Breathing in the future: prenatal exposure to air pollution and infants' health outcomes in the USA.

OBJECTIVES: This study aimed to investigate the impact of air pollution on birth outcomes in the USA over several decades. STUDY DESIGN: Approximately 70 million birth records were assessed for the years 1980-2020. This study focussed on seven measures of birth outcomes, including birth weight, low birth weight, very low birth weight, full-term birth weight, foetal growth, gestational age and very premature birth. METHODS: An instrumental variable identification strategy was used that exploited within county-month and within month-year of birth variations in exposure to precipitation-induced changes in air pollution. RESULTS: Air pollution was found to have negative and large effects on a wide range of birth outcomes. The study findings suggest that a one-standard-deviation increase in ozone was associated with a 6.4% and 12.8% increase (from the mean) in the proportion of low birth weight and very preterm birth infants, respectively. Further analyses suggest that these effects were heterogeneous across trimesters of pregnancy and reveal larger impacts during the second and third trimesters. CONCLUSIONS: The results suggest that the ordinary least square estimates of previous studies considerably underestimate the true effects of pollution on birth outcomes. Policies that aim to improve the health capital of future generations should allocate more resources and initiatives to improving environmental air quality.

[Antidepressive agents and hypertension: A case/no-case study in French pharmacovigilance database]. / Antidépresseurs et hypertension artérielle : étude cas /non-cas dans la base nationale de pharmacovigilance.

INTRODUCTION: Drug-induced hypertension was described with several pharmacological classes. The association between hypertension and antidepressant drugs (AD) is controversial. The objective of this study was to evaluate the link between hypertension and ADs. MATERIALS AND METHODS: A retrospective disproportionality analysis from observations consecutively reported to the French pharmacovigilance database between 1985 and 2020 was performed. The relationship between the suspected ADs and the occurrence of hypertension was assessed by calculating the reporting odds ratio (ROR) in a case/non-case design. A negative (paracetamol) and a positive (celecoxib) control were used to validated this disproportionality method. RESULTS: We compared 6725 cases (including 464 AD-related cases) to 789,483 non-cases (including 56,440 AD-related cases). The reporting of hypertension was significantly associated with serotonin/norepinephrine reuptake inhibitors (SNRI) (ROR 1.43, 95 % CI 1.26-1.64) and monoamine oxidase inhibitors (MAOI) (ROR 6.41, 95 % CI 4.25-9.67) but not with other ADs classes. Concerning ADs analyzed independently of their AD class, a significant signal was observed with many SNRIs (duloxetin, milnacipran and venlafaxin) and with all MAOIs (moclobemide, iproniazide) (ROR between 2.04 and 17.93) but not with others ADs. The ROR value of positive (celecoxib) and negative (paracetamol) controls were ROR=1.53; IC95 %=1.04-2.26 and ROR=0.72; IC95 %=0.65-0.80, respectively. CONCLUSION: We found a significant association between development or worsening of hypertension and SNRIs and MAOIs but not with others ADs, in this study performed in real conditions of life. It is therefore advisable to remain cautious when prescribing ADs and to check systematically for hypertension.

Active tuberculosis in psoriasis patients treated with TNF antagonists: a French nationwide retrospective study.

