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Gynecologic Oncology Reports Aug 2019Cervical cancer is the most common cancer in Tanzania. After excluding human immunodeficiency virus, lower respiratory infections, malaria, diarrheal diseases, and... (Review)
Review
Cervical cancer is the most common cancer in Tanzania. After excluding human immunodeficiency virus, lower respiratory infections, malaria, diarrheal diseases, and tuberculosis, cervical cancer kills more women than any other form of illness in the country. Unfortunately, Tanzania has a low doctor-to-patient ratio (1:50,000) and nearly 7000 women die each year from this disease. The clinical problem is further magnified by the country's lack of resources and prevailing poverty, sporadic cervical cancer screening, prevalence of high-risk oncogenic human papillomavirus subtypes, and relatively high rates of human immunodeficiency virus co-infection. In recent years, addressing the cervical cancer problem has become a priority for the Tanzanian government. In this systematic review of 39 peer-reviewed publications that appeared in the PubMed/MEDLINE (NCBI) database from 2013 to 2018, we synthesize the growing body of literature to capture current trends in Tanzania's evolving cervical cancer landscape. Six domains were identified, including risk factors, primary prevention, barriers to screening, treatment, healthcare worker education, and sustainability. In addition to traditional risk factors associated with sexual behavior, acetowhite changes observed during visual inspection of the cervix with acetic acid, lower education, rural setting, and HIV positivity also have a noteworthy clinical impact.
PubMed: 31309135
DOI: 10.1016/j.gore.2019.05.008 -
Gastro Hep Advances 2023Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder that may complicate conditions such as obstructive airway disease. Our group has...
BACKGROUND AND AIMS
Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder that may complicate conditions such as obstructive airway disease. Our group has identified predictive biomarkers of GERD in particulate exposed first responders with obstructive airway disease. In addition, GERD diagnosis and treatment is costly and invasive. In light of these clinical concerns, we aimed to systematically review studies identifying noninvasive, multiOmic, and multicompartmental biomarkers of GERD.
METHODS
A systematic review of PubMed and Embase was performed using keywords focusing on reflux disease and biomarkers and registered with PROSPERO. We included original human studies in English, articles focusing on noninvasive biomarkers of GERD published after December 31, 2009. GERD subtypes (non-erosive reflux disease and erosive esophagitis) and related conditions (Barrett's Esophagus [BE] and Esophageal Adenocarcinoma). Predictive measures were synthesized and risk of bias assessed (Newcastle-Ottawa Scale).
RESULTS
Initial search identified n = 238 studies andn 13 articles remained after applying inclusion/exclusion criteria. Salivary pepsin was the most studied biomarker with significant sensitivity and specificity for GERD. Serum assessment showed elevated levels of Tumor Necrosis Factor-alpha in both GERD and Barrett's. Exhaled breath volatile sulfur compounds and acetic acid were associated with GERD. Oral Microbiome: Models with , , and showed the greatest discrimination between BE and controls vs ; ROC 0.94 (95% confidence interval; 0.85-1.00).
CONCLUSION
Prior studies identified significant multiOmic, multicompartmental noninvasive biomarker risks for GERD and BE. However, studies have a high risk of bias and the reliability and accuracy of the biomarkers identified are greatly limited, which further highlights the need to discover and validate clinically relevant noninvasive biomarkers of GERD.
PubMed: 38009162
DOI: 10.1016/j.gastha.2023.01.014 -
BMC Medicine Oct 2022The beneficial role of gut microbiota and bacterial metabolites, including short-chain fatty acids (SCFAs), is well recognized, although the available literature around... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The beneficial role of gut microbiota and bacterial metabolites, including short-chain fatty acids (SCFAs), is well recognized, although the available literature around their role in colorectal cancer (CRC) has been inconsistent.
METHODS
We performed a systematic review and meta-analysis to examine the associations of fecal SCFA concentrations to the incidence and risk of CRC. Data extraction through Medline, Embase, and Web of Science was carried out from database conception to June 29, 2022. Predefined inclusion/exclusion criteria led to the selection of 17 case-control and six cross-sectional studies for quality assessment and analyses. Studies were categorized for CRC risk or incidence, and RevMan 5.4 was used to perform the meta-analyses. Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated using a random-effects model. Studies lacking quantitation were included in qualitative analyses.
