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Background: Single chamber atrial pacemaker should be sufficient for patients with sinus node dysfunction (SND) with normal atrioventricular (AV) conduction. However, most patients undergo dual chamber pacemaker implantation because of concern of new onset AV block. The annual incidence of new AV block has been reported from 0.6 to 4.4 % in various studies. Objectives: Our aim is to assess mode survival in sinus node dysfunction with normal AV conduction patients implanted with AAIR. Methods: Patients who underwent single chamber atrial pacemaker implantation for SND with normal AV conduction between January 2014 and December 2021 were followed up for pacemaker device change, new onset AV block, bundle branch block, atrial fibrillation (AF), lead complications, reoperation and mortality rate. Results: A total of 113 patients underwent single chamber atrial pacemaker implantation for SND during the study period. Mean age was 55.6 ± 12.7 years. During a mean follow up of 48.7 ± 24.9 months, none of the patients required pacemaker device change to VVIR/DDDR. Nine patients underwent reoperation, 5 for lead dislodgment, 1 for high threshold, 1 for pocket site erosion and 3 for pulse generator change. None developed AV block or AF with slow ventricular rate. Only 4 patients developed AF (3 paroxysmal,1 permanent). There were 3 deaths during follow up and none were sudden deaths. Conclusion: Single chamber atrial pacing is an acceptable mode of pacing in patients with SND in developing countries. Development of AV conduction abnormalities is rare in this relatively younger population.

Primary membranoproliferative glomerulonephritis (MPGN) is a group of ultra rare kidney disorders associated with complement activation. MPGN often appears in young age and isincurable. Current treatments have varying efficiency and new clinical trials are underway to identify better and more tailored treatment pathways. We conducted semi-structured digital interviews with an international sample of MPGN patients and parents of MPGN patients to understand how they would make any potential decision to participate in future clinical trials. Six main factors influenced the decision-making process: the trial design and practical aspects, personal motivation, concerns about participation, expert advice, current state of illness, and family situation. More specifically, patients and parents considered important that participation in clinical trials is compatible with work and family life and that the expected side effects are limited. They would be motivated by the prospect of maintaining or improving their kidney function or if their current condition was poor. Providing comprehensive information about the risks and benefits of participation, co-designing trials in partnership with patients and limiting the burdens associated with participation may positively impact recruitment and adherence rates.

ABSTRACT: Objectives: Consumption trends of four broad-spectrum antimicrobials and their correlation with antimicrobial resistance in Gram-negative bacilli (GNB) from 2013–2017 within intensive care units (ICUs) were explored. Methods: Consumption of meropenem (MEM), polymyxin B (PMB), piperacillin/tazobactam (TZP) and cefepime (FEP) in defined daily doses per 1000 patient-days (DDD/1000PD) was measured. Infection-related GNB isolates were grouped according to specific resistance profiles. Time series of antimicrobial consumption and their parametric correlation with each grouped resistant GNB were explored. Results: A total of 1423 GNB were evaluated. A significant linear decline in consumption was observed for MEM [slope –3.88, 95% confidence interval (CI) –4.96 to –2.81; P < 0.0001] and PMB (slope –3.51, 95% CI –5.528 to –1.495; P = 0.0009). A significant decline in MEM-non-susceptible Acinetobacter spp. (R2 = 0.476; P = 0.006) and an increase in FEP-non-susceptible Escherichia coli (R2 = 0.124; P = 0.006) was observed. A significant correlation between MEM consumption and MEM-non-susceptible Acinetobacter spp. (r = 0.43; P = 0.001) was observed. MEM consumption and MEM-non-susceptible Acinetobacter spp. showed a positive correlation. Conclusion: Reduction in the consumption of broad-spectrum antimicrobials may alter the frequency of infection-related isolates and their antimicrobial resistance profiles.

This paper provides a systematic weight-of-evidence method for read-across analyses of data-poor chemicals. The read-across technique extrapolates toxicity from analogous chemicals for which suitable test data are available to a target chemical. To determine that a candidate analogue is the 'best' and is sufficiently similar, the evidence for similarity of each candidate analogue to the target is weighed. We present a systematic weight of evidence method that provides transparency and imposes a consistent and rigorous inferential process. The method assembles relevant information concerning structure, physicochemical attributes, toxicokinetics, and toxicodynamics of the target and analogues. The information is then organized by evidence types and subtypes and weighted in terms of properties: relevance, strength, and reliability into weight levels, expressed as symbols. After evidence types are weighted, the bodies of evidence are weighted for collective properties: number, diversity, and coherence. Finally, the weights for the types and bodies of evidence are weighed for each analogue, and, if the overall weight of evidence is sufficient for one or more analogues, the analogue with the greatest weight is used to estimate the endpoint effect. We illustrate this WoE approach with a read-across analysis for screening the organochlorine contaminant, p,p'-dichlorodiphenyldichloroethane (DDD), for noncancer oral toxicity., (Published by Elsevier Inc.)

