Fatigue and health-related quality of life in paroxysmal nocturnal haemoglobinuria: A post hoc analysis of the pegcetacoplan PEGASUS trial data.

OBJECTIVES: Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, non-malignant haematological disorder associated with disabling fatigue and reduced health-related quality of life. Post hoc analysis of PEGASUS phase 3 trial (NCT03500549) characterised improvements in patient-reported fatigue measured by functional assessment of chronic illness therapy-fatigue (FACIT-fatigue) instrument item-level ratings for pegcetacoplan and eculizumab for the treatment of PNH. METHODS: Item-level responder analysis was conducted on a ≥2-level change from baseline (CFB) clinically important response (CIR) for the FACIT-fatigue 13 individual items rated on a 5-level Likert scale. We evaluated ≥2-level change against the minimal clinically important difference (MCID) of the FACIT-fatigue total score (≥5 points) and clinical parameters, haemoglobin (Hb; ≥1 g/dL) and normalised absolute reticulocyte count (ARC; 30-100 pg/cells). Logistic regressions estimated baseline-to-Week-16 FACIT-fatigue item-level transitional probabilities; Kaplan-Meier analysis estimated time to FACIT-fatigue item CIR. RESULTS: Pegcetacoplan versus eculizumab was associated with significantly greater odds of Week 16 CIR across 8/13 items and on total score MCID (OR [CI] = 11.19 [3.73, 33.57]) and faster times to responses. The item-level CIR threshold also showed clinical relevance on Hb level and ARC normalization. CONCLUSIONS: Compared with eculizumab, pegcetacoplan was associated with clinically meaningful greater improvements on a majority of FACIT-fatigue items.

A tetrahydroacridine derivative and its conjugate with gold nanoparticles: promising agents for the treatment of Alzheimer's disease.

A new tetrahydroacridine derivative (CHDA) with acetylcholinesterase inhibitory properties was synthesized. Using a range of physicochemical techniques, it was shown that the compound strongly adsorbs onto the surface of planar macroscopic or nanoparticulate gold, forming a nearly full monolayer. The adsorbed CHDA molecules reveal well-defined electrochemical behavior, being irreversibly oxidized to electroactive species. The CHDA also exhibits strong fluorescence, which is effectively quenched after adsorption onto gold via a static quenching mechanism. Both CHDA and its conjugate reveal considerable inhibitory properties against acetylcholinesterase activity, which is promising from the perspective of therapeutic application in the treatment of Alzheimer's disease. Moreover, both agents appear to be non-toxic as demonstrated using in vitro studies. On the other hand, conjugation of CHDA with nanoradiogold particles (Au-198) offers new potential diagnostic perspectives in medical imaging.

The Role of Vitamins in the Pathogenesis of Asthma.

Vitamins play a crucial role in the proper functioning of organisms. Disturbances of their levels, seen as deficiency or excess, enhance the development of various diseases, including those of the cardiovascular, immune, or respiratory systems. The present paper aims to summarize the role of vitamins in one of the most common diseases of the respiratory system, asthma. This narrative review describes the influence of vitamins on asthma and its main symptoms such as bronchial hyperreactivity, airway inflammation, oxidative stress, and airway remodeling, as well as the correlation between vitamin intake and levels and the risk of asthma in both pre- and postnatal life.

Non-Opioid Peptides Targeting Opioid Effects.

Opioids are the most potent widely used analgesics, primarily, but not exclusively, in palliative care. However, they are associated with numerous side effects, such as tolerance, addiction, respiratory depression, and cardiovascular events. This, in turn, can result in their overuse in cases of addiction, the need for dose escalation in cases of developing tolerance, and the emergence of dose-related opioid toxicity, resulting in respiratory depression or cardiovascular problems that can even lead to unintentional death. Therefore, a very important challenge for researchers is to look for ways to counteract the side effects of opioids. The use of peptides and their related compounds, which have been shown to modulate the effects of opioids, may provide such an opportunity. This short review is a compendium of knowledge about the most important and recent findings regarding selected peptides and their modulatory effects on various opioid actions, including cardiovascular and respiratory responses. In addition to the peptides more commonly reported in the literature in the context of their pro- and/or anti-opioid activity-such as neuropeptide FF (NPFF), cholecystokinin (CCK), and melanocyte inhibiting factor (MIF)-we also included in the review nociceptin/orphanin (N/OFQ), ghrelin, oxytocin, endothelin, and venom peptides.