BACKGROUND: There is limited information about active tuberculosis (TB) occurring in psoriasis patients treated with Tumor necrosis factor (TNF) antagonists. OBJECTIVE: To describe the clinical characteristics of TB in psoriasis patients treated with TNF antagonists. METHODS: Nationwide retrospective study of psoriasis patients having experienced TB. Cases of TB were collected via three methods: search in the national pharmacosurveillance database, questionnaire to members of the French psoriasis research group, the college of French dermatology professors. We collected demographic data, TNF antagonist used, screening for latent tuberculosis infection, median time between TNF antagonists introduction and first symptoms, tests used for diagnosing TB infection, clinical features of tuberculosis and outcome. RESULTS: Eight centres reported 12 cases of TB between 2006 and 2014. They were nine men and three women with mean age of 49 years. All patients had adequate screening for latent tuberculosis. Three patients had stayed in endemic areas, three reported contact with a patient with TB. Tuberculosis presentation was extrapulmonary in 10 patients. Seven patients were treated with infliximab, four with adalimumab and one with certolizumab. The median time between TNF antagonist introduction and first symptoms of tuberculosis was 23.4 weeks (2-176). Six of the 12 patients had a positive direct examination and/or positive culture for Mycobacterium tuberculosis. Histological samples of affected organs taken from seven patients showed granulomatous inflammation in six, with caseating necrosis in five. Two of the 12 patients died of disseminated TB. CONCLUSION: This study shows tuberculosis in patients treated with TNF antagonists still occurs despite adherence to tuberculosis prevention guidelines. Prophylactic measures do not fully prevent the occurrence of tuberculosis. Rapid initiation of effective anti-tuberculosis treatment is important even in patients with negative mycobacteriological examination presenting with suggestive symptoms and organ involvement.

Ischaemic stroke after exposure to aflibercept: interaction with vitamin K antagonist and/or direct pharmacodynamic effect?

WHAT IS KNOWN AND OBJECTIVE: Vascular endothelial growth factor (VEGF) proteins are involved in the regulation of vascular endothelium, and their inhibition led to the development of a number of drugs used for malignancies or exudative neo-vascular age-related macular degeneration (AMD). CASE SUMMARY: We report a case of ischemic stroke in an 87-year-old woman having received intravitreal aflibercept, a new anti-VEGF for AMD. She had been treated with ranibizumab since 2007. In 2013, ranibizumab was replaced with aflibercept, followed by a decrease in the International Normalized Ratio, complicated by a stroke a few days later. The rechallenge was positive. WHAT IS NEW AND CONCLUSION: A potential time-dependent interaction between aflibercept and VKA antagonist and/or a direct effect of aflibercept may have contributed to the occurrence of the ischaemic stroke. Currently available data suggest some pharmacokinetic and pharmacodynamic effects of aflibercept by explaining its pro-thrombotic profile.

Interaction effects of cell diffusion, cell density and public goods properties on the evolution of cooperation in digital microbes.

Microbial cooperation typically consists in the sharing of secreted metabolites (referred to as public goods) within the community. Although public goods generally promote population growth, they are also vulnerable to exploitation by cheating mutants, which no longer contribute, but still benefit from the public goods produced by others. Although previous studies have identified a number of key factors that prevent the spreading of cheaters, little is known about how these factors interact and jointly shape the evolution of microbial cooperation. Here, we address this issue by investigating the interaction effects of cell diffusion, cell density, public good diffusion and durability (factors known to individually influence costs and benefits of public goods production) on selection for cooperation. To be able to quantify these effects across a wide parameter space, we developed an individual-based simulation platform, consisting of digital cooperator and cheater bacteria inhabiting a finite two-dimensional continuous toroidal surface. Our simulations, which closely mimic microbial microcolony growth, revealed that: (i) either reduced cell diffusion (which keeps cooperators together) or reduced public good diffusion (which keeps the public goods closer to the producer) is not only essential but also sufficient for cooperation to be promoted; (ii) the sign of selection for or against cooperation can change as a function of cell density and in interaction with diffusion parameters; and (iii) increased public goods durability has opposing effects on the evolution of cooperation depending on the level of cell and public good diffusion. Our work highlights that interactions between key parameters of public goods cooperation give rise to complex fitness landscapes, a finding that calls for multifactorial approaches when studying microbial cooperation in natural systems.

Adverse drug reactions in an emergency medical dispatching centre.

