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Journal of Dental Research Dec 2021Dentistry increasingly integrates artificial intelligence (AI) to help improve the current state of clinical dental practice. However, this revolutionary technological... (Review)
Review
Dentistry increasingly integrates artificial intelligence (AI) to help improve the current state of clinical dental practice. However, this revolutionary technological field raises various complex ethical challenges. The objective of this systematic scoping review is to document the current uses of AI in dentistry and the ethical concerns or challenges they imply. Three health care databases (MEDLINE [PubMed], SciVerse Scopus, and Cochrane Library) and 2 computer science databases (ArXiv, IEEE Xplore) were searched. After identifying 1,553 records, the documents were filtered, and a full-text screening was performed. In total, 178 studies were retained and analyzed by 8 researchers specialized in dentistry, AI, and ethics. The team used Covidence for data extraction and Dedoose for the identification of ethics-related information. PRISMA guidelines were followed. Among the included studies, 130 (73.0%) studies were published after 2016, and 93 (52.2%) were published in journals specialized in computer sciences. The technologies used were neural learning techniques for 75 (42.1%), traditional learning techniques for 76 (42.7%), or a combination of several technologies for 20 (11.2%). Overall, 7 countries contributed to 109 (61.2%) studies. A total of 53 different applications of AI in dentistry were identified, involving most dental specialties. The use of initial data sets for internal validation was reported in 152 (85.4%) studies. Forty-five ethical issues (related to the use AI in dentistry) were reported in 22 (12.4%) studies around 6 principles: prudence (10 times), equity (8), privacy (8), responsibility (6), democratic participation (4), and solidarity (4). The ratio of studies mentioning AI-related ethical issues has remained similar in the past years, showing that there is no increasing interest in the field of dentistry on this topic. This study confirms the growing presence of AI in dentistry and highlights a current lack of information on the ethical challenges surrounding its use. In addition, the scarcity of studies sharing their code could prevent future replications. The authors formulate recommendations to contribute to a more responsible use of AI technologies in dentistry.
Topics: Artificial Intelligence; Delivery of Health Care; Dentistry; Forecasting
PubMed: 34060359
DOI: 10.1177/00220345211013808 -
The Cochrane Database of Systematic... Jun 2022Ivermectin, an antiparasitic agent, inhibits the replication of viruses in vitro. The molecular hypothesis of ivermectin's antiviral mode of action suggests an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ivermectin, an antiparasitic agent, inhibits the replication of viruses in vitro. The molecular hypothesis of ivermectin's antiviral mode of action suggests an inhibitory effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in early stages of infection. Currently, evidence on ivermectin for prevention of SARS-CoV-2 infection and COVID-19 treatment is conflicting.
OBJECTIVES
To assess the efficacy and safety of ivermectin plus standard of care compared to standard of care plus/minus placebo, or any other proven intervention for people with COVID-19 receiving treatment as inpatients or outpatients, and for prevention of an infection with SARS-CoV-2 (postexposure prophylaxis).
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register, Web of Science (Emerging Citation Index and Science Citation Index), WHO COVID-19 Global literature on coronavirus disease, and HTA database weekly to identify completed and ongoing trials without language restrictions to 16 December 2021. Additionally, we included trials with > 1000 participants up to April 2022.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing ivermectin to standard of care, placebo, or another proven intervention for treatment of people with confirmed COVID-19 diagnosis, irrespective of disease severity or treatment setting, and for prevention of SARS-CoV-2 infection. Co-interventions had to be the same in both study arms. For this review update, we reappraised eligible trials for research integrity: only RCTs prospectively registered in a trial registry according to WHO guidelines for clinical trial registration were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
We assessed RCTs for bias, using the Cochrane RoB 2 tool. We used GRADE to rate the certainty of evidence for outcomes in the following settings and populations: 1) to treat inpatients with moderate-to-severe COVID-19, 2) to treat outpatients with mild COVID-19 (outcomes: mortality, clinical worsening or improvement, (serious) adverse events, quality of life, and viral clearance), and 3) to prevent SARS-CoV-2 infection (outcomes: SARS-CoV-2 infection, development of COVID-19 symptoms, admission to hospital, mortality, adverse events and quality of life).