Regulatory Peptides in Asthma.

Numerous regulatory peptides play a critical role in the pathogenesis of airway inflammation, airflow obstruction and hyperresponsiveness, which are hallmarks of asthma. Some of them exacerbate asthma symptoms, such as neuropeptide Y and tachykinins, while others have ameliorating properties, such as nociception, neurotensin or ß-defensin 2. Interacting with peptide receptors located in the lungs or on immune cells opens up new therapeutic possibilities for the treatment of asthma, especially when it is resistant to available therapies. This article provides a concise review of the most important and current findings regarding the involvement of regulatory peptides in asthma pathology.

Intracerebroventricular Neuropeptide FF Diminishes the Number of Apneas and Cardiovascular Effects Produced by Opioid Receptors' Activation.

The opioid-induced analgesia is associated with a number of side effects such as addiction, tolerance and respiratory depression. The involvement of neuropeptide FF (NPFF) in modulation of pain perception, opioid-induced tolerance and dependence was well documented in contrast to respiratory depression. Therefore, the aim of the present study was to examine the potency of NPFF to block post-opioid respiratory depression, one of the main adverse effects of opioid therapy. Urethane-chloralose anaesthetized Wistar rats were injected either intravenously (iv) or intracerebroventricularly (icv) with various doses of NPFF prior to iv endomorphin-1 (EM-1) administration. Iv NPFF diminished the number of EM-1-induced apneas without affecting their length and without influence on the EM-1 induced blood pressure decline. Icv pretreatment with NPFF abolished the occurrence of post-EM-1 apneas and reduced also the maximal drop in blood pressure and heart rate. These effects were completely blocked by the NPFF receptor antagonist RF9, which was given as a mixture with NPFF before systemic EM-1 administration. In conclusion, our results showed that centrally administered neuropeptide FF is effective in preventing apnea evoked by stimulation of µ-opioid receptors and the effect was due to activation of central NPFF receptors. Our finding indicates a potential target for reversal of opioid-induced respiratory depression.

Sulforaphane-conjugated selenium nanoparticles: towards a synergistic anticancer effect.

Sulforaphane-modified selenium nanoparticles can be prepared in a simple aqueous-phase redox reaction through reduction of selenite with ascorbic acid. The sulforaphane molecules present in the reaction mixture adsorb on the nanoparticle surface, forming an adlayer. The resulting conjugate was examined with several physicochemical techniques, including microscopy, spectroscopy, x-ray diffraction, dynamic light scattering and zeta potential measurements. As shown in in vivo investigations on rats, the nanomaterial administered intraperitoneally is eliminated mainly in urine (and, to a lesser extent, in feces); however, it is also retained in the body. The modified nanoparticles mainly accumulate in the liver, but the basic parameters of blood and urine remain within normal limits. The sulforaphane-conjugated nanoparticles reveal considerable anticancer action, as demonstrated on several cancer cell cultures in vitro. This finding is due to the synergistic effect of elemental selenium and sulforaphane molecules assembled in one nanostructure (conjugate). On the other hand, the cytotoxic action on normal cells is relatively low. The high antitumor activity and selectivity of the conjugate with respect to diseased and healthy cells is extremely promising from the point of view of cancer treatment.

Sokrat II - An International, Prospective, Multicenter, Phase IV Diagnostic Trial to Evaluate the Efficacy of the Wrist SAFE Algorithm in Fracture Sonography of Distal Forearm Fractures in Children.