PURPOSE: The purpose of this study is to assess the incidence of adverse drug reactions (ADR) leading to call an emergency medical dispatching centre. METHODS: A prospective, observational, monocentric clinical study performed over a 2-year period (2011-2012) in a French prehospital emergency dispatching centre, the Service d'Aide Médicale Urgente (SAMU) covering 1,156,000 inhabitants. All adult patients (age≥18) who called for any cause were included. We created an electronic trigger 'iatrogenic event' implemented by the dispatching physician for each suspected case of ADR, then we completed the analyses of all the cases with a chief complain represented in more than 1% of the triggered cases. The primary outcome variable was the occurrence of any possible ADR. We then used the French method of causal relationship assessment. RESULTS: The SAMU dispatched 339,915 calls during the study. In total, 1,467 ADRs were identified, representing 0.95% (CI 95% 0.90-1.00%) of cases. ADRs were as serious (SADR) in 51.06% (CI 95% 48.45-53.67%) of cases. The major ADR observed was haemorrhage, (42.81% (CI 95% 40.62-45.00%), n=628) followed by allergy, hypoglycaemia, vomiting, dizziness and drowsiness. The class of drugs most frequently involved was antithrombotic (43.69% (CI 95% 41.45-45.93%), n=641), followed by insulin (17.98% (CI 95%:17.06-18.90%), n=264). CONCLUSIONS: Emergency calls concerning ADRs were estimated as 9/1,000, and one out of two is serious.

Analysis of patients' narratives posted on social media websites on benfluorex's (Mediator® ) withdrawal in France.

WHAT IS KNOWN AND OBJECTIVE: Websites and discussion lists on health issues are among the most popular resources on the Web. Use experience reported on social media websites may provide useful information on drugs and their adverse reactions (ADRs). Clear communication on the benefit/harm balance of drugs is important to inform proper use of drugs. Some data have shown that communication (advisories or warnings) is difficult. This study aimed to explore the Internet as a source of data on patients' perception of risk associated with benfluorex and the impact of wider media coverage. METHODS: Three French websites were selected: Doctissimo, Atoute.org considered the best-known and visited website in France for health questions and Vivelesrondes (Long live the Tubbies) for overweight people. Three periods were chosen: (1) before November 2009 (i.e. before benfluorex withdrawal), (2) between November 2009 and November 2010 (when the risk of valvulopathy with benfluorex appeared in social media) and (3) after November 2010. RESULTS AND DISCUSSION: Two hundred twenty initial postings were analysed. These lead to 660 secondary postings which were analysed separately. In period 1, 114 initial postings were analysed, mostly concerning efficacy of the drug (72%). In period 2, 42 initial postings were analysed involving mainly ADRs or warnings (73%). In period 3, 64 initial postings were analysed; most frequent expressing anger directed at the healthcare system (58%) and anxiety about cardiovascular ADRs (30%). Online consumer postings showed that there were drastic changes in consumers' perceptions following media coverage. WHAT IS NEW AND CONCLUSION: This study suggests that analysis of website data can inform on drug ADRs. Social media are important for communicating information on drug ADRs and for assessing consumer behaviour and their risk perception.

Environmental, developmental, and genetic factors controlling root system architecture.

A better understanding of the development and architecture of roots is essential to develop strategies to increase crop yield and optimize agricultural land use. Roots control nutrient and water uptake, provide anchoring and mechanical support and can serve as important storage organs. Root growth and development is under tight genetic control and modulated by developmental cues including plant hormones and the environment. This review focuses on root architecture and its diversity and the role of environment, nutrient, and water as well as plant hormones and their interactions in shaping root architecture.

Mesoporous organosilicas with highly-content tyrosine framework as extractive phases for non-steroidal anti-inflammatory drugs in aquatic media.