RESULTS
Combined analysis of acetic, propionic, and butyric acid revealed significantly lower concentrations of these SCFAs in individuals with a high-risk of CRC (SMD = 2.02, 95% CI 0.31 to 3.74, P = 0.02). Additionally, CRC incidence was higher in individuals with lower levels of SCFAs (SMD = 0.45, 95% CI 0.19 to 0.72, P = 0.0009), compared to healthy individuals. Qualitative analyses identified 70.4% of studies reporting significantly lower concentrations of fecal acetic, propionic, butyric acid, or total SCFAs in those at higher risk of CRC, while 66.7% reported significantly lower concentrations of fecal acetic and butyric acid in CRC patients compared to healthy controls.
CONCLUSIONS
Overall, lower fecal concentrations of the three major SCFAs are associated with higher risk of CRC and incidence of CRC.
Topics: Butyrates; Colorectal Neoplasms; Cross-Sectional Studies; Fatty Acids, Volatile; Feces; Humans; Incidence
PubMed: 36184594
DOI: 10.1186/s12916-022-02529-4 -
Microbiology (Reading, England) Jul 2023, a combination of honey and vinegar, has been used as a remedy for wounds and infections in historical and traditional medical settings. While honey is now clinically...
, a combination of honey and vinegar, has been used as a remedy for wounds and infections in historical and traditional medical settings. While honey is now clinically used to treat infected wounds, this use of a complex, raw natural product (NP) mixture is unusual in modern western medicine. Research into the antimicrobial activity of NPs more usually focuses on finding a single active compound. The acetic acid in vinegar is known to have antibacterial activity at low concentrations and is in clinical use to treat burn wound infections. Here, we investigated the potential for synergistic activity of different compounds present in a complex ingredient used in historical medicine (vinegar) and in an ingredient mixture (). We conducted a systematic review to investigate published evidence for antimicrobial effects of vinegars against human pathogenic bacteria and fungi. No published studies have explicitly compared the activity of vinegar with that of a comparable concentration of acetic acid. We then characterized selected vinegars by HPLC and assessed the antibacterial and antibiofilm activity of the vinegars and acetic acid, alone and in combination with medical-grade honeys, against and . We found that some vinegars have antibacterial activity that exceeds that predicted by their acetic acid content alone, but that this depends on the bacterial species being investigated and the growth conditions (media type, planktonic vs. biofilm). Pomegranate vinegars may be particularly interesting candidates for further study. We also conclude that there is potential for acetic acid, and some vinegars, to show synergistic antibiofilm activity with manuka honey.
Topics: Humans; Acetic Acid; Honey; Anti-Bacterial Agents; Biofilms; Biological Products
PubMed: 37435775
DOI: 10.1099/mic.0.001351 -
European Radiology Mar 2022Effective and non-invasive biomarkers to predict and avoid posthepatectomy liver failure (PHLF) are urgently needed. This systematic review aims to evaluate the efficacy... (Review)
Review
OBJECTIVES
Effective and non-invasive biomarkers to predict and avoid posthepatectomy liver failure (PHLF) are urgently needed. This systematic review aims to evaluate the efficacy of gadoxetic acid-enhanced MRI-derived parameters as an imaging biomarker in preoperative prediction of PHLF.
METHODS
A systematic literature search was performed in the databases of PubMed/Medline, Web of Science, Embase, and Cochrane Library up to 11 December 2020. Studies evaluating the incidence of PHLF on patients who underwent hepatectomy with preoperative liver function assessment using gadoxetic acid-enhanced MRI were included. Data was extracted using pre-designed tables. The Quality In Prognostic Studies (QUIPS) tool was adopted to evaluate the risk of bias.
RESULTS
A total of 15 studies were identified for qualitative synthesis and most studies were marked as low to moderate risk of bias in each domain of QUIPS. The most commonly used parameter was relative liver enhancement or its related parameters. The reported incidence of PHLF ranged from 3.9 to 40%. The predictive sensitivity and specificity of gadoxetic acid-enhanced MRI parameters varied from 75 to 100% and from 54 to 93% in ten reported studies. A majority of the studies revealed that the gadoxetic acid-enhanced MRI parameter was a predictor for PHLF.
CONCLUSIONS
Gadoxetic acid-enhanced MRI showed a high predictive capacity for PHLF and represents a promising imaging biomarker in prediction of PHLF. Multicenter, prospective trials with large sample size and reliable, unified liver function parameters are required to validate the efficacy of individual liver function parameters.
KEY POINTS
• There is an obvious heterogeneity of the published studies, not only in variance of MRI liver function parameters but also in indication and extent of the liver resection. • Signal intensity (SI)-based parameters derived from gadoxetic acid-enhanced MRI are the commonly used method for PHLF prediction. • Gadoxetic acid-enhanced MRI-derived parameters showed high predictive efficacy for PHLF and can potentially serve as a predictor for the incidence of PHLF.
