experience (CEFTABUSE II Study).

BACKGROUND: Few data are reported in the literature about the outcome of patients with severe extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) infections treated with ceftolozane/tazobactam (C/T), in empiric or definitive therapy. METHODS: A multicenter retrospective study was performed in Italy (June 2016-June 2019). Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to ESBL-E infection and lack of microbiological evidence of infection. The primary end point was to identify predictors of clinical failure of C/T therapy. RESULTS: C/T treatment was documented in 153 patients: pneumonia was the most common diagnosis (n = 46, 30%), followed by 34 cases of complicated urinary tract infections (22.2%). Septic shock was observed in 42 (27.5%) patients. C/T was used as empiric therapy in 46 (30%) patients and as monotherapy in 127 (83%) patients. Favorable clinical outcome was observed in 128 (83.7%) patients; 25 patients were considered to have failed C/T therapy. Overall, 30-day mortality was reported for 15 (9.8%) patients. At multivariate analysis, Charlson comorbidity index >4 (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9-3.5; P = .02), septic shock (OR, 6.2; 95% CI, 3.8-7.9; P < .001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9-5.3; P = .001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01-0.34; P < .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14-0.55; P < .001) were associated with clinical success. CONCLUSIONS: Data show that C/T could be a valid option in empiric and/or targeted therapy in patients with severe infections caused by ESBL-producing Enterobacterales. Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT.

Sphingomonas paucimobilis outbreak in a dialysis room: Case report and literature review of an emerging healthcare associated infection.

Sphingomonas paucimobilis is an emerging aerobic, nonfermenting gram-negative, opportunistic bacterium involved in many healthcare-associated infections. We herein report the first outbreak of S paucimobilis catheter related bacteriemia occurred on the same day in 3 patients sharing a dialysis room. This report suggests that S paucimobilis could represent a further emerging cause of rapidly spreading healthcare-associated infections, and highlights the importance of a high level of surveillance and control measures.

Sugar-sweetened beverage affordability and the prevalence of overweight and obesity in a cross section of countries.

BACKGROUND: A key component of 'obesogenic environments' is the ready availability of convenient, calorie-dense foods, in the form of hyper-palatable and relatively inexpensive ultra-processed products. Compelling evidence indicates that the regular consumption of soft drinks, specifically carbonated and non-carbonated sugar-sweetened beverages (SSBs), has a significant impact on the prevalence of overweight and obesity. However, to implement country-level effective prevention programmes we need to supplement this evidence with quantitative knowledge of the relationships between overweight/obesity and the main determinants of SSB consumption, notably SSB prices and consumers' disposable income. METHOD: Affordability considers the simultaneous effects of both price and disposable income on the buying decision. The purpose of this study was to investigate the effect of SSB affordability on the consumers' purchasing behaviour and weight-related health outcomes. Our study was divided into three parts. First, we computed SSB consumption and affordability for approximately 150 countries worldwide. Second, we estimated a demand function for SSBs to assess the impact of affordability on consumption at the country level. Third, we used a multivariate regression model and country data on the prevalence of overweight and obesity to test the role of SSB affordability in the current obesity epidemic. RESULTS: The analysis reveals that SSB affordability: 1) showed both a large variability across countries and a clear tendency to increase substantially with the level of economic development; 2) played a key role in determining cross-country differences in the amount of soft drink consumed per capita; and 3) was significantly associated with the prevalence rates of both overweight and obesity. Specifically, we show that a 10 % increase in SSB affordability was associated, on average, with approximately 0.4 more overweight/obese adults per 100 inhabitants. CONCLUSIONS: By controlling for the main possible confounding factors, our results clearly indicate that affordability is a major driver of purchasing behaviours and is significantly associated with the prevalence rates of both overweight and obesity. We thus suggest a fiscal approach to curb SSB consumption based on the effectiveness of 'soda taxes' to affect the long-term dynamic of SSB affordability.

Simple vs. Complex Carbohydrate Dietary Patterns and the Global Overweight and Obesity Pandemic.

