Comparative analysis of C-Reactive protein levels among Non-comorbid, Comorbid, and Multimorbid Hospitalized COVID-19 patients.

C-reactive protein (CRP) is one of the most commonly monitored inflammatory markers in patients with COVID-19 to gain insight into the inflammation level in the body and to adopt effective disease management and therapeutic strategies. COVID-19 is now less prevalent, and the study of CRP as a biomarker of inflammation still needs deeper understanding, particularly in understanding its role among patients with comorbidities, which are known to influence inflammatory responses and increase the risk of severe outcomes during acute and chronic infectious diseases. The objective of this study was to evaluate the association of major comorbidities such as ischemic heart diseases, diabetes, chronic kidney disease, hypertension, and lung infections e.g. tuberculosis with serum CRP levels in hospitalized COVID-19 patients. This study involves a retrospective observational framework to monitor CRP levels among hospitalized COVID-19 patients after getting ethical approval and patient consent. The information on underlying health conditions or comorbidities and age was collected from the patient data files. The requirement of ventilation, ICU admission, mortality & survival, and CRP levels were monitored based on their daily updates in the data file. Furthermore, the association of CRP levels was evaluated with disease severity and mortality. In this study 618 out of 750 hospitalized COVID-19 patients, of which 62.6% were male and 37.4% were female, the levels of serum CRP were significantly influenced by age and comorbidities. No case of hospitalization was observed in children (≤ 14 years) during the study period, while 38.3% of patients belonged to the old age group (≥ 65 years). Comorbidity status varied, with 36.1% of patients without having any comorbidities, 27.8% with one, 23.6% with two, and 12.5% with three or more comorbidities. Descriptive statistics revealed that the CRP levels in the study population averaged 88.92 mg/L (SD = 63.95), ranging from < 1 mg/L to 900 mg/L, with significant variations observed across different comorbidities and age groups. CRP levels, analyzed by the Kruskal-Wallis test, showed significant variations in different age groups of COVID-19 patients (χ² = 66.741, df = 3, p < 0.001). Moreover, pairwise comparisons showed considerable differences between young and middle-aged groups (Z = -2.724, p < 0.01) and young and old age groups of COVID-19 patients (Z = -3.970, p < 0.001). The most prevalent comorbidities observed in COVID-19 patients in this study were hypertension (42.1%), diabetes (33.8%), ischemic heart disease (16.5%), asthma (11.2%), chronic kidney disease (7.9%) and Tuberculosis (1.9%). The CRP levels fluctuate and also significantly differ among different comorbidities. COVID-19 patients with diabetes were observed to have higher CRP levels than non-diabetics (mean CRP: 126.96 mg/L vs. 88.92 mg/L, Z = -5.724, p < 0.001), and those with hypertension also encountered elevated CRP (mean CRP: 355.37 vs. 276.19 mg/L, Z = -5.447, p < 0.001). Similar tendencies were detected in COVID-19 patients with ischemic heart disease (mean CRP: 385.43 mg/L, Z = -4.704, p < 0.001), chronic kidney disease (mean CRP: 412.37 mg/L, Z = -4.206, p < 0.001) as well as with tuberculosis (mean CRP: 458.08 mg/L, Z = -2.914, p < 0.01). CRP levels on days 1 and 3 of hospitalization showed a decline (88.92 mg/L to 67.89 mg/L), representative of a response to treatment to reduce the inflammation in the body. Furthermore, high levels of CRP were significantly associated with a high requirement of non-invasive ventilation (mean CRP: 110.80 mg/L vs. 76.82 mg/L, p < 0.05), mechanical ventilation (mean CRP: 134.46 mg/L vs. 77.25 mg/L, p < 0.05) and ICU admission (mean CRP: 126.96 mg/L vs. 72.79 mg/L, p < 0.05). The Cox regression analysis showed that there is a considerable association of CRP level with the expected length of hospitalization, each 1-unit increase in CRP levels was associated with a 0.6% increase in extended stay risk (hazard ratio = 1.006, 95% CI: 1.004-1.008, p < 0.001). Furthermore, the logistic regression analysis performed on CRP levels that was monitored on the first day of hospitalization, revealed that there was a 2.7% increase in mortality odds with each unit increase in CRP (odds ratio = 1.027, 95% CI: 1.022-1.033, p < 0.001), which suggest CRP as a potential mortality predictor. Elevated CRP levels in COVID-19 patients with comorbidities like diabetes, hypertension, ischemic heart disease, and chronic kidney disease were strongly associated with increased disease severity, including higher ventilation requirements and mortality. Patients with these comorbidities showed significantly higher CRP levels, which correlated with worse outcomes, including ICU admissions and prolonged hospital stays, emphasizing the importance of CRP as a predictor for severe complications in patients with infectious diseases along with one or more comorbidities.