Purpose: Increase in the antimicrobial resistance causes a concern globally. To mitigate the rapidly rising antimicrobial resistance in the health system globally antimicrobial stewardship programs (AMSP) have been advocated. Therefore, we aim to measure aggregate antibiotic consumption by both Defined Daily Dosage (DDD) and Days of Therapy (DOT) methods., Methods: As a part of Indian Council of Medical Research initiative to develop local AMSP, this prospective study of six months was conducted at a level -1 Trauma Centre of AIIMS, New Delhi. In this, we have included all the patients of polytrauma and neurosurgical Intensive care units between April to October 2019. Consumption of antibiotics data were collected manually daily by infection control practitioners. Data were presented as Days of Therapy (DOT) and Defined Daily Dose (DDD)., Results: During the six months of study, antimicrobial consumption of ICU was compared with empirical therapy v/s culture-based therapy. Overall average antimicrobial consumption for the six months for both empirical therapy and culture-based therapy DDD/1000 patient days was 531.8 and 460.7 whereas DOT/1000 patient days 489.9 and 426.04 respectively., Conclusions: Antimicrobial Stewardship activities aim to ensure judicious consumption of antimicrobials. Such data will be of value in establishing, evaluating and monitoring the function of the AMSP in the healthcare settings., Competing Interests: Declaration of competing interest All authors report no conflict of interest relevant to this article., (Copyright © 2021 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Many developing countries including China have launched command-and-control regulation (CCR) to achieve sustainable development. However, we know little about whether CCR promotes green innovation performance. This study empirically analyses the impact of CCR, which is represented by China's eleventh Five-Year Plan (FYP) environmental regulation, on enterprise green innovation performance and use green innovation efficiency as the measure of innovation. Super-SBM DEA model, difference-in-differences (DID) and difference-in-difference-in-differences (DDD) methods are employed to investigate 496 industrial enterprises in China's A-share market for the 2002-2017 period. Moreover, we distinguish each treat group from the control group by using continuous variables and consider enterprise features in the analysis. The results find that, in general, the eleventh FYP environmental regulation negatively influences enterprise green innovation efficiency in a short-term through reducing cash flows. More specifically, the eleventh FYP CCR generates a detrimental effect on small enterprises, state-owned enterprises, and enterprises in China's western and eastern regions. Overall, this empirical analysis suggests that the government should consider the effect of CCR on economy and focus on the heterogeneity of enterprises during designing environmental policies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: This study aimed to analyze radiologic and clinical results with a minimum 5 years follow-up (FUP) of lateral lumbar total disc replacement for the treatment of symptomatic lumbar degenerative disc disease., Methods: We performed a prospective, single-center, clinical, and radiologic study. Patients were treated with lumbar total disc replacement (extreme lateral total disc replacement) by a lateral transpsoas approach. From 2005 to 2012, 60 patients were enrolled (31 male, 29 female; total, 66 levels; average age, 42.8 years [standard deviation (SD), 9.7 years, range, 22-64 years]; mean body mass index, 26.0 [SD, 3.4]). Clinical end points included visual analog scale and Oswestry Disability Index questionnaires, complications, and reoperation. Radiographic end points included heterotopic ossification (McAfee classification), adjacent level disease, and prosthesis migration or subluxation., Results: The mean surgical duration was 122 minutes (SD, 45 minutes) with mean 58 mL (SD, 21 mL) of estimated blood loss. No intraoperative complication occurred. The exceptions were 1 patient with postanesthesia apnea and 2 patients with quadriceps motor deficit (resolved within 4 months with physiotherapy). Of 60 patients, 9 were missed to FUP and 51 (85%) were enrolled in the study, with mean FUP of 92 months (range, 60-122 months). In total, 5 levels (9%; 5 of 55) required to be fused. Both removal of the prostheses and interbody fusion were performed by the lateral transpsoas approach. One patient experienced CrCo allergy (at 2 months); 4 experienced persistent pain from different causes (at 7, 9, 24, and 88 months). Five patients (10%) presented with progression at adjacent levels and 2 (4%) required surgery. One patient required sacroiliac fusion at 63 months. There were no complications during the retrieval surgeries. One partial disc migration occurred but the patient refused retrieval. There was no bone bridging in 9% of the discs (grade 0 heterotopic ossification): grade I, 22%; grade II, 31%; grade III, 20%; grade IV (fusion), 18%. Most heterotopic ossification cases (93%) occurred in the lateral aspect of the disc space, and mostly at the contralateral side of the surgical approach. Patient-reported