BACKGROUND: Attentions regarding ordered mesoporous silica materials (OMSs), with large specific surface areas and narrow pore size distribution, which are prepared via self-assembly techniques, have been raised in sorption, separation, and sample preparation. However, in order to extend and improve their applications, a functionalization step is required. Organic units can be anchored on the inner or outer surface as well as in the silica wall framework by co-condensation-, grafting-, and periodic mesoporous organosilica (PMO) preparation approaches. Apparently, by synthesizing PMO with extensive and flexible organic bridging groups within the mesoporous wall, an efficient extractive phase can be achieved. RESULTS: We employed tyrosine amino acid to synthesize a PMO-based extractive phase. The FT-IR, 1H NMR, HR-ESI-MS, Low angle-XRD, TEM, FESEM, BET, and EDX-MAP analyses confirmed the successful synthesis of PMO within the salt-assisted templating method. A comprehensive study on sorption behavior of PMO was performed and its efficiency was evaluated against the grafting and co-condensation methods. Then, it was implemented to the pipette tip-micro solid phase extraction (PT-µ-SPE) of widely used non-steroidal anti-inflammatory drugs (NSAIDs) in water/wastewaters. Limits of detection and quantification were obtained in the range of 0.1-1.5 and 0.3-5 µg L-1, respectively. The calibration plots are linear in the 1-1000, 3-1000, 10-750, and 3-750 µg L-1, respectively. The intra-and inter-day precision at 50 and 200 µg L-1 levels are 2.9-7.1 % and 3.5-8%, while recoveries are between 84 and 111 %. SIGNIFICANCE: High-capacity tyrosine functionalized PMO with 2D hexagonal symmetry silica mesoporous structures found to be highly efficient extractive media. Despite the bulkiness and flexibility of the bridging group within the mesoporous wall, the synthesis condition was optimized in order to load more organic content in the PMO structure. The PMO performance was superior over organically modified ordered mesoporous silica materials prepared by the grafting and co-condensation methods.

Effects of cyclic static stretch on fatigue recovery of triceps surae in female basketball players.

Static stretch is a safe and feasible method which usually is used before exercise to avoid muscle injury and to improve muscle performance. The purpose of this study was to determine the effects of cyclic static stretch (CSS) on fatigue recovery of triceps surae (TS) in female basketball players. Nine athlete volunteers between 20 and 30 years participated in this study containing two sessions. After warm-up a pressure cuff was fastened above the knee joint and its pressure was increased to 140 mmHg. The subjects were asked to perform one maximum voluntary contraction (MVC) followed by a fatigue test including maximum isometric fatiguing contraction of TS. These steps were similar in both sessions. Then, a two-minute rest was included in the first session while 4 static stretches were performed to TS in the second session. After interventions, one MVC was done and the pressure cuff was released. During these steps, peak torque (PT) and electromyography (EMG) were recorded. The amount of lower leg pain was determined by the visual analogue scale (VAS). The value of PT increased significantly after CSS but its increase was not significant after rest. It seems that the effects of rest and CSS on the EMG parameters, PT and pain are similar.

Contact photoallergy to isothipendyl chlorhydrate.

Isothipendyl chlorhydrate is an azaphenothiazine, an active ingredient of an antipruriginous gel, Apaisyl gel® (Merck Médication Familiale, Dijon, France). Although Apaisyl gel is registered and used worldwide, we present the first case of contact photoallergy to isothipendyl chlorhydrate to our knowledge. The diagnosis suspected on the basis of a positive UVA photopatch test to chlorpromazine was confirmed by a strongly positive UVA Apaisyl gel photopatch test and our photophysical studies. This case confirms the need to keep the phenothiazines in the photopatch test standard series as a diagnostic marker of phenothiazine photoallergy.

Lymphoma in patients treated with anti-TNF: results of the 3-year prospective French RATIO registry.

OBJECTIVE: To describe cases of lymphoma associated with anti-TNF therapy, identify risk factors, estimate the incidence and compare the risks for different anti-TNF agents. METHODS: A national prospective registry was designed (Research Axed on Tolerance of bIOtherapies; RATIO) to collect all cases of lymphoma in French patients receiving anti-TNF therapy from 2004 to 2006, whatever the indication. A case-control analysis was conducted including two controls treated with anti-TNF per case and an incidence study of lymphoma with the French population was used as the reference. RESULTS: 38 cases of lymphoma, 31 non-Hodgkin's lymphoma (NHL) (26 B cell and five T cell), five Hodgkin's lymphoma (HL) and two Hodgkin's-like lymphoma were collected. Epstein-Barr virus was detected in both of two Hodgkin's-like lymphoma, three of five HL and one NHL. Patients receiving adalimumab or infliximab had a higher risk than those treated with etanercept: standardised incidence ratio (SIR) 4.1 (2.3-7.1) and 3.6 (2.3-5.6) versus 0.9 (0.4-1.8). The exposure to adalimumab or infliximab versus etanercept was an independent risk factor for lymphoma in the case-control study: odds ratio 4.7 (1.3-17.7) and 4.1 (1.4-12.5), respectively. The sex and age-adjusted incidence rate of lymphoma was 42.1 per 100 000 patient-years. The SIR was 2.4 (95% CI 1.7 to 3.2). CONCLUSION: The two to threefold increased risk of lymphoma in patients receiving anti-TNF therapy is similar to that expected for such patients with severe inflammatory diseases. Some lymphomas associated with immunosuppression may occur, and the risk of lymphoma is higher with monoclonal-antibody therapy than with soluble-receptor therapy.