Shoukat M ，Khan H ，Nazish M ，Rehman A ，Raashid S ，Ahmed S ，Munir W ，Alrefaei AF ，Umair M ，Bin Abid MO ，Akhtar N ，Zaman W ，Badshah M ... -  《BMC INFECTIOUS DISEASES》

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

《Jove-Journal of Visualized Experiments》

RETRACTED: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.

Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the effect of hydroxychloroquine on respiratory viral loads. French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point. Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported in the litterature for untreated patients. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination. Despite its small sample size, our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin. This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/locate/withdrawalpolicy). Concerns have been raised regarding this article, the substance of which relate to the articles' adherence to Elsevier's publishing ethics policies and the appropriate conduct of research involving human participants, as well as concerns raised by three of the authors themselves regarding the article's methodology and conclusions. Elsevier's Research Integrity and Publishing Ethics Team, in collaboration with the journal's co-owner, the International Society of Antimicrobial Chemotherapy (ISAC), and with guidance from an impartial field expert acting in the role of an independent Publishing Ethics Advisor, Dr. Jim Gray, Consultant Microbiologist at the Birmingham Children's and Women's Hospitals, U.K., conducted an investigation and determined that the below points constituted cause for retraction: • The journal has been unable to confirm whether any of the patients for this study were accrued before ethical approval had been obtained. The ethical approval dates for this article are stated as being 5th and 6th of March 2020 (ANSM and CPP respectively), while the article states that recruitment began in “early March”. The 17th author, Prof. Philippe Brouqui, has confirmed that the start date for patient accrual was 6th March 2020. The journal has not been able to establish whether all patients could have entered into the study in time for the data to have been analysed and included in the manuscript prior to its submission on the 20th March 2020, nor whether all patients were enrolled in the study upon admission as opposed to having been hospitalised for some time before starting the treatment described in the article. Additionally, the journal has not been able to establish whether there was equipoise between the study patients and the control patients. • The journal has not been able to establish whether the subjects in this study should have provided informed consent to receive azithromycin as part of the study. The journal has concluded that that there is reasonable cause to conclude that azithromycin was not considered standard care at the time of the study. The 17th author, Prof. Philippe Brouqui has attested that azithromycin treatment was not, at the time of the study, an experimental treatment but a possible treatment for, or preventative measure against, bacterial superinfections of viral pneumonia as described in section 2.4 of the article, and as such the treatment should be categorised as standard care that would not require informed consent. This does not fully address the journal's concerns around the use of azithromycin in the study. In section 3.1 of the article, it is stated that six patients received azithromycin to prevent (rather than treat) bacterial superinfection. All of these were amongst the patients who also received hydroxychloroquine (HCQ). None of the control patients are reported to have received azithromycin. This would indicate that only patients in the HCQ arm received azithromycin, all of whom were in one center. The recommendations for use of macrolides in France at the time the study was conducted indicate that azithromycin would not have been a logical agent to use as first-line prophylaxis against pneumonia due to the frequency of macrolide resistance amongst bacteria such as pneumococci. These two points suggest that azithromycin would not have been standard practice across southern France at the time the study was conducted and would have required informed consent. • Three of the authors of this article, Dr. Johan Courjon, Prof. Valérie Giordanengo, and Dr. Stéphane Honoré have contacted the journal to assert their opinion that they have concerns regarding the presentation and interpretation of results in this article and have stated they no longer wish to see their names associated with the article. • Author Prof. Valérie Giordanengo informed the journal that while the PCR tests administered in Nice were interpreted according to the recommendations of the national reference center, it is believed that those carried out in Marseille were not conducted using the same technique or not interpreted according to the same recommendations, which in her opinion would have resulted in a bias in the analysis of the data. This raises concerns as to whether the study was partially conducted counter to national guidelines at that time. The 17th author, Prof. Philippe Brouqui has attested that the PCR methodology was explained in reference 17 of the article. However, the article referred to by reference 17 describes several diagnostic approaches that were used (one PCR targeting the envelope protein only; another targeting the spike protein; and three commercially produced systems by QuantiNova, Biofire, and FTD). This reference does not clarify how the results were interpreted. It has also been noted during investigation of these concerns that only 76% (19/25) of patients were viral culture positive, resulting in uncertainty in the interpretation of PCR reports as has been raised by Prof. Giordanengo. As part of the investigation, the corresponding author was contacted and asked to provide an explanation for the above concerns. No response has been received within the deadline provided by the journal. Responses were received by the 3rd and 17th authors, Prof. Philippe Parola and Prof. Philippe Brouqui, respectively, and were reviewed as part of the investigation. These two authors, in addition to 1st author Dr. Philippe Gautret, 13th author Prof. Philippe Colson, and 15th author Prof. Bernard La Scola, disagreed with the retraction and dispute the grounds for it. Having followed due process and concluded the aforementioned investigation and based on the recommendation of Dr. Jim Gray acting in his capacity as independent Publishing Ethics Advisor, the co-owners of the journal (Elsevier and ISAC) have therefore taken the decision to retract the article.