outcomes significantly improved (P < 0.01) at the last FUP. Visual analog scale back pain score was preoperatively 8.5, early postoperatively 2.5, and at last FUP 3.1. Oswestry Disability Index was preoperatively 55%, early postoperatively 31%, and at last FUP 21%., Conclusions: This study presents mid-term to long-term results of extreme lateral total disc replacement artificial disc for the treatment of lumbar degenerative disease, with fast mobilization, sustained pain relief, and improved physical function. Despite the low rate of ALDis, some discs evolved to ankyloses and others were retrieved. Lumbar artificial disc replacement by the lateral approach seems to be a safe and effective treatment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: This study critically evaluates the long-term results of standalone anterior lumbar interbody fusion (ALIF), without use of rhBMP-2, as a therapeutic option for symptomatic patients with degenerative disc disease (DDD). Furthermore, this study intends to identify predictive parameters for anterior lumbar interbody fusion outcome., Methods: A retrospective cohort study with additional telephone interview to obtain missing data was performed. All patients who underwent an L4-L5 or L5-S1 ALIF-procedure, or both, in the period between 2006 and 2011 were identified. The medical files of 123 patients with 154 fusion levels were reviewed. All patients were contacted by telephone to gather supplementary and missing information. Pain and functionality scores (Visual Analogue Scale [VAS] and Oswestry Disability Index [ODI]), radiologic (intervertebral disc height, Modic and Pfirrmann classifications), and different clinical parameters were gathered., Results: The mean age of the population at surgery was 46.2 years. Overall, 59 female and 64 male patients were included in the study. The mean VAS score for back and leg pain improved significantly (P < 0.001) with 5 and 4.4 points respectively at 3-year follow-up. Modic-type I changes are associated with a better improvement in VAS score for back pain (P = 0.026), Pfirrmann-grades IV and V and an intervertebral disc height of less than 5 mm are associated with a better improvement in leg pain (respective P-values: 0.045 and 0.033). Overall, 89% of patients would reconsider the surgical intervention., Conclusions: The ALIF technique is a durable treatment option for patients with DDD. This study suggests different predictive parameters for treatment outcome., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We analyzed dated sediment cores for evidence of Rhothane (dichlorodiphenyldichloroethane; DDD) applications to the Saint Lawrence River at Montreal, QC, Canada for the World Exposition of 1967 (Expo 67). More than 16,000kg of this pesticide were applied between 1965 and 1967 to abate nuisance shadflies that threatened visitor enjoyment. Concentrations of DDD and DDE in Lake Saint-François, 70km upstream of Expo 67, reached 12.2 and 11.5μg/kg dry weight (dw), respectively, with clear peaks between 1945 and 1970, consistent with historical use patterns; DDT was not detected. In Lake Saint-Pierre, ~100km downstream, DDD and DDE concentrations were 2 to 5 times higher, exceeding sediment quality guidelines, and DDT concentrations were as high as 3.8μg/kg. Once normalized for grain size and organic carbon, peaks of DDD, DDE and DDT were observed between 1945 and 1990 in the sediment record. Ratios of DDD to DDE were 1.0 or less in Lake Saint-François, consistent with their formation as degradation products of DDT. In contrast, ratios exceeded 1.0 in Lake Saint Pierre between 1965 and 1970, coinciding with Rhothane applications at Expo 67. Downstream, subfossil diatom assemblages showed little response to DDD inputs, but the abundance of some chironomid taxa increased while others decreased in tandem with elevated DDD concentrations. Overall, contamination of river sediments and impacts on insect communities by DDD applications at Expo 67 were still evident in sediment records 100km downstream of Montreal., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The objective of the article was to: a) present results from a case cohort pilot study comparing stand-alone ALIF and TLIF and, b) review the literature on studies comparing the clinical outcome of stand-alone ALIF with posterior instrumentation including TLIF or PLIF, in patients with disabling low back pain resulting from degenerative disc disease. ALIF surgery has previously been linked with certain high risk complications and unfavorable long term fusion results. Newer studies suggest that stand-alone ALIF can possibly be advantageous compared to other types of posterior instrumented interbody fusion for a selected group of DDD patients. The methods and material consisted of a cohort pilot study of patients, with DDD treated with stand-alone ALIF or TLIF followed by a literature review conducted through a comprehensive PubMed database search of the English literature. Studies comparing stand-alone ALIF with posterior instrumented interbody fusion were selected and reviewed. Results from the pilot study, n = 21, showed a reduced perioperative blood loss, shorter operative time and a trend towards better pain reduction and decreased