Topics: Contrast Media; Gadolinium DTPA; Hepatectomy; Humans; Liver; Liver Failure; Liver Neoplasms; Magnetic Resonance Imaging; Multicenter Studies as Topic; Postoperative Complications; Prospective Studies; Retrospective Studies
PubMed: 34562137
DOI: 10.1007/s00330-021-08297-8 -
Critical Care (London, England) Feb 2023Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically,...
Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically, treatment of EG toxicity included supportive care, correction of acid-base disturbances and antidotes (ethanol or fomepizole), and extracorporeal treatments (ECTRs), such as hemodialysis. With the wider availability of fomepizole, the indications for ECTRs in EG poisoning are debated. We conducted systematic reviews of the literature following published EXTRIP methods to determine the utility of ECTRs in the management of EG toxicity. The quality of the evidence and the strength of recommendations, either strong ("we recommend") or weak/conditional ("we suggest"), were graded according to the GRADE approach. A total of 226 articles met inclusion criteria. EG was assessed as dialyzable by intermittent hemodialysis (level of evidence = B) as was glycolate (Level of evidence = C). Clinical data were available for analysis on 446 patients, in whom overall mortality was 18.7%. In the subgroup of patients with a glycolate concentration ≤ 12 mmol/L (or anion gap ≤ 28 mmol/L), mortality was 3.6%; in this subgroup, outcomes in patients receiving ECTR were not better than in those who did not receive ECTR. The EXTRIP workgroup made the following recommendations for the use of ECTR in addition to supportive care over supportive care alone in the management of EG poisoning (very low quality of evidence for all recommendations): i) Suggest ECTR if fomepizole is used and EG concentration > 50 mmol/L OR osmol gap > 50; or ii) Recommend ECTR if ethanol is used and EG concentration > 50 mmol/L OR osmol gap > 50; or iii) Recommend ECTR if glycolate concentration is > 12 mmol/L or anion gap > 27 mmol/L; or iv) Suggest ECTR if glycolate concentration 8-12 mmol/L or anion gap 23-27 mmol/L; or v) Recommend ECTR if there are severe clinical features (coma, seizures, or AKI). In most settings, the workgroup recommends using intermittent hemodialysis over other ECTRs. If intermittent hemodialysis is not available, CKRT is recommended over other types of ECTR. Cessation of ECTR is recommended once the anion gap is < 18 mmol/L or suggested if EG concentration is < 4 mmol/L. The dosage of antidotes (fomepizole or ethanol) needs to be adjusted during ECTR.
Topics: Humans; Antidotes; Fomepizole; Ethanol; Renal Dialysis; Glycolates; Ethylene Glycol; Poisoning
PubMed: 36765419
DOI: 10.1186/s13054-022-04227-2 -
Diagnostics (Basel, Switzerland) Feb 2023Visual inspection with acetic acid (VIA) is one of the methods recommended by the World Health Organization for cervical cancer screening. VIA is simple and low-cost;... (Review)
Review
Visual inspection with acetic acid (VIA) is one of the methods recommended by the World Health Organization for cervical cancer screening. VIA is simple and low-cost; it, however, presents high subjectivity. We conducted a systematic literature search in PubMed, Google Scholar and Scopus to identify automated algorithms for classifying images taken during VIA as negative (healthy/benign) or precancerous/cancerous. Of the 2608 studies identified, 11 met the inclusion criteria. The algorithm with the highest accuracy in each study was selected, and some of its key features were analyzed. Data analysis and comparison between the algorithms were conducted, in terms of sensitivity and specificity, ranging from 0.22 to 0.93 and 0.67 to 0.95, respectively. The quality and risk of each study were assessed following the QUADAS-2 guidelines. Artificial intelligence-based cervical cancer screening algorithms have the potential to become a key tool for supporting cervical cancer screening, especially in settings where there is a lack of healthcare infrastructure and trained personnel. The presented studies, however, assess their algorithms using small datasets of highly selected images, not reflecting whole screened populations. Large-scale testing in real conditions is required to assess the feasibility of integrating those algorithms in clinical settings.
