Impact of the pandemic and its containment measures in Europe upon aspects of affective impairments: a Google Trends informetrics study.

BACKGROUND: In late 2019, a new virus began spreading in Wuhan, China. By the end of 2021, more than 260 million people worldwide had been infected and 5.2 million people had died because of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Various countermeasures have been implemented to contain the infections, depending on the country, infection prevalence, and political and infrastructural resources. The pandemic and the containment measures have induced diverse psychological burdens. Using internet queries as a proxy, this study examines the psychological consequences on a European level of SARS-CoV-2 containment measures. METHODS: Using informetric analyses, this study reviews within 32 European countries a total of 28 search parameters derived from the International Statistical Classification of Diseases and Related Health Problems (ICD-10) as aspects of affective disorder. RESULTS: Our results show that there are several psychological aspects which are significantly emphasized during the pandemic and its containment measures: 'anxiety', 'dejection', 'weariness', 'listlessness', 'loss of appetite', 'loss of libido', 'panic attack', and 'worthlessness'. These terms are significantly more frequently part of a search query during the pandemic than before the outbreak. Furthermore, our results revealed that search parameters such as 'psychologist', 'psychotherapist', 'psychotherapy' have increased highly significantly (p < 0.01) since the pandemic. CONCLUSIONS: The psychological distress caused by the pandemic correlates significantly with the frequency of people searching for psychological and psychotherapeutic support on the Internet.

Simplified Pain Management Including Fentanyl TTS in PACU Patients With Hip Fracture Surgery to Improve Patients' Well-Being: A Double-Blind Randomized Trial.

PURPOSE: Adequate pain management is eminently relevant for elderly and more vulnerable patients with hip fractures in the setting of pre and postoperative pain. This study compares postoperative hip fracture patients treated with standard pain management with a variety of medications or an approach with only one option in each medication category (nonopioid: acetaminophen; opioid: fentanyl TTS 12,5 mcg/hour; rescue medication: piritramide) to simplify the treatment algorithm for nurses and improve patient well-being. DESIGN: Double-blind randomized controlled trial. METHODS: The sample was cognitively intact patients (N = 141) with hip fractures in a tertiary university hospital. Administration of fentanyl 12 mcg/hour transdermal therapeutic system was administered by the nurses in the postanesthesia care unit (PACU) to address basal wound pain to improve patient well-being and patient treatment in the PACU for 24 hours to better control for early complications. FINDINGS: Well-being was equally increased in both groups in comparison to our preintervention data from 35.7% to over 60% and did not differ significantly between the intervention and control group. No statistically significant differences in numeric rating scale scores, rescue opioid dosage (piritramide i.v.) or in complications were present. CONCLUSIONS: This one-size-fits-all simplified pain management approach did not improve patient well-being or any other outcome but highlighted the importance of adequate pain management and a sufficient nurse-to-patient ratio.

Preemptive local analgesia at vaginal hysterectomy: a systematic review.

INTRODUCTION AND HYPOTHESIS: We conducted a systematic review of the effectiveness of local preemptive analgesia for postoperative pain control in women undergoing vaginal hysterectomy. METHODS: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews were searched systematically to identify eligible studies published through September 25, 2019. Only randomized controlled trials and systematic reviews addressing local preemptive analgesia compared to placebo at vaginal hysterectomy were considered. Data were extracted by two independent reviewers. Results were compared, and disagreement was resolved by discussion. Forty-seven studies met inclusion criteria for full-text review. Four RCTs, including a total of 197 patients, and two SRs were included in the review. RESULTS: Preemptive local analgesia reduced postoperative pain scores up to 6 h and postoperative opioid requirements in the first 24 h after surgery. CONCLUSION: Preemptive local analgesia at vaginal hysterectomy results in less postoperative pain and less postoperative opioid consumption.

Migraine, interferon ß1a and siponimod immunomodulator therapies.