MAIN RESULTS
We excluded seven of the 14 trials included in the previous review version; six were not prospectively registered and one was non-randomized. This updated review includes 11 trials with 3409 participants investigating ivermectin plus standard of care compared to standard of care plus/minus placebo. No trial investigated ivermectin for prevention of infection or compared ivermectin to an intervention with proven efficacy. Five trials treated participants with moderate COVID-19 (inpatient settings); six treated mild COVID-19 (outpatient settings). Eight trials were double-blind and placebo-controlled, and three were open-label. We assessed around 50% of the trial results as low risk of bias. We identified 31 ongoing trials. In addition, there are 28 potentially eligible trials without publication of results, or with disparities in the reporting of the methods and results, held in 'awaiting classification' until the trial authors clarify questions upon request. Ivermectin for treating COVID-19 in inpatient settings with moderate-to-severe disease We are uncertain whether ivermectin plus standard of care compared to standard of care plus/minus placebo reduces or increases all-cause mortality at 28 days (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.14 to 2.51; 3 trials, 230 participants; very low-certainty evidence); or clinical worsening, assessed by participants with new need for invasive mechanical ventilation or death at day 28 (RR 0.82, 95% CI 0.33 to 2.04; 2 trials, 118 participants; very low-certainty evidence); or serious adverse events during the trial period (RR 1.55, 95% CI 0.07 to 35.89; 2 trials, 197 participants; very low-certainty evidence). Ivermectin plus standard of care compared to standard of care plus placebo may have little or no effect on clinical improvement, assessed by the number of participants discharged alive at day 28 (RR 1.03, 95% CI 0.78 to 1.35; 1 trial, 73 participants; low-certainty evidence); on any adverse events during the trial period (RR 1.04, 95% CI 0.61 to 1.79; 3 trials, 228 participants; low-certainty evidence); and on viral clearance at 7 days (RR 1.12, 95% CI 0.80 to 1.58; 3 trials, 231 participants; low-certainty evidence). No trial investigated quality of life at any time point. Ivermectin for treating COVID-19 in outpatient settings with asymptomatic or mild disease Ivermectin plus standard of care compared to standard of care plus/minus placebo probably has little or no effect on all-cause mortality at day 28 (RR 0.77, 95% CI 0.47 to 1.25; 6 trials, 2860 participants; moderate-certainty evidence) and little or no effect on quality of life, measured with the PROMIS Global-10 scale (physical component mean difference (MD) 0.00, 95% CI -0.98 to 0.98; and mental component MD 0.00, 95% CI -1.08 to 1.08; 1358 participants; high-certainty evidence). Ivermectin may have little or no effect on clinical worsening, assessed by admission to hospital or death within 28 days (RR 1.09, 95% CI 0.20 to 6.02; 2 trials, 590 participants; low-certainty evidence); on clinical improvement, assessed by the number of participants with all initial symptoms resolved up to 14 days (RR 0.90, 95% CI 0.60 to 1.36; 2 trials, 478 participants; low-certainty evidence); on serious adverse events (RR 2.27, 95% CI 0.62 to 8.31; 5 trials, 1502 participants; low-certainty evidence); on any adverse events during the trial period (RR 1.24, 95% CI 0.87 to 1.76; 5 trials, 1502 participants; low-certainty evidence); and on viral clearance at day 7 compared to placebo (RR 1.01, 95% CI 0.69 to 1.48; 2 trials, 331 participants; low-certainty evidence). None of the trials reporting duration of symptoms were eligible for meta-analysis.
AUTHORS' CONCLUSIONS
For outpatients, there is currently low- to high-certainty evidence that ivermectin has no beneficial effect for people with COVID-19. Based on the very low-certainty evidence for inpatients, we are still uncertain whether ivermectin prevents death or clinical worsening or increases serious adverse events, while there is low-certainty evidence that it has no beneficial effect regarding clinical improvement, viral clearance and adverse events. No evidence is available on ivermectin to prevent SARS-CoV-2 infection. In this update, certainty of evidence increased through higher quality trials including more participants. According to this review's living approach, we will continually update our search.