The reliability measurements of lateral scapular slide test at three different degrees of shoulder joint abduction.

BACKGROUND: Lateral scapular slide test (LSST) quantitatively measures the distance between thoracic spine (T7) and inferior angle of scapula. OBJECTIVE: In this study, the intra-rater reliability, inter-rater reliability and diagnostic accuracy of LSST were measured using a caliper. METHODS: Three measurements of each test position were obtained bilaterally. Intraclass correlation coefficient (ICC) (2.1), 95% CI and 2 SEMs were calculated for intra-rater and inter-rater reliability of the absolute scapular distance. Sensitivity, specificity, positive and negative likelihood ratios were determined. RESULTS: 27 people with and 30 people without shoulder pain participated. The mean age (SD) for the participant was 47.7 (11.6) years and 33.5 (11.7) years, respectively. The ICCs for intra-rater reliability were high. A range of poor to good ICCs was found for inter-rater reliability. The 2 SEMs ranged from 4.6 to 7.9 mm for intra-rater reliability and from 6.8 to 13.4 mm for inter-rater reliability for people with shoulder pain. Positive and negative likelihood ratios from 0.94 to 1.22 and from 0.21 to 2.5, respectively, were demonstrated. CONCLUSION: SST did not show a consistent high reliability. The diagnostic accuracy of the LSST was low, which questions the clinical importance of the tests outcomes.

Modulation of the ipsilateral and contralateral H reflexes following ipsilateral mechanical pressure of the foot in normal subjects.

OBJECTIVE: Mechanoreceptors from the foot sole likely contribute in the reflex regulations. Therefore, it was hypothesized that repetitive low threshold afferents stimulation would have an inhibitory effect on the soleus H-reflexes. METHODS: Sixteen normal subjects voluntarily, participated in the study and were randomly allocated. Subjects were remained in prone position. The Cutaneous Mechanical Pressure (CMP equal to 50% of leg and foot weight) was applied to the ipsilateral lateral and Medial plantar surface by a designed instrument through a square plate (30 x 30 mm). H reflex as an indicator for excitability of motoneurones was bilaterally elicited before and after the application of the CMP. The H-reflex parameters were estimated. RESULTS: Mechanical pressure significantly depressed soleus H-reflex excitability in ipsilateral and contralateral feet in all subjects. CONCLUSION: The demonstration of a decrease in H-reflex excitability as a result of applied pressure to the foot sole suggests that the change in reflex excitability is the result of a common spinal mechanism. The results highlight the modulatory effects that natural stimulation of afferents can have on reflex excitability. SIGNIFICANCE: The placement of a small flat plate, in order to apply pressure to the plantar eminence, may be useful for modulation of muscle tone. In addition, these findings might be useful for reducing spasticity; because spasticity is at least partially caused by hyperexcitability of the motorneuron pool.

Drug exposure and perceived adverse drug events reported by liver-transplant patients.