BACKGROUND: Autoimmunity seems to play a great role in the pathogenesis of migraine headache pain. There is far more evidence that interferon can exacerbate migraines. We report a case where remission of severe comorbid migraine attacks happened with the start of interferon ß1a (Merck, Netherlands) immunomodulation therapy. Therapy for multiple sclerosis was decided according to the severity of the debilitating comorbid migraine headache pain rather than the evolution of multiple sclerosis the far more serious disease. CASE PRESENTATION: A 63-years old patient suffered for 30-years from migraine headache of severe disability assessment scale (MIDAS) Grade-IV = 27. He also suffered for 25-years from optic-sensory relapsing remitting multiple sclerosis (RRMS). Subcutaneous interferon ß1a 44-µg immunomodulation therapy for 4-years resulted in multiple sclerosis complete remission. The start of interferon ß1a therapy for multiple sclerosis seemed to help resolving the comorbid migraine attacks. The visual aura premonitory symptom preceding migraine headache would end up with a feeling of post visual aura clearer field of vision and a feeling of wellbeing. As the patient developed secondary progressive multiple sclerosis (SPMS), oral siponimod 2 mg (Novartis, Ireland), currently the only available therapy for SPMS, replaced his interferon therapy. This was associated with a relapse of migraine severe attacks. Reverting back to interferon therapy was again associated with migraine headache remission. CONCLUSIONS: Interferon ß1a might be an efficic therapy for "autoimmune migraine". With numerous immunomodulators currently available for other systemic autoimmune diseases associated with comorbid migraine; examining the effect of these immunomodulatory therapies on comorbid migraine headache could be beneficial in finding a specific immunomodulator therapy for "autoimmune migraine".

Combined femoral and popliteal nerve block is superior to local periarticular infiltration anaesthesia for postoperative pain control after total knee arthroplasty.

INTRODUCTION: After primary total knee arthroplasty (TKA), local periarticular infiltration anaesthesia (LIA) is a fast and safe method for postoperative pain control. Moreover, ultrasound-guided regional anaesthesia (USRA) with femoral and popliteal block is a standard procedure in perioperative care. Two analgesic regimens for TKA-LIA versus URSA with dexmedetomidine-were compared as an additive to ropivacaine. We hypothesised that the use of URSA provides a superior opioid sparing effect for TKA compared with LIA. METHODS: Fifty patients (planned 188 participants; safety analysis was performed after examining the first 50 participants) were randomised. These patients received LIA into the knee capsule during surgery with 60 ml of ropivacaine 0.5% and 1 ml of dexmedetomidine (100 µg ml-1) or two single-shot URSA blocks (femoral and popliteal block) before surgery with 15 ml of ropivacaine 0.5% and 0.5 ml of dexmedetomidine for each block. Postoperative opioid consumption in the first 48 h, pain assessment and complications were analysed. RESULTS: In the safety analysis, there was a significantly higher need for opioids in the LIA group, with a median oral morphine equivalent of 42.0 [interquartile range (IQR) 23.5-57.0] mg versus 27.0 [IQR 0.0-33.5] mg (P = 0.022). Due to this finding, the study was terminated for ethical considerations according to the protocol. CONCLUSION: This is the first study presenting data on LIA application in combination with dexmedetomidine. A superior opioid-sparing effect of URSA was observed when compared with LIA in TKA when dexmedetomidine is added to local anaesthetics. Also, a longer lasting opioid-sparing effect in the LIA group was observed when compared with the recently published literature; this difference could be attributed to the addition of dexmedetomidine. Therefore, multimodal analgesia regimens could be further improved when LIA or USRA techniques are combined with dexmedetomidine.

Perioperative use of physostigmine to reduce opioid consumption and peri-incisional hyperalgesia: a randomised controlled trial.