BACKGROUND: Distal forearm fractures are the most common fractures in childhood and can be diagnosed with ultrasound. The aim of this study was to demonstrate the eligibility of Wrist SAFE for clinical use and the avoidance of X-ray application in children. METHODS: We enrolled patients from 0 - 12 years with suspected distal forearm fractures. They were treated according to the Wrist SAFE algorithm, a detailed pathway for ultrasound fracture diagnosis, treatment decisions and control options. Additionally, 9 clinical predictors were tested. Depending on sonographic and clinical findings, patients were treated with functional movement, immobilization or surgery. Follow-up was conducted after 5 days and 3 months. RESULTS: 16 physicians (6 specialists, 10 assistants) at 5 study sites examined 498 (234 boys, 251 girls, 13 not specified) patients with ultrasound, age 8.4 (0 - 12) years. 321 (64 %) patients were diagnosed with a fracture, 5 (0.8 %) with suspected fracture; X-rays were conducted in 58 cases (12 %), 9 (1.8 %) of them on day 1 and 49 (9.8 %) on day 5; sonographic diagnosis was confirmed in 57 of 58 (98 %) cases; in one case, the sonographic diagnosis of "contusion" was revised to "radius fracture". 381 patients (77 %) underwent final follow-up after an average of 96 (62 - 180) days. All patients were symptom-free at that time. Palpatory bone pain over the radius/ulna and swelling were identified as clinical predictors. 81 % of X-rays were avoided. CONCLUSION: Wrist SAFE enables the safe diagnosis and therapy of distal forearm fractures in children. Findings can be reviewed safely, also enabling physicians in training to use the method. 81 % of X-rays can be avoided, a figure that corresponds to 2.8 million X-rays in the G10 member states. After performing 100 examinations, physician have acquired the necessary sonography skills.

Neuropeptides and breathing in health and disease.

Regulatory neuropeptides control and regulate breathing in physiological and pathophysiological conditions. While they have been identified in the neurons of major respiratory areas, they can be active not only at the central level, but also at the periphery via chemoreceptors, vagal afferents, or locally within lungs and airways. Some neuropeptides, such as leptin or substance P, are respiratory stimulants; others, such as neurotensin, produce variable effects on respiration depending on the site of application. Some neuropeptides have been implicated in pathological states, such as obstructive sleep apnea or asthma. This article provides a concise review of the possible role and functions of several selected neuropeptides in the process of breathing in health and disease and in lung pathologies.

Adrenal suppression by inhaled corticosteroids in patients with asthma: A systematic review and quantitative analysis.

BACKGROUND: Inhaled corticosteroids used for treating persistent asthma can suppress adrenal cortisol secretion. This inhibition of endogenous cortisol secretion is an important marker of systemic steroid activity. Although meta-analyses have demonstrated a dose-dependent suppression of cortisol by inhaled corticosteroids, regardless of inhaler type, the impact of novel freon-free inhaled corticosteroid preparations has not been reviewed. OBJECTIVE: The aim of this study was to synthesize all currently available studies on novel inhaled corticosteroid preparations, including ciclesonide, beclomethasone dipropionate, budesonide, and fluticasone propionate. In particular, we aimed to compare the effect of ciclesonide on cortisol suppression with other existing preparations. METHODS: We carried out a systematic review of the medical data bases on cortisol suppression in patients due to inhaled corticosteroids. A multivariate regression model was used to determine dose-dependent relationships between each inhaled corticosteroid and cortisol suppression with respect to age, type of inhaler, and study design. RESULTS: From analysis of 64 studies identified in the review, the strongest dose-response urinary cortisol suppression was observed in patients treated with beclomethasone (8.4% per 100 µg; p = 0.029), followed by fluticasone (3.2% per 100 µg; p < 0.001), and budesonide (3.1% per 100 µg; p = 0.001). No significant urinary cortisol suppression was associated with ciclesonide treatment (1.8% per 100 µg; p = 0.267). Although ciclesonide did not affect cortisol levels, this appeared to be due to its unique pharmacokinetic properties rather than the use of a novel formulation. CONCLUSION: Our findings indicated that the introduction of novel freon-free delivery technologies for inhaled corticosteroids had not eliminated adverse adrenal suppression of cortisol secretion.