PubMed: 36899979
DOI: 10.3390/diagnostics13050836 -
Systematic Reviews Jun 2023Cervical cancer is a major global health issue, with 89% of cases occurring in low- and middle-income countries (LMICs). Human papillomavirus (HPV) self-sampling tests... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cervical cancer is a major global health issue, with 89% of cases occurring in low- and middle-income countries (LMICs). Human papillomavirus (HPV) self-sampling tests have been suggested as an innovative way to improve cervical cancer screening uptake and reduce the burden of disease. The objective of this review was to examine the effect of HPV self-sampling on screening uptake compared to any healthcare provider sampling in LMICs. The secondary objective was to estimate the associated costs of the various screening methods.
METHOD
Studies were retrieved from PubMed, Embase, CINAHL, CENTRAL (by Cochrane), Web of Science, and ClinicalTrials.gov up until April 14, 2022, and a total of six trials were included in the review. Meta-analyses were performed mainly using the inverse variance method, by pooling effect estimates of the proportion of women who accepted the screening method offered. Subgroup analyses were done comparing low- and middle-income countries, as well as low- and high-risk bias studies. Heterogeneity of the data was assessed using I. Cost data was collected for analysis from articles and correspondence with authors.
RESULTS
We found a small but significant difference in screening uptake in our primary analysis: RR 1.11 (95% CI: 1.10-1.11; I = 97%; 6 trials; 29,018 participants). Our sensitivity analysis, which excluded one trial that measured screening uptake differently than the other trials, resulted in a clearer effect in screening uptake: RR: 1.82 (95% CI: 1.67-1.99; I = 42%; 5 trials; 9590 participants). Two trials reported costs; thus, it was not possible to make a direct comparison of costs. One found self-sampling more cost-effective than the provider-required visual inspection with acetic acid method, despite the test and running costs being higher for HPV self-sampling.
CONCLUSION
Our review indicates that self-sampling improves screening uptake, particularly in low-income countries; however, to this date, there remain few trials and associated cost data. We recommend further studies with proper cost data be conducted to guide the incorporation of HPV self-sampling into national cervical cancer screening guidelines in low- and middle-income countries.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020218504.
Topics: Female; Humans; Uterine Cervical Neoplasms; Early Detection of Cancer; Developing Countries; Papillomavirus Infections; Mass Screening; Health Personnel
PubMed: 37349822
DOI: 10.1186/s13643-023-02252-y -
The Cochrane Database of Systematic... May 2021This is an updated version of the Cochrane review published in 2015. Around half of people with epilepsy will not achieve seizure freedom on their first antiepileptic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is an updated version of the Cochrane review published in 2015. Around half of people with epilepsy will not achieve seizure freedom on their first antiepileptic drug; many will require add-on therapy. Around a third of people fail to achieve complete seizure freedom despite multiple antiepileptic drugs. Lacosamide has been licenced as an add-on therapy for drug-resistant focal epilepsy.
OBJECTIVES
To evaluate the efficacy and tolerability of lacosamide as an add-on therapy for children and adults with drug-resistant focal epilepsy.
SEARCH METHODS
We searched the following databases (22 August 2019): the Cochrane Register of Studies (CRS Web), including the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to 20 August 2019), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP), with no language restrictions. We contacted UCB Pharma (sponsors of lacosamide).
SELECTION CRITERIA
Randomised controlled trials of add-on lacosamide in people with drug-resistant focal epilepsy.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology, assessing the following outcomes: 50% or greater reduction in seizure frequency; seizure freedom; treatment withdrawal; adverse events; quality of life; and cognitive changes. The primary analyses were intention-to-treat. We estimated summary risk ratios (RR) for each outcome presented with 99% confidence intervals (CI), except for 50% or greater seizure reduction, seizure freedom and treatment withdrawal which were presented with 95% CIs. We performed subgroup analyses according to lacosamide dose and sensitivity analyses according to population age, whereby data from children were excluded from the meta-analysis.