BACKGROUND: Several studies have shown that cholinergic mechanisms play a pivotal role in the anti-nociceptive system by acting synergistically with morphine and reducing postoperative opioid consumption. In addition, the anti-cholinesterase drug physostigmine that increases synaptic acetylcholine concentrations has anti-inflammatory effects. METHODS: In this randomised placebo-controlled trial including 110 patients undergoing nephrectomy, we evaluated the effects of intraoperative physostigmine 0.5 mg h-1 i.v. for 24 h on opioid consumption, hyperalgesia, pain scores, and satisfaction with pain control. RESULTS: Physostigmine infusion did not affect opioid consumption compared with placebo. However, the mechanical pain threshold was significantly higher (2.3 [sd 0.3]) vs 2.2 [0.4]; P=0.0491), and the distance from the suture line of hyperalgesia (5.9 [3.3] vs 8.5 [4.6]; P=0.006), wind-up ratios (2.2 [1.5] vs 3.1 [1.5]; P=0.0389), and minimum and maximum postoperative pain scores at 24 h (minimum 1.8 [1.0] vs 2.4 [1.2]; P=0.0451; and maximum 3.2 [1.4] vs 4.2 [1.4]; P=0.0081) and 48 h (minimum 0.9 [1.0] vs 1.6 [1.1]; P=0.0101; and maximum 2.0 [1.5] vs 3.2 [1.6]; P=0.0029) were lower in the study group. Pain Disability Index was lower and satisfaction with pain control was higher after 3 months in the physostigmine group. CONCLUSIONS: In contrast to previous trials, physostigmine did not reduce opioid consumption. As pain thresholds were higher and hyperalgesia and wind-up lower in the physostigmine group, we conclude that physostigmine has anti-hyperalgesic effects and attenuates sensitisation processes. Intraoperative physostigmine may be a useful and safe addition to conventional postoperative pain control. CLINICAL TRIAL REGISTRATION: EudraCT number 2012-000130-19.

Google Trends for Pain Search Terms in the World's Most Populated Regions Before and After the First Recorded COVID-19 Case: Infodemiological Study.

BACKGROUND: Web-based analysis of search queries has become a very useful method in various academic fields for understanding timely and regional differences in the public interest in certain terms and concepts. Particularly in health and medical research, Google Trends has been increasingly used over the last decade. OBJECTIVE: This study aimed to assess the search activity of pain-related parameters on Google Trends from among the most populated regions worldwide over a 3-year period from before the report of the first confirmed COVID-19 cases in these regions (January 2018) until December 2020. METHODS: Search terms from the following regions were used for the analysis: India, China, Europe, the United States, Brazil, Pakistan, and Indonesia. In total, 24 expressions of pain location were assessed. Search terms were extracted using the local language of the respective country. Python scripts were used for data mining. All statistical calculations were performed through exploratory data analysis and nonparametric Mann-Whitney U tests. RESULTS: Although the overall search activity for pain-related terms increased, apart from pain entities such as headache, chest pain, and sore throat, we observed discordant search activity. Among the most populous regions, pain-related search parameters for shoulder, abdominal, and chest pain, headache, and toothache differed significantly before and after the first officially confirmed COVID-19 cases (for all, P<.001). In addition, we observed a heterogenous, marked increase or reduction in pain-related search parameters among the most populated regions. CONCLUSIONS: As internet searches are a surrogate for public interest, we assume that our data are indicative of an increased incidence of pain after the onset of the COVID-19 pandemic. However, as these increased incidences vary across geographical and anatomical locations, our findings could potentially facilitate the development of specific strategies to support the most affected groups.

Optimizing peer review to minimize the risk of retracting COVID-19-related literature.

Retractions of COVID-19 literature in both preprints and the peer-reviewed literature serve as a reminder that there are still challenging issues underlying the integrity of the biomedical literature. The risks to academia become larger when such retractions take place in high-ranking biomedical journals. In some cases, retractions result from unreliable or nonexistent data, an issue that could easily be avoided by having open data policies, but there have also been retractions due to oversight in peer review and editorial verification. As COVID-19 continues to affect academics and societies around the world, failures in peer review might also constitute a public health risk. The effectiveness by which COVID-19 literature is corrected, including through retractions, depends on the stringency of measures in place to detect errors and to correct erroneous literature. It also relies on the stringent implementation of open data policies.