Comparison of cultures and 16S rRNA sequencing for identification of bacteria in two-stage revision arthroplasties: preliminary report.

BACKGROUND: The use of a prefabricated spacer in two-stage revision arthroplasty remains one of the few surgery strategies for infected-joint arthroplasty treatment, despite the many unidentified microorganisms in the infected joint replacements reported in some recent studies. The aim of this prospective survey was to investigate if the sonication followed by polymerase chain reaction (PCR) can improve bacterial identification on the surfaces of prefabricated spacers and if the systemic laboratory mediators of infection and positive microbiological results can take a role of predictive factors of infection and clinical failures in 2-years follow-up. METHODS: Thirteen patients with prosthetic joint infection were investigated. Bacterial culture and deoxyribonucleic acid (DNA) sequencing were used to detect bacteria on the surface of prefabricated spacers removed during the second stage of revision arthroplasty. The results of pre- and intraoperative culture and DNA sequencing were compared. Minimum follow-up was 2 years. RESULTS: The result of tissue cultures in second-stage revision arthroplasties revealed positive results in 15 % of patients with Coagulase-negative Staphylococci (CNS) growth. Bacterial DNA was found in over 90 % of patients with negative synovial fluid culture. Positive PCR results revealed potential pathogenic bacteria and species of human and environmental microflora with low virulence. Clinical failures at final follow-up were recorded in 2 (16.6 %) patients. CONCLUSION: The lack of clinical signs of infection, negative culture of preoperative joint aspirate, and intraoperative specimens do not exclude the presence of bacteria on the surfaces of spacers. The positive results of sonication and molecular tests should be interpreted as real pathogenicity factors in the light of the clinical and laboratory data, especially for patients with immunodeficiency. We confirmed our previous results that sonication followed by PCR and sequencing improved bacterial identification.

A bioresorbable polylactide implant used in bone cyst filling.

The aims in treating patients diagnosed with critical-sized bone defects resulting from bone cysts are to replace the lost bone mass after its removal and to restore function. The standard treatment is autologous or allogeneic bone transplantation, notwithstanding the known consequences and risks due to possible bone infection, donor site morbidity, bleeding and nerve injury and possible undesirable immune reactions. Additionally, allogeneic grafts are inhomogeneous, with a mosaic of components with difficult-to-predict regenerative potential, because they consist of cancellous bone obtained from different bones from various cadavers. In the present study, a 22-year-old patient with a history of right humerus fracture due to bone cysts was diagnosed with recurrent cystic lesions based on X-ray results. The patient qualified for an experimental program, in which he was treated with the application of a bioresorbable polylactide hybrid sponge filled with autologous platelet-rich plasma. Computed tomography and magnetic resonance imaging performed 3, 6, and 36 months after surgery showed progressive ossification and bone formation inside the defect cavity in the humerus. Three years after treatment with the bone substitute, the patient is pain free, and the cystic lesions have not reoccurred.

BioShell Threader: protein homology detection based on sequence profiles and secondary structure profiles.

The BioShell package has recently been extended with a web server for protein homology detection based on profile-to-profile alignment (known as 1D threading). Its aim is to assign structural templates to each domain of the query. The server uses sequence profiles that describe observed sequence variability and secondary structure profiles providing expected probability for a certain secondary structure type at a given position in a protein. Three independent predictors are used to increase the rate of successful predictions. Careful evaluation shows that there is nearly 80% chance that the query sequence belongs to the same SCOP family as the top scoring template. The Bioshell Threader server is freely available at: http://www.bioshell.pl/threader/.