use of opioid analgesics in patients undergoing stand-alone ALIF compared to posterior instrumented fusion with TLIF. The literature review included three studies, n = 630. All three studies were retrospective cohort studies. The average patient follow-up was 2-years but with heterogeneous selected outcomes. Two of three articles documented significant advantages when using stand-alone ALIF on outcomes such as ODI, VAS, surgical time, blood loss and patient satisfaction. No study found stand-alone ALIF inferior in chosen outcomes including fusion. In conclusion the pilot study and the literature review, finds similar clinical outcomes and fusion rates after stand-alone ALIF and posterior interbody fusion. Stand-alone ALIF was associated with a shorter duration of surgery, less perioperative blood loss and a faster improvement post-operatively. Therefore stand-alone ALIF is a viable and important surgical option, which could be considered first choice as surgical treatment., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Cascade and restrictive reporting are useful strategies to enhance antibiotic stewardship programs., Methods: We combined both strategies to improve the prescribing of antibiotics aimed at Gram-negative infections., Results: For Enterobacter aerogenes, the susceptibility rates to amikacin increased from 10% to 100%; for third generation cephalosporins, these rates increased from 55% to 89%. The susceptibility rates of E. aerogenes to cefepime and piperacillin-tazobactam changed little, and the ampicillin susceptibility decreased from 30% in 2009 to 11% in 2010. For Proteus mirabilis, the susceptibility rates increased for third-generation cephalosporins (48% vs. 92%) and piperacillin-tazobactam (10% vs. 98%), with minimal changes for cefepime (96% vs. 93%), ampicillin (69% vs. 73%) and amikacin (96% vs. 84%). For Pseudomonas aeruginosa, the susceptibility rates improved slightly for third-generation cephalosporins (81% vs. 91%) but reduced for piperacillin-tazobactam (99% vs. 59%). Hospital-acquired Clostridium difficile infections decreased from 0.11 to 0.07 per 1000 patient days., Conclusions: Selective reporting helps physicians choose the most appropriate antibiotics for their patients within a stewardship program, with reduced C. difficile infection., (Copyright © 2014 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.)

Based on evidence of an increased risk of death, drug agencies issued safety warnings about the use of second generation antipsychotics (SGAs) in the elderly with dementia. The French agency issued a warning in 2004. which was extended to all antipsychotics in 2008. Little is known about the impact of these warnings on use. We conducted a quasi-experimental study (interrupted time-series) in France, for 2003-2011, including subjects aged ≥65 with dementia and subjects aged ≥65 without dementia in the EGB database (1/97th representative random sample of claims from the main Health Insurance scheme). Outcomes were monthly rates of use of antipsychotics (by class and agent) and of five comparison drug classes (antidepressants, benzodiazepines, dermatologicals, antidiabetics, antiasthmatics). Trends were analyzed by joinpoint regression, impact of warnings by linear segmented regression. In patients with dementia (n=7169), there was a 40% reduction in antipsychotic use from 14.2% in 2003 to 10.2% in 2011. The reduction began before 2004 and was unaffected by the warnings. Use of first generation antipsychotics declined over the period, while use of SGAs increased and leveled off from 2007. Use of the five comparison drug classes increased on the period. In subjects without dementia (n=91,942), rates of overall antipsychotic use decreased from 2.3% in 2003 to 1.8% in 2011 with no effect of the warnings. Meanwhile, use of SGAs continuously increased from 0.37% to 0.64%. Antipsychotic use decreased in the elderly between 2003 and 2011, especially in dementia. The timing of the decrease, however, did not coincide with safety warnings., (© 2013 Published by Elsevier B.V. and ECNP.)

Persistent organic pollutants (POPs) are major environmental concern due to their persistence, long-range transportability, bio-accumulation and potentially adverse effects on living organisms. Analytical chemistry plays an essential role in the measurement of POPs and provides important information on their distribution and environmental transformations. Much effort has been devoted during the last two decades to the development of faster, safer, more reliable and more sensitive analytical techniques for these pollutants. Since the Stockholm Convention (SC) on POPs was adopted 12 years ago, analytical methods have been extensively developed. This review article introduces recent analytical techniques and applications for the determination of POPs in environmental and biota samples, and summarizes the extraction, separation and instrumental analyses of the halogenated POPs. Also, this review covers important aspects for the analyses of SC POPs (e.g. lipid determination and quality assurance/quality control (QA/QC)), and finally discusses future trends for improving the POPs analyses and for potential new POPs., (Copyright © 2013 Elsevier B.V. All rights reserved.)