Topics: COVID-19; Humans; Ivermectin; Randomized Controlled Trials as Topic; Respiration, Artificial; SARS-CoV-2; Severity of Illness Index
PubMed: 35726131
DOI: 10.1002/14651858.CD015017.pub3 -
International Journal of Molecular... Jul 2022Ovarian cancer is the most lethal gynecologic malignancy in the United States. Some patients affected by ovarian cancers often present genome instability with one or... (Review)
Review
Ovarian cancer is the most lethal gynecologic malignancy in the United States. Some patients affected by ovarian cancers often present genome instability with one or more of the defects in DNA repair pathways, particularly in homologous recombination (HR), which is strictly linked to mutations in breast cancer susceptibility gene 1 (BRCA 1) or breast cancer susceptibility gene 2 (BRCA 2). The treatment of ovarian cancer remains a challenge, and the majority of patients with advanced-stage ovarian cancers experience relapse and require additional treatment despite initial therapy, including optimal cytoreductive surgery (CRS) and platinum-based chemotherapy. Targeted therapy at DNA repair genes has become a unique strategy to combat homologous recombination-deficient (HRD) cancers in recent years. Poly (ADP-ribose) polymerase (PARP), a family of proteins, plays an important role in DNA damage repair, genome stability, and apoptosis of cancer cells, especially in HRD cancers. PARP inhibitors (PARPi) have been reported to be highly effective and low-toxicity drugs that will tremendously benefit patients with HRD (i.e., BRCA 1/2 mutated) epithelial ovarian cancer (EOC) by blocking the DNA repair pathways and inducing apoptosis of cancer cells. PARP inhibitors compete with NAD at the catalytic domain (CAT) of PARP to block PARP catalytic activity and the formation of PAR polymers. These effects compromise the cellular ability to overcome DNA SSB damage. The process of HR, an essential error-free pathway to repair DNA DSBs during cell replication, will be blocked in the condition of BRCA 1/2 mutations. The PARP-associated HR pathway can also be partially interrupted by using PARP inhibitors. Grossly, PARP inhibitors have demonstrated some therapeutic benefits in many randomized phase II and III trials when combined with the standard CRS for advanced EOCs. However, similar to other chemotherapy agents, PARP inhibitors have different clinical indications and toxicity profiles and also face drug resistance, which has become a major challenge. In high-grade epithelial ovarian cancers, the cancer cells under hypoxia- or drug-induced stress have the capacity to become polyploidy giant cancer cells (PGCCs), which can survive the attack of chemotherapeutic agents and start endoreplication. These stem-like, self-renewing PGCCs generate mutations to alter the expression/function of kinases, p53, and stem cell markers, and diploid daughter cells can exhibit drug resistance and facilitate tumor growth and metastasis. In this review, we discuss the underlying molecular mechanisms of PARP inhibitors and the results from the clinical studies that investigated the effects of the FDA-approved PARP inhibitors olaparib, rucaparib, and niraparib. We also review the current research progress on PARP inhibitors, their safety, and their combined usage with antiangiogenic agents. Nevertheless, many unknown aspects of PARP inhibitors, including detailed mechanisms of actions, along with the effectiveness and safety of the treatment of EOCs, warrant further investigation.
Topics: Antineoplastic Agents; Carcinoma, Ovarian Epithelial; Clinical Trials, Phase II as Topic; Female; Genes, BRCA2; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Randomized Controlled Trials as Topic
PubMed: 35897700
DOI: 10.3390/ijms23158125 -
Journal of Sleep Research Dec 2023Longitudinal studies observed that individuals suffering from insomnia disorder have a higher vulnerability to develop symptoms of psychopathology compared with good... (Meta-Analysis)
Meta-Analysis Review
Longitudinal studies observed that individuals suffering from insomnia disorder have a higher vulnerability to develop symptoms of psychopathology compared with good sleepers. Particularly, insomnia disorder has been associated with an increased risk for depression. Previous studies indicate relatively stable effects; however, replication is needed as the last meta-analysis on the topic has been published 4 years ago. We conducted a replication of a previous systematic review and meta-analysis evaluating the longitudinal association between insomnia disorder and psychopathology, including original works published between 2018 and 2022. Literature search was conducted from April 2018 to August 2022 using key words identifying longitudinal studies that evaluate individuals with insomnia disorder compared with good sleepers at baseline, and the onset of all possible mental disorders at long-term follow-up. Only one work was added to the previous sample of studies published in 2019 looking at the longitudinal association between insomnia disorder and depression. Meta-analytic results confirmed the previous observation, with an even higher observed effect for the link between insomnia and depression. This again recognizes insomnia disorder as a possible transdiagnostic process in psychopathology, with consequent important clinical implications. Nevertheless, more longitudinal studies are needed evaluating the link between insomnia disorder and mental disorders.
Topics: Humans; Longitudinal Studies; Mental Disorders; Risk Factors; Sleep Initiation and Maintenance Disorders
PubMed: 37211915
DOI: 10.1111/jsr.13930 -
Personalized Medicine in Psychiatry 2023Research into misophonia treatments has been limited and it is unclear what treatment approaches may be effective. This systematic review extracted and synthesized...