Comprehensive evaluation of 45 augmentation drugs for schizophrenia: a network meta-analysis.

Background: Antipsychotics are the gold standard treatment for schizophrenia, but many patients who receive treatment experience persistent symptoms. The aim of this network meta-analysis was to determine the efficacy of augmentation drugs for the treatment of schizophrenia. Methods: In accordance with the PRISMA statement, the PubMed, Web of Science, Google Scholar, CENTRAL, clinical trial and EUDRACT databases were searched from inception to May 15th, 2023. To ensure the robustness of the results, only double-blind randomised controlled trials with a low risk of bias (measured by the Risk Of Bias v2 (ROB2) tool) were included. The studies were categorised according to the background regimen: participants were treated with risperidone, mixed antipsychotics or clozapine. A Bayesian network meta-analysis was conducted using a random effects model. PROSPERO register: CRD42023420964. Findings: A total of 44 trials (comprising 45 augmentation drugs and 3358 participants) were included in the analysis. One-third of the drugs (16 drugs) demonstrated significant efficacy vs. placebo for at least one outcome. The most notable effect sizes (ESs) were observed for the use of tropisetron (standard mean difference: -0.83 [95% interval confidence -1.12 to -0.55]), memantine (-0.50 [-0.66 to -0.32]) and minocycline (-0.56 [-0.72 to -0.39]) to treat negative symptoms among patients treated with risperidone (moderate-to-high ESs). Studies involving mixed antipsychotics yielded lower ESs (small-to-moderate). Sodium benzoate (-0.41 [-0.60 to -0.21]) and memantine (-0.23 [-0.36 to -0.11]) were found have significant effects on positive symptoms, while memantine demonstrated efficacy for negative symptoms (-0.32 [-0.45 to -0.19]) and general psychopathology (-0.32 [-0.44 to -0.20]). Studies focusing exclusively on patients treated with clozapine revealed that duloxetine produced the best results (negative symptoms: -1.12 [-1.35 to -0.91]). Sodium benzoate was the only augmentation drug that demonstrated efficacy in relieving persistent positive symptoms (-0.32 [-0.59 to -0.08]) among patients treated with clozapine. Treatment with clozapine in combination with antipsychotics yielded small-to-moderate ESs. Interpretation: The GRADE framework indicated that the quality of the evidence among the included studies was moderate, primarily due to the limited number of randomised controlled trials with a low risk of bias. Important drugs did not appear in these results due to insufficient low-risk-of-bias data for these medications. These results highlight new pathways for treating schizophrenia that should be incorporated into future guidelines after further validation. Funding: No funding.

Identification of silent prosthetic joint infection: preliminary report of a prospective controlled study.

PURPOSE: We will test the hypothesis that ultrasound supported by polymerase chain reaction (PCR) could improve bacterial identification in non-infected prosthetic joint loosening. The aim was to detect bacterial species in non-infected prosthetic joint loosening using ultrasound and 16S rRNA gene sequencing. METHODS: A total of 16 patients (11 women and five men) aged 46-80 years (mean age 65.7) with diagnosed knee or hip implant loosening (mean implant survival of 102.1 months) were investigated. Bacterial culture and DNA sequencing were used to detect bacteria on the surface of failed implants removed during revision arthroplasty. The results of pre- and intraoperative culture and DNA sequencing were compared. Histopathological analysis was also performed. RESULTS: The number of positive cultures rises with a higher level of C-reactive protein (CRP). The results of the cultures from synovial fluid obtained through joint aspiration were consistent with sonicates from components of prostheses in 12 cases (75%). Bacterial DNA was found in 90% of patients with negative synovial fluid culture. PCR revealed two or more bacterial species, often of the same genus: Ralstonia pickettii, Pseudomonas spp., Brevibacterium spp., Lactobacillus spp., Propionibacterium spp. and Staphylococcus spp.These are micro-organisms present in the environment or on the human body and often associated with compromised immunity. CONCLUSIONS: The ultrasound procedure followed by PCR and sequencing improve bacterial identification in silent prosthetic joint infection. The lack of clinical signs of infection and negative preoperative and intraoperative cultures do not exclude the presence of micro-organisms on the implants.