MAIN RESULTS
We included five trials (2199 participants). The risk of bias for all studies was low to unclear. All studies were placebo-controlled and assessed doses from 200 mg to 600 mg per day. One study evaluated lacosamide in children; all other studies were in adults. Trial duration ranged from 24 to 26 weeks. All studies used adequate methods of randomisation and were double-blind. Overall, the certainty of the evidence for the outcomes was judged as moderate to high, with the exception of seizure freedom which was low. The RR for a 50% or greater reduction in seizure frequency for all doses of lacosamide compared with placebo was 1.79 (95% CI 1.55 to 2.08; 5 studies; 2199 participants; high-certainty evidence). The RR for seizure freedom for all doses of lacosamide compared with placebo was 2.27 (95% CI 1.35 to 3.83; 5 studies; 2199 participants; low-certainty evidence). The RR for treatment withdrawal for all doses of lacosamide compared with placebo was 1.57 (95% CI 1.24 to 1.98; 5 studies; 2199 participants; moderate-certainty evidence). The estimated effect size for most outcomes did not change considerably following sensitivity analysis. For seizure freedom, however, the RR nearly doubled upon the exclusion of data from children (RR 4.04, 95% CI 1.52 to 10.73). Adverse events associated with lacosamide included: abnormal co-ordination (RR 6.12, 99% CI 1.35 to 27.77), blurred vision (RR 4.65, 99% CI 1.24 to 17.37), diplopia (RR 5.59, 99% CI 2.27 to 13.79), dizziness (RR 2.96, 99% CI 2.09 to 4.20), nausea (RR 2.35, 99% CI 1.37 to 4.02), somnolence (RR 2.04, 99% CI 1.22 to 3.41), vomiting (RR 2.94, 99% CI 1.54 to 5.64), and number of participants experiencing one or more adverse events (RR 1.12, 99% CI 1.01 to 1.24). Adverse events that were not significant were: vertigo (RR 3.71, 99% CI 0.86 to 15.95), rash (RR 0.58, 99% CI 0.17 to 1.89), nasopharyngitis (RR 1.41, 99% CI 0.87 to 2.28), headache (RR 1.34, 99% CI 0.90 to 1.98), fatigue (RR 2.11, 99% CI 0.92 to 4.85), nystagmus (RR 1.47, 99% CI 0.61 to 3.52), and upper respiratory tract infection (RR 0.70, 99% CI 0.43 to 1.15).
AUTHORS' CONCLUSIONS
Lacosamide is effective and well-tolerated in the short term when used as add-on treatment for drug-resistant focal epilepsy. Lacosamide increases the number of people with 50% or greater reduction in seizure frequency and may increase seizure freedom, compared to placebo. Higher doses of lacosamide may be associated with higher rates of adverse events and treatment withdrawal. Additional evidence is required assessing the use of lacosamide in children and on longer-term efficacy and tolerability.
Topics: Adult; Anticonvulsants; Bias; Child; Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsies, Partial; Humans; Lacosamide; Placebos; Randomized Controlled Trials as Topic; Seizures
PubMed: 33998660
DOI: 10.1002/14651858.CD008841.pub3 -
Seizure Jul 2023The late onset myoclonic epilepsy in Down Syndrome (LOMEDS) is a peculiar epilepsy type characterized by cortical myoclonus and generalized tonic-clonic seizures (GTCS),... (Review)
Review
INTRODUCTION
The late onset myoclonic epilepsy in Down Syndrome (LOMEDS) is a peculiar epilepsy type characterized by cortical myoclonus and generalized tonic-clonic seizures (GTCS), in people suffering from cognitive decline in Down syndrome (DS). In this review, we analyzed available data on the diagnostic and therapeutic management of individuals with LOMEDS.
METHODS
We performed a systematic search of the literature to identify the diagnostic and therapeutic management of patients with LOMEDS. The following databases were used: PubMed, Google Scholar, EMBASE, CrossRef. The protocol was registered on PROSPERO (registration code: CRD42023390748).
RESULTS
Data from 46 patients were included. DS was diagnosed according to the patient's clinical and genetic characteristics. Diagnosis of Alzheimer's dementia (AD) preceded the onset of epilepsy in all cases. Both myoclonic seizures (MS) and generalized tonic-clonic seizures (GTCS) were reported, the latter preceding the onset of MS in 28 cases. EEG was performed in 45 patients, showing diffuse theta/delta slowing with superimposed generalized spike-and-wave or polyspike-and-wave. A diffuse cortical atrophy was detected in 34 patients on neuroimaging. Twenty-seven patients were treated with antiseizure medication (ASM) monotherapy, with reduced seizure frequency in 17 patients. Levetiracetam and valproic acid were the most used ASMs. Up to 41% of patients were unresponsive to first-line treatment and needed adjunctive therapy for seizure control.
CONCLUSIONS
AD-related pathological changes in the brain may play a role in LOMEDS onset, although the mechanism underlying this phenomenon is still unknown. EEG remains the most relevant investigation to be performed. A significant percentage of patients developed a first-line ASM refractory epilepsy. ASMs which modulate the glutamatergic system may represent a good therapeutic option.
Topics: Humans; Down Syndrome; Epilepsy; Epilepsies, Myoclonic; Levetiracetam; Seizures; Alzheimer Disease; Electroencephalography; Anticonvulsants; Epilepsy, Generalized
PubMed: 37267668
DOI: 10.1016/j.seizure.2023.05.017