Research into misophonia treatments has been limited and it is unclear what treatment approaches may be effective. This systematic review extracted and synthesized relevant treatment research on misophonia to examine the efficacy of various intervention modalities and identify current trends in order to guide future treatment research. PubMed, PsycINFO, Google Scholar, and Cochrane Central were searched 4using the keywords "misophonia," "decreased sound tolerance," "selective sound sensitivity," or "decreased sound sensitivity." Of the 169 records available for initial screening, 33 studied misophonia treatment specifically. Data were available for one randomized controlled trial, one open label trial, and 31 case studies. Treatments included various forms of psychotherapy, medication, and combinations of the two. Cognitive-behavioral therapy (CBT) incorporating various components has been the most often utilized and effective treatment for reduction of misophonia symptoms in one randomized trial and several case studies/series. Beyond CBT, various case studies suggested possible benefit from other treatment approaches depending on the patient's symptom profile, although methodological rigor was limited. Given the limitations in the literature to date, including overall lack of rigor, lack of comparative studies, limited replication, and small sample size, the field would benefit from the development of mechanism-informed treatments, rigorous randomized trials, and treatment development with an eye towards dissemination and implementation.
PubMed: 37333720
DOI: 10.1016/j.pmip.2023.100104 -
Journal of Sleep Research Dec 2023Insomnia nosology has significantly evolved since the Diagnostic and Statistical Manual (DSM)-III-R first distinguished between 'primary' and 'secondary' insomnia. Prior... (Review)
Review
Insomnia nosology has significantly evolved since the Diagnostic and Statistical Manual (DSM)-III-R first distinguished between 'primary' and 'secondary' insomnia. Prior International Classification of Sleep Disorders (ICSD) nosology 'split' diagnostic phenotypes to address insomnia's heterogeneity and the DSM nosology 'lumped' them into primary insomnia, while both systems assumed causality for insomnia secondary to health conditions. In this systematic review, we discuss the historical phenotypes in prior insomnia nosology, present findings for currently proposed insomnia phenotypes based on more robust approaches, and critically appraise the most relevant ones. Electronic databases PsychINFO, PubMED, Web of Science, and references of eligible articles, were accessed to find diagnostic manuals, literature on insomnia phenotypes, including systematic reviews or meta-analysis, and assessments of the reliability or validity of insomnia diagnoses, identifying 184 articles. The data show that previous insomnia diagnoses lacked reliability and validity, leading current DSM-5-TR and ICSD-3 nosology to 'lump' phenotypes into a single diagnosis comorbid with health conditions. However, at least two new, robust insomnia phenotyping approaches were identified. One approach is multidimensional-multimethod and provides evidence for self-reported insomnia with objective short versus normal sleep duration linked to clinically relevant outcomes, while the other is multidimensional and provides evidence for two to five clusters (phenotypes) based on self-reported trait, state, and/or life-history data. Some approaches still need replication to better support whether their findings identify true phenotypes or simply different patterns of symptomatology. Regardless, these phenotyping efforts aim at improving insomnia nosology both as a classification system and as a mechanism to guide treatment.
Topics: Humans; International Classification of Diseases; Phenotype; Reproducibility of Results; Self Report; Sleep Initiation and Maintenance Disorders
PubMed: 37122153
DOI: 10.1111/jsr.13910 -
The Lancet. Psychiatry Oct 2023Ketamine is an effective antidepressant, but there is substantial variability in patient response and the precise mechanism of action is unclear. Neuroimaging can... (Review)
Review
Ketamine is an effective antidepressant, but there is substantial variability in patient response and the precise mechanism of action is unclear. Neuroimaging can provide predictive and mechanistic insights, but findings are limited by small sample sizes. This systematic review covers neuroimaging studies investigating baseline (pre-treatment) and longitudinal (post-treatment) biomarkers of responses to ketamine. All modalities were included. We performed searches of five electronic databases (from inception to April 26, 2022). 69 studies were included (with 1751 participants). There was substantial methodological heterogeneity and no well replicated biomarker. However, we found convergence across some significant results, particularly in longitudinal biomarkers. Response to ketamine was associated with post-treatment increases in gamma power in frontoparietal regions in electrophysiological studies, post-treatment increases in functional connectivity within the prefrontal cortex, and post-treatment increases in the functional activation of the striatum. Although a well replicated neuroimaging biomarker of ketamine response was not identified, there are biomarkers that warrant further investigation.