Potential of Lactoferrin in the Treatment of Lung Diseases.

Lactoferrin (LF) is a multifunctional iron-binding glycoprotein that exhibits a variety of properties, such as immunomodulatory, anti-inflammatory, antimicrobial, and anticancer, that can be used to treat numerous diseases. Lung diseases continue to be the leading cause of death and disability worldwide. Many of the therapies currently used to treat these diseases have limited efficacy or are associated with side effects. Therefore, there is a constant pursuit for new drugs and therapies, and LF is frequently considered a therapeutic agent and/or adjunct to drug-based therapies for the treatment of lung diseases. This article focuses on a review of the existing and most up-to-date literature on the contribution of the beneficial effects of LF on the treatment of lung diseases, including asthma, viral infections, cystic fibrosis, or lung cancer, among others. Although in vitro and in vivo studies indicate significant potency of LF in the treatment of the listed diseases, only in the case of respiratory tract infections do human studies seem to confirm them by demonstrating the effectiveness of LF in reducing episodes of illness and shortening the recovery period. For lung cancer, COVID-19 and sepsis, the reports are conflicting, and for other diseases, there is a paucity of human studies conclusively confirming the beneficial effects of LF.

Efficacy of rFIXFc versus N9-GP Prophylaxis in Patients with Hemophilia B: Matching-Adjusted Indirect Comparison of B-LONG and PARADIGM 2 Trials.

Purpose: For patients with hemophilia B, extended half-life factor IX (FIX) products are available for prophylaxis and for treating bleeds. Different methods are used to extend the half-lives of recombinant FIX Fc fusion protein (rFIXFc) and nonacog beta pegol (N9-GP). This affects their biodistribution and plasma FIX levels, although differences do not always correlate with clinical outcomes. A matching-adjusted indirect comparison (MAIC) of prophylaxis with rFIXFc and N9-GP was performed, based on licensed dosing in the European Union. Patients and Methods: Combined rFIXFc data from the weekly and individualized interval prophylaxis arms of the B-LONG clinical trial, and N9-GP data from the 40 IU/kg once-weekly prophylaxis arm of PARADIGM 2 were used in a MAIC. Individual patient data for rFIXFc (n=87) were matched to aggregated data for N9-GP (n=29). Estimated annualized bleeding rates (ABRs) for rFIXFc were recalculated using a Poisson regression model with adjustment for over-dispersion, and compared with ABRs reported for N9-GP, using incidence rate ratios (IRRs) with 95% confidence interval (CI). Results: There was no evidence of significant differences in estimated ABRs between prophylaxis with rFIXFc and N9-GP. Analysis of pooled rFIXFc weekly and interval-adjusted dosing compared with N9-GP 40 IU/kg once weekly produced estimated ABRs of 2.59 versus 2.51 (IRR 1.03; 95% CI 0.56-1.89), as well as 1.34 versus 1.22 (IRR 1.10; 95% CI 0.42-2.91) and 1.13 versus 1.29 (IRR 0.88; 95% CI 0.47-1.63) for overall, spontaneous, and traumatic bleeding events, respectively. Conclusion: The study did not reveal any significant differences in the efficacy of rFIXFc and N9-GP prophylaxis. Given differences in trough levels (rFIXFc dosing was targeted to achieve a trough 1-3 IU/dL above baseline versus a reported estimated N9-GP mean trough of 27.3 IU/dL), interpreting plasma FIX levels as potential surrogate efficacy markers requires consideration of compound-specific pharmacokinetic profiles.

Mapping the EORTC QLQ-C30 onto the EQ-5D-5L index for patients with paroxysmal nocturnal hemoglobinuria in France.