Nowadays, obesity and being overweight are among the major global health concerns. Many, diet-related diseases impose high tangible and intangible costs, and threaten the sustainability of health-care systems worldwide. In this study, we model, at the macroeconomic level, the impact of energy intake from different types of carbohydrates on the population's BMI (body mass index). We proceed in three steps. First, we develop a framework to analyse both the consumption choices between simple and complex carbohydrates and the effects of these choices on people health conditions. Second, we collect figures for 185 countries (over the period 2012-2014) regarding the shares of simple (sugar and sweetener) and complex (cereal) carbohydrates in each country's total dietary energy supply. Third, we use regression techniques to: (1) estimate the impact of these shares on the country's prevalence of obesity and being overweight; (2) compute for each country an indicator of dietary pattern based on the ratio between simple and complex carbohydrates, weighted by their estimated effects on the prevalence of obesity and being overweight; and (3) measure the elasticity of the prevalence of obesity and being overweight with respect to changes in both carbohydrate dietary pattern and income per capita. We find that unhealthy eating habits and the associated prevalence of excessive body fat accumulation tend to behave as a 'normal good' in low, medium- and high-HDI (Human Development Index) countries, but as an 'inferior good' in very high-HDI countries.

Gender discrimination, gender disparities in obesity and human development.

Measuring gender inequality and women's empowerment is essential to understand the determinants of gender gaps, evaluate policies and monitor countries' progress. With this aim, over the past two decades, research has mainly been directed towards the development of composite indices. The purpose of this paper is to introduce a new and interdisciplinary perspective to the current debate on measuring gender inequality in human development. As a starting point, we develop a simple macroeconomic model of the interdependence between human development and gender inequality. We then introduce a biometric indicator, based on the ratio of female to male body mass index, to measure women's empowerment at the country level. Finally, by using the latest available data, we examine the ability of this biometric indicator to capture countries' performance in achieving gender equality. We obtain five main results: 1) we provide a theoretical framework to explain the joint determination of human development and gender inequality; 2) we show how to use this framework to simulate the impact of exogenous shocks or policy changes; 3) we demonstrate that exogenous changes have a direct and a multiplier effect on human development and gender inequality; 4) we find that the distribution of obesity between the female and male populations represents a useful proxy variable for measuring gender equality at the country level; 5) finally, we use these results to integrate and develop existing knowledge on the 'ecological' approach to the overweight and obesity pandemic.

Look what I am doing: does observational learning take place in evocative task-sharing situations?

Two experiments were conducted to investigate whether physical and observational practice in task-sharing entail comparable implicit motor learning. To this end, the social-transfer-of-learning (SToL) effect was assessed when both participants performed the joint practice task (Experiment 1--complete task-sharing), or when one participant observed the other performing half of the practice task (Experiment 2--evocative task-sharing). Since the inversion of the spatial relations between responding agent and stimulus position has been shown to prevent SToL, in the present study we assessed it in both complete and evocative task-sharing conditions either when spatial relations were kept constant or changed from the practice to the transfer session. The same pattern of results was found for both complete and evocative task-sharing, thus suggesting that implicit motor learning in evocative task-sharing is equivalent to that obtained in complete task-sharing. We conclude that this motor learning originates from the simulation of the complementary (rather than the imitative) action.

Facilitation and interference components in the joint Simon task.

Two experiments were conducted to assess whether the joint Simon effect is composed of facilitation and interference and whether facilitation is increased by a joint spatially compatible practice performed before performing the joint Simon task. In both experiments, participants were required to perform a Simon task along another person. Trials could be corresponding, non-corresponding, and neutral. In Experiment 1, participants performed only the Simon task. In Experiment 2, participants first practiced on a joint spatial compatibility task with a compatible mapping and, after a 5-min delay, transferred to a joint Simon task. Results indicated that the joint Simon effect consisted primarily of interference, which was significantly increased by a spatially compatible practice performed jointly. These results allow us to better define in what ways the presence of the other influences performance, in showing that when participants perform a task along with another individual, they display a disadvantage (i.e., slower RTs) when they have to respond to stimuli appearing on the other agent's side.