Topics: Humans; Ketamine; Brain; Antidepressive Agents; Neuroimaging; Biomarkers
PubMed: 37625426
DOI: 10.1016/S2215-0366(23)00183-9 -
Clinical and Translational Allergy Nov 2022Several risk factors for asthma have been proposed; however, the causality of these associations is sometimes unclear. Mendelian randomization is a powerful... (Review)
Review
BACKGROUND
Several risk factors for asthma have been proposed; however, the causality of these associations is sometimes unclear. Mendelian randomization is a powerful epidemiological approach that can help elucidate the causality of risk factors. The aim of the present study was to identify causal risk factors for asthma through Mendelian Randomization studies.
METHODS
A systematic search of PubMed and EMBASE was conducted, to identify studies investigating risk factors for asthma or respiratory allergies through Mendelian Randomization. When two or more studies investigated the same risk factor a meta-analysis was conducted. Of 239 studies initially identified, 41 were included.
RESULTS
A causal association between adiposity and adult asthma risk was found in 10 out of 12 studies with a summary risk ratio of 1.05 per kg/m increase in BMI (95% CI: 1.03-1.07). Puberty timing (n = 3), alcohol (n = 2), and linoleic acid (n = 1) had causal effects on asthma risk, while vitamins/minerals (n = 6) showed no consistent effect on asthma. The effect of smoking on adult asthma conflicted between studies. Several of the significant associations of asthma with immune related proteins (n = 5) and depression (n = 2) investigated through multiple traits analyses could generally benefit from replications in independent datasets.
CONCLUSION
This systematic review and meta-analysis found evidence for causal effects of adiposity, puberty timing, linoleic acid, alcohol, immune related proteins, and depression on risk of asthma.
PubMed: 36434743
DOI: 10.1002/clt2.12207 -
Current Medical Research and Opinion Feb 2022With constantly emerging new information regarding the epidemiology, pathogenesis, diagnosis and management of Coronavirus Disease 2019 (COVID-19), reviewing literature... (Meta-Analysis)
Meta-Analysis
With constantly emerging new information regarding the epidemiology, pathogenesis, diagnosis and management of Coronavirus Disease 2019 (COVID-19), reviewing literature related to it has become increasingly complicated and resource-intensive. In the setting of this global pandemic, clinical decisions are being guided by the results of multiple pertinent studies; however, it has been observed that these studies are often heterogenous in design and population characteristics and results of initial trials may not be replicated in subsequent studies. The resulting clinical conundrum can be resolved by high-quality systematic review and meta-analysis with a robust and reliable methodology, encapsulating and critically appraising all the available literature relevant to the clinical scenario under scrutiny. It can condense the large volume of scientific information available and can also identify the cause of differences in the degree of effect under consideration across different studies. It can identify optimal diagnostic algorithms, assess efficacy of treatment strategies, and analyze inherent factors influencing the efficacy of treatment for COVID-19. The current review aims to provide a basic guide to plan and conduct a high-quality systematic review and meta-analysis pertaining to COVID-19, describing the main steps and addressing the pitfalls commonly encountered at each step. Knowledge of the basic steps would also allow the reader to critically appraise published systematic review and meta-analysis and the quality of evidence provided therein.
Topics: COVID-19; Humans; Pandemics; SARS-CoV-2
PubMed: 34870545
DOI: 10.1080/03007995.2021.2015160 -
International Journal of Environmental... Dec 2023The outbreak of coronavirus disease in 2019 has become a serious threat to human health. Whether meteorological conditions could influence the transmission and virulence... (Review)
Review
The outbreak of coronavirus disease in 2019 has become a serious threat to human health. Whether meteorological conditions could influence the transmission and virulence of COVID-19 remains controversial. In this study, we systematically reviewed the impact of temperature and humidity on the replication, morbidity, and mortality of COVID-19. We also discussed the main factors underlying the inconsistency across studies. Pubmed, Web of Science, Embase, and Scopus were used to identify papers published up to 7 December 2020. We initially identified 3515 papers, and 28 articles met the inclusion criteria after screening. Most studies showed high temperature and high humidity can partly reduce the reproduction, morbidity, and mortality of COVID-19. But the rest papers failed to identify a significant association. The discrepant results may be related to the difference in the climate context, study design, exposure assessment, policy intervention, socioeconomic status, and public health service.
Topics: Humans; COVID-19; SARS-CoV-2; Temperature; Climate; Meteorological Concepts
PubMed: 35674116
DOI: 10.1080/09603123.2022.2083090