Aim: To map patient-level data collected on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC) QLQ-C30 to EQ-5D-5L data for estimating health-state utilities in patients with paroxysmal nocturnal hemoglobinuria (PNH). Materials & methods: European cross-sectional PNH patient survey data populated regression models mapping EORTC QLQ-C30 domains (covariates: sex and baseline age) to utilities calculated with the EQ-5D-5L French value set. A genetic algorithm allowed selection of the best-fitting between a set of models with and without interaction terms. We validated the selected algorithm using EQ-5D-5L utilities converted from EORTC QLQ-C30 data collected in the PEGASUS phase III, randomized controlled trial of pegcetacoplan versus eculizumab in adults with PNH. Results: Selected through the genetic algorithm, the ordinary least squares model without interactions provided highly stable results across study visits (mean [±SD] utilities 0.58 [±0.42] to 0.89 [±0.10]), and showed the best predictive validity. Conclusion: The new PNH EQ-5D-5L direct mapping developed using a genetic algorithm enabled calculation of reliable health-state utility data required for cost-utility analysis in health technology assessments supporting treatments of PNH.

Risk factors for intraoperative periprosthetic femoral fractures during the total hip arthroplasty.

BACKGROUND: Intraoperative periprosthetic femoral fracture (IPFF) is one of the most frequent complication of total hip arthroplasty (THA). This complication is a very important factor affecting rehabilitation, hospitalization time and cost of treatment. It may occur during the intramedullary reaming, removal or fixation of the stem The aim of the study was to identify risk factors of IPFF, in order to devise strategies that would minimize incidence of this complication in the future. MATERIAL/METHODS: The study group consisted of patients who underwent hip surgery at the Department of Orthopaedics and Traumatology, Medical University of Silesia in Katowice between January 2002 and December 2006. We included cases of primary total hip replacement (both cemented and uncemented), hemiarthroplasties, revision THAs with exchange of at least one of the elements and the Girdlestone procedures. RESULTS: The IPFF was diagnosed in 105 cases (101 patients), out of 1188 surgeries. We found the following risk factors for the primary THA: female gender, younger age, uncemented implant, the use of straight or revision stem, secondary osteoarthritis. For revision surgery there were: left hip surgery and implantation of revision stem. CONCLUSIONS: We hope that identification of risk factors for the intraoperative periprosthetic femoral fracture would allow orthopaedic surgeons to select the group of patients with high risk of fracture and to devise strategies that would minimize incidence of this complication in the future.

Impact of the COVID-19 pandemic on the conduct of clinical trials: a quantitative analysis.

Background: Globally, healthcare has shouldered much of the socioeconomic brunt of the COVID-19 pandemic leading to numerous clinical trials suspended or discontinued. Objective: To estimate the COVID-19 impact on the number of clinical trials worldwide. Methods: Data deposited by 219 countries in the ClinicalTrials.gov database (2007-2020) were interrogated using targeted queries. A time series model was fitted to the data for studies ongoing, initiated, or ended between 2007 Quarter (Q) 1 and 2019 Q4 to predict the expected trials number in 2020 in the COVID-19 absence. The predicted values were compared with the actual 2020 data to quantify the pandemic impact. Results: The ongoing registered trials number grew from 2007 Q1 (33,739) to 2019 Q4 (80,319). By contrast, there were markedly fewer ongoing trials in all four quarters of 2020 compared with forecasted values (1.6%-2.8% decrease). When excluding COVID-19-related studies, this disparity grew further (3.4%-5.8% decrease), to a peak of almost 5,000 fewer ongoing trials than estimated for 2020 Q2. The initiated non-COVID-19 trials number was higher than predicted in 2020 Q4 (9.9%). Conclusions: This pandemic has impacted clinical trials. Provided that current trends persist, clinical trial activities may soon recover to at least pre-COVID-19 levels.