Gautret P ，Lagier JC ，Parola P ，Hoang VT ，Meddeb L ，Mailhe M ，Doudier B ，Courjon J ，Giordanengo V ，Vieira VE ，Tissot Dupont H ，Honoré S ，Colson P ，Chabrière E ，La Scola B ，Rolain JM ，Brouqui P ，Raoult D ... -  《-》

Group B streptococcus colonization in pregnancy and neonatal outcomes: a three-year monocentric retrospective study during and after the COVID-19 pandemic.

Serra G ，Scalzo LL ，Giordano M ，Giuffrè M ，Trupiano P ，Venezia R ，Corsello G ... -  《-》

Falls prevention interventions for community-dwelling older adults: systematic review and meta-analysis of benefits, harms, and patient values and preferences.

About 20-30% of older adults (≥ 65 years old) experience one or more falls each year, and falls are associated with substantial burden to the health care system, individuals, and families from resulting injuries, fractures, and reduced functioning and quality of life. Many interventions for preventing falls have been studied, and their effectiveness, factors relevant to their implementation, and patient preferences may determine which interventions to use in primary care. The aim of this set of reviews was to inform recommendations by the Canadian Task Force on Preventive Health Care (task force) on fall prevention interventions. We undertook three systematic reviews to address questions about the following: (i) the benefits and harms of interventions, (ii) how patients weigh the potential outcomes (outcome valuation), and (iii) patient preferences for different types of interventions, and their attributes, shown to offer benefit (intervention preferences). We searched four databases for benefits and harms (MEDLINE, Embase, AgeLine, CENTRAL, to August 25, 2023) and three for outcome valuation and intervention preferences (MEDLINE, PsycINFO, CINAHL, to June 9, 2023). For benefits and harms, we relied heavily on a previous review for studies published until 2016. We also searched trial registries, references of included studies, and recent reviews. Two reviewers independently screened studies. The population of interest was community-dwelling adults ≥ 65 years old. We did not limit eligibility by participant fall history. The task force rated several outcomes, decided on their eligibility, and provided input on the effect thresholds to apply for each outcome (fallers, falls, injurious fallers, fractures, hip fractures, functional status, health-related quality of life, long-term care admissions, adverse effects, serious adverse effects). For benefits and harms, we included a broad range of non-pharmacological interventions relevant to primary care. Although usual care was the main comparator of interest, we included studies comparing interventions head-to-head and conducted a network meta-analysis (NMAs) for each outcome, enabling analysis of interventions lacking direct comparisons to usual care. For benefits and harms, we included randomized controlled trials with a minimum 3-month follow-up and reporting on one of our fall outcomes (fallers, falls, injurious fallers); for the other questions, we preferred quantitative data but considered qualitative findings to fill gaps in evidence. No date limits were applied for benefits and harms, whereas for outcome valuation and intervention preferences we included studies published in 2000 or later. All data were extracted by one trained reviewer and verified for accuracy and completeness. For benefits and harms, we relied on the previous review team's risk-of-bias assessments for benefit outcomes, but otherwise, two reviewers independently assessed the risk of bias (within and across study). For the other questions, one reviewer verified another's assessments. Consensus was used, with adjudication by a lead author when necessary. A coding framework, modified from the ProFANE taxonomy, classified interventions and their attributes (e.g., supervision, delivery format, duration/intensity). For benefit outcomes, we employed random-effects NMA using a frequentist approach and a consistency model. Transitivity and coherence were assessed using meta-regressions and global and local coherence tests, as well as through graphical display and descriptive data on the composition of the nodes with respect to major pre-planned effect modifiers. We assessed heterogeneity using prediction intervals. For intervention-related adverse effects, we pooled proportions except for vitamin D for which we considered data in the control groups and undertook random-effects pairwise meta-analysis using a relative risk (any adverse effects) or risk difference (serious adverse effects). For outcome valuation, we pooled disutilities (representing the impact of a negative event, e.g. fall, on one's usual quality of life, with 0 = no impact and 1 = death and ~ 0.05 indicating important disutility) from the EQ-5D utility measurement using the inverse variance method and a random-effects model and explored heterogeneity. When studies only reported other data, we compared the findings