Establishing Sensible and Practical Guidelines for Desk Rejections.

Publishing has become, in several respects, more challenging in recent years. Academics are faced with evolving ethics that appear to be more stringent in a bid to reduce scientific fraud, the emergence of science watchdogs that are now scrutinizing the published literature with critical eyes to hold academics, editors and publishers more accountable, and a barrage of checks and balances that are required between when a paper is submitted and eventually accepted, to ensure quality control. Scientists are often under increasing pressure to produce papers in an increasingly stringent publishing environment. In such a climate, timing is everything, as is the efficiency of the process. Academics appreciate that rejections are part of the fabric of attempting to get a paper published, but they expect the reason to be clear, based on careful evaluation of their work, and not on superficial or unsubstantiated excuses. A desk rejection occurs when a paper gets rejected even before it has entered the peer review process. This paper examines the features of some desk rejections and offers some guidelines that would make desk rejections valid, fair and ethical. Academics who publish are under constant pressure to do so quickly, but effectively. They are dependent on the editors' good judgment and the publisher's procedures. Unfair, unsubstantiated, or tardy desk rejections disadvantage academics, and editors and publishers must be held accountable for wasting their time, resources, and patience.

Perpetuation of Retracted Publications Using the Example of the Scott S. Reuben Case: Incidences, Reasons and Possible Improvements.

In 2009, Scott S. Reuben was convicted of fabricating data, which lead to 25 of his publications being retracted. Although it is clear that the perpetuation of retracted articles negatively effects the appraisal of evidence, the extent to which retracted literature is cited had not previously been investigated. In this study, to better understand the perpetuation of discredited research, we examine the number of citations of Reuben's articles within 5 years of their retraction. Citations of Reuben's retracted articles were assessed using the Web of Science Core Collection (Thomson Reuters, NY). All citing articles were screened to discriminate between articles in which Reuben's work was quoted as retracted, and articles in which his data was wrongly cited without any note of the retraction status. Twenty of Reuben's publications had been cited 274 times between 2009 and 1024. In 2014, 45 % of the retracted articles had been cited at least once. In only 25.8 % of citing articles was it clearly stated that Reuben's work had been retracted. Annual citations decreased from 108 in 2009 to 18 in 2014; however, the percentage of publications correctly indicating the retraction status also declined. The percentage of citations in top-25 %-journals, as well as the percentage of citations in journals from Reuben's research area, declined sharply after 2009. Our data show that even 5 years after their retraction, nearly half of Reuben's articles are still being quoted and the retraction status is correctly mentioned in only one quarter of the citations.

Ketamine as Treatment for Cluster Headache: A Systematic Review of Literature and a Case Series.

INTRODUCTION: Cluster headache is a severe and debilitating neurological condition characterized by intense, excruciating pain with a significant impact on patients' wellbeing. Although different treatment options are available, many patients continue to experience inadequate relief. Therefore, experimental strategies are increasingly studied. One of the more promising approaches is the use of ketamine. We present the currently available evidence and our own data. METHODS: In this mixed-methods paper, we first summarize the available evidence of ketamine for treatment of cluster headache based on a systematic review of literature in MEDLINE, EMBASE and the Cochrane library of systematic reviews. As the level of evidence is quite limited, we report our own cohort study with ten patients treated with ketamine infusions for cluster headache. They were followed up to investigate the patients' experience of treatment success and quality of life. RESULTS: The search and review of literature identified four reports with a total of 68 patients. All were uncontrolled case series. The current literature suggests that ketamine might decrease cluster headache. However, as the applied regimes and reported outcomes are highly heterogeneous, further analysis was futile. Our own data show high patient satisfaction with ketamine treatment. CONCLUSION: Despite the limited evidence, ketamine might be considered a potential therapeutic approach for cluster headache. Therefore, further research including randomized controlled trials should be encouraged.