INTRODUCTION: Posttransplant patient outcome and quality of life are affected by different factors, such as post-graft context, psychological state, and polymedication. Many surveys have been carried out to study immunosuppressant ADRs, and have mainly used a questionnaire completed by patients, but few have asked patients about their drug exposure. The aim of this study is to describe drug exposure and adverse drug events (ADEs) reported by liver-transplant patients (LTP). METHODS: This observational, retrospective study assessed questionnaires from LTPs concerning demographic data, drug exposure, and ADEs. RESULTS: 118 LTPs exposed to 5.9 (+/- 2.8) drugs with immunosuppressive regimens, consisting mainly of tacrolimus (79.3%), cyclosporine (18.1%), or sirolimus (2.6%), were also exposed to antihypertensive drugs (43.2%), protonpump inhibitors (30.5%), statins (28.8%), drugs acting on bile composition (26.3%), and diuretics (19.5%). 1,389 ADEs were reported: 30.1% neurological, 13.4% cutaneous, 12.4% hematological, 11.1% digestive, 10.1% osteomuscular, 6.6% cardiovascular, and 16.3% others. Significantly more ADEs were reported by patients exposed to cyclosporine than those receiving tacrolimus (p < 0.05). Patients with a transplant for < 18 months had more tremors and those with a transplant for > 79 months reported more hirsutism, gingival hypertrophia, and arterial hypertension. CONCLUSIONS: This study shows the value of patient-reporting via structured interviews for both drug exposure and ADEs, and the importance of this approach to complement total data collection.

Overview of adverse reactions to nefopam: an analysis of the French Pharmacovigilance database.

Nefopam is widely used for the relief of moderate acute pain. Its safety profile remains to be specified. The objective of the study was to review adverse reactions to nefopam spontaneously reported to the French Pharmacovigilance system. All cases of adverse drug reactions (ADRs) associated with nefopam, registered in the French Pharmacovigilance database from January 1, 1995 to December 31, 2004, were reviewed. For each reported ADR, information about patient (age, gender, medical history), drug exposure (suspected and concomitantly used drugs), characteristics of ADRs (imputability score, time of onset, seriousness, outcome) were collected. A total of 114 ADRs with an imputability rated from 'plausible' (I2) to 'likely' (I3) and 'very likely' (I4) was analysed. The most frequent ADRs included 'expected' ADRs such as sweating, nausea, tachycardia, malaise or vomiting; 61 ADRs were 'unexpected. No overdose was reported; 26 ADRs (23%) were considered as 'serious'. Most of them were 'unexpected', including neuropsychiatric (hallucinations, convulsions) or cutaneous (pruritus, erythema, urticaria) ADRs. Six cases of anaphylactic ADRs (two angioedema and four anaphylactic shocks) were reported, all occurring shortly after use of nefopam during the post-operative period. Physicians should be aware of the possible occurrence of some serious ADRs when using nefopam such as convulsions and anaphylactic shocks, especially when the drug is used in special medical conditions, like post-operative periods.

Therapeutic ultrasound in the treatment of ankle plantarflexor spasticity in a unilateral stroke population: a randomized, single-blind, placebo-controlled trial.

Spasticity is a common and disabling symptom associated with Upper Motor Neuron Syndrome. The current methods of treatment for muscle spasticity have been claimed as unsatisfactory. Therapeutic ultrasound (US) is a common therapeutic modality in physiotherapy used for treating a wide variety of disorders. The aim of present study was to quantify the effects of continuous US on ankle plantarflexor spasticity in a randomized, single-blind, placebo-controlled trial. Twelve stroke patients (6 women and 6 men) randomly allocated to ultrasound (n = 6) or placebo (n = 6) groups. The patients were treated with either US or sham US for three days per week, every other day for 15 treatment sessions. The primary efficacy measures were the H-reflex and the Ashworth Scale (AS). In experimental group there was a significant reduction in the Hmax/Mmax ratio (p = 0.03). The Hmax/Mmax ratio was increased in the placebo group patients (p > 0.05). The difference between two groups was statistically significant (p = 0. 02). In both groups there was a reduction in the posttreatment AS scores. The Ashworth scores demonstrated statistically significant changes in the US group (p = 0.04). There was no statistical difference, however, when these two groups were compared (p > 0.05). Results from the present study show that treatment with US can reduce HmaxlMmax ratio as a measure of alpha motoneuron excitability and spasticity measure of AS in stroke patients with ankle plantarflexor spasticity.