with our main analysis. For intervention preferences, we used a coding schema identifying whether there were strong, clear, no, or variable preferences within, and then across, studies. We assessed the certainty of evidence for each outcome using CINeMA for benefit outcomes and GRADE for all other outcomes. A total of 290 studies were included across the reviews, with two studies included in multiple questions. For benefits and harms, we included 219 trials reporting on 167,864 participants and created 59 interventions (nodes). Transitivity and coherence were assessed as adequate. Across eight NMAs, the number of contributing trials ranged between 19 and 173, and the number of interventions ranged from 19 to 57. Approximately, half of the interventions in each network had at least low certainty for benefit. The fallers outcome had the highest number of interventions with moderate certainty for benefit (18/57). For the non-fall outcomes (fractures, hip fracture, long-term care [LTC] admission, functional status, health-related quality of life), many interventions had very low certainty evidence, often from lack of data. We prioritized findings from 21 interventions where there was moderate certainty for at least some benefit. Fourteen of these had a focus on exercise, the majority being supervised (for > 2 sessions) and of long duration (> 3 months), and with balance/resistance and group Tai Chi interventions generally having the most outcomes with at least low certainty for benefit. None of the interventions having moderate certainty evidence focused on walking. Whole-body vibration or home-hazard assessment (HHA) plus exercise provided to everyone showed moderate certainty for some benefit. No multifactorial intervention alone showed moderate certainty for any benefit. Six interventions only had very-low certainty evidence for the benefit outcomes. Two interventions had moderate certainty of harmful effects for at least one benefit outcome, though the populations across studies were at high risk for falls. Vitamin D and most single-component exercise interventions are probably associated with minimal adverse effects. Some uncertainty exists about possible adverse effects from other interventions. For outcome valuation, we included 44 studies of which 34 reported EQ-5D disutilities. Admission to long-term care had the highest disutility (1.0), but the evidence was rated as low certainty. Both fall-related hip (moderate certainty) and non-hip (low certainty) fracture may result in substantial disutility (0.53 and 0.57) in the first 3 months after injury. Disutility for both hip and non-hip fractures is probably lower 12 months after injury (0.16 and 0.19, with high and moderate certainty, respectively) compared to within the first 3 months. No study measured the disutility of an injurious fall. Fractures are probably more important than either falls (0.09 over 12 months) or functional status (0.12). Functional status may be somewhat more important than falls. For intervention preferences, 29 studies (9 qualitative) reported on 17 comparisons among single-component interventions showing benefit. Exercise interventions focusing on balance and/or resistance training appear to be clearly preferred over Tai Chi and other forms of exercise (e.g., yoga, aerobic). For exercise programs in general, there is probably variability among people in whether they prefer group or individual delivery, though there was high certainty that individual was preferred over group delivery of balance/resistance programs. Balance/resistance exercise may be preferred over education, though the evidence was low certainty. There was low certainty for a slight preference for education over cognitive-behavioral therapy, and group education may be preferred over individual education. To prevent falls among community-dwelling older adults, evidence is most certain for benefit, at least over 1-2 years, from supervised, long-duration balance/resistance and group Tai Chi interventions, whole-body vibration, high-intensity/dose education or cognitive-behavioral therapy, and interventions of comprehensive multifactorial assessment with targeted treatment plus HHA, HHA plus exercise, or education provided to everyone. Adding other interventions to exercise does not appear to substantially increase benefits. Overall, effects appear most applicable to those with elevated fall risk. Choice among effective interventions that are available may best depend on individual patient preferences, though when implementing new balance/resistance programs delivering individual over group sessions when feasible may be most acceptable. Data on more patient-important outcomes including fall-related fractures and adverse effects would be beneficial, as would studies focusing on equity-deserving populations and on programs delivered virtually. Not registered.

Pillay J ，Gaudet LA ，Saba S ，Vandermeer B ，Ashiq AR ，Wingert A ，Hartling L ... -  《Systematic Reviews》