This article discusses the potential use of ketamine for the treatment of cluster headache, a severe neurological condition that can have a significant impact on patients' quality of life. The authors conducted a systematic review of the existing literature on ketamine for the treatment of cluster headache. Additionally, they also presented their own cohort study of ten patients receiving ketamine infusions. The review of the literature revealed four reports with a total of 68 patients, all of which were uncontrolled case series. While the current literature suggests that ketamine may be effective in relieving cluster headache symptoms, the heterogeneity of treatment regimens and reported outcomes makes it difficult to draw definitive conclusions. The authors' own cohort study found that patients were very satisfied with ketamine treatment, indicating a potential benefit of this approach. However, due to the limited evidence available, further research, including randomized controlled trials, is needed to better understand the efficacy of ketamine in the treatment of cluster headaches.

Beyond disclaimers: the need for a curation-based model of PubMed.

According to its own description, the biomedical meta-database PubMed exists "with the aim of improving health-both globally and personally." Unfortunately, PubMed contains an increasing amount of low-quality research that may detract from this goal. Currently, PubMed warns its users and protects itself from such problems with a disclaimer stating that the presence of any article, book, or document in PubMed does not imply an endorsement of, or concurrence with, its contents by the NLM, the National Institutes of Health (NIH), or the U.S. Federal Government. However, we are critical of a "disclaimer-only" stance and encourage PubMed to take further action against low-quality research being found and indexed in its database, and thus available for use. To address this problem, we offer two lines of reasoning to argue that PubMed should not function merely as a passive index of health-related research. Instead, we first argue that only trustworthy published research is able to further PubMed's goal of health improvement. Secondly, on the basis of surveys, we argue that researchers place a high level of trust in articles that are referenced in this meta-database. We cannot expect any one set of actors to ensure trustworthy content on PubMed, which requires collective responsibility among authors, peer reviewers, editors, and indexers alike. Instead, we propose a curation-based model that incorporates three mechanisms of collaborative content curation: open expert feedback on indexed content, journal auditing, and constant transparent reassessment of indexed entities.

The Dose-Response Relationship between Opioid Agonist Therapy and Alterations in Pain Pathways in Patients with Opioid Use Disorders: A Cross-Sectional Study.

INTRODUCTION: The administration of opioids can be followed by enduring neuroplastic changes in the peripheral and central nervous systems. This remodeling can lead to opioid-induced hyperalgesia, causing an increased sensitivity to painful stimuli. The description of opioid-induced changes in the somatosensory system has seldom been described in the setting of opioid agonist therapy in the treatment of opioid use disorders, and the few existing reports provide no guidance with respect to the effect of varied doses or substances. OBJECTIVE: The aim of the present study was to assess alterations of pain pathways among patients receiving opioid agonist therapy and to elucidate the dose-response relationship. METHODS: This study was planned as cross-sectional in an outpatient clinic in Graz, Austria. Patients receiving opioid agonist therapy for opioid use disorders (including methadone, levomethadone, buprenorphine, and extended-release morphine) were asked to fill out a questionnaire, including the central sensitization inventory. A battery of somatosensory system assessments was then performed. RESULTS: A total of 120 patients participated (85 men/35 women). The mean oral morphine milligram equivalent (MME) was 694 ± 249 mg/day. Our study found significant alterations in pain perception, conditioned pain modulation, and wind-up. We demonstrated a moderate dose-response relationship between high-dose opioids and markers of central sensitization. CONCLUSION: The present trial demonstrates the clear effects of opioid agonist therapy on the somatosensory system. Both central sensitization and descending pain modulation are negatively affected by high doses of opioids and our data elucidate a moderate dose-response relationship for these phenomena.