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Children (Basel, Switzerland) Mar 2023Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) is a new CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) modulator treatment, used over the last few years,... (Review)
Review
Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) is a new CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) modulator treatment, used over the last few years, which has shown an improvement in different clinical outcomes in patients with cystic fibrosis (CF). The objective of this study was a systematic research of the literature on the efficacy and safety of this CFTR modulator on patients with CF. A search of Pubmed was conducted for randomized clinical trials and observational studies published from 2012 to September 2022. The included full manuscripts comprised nine clinical trials and 16 observational studies, whose participants were aged ≥12 years or were children 6-11 years old with at least one Phe508del mutation and/or advanced lung disease (ALD). These studies reported that ELX/TEZ/IVA has a significant positive effect on the lung function of patients with CF, by ameliorating parameters such as FEV, LCI, pulmonary exacerbations or sweat chloride concentration, increasing BMI and improving quality of their life. Its role in cystic fibrosis-related diabetes (CFRD) is not yet clear. It was found that this new CFTR modulator has an overall favorable safety profile, with mild to moderate adverse events. Further studies are needed for a deeper understanding of the impact of CFTR modulators on other CF manifestations, or the possibility of treating with ELX/TEZ/IVA CF patients with rare CFTR mutations.
PubMed: 36980112
DOI: 10.3390/children10030554 -
Medicina (Kaunas, Lithuania) Dec 2021: Migraine headaches are chronic neurological diseases that reduce the quality of life by causing severe headaches and autonomic nervous system dysfunction, such as... (Meta-Analysis)
Meta-Analysis Review
: Migraine headaches are chronic neurological diseases that reduce the quality of life by causing severe headaches and autonomic nervous system dysfunction, such as facial flushing, nasal stuffiness, and sweating. Their major treatment methods include medication and cognitive behavioral therapy (CBT). CBT has been used for pain treatment and various psychogenic neurological diseases by reducing pain, disability, and emotional disorders caused by symptoms of mental illness and improving the understanding of mental health. This study aimed to evaluate the effectiveness and safety of CBT in treating migraines. : Seven electronic databases were searched from the date of inception to December 2020. Randomized controlled studies (RCTs) using CBT as an intervention for migraine were included. The primary outcome of this study was to determine the frequency of migraines and the intensity of migraines on Visual Analog Scale (VAS), the frequency of drug use, Migraine Disability Assessment (MIDAS), and Headache Impact Test (HIT-6) index. The two authors independently conducted the data extraction and quality assessment of the included RCTs, and conducted meta-analysis with RevMan V.5.4. : Among the 373 studies, 11 RCTs were included in this systematic review. Seven out of the 11 RCTs were conducted in the USA, and four were conducted in the UK, Germany, Iran, and Italy, respectively. Headache frequency and MIDAS scores were statistically significant reduced. In the subgroup analysis, headache strength was significantly reduced. Two of the included studies reported adverse effects, including worsening of migraine intensity and frequency, respiratory symptoms, and vivid memory of a traumatic event. : CBT for migraine effectively reduced headache frequency and MIDAS score in meta-analysis and headache intensity subgroup analysis, with few adverse events. Additional RCTs with CBT for migraine headaches are needed for a more accurate analysis.
Topics: Cognitive Behavioral Therapy; Disability Evaluation; Headache; Humans; Migraine Disorders; Pain Measurement
PubMed: 35056352
DOI: 10.3390/medicina58010044 -
The Cochrane Database of Systematic... Nov 2023A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as racing heart, chest pain, sweating, shaking, dizziness, flushing, churning stomach, faintness and breathlessness. Other recognised panic attack symptoms involve fearful cognitions, such as the fear of collapse, going mad or dying, and derealisation (the sensation that the world is unreal). Panic disorder is common in the general population with a prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions, including antidepressants and benzodiazepines.
OBJECTIVES
To compare, via network meta-analysis, individual drugs (antidepressants and benzodiazepines) or placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank individual active drugs for panic disorder (antidepressants, benzodiazepines and placebo) according to their effectiveness and acceptability. To rank drug classes for panic disorder (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), mono-amine oxidase inhibitors (MAOIs) and benzodiazepines (BDZs) and placebo) according to their effectiveness and acceptability. To explore heterogeneity and inconsistency between direct and indirect evidence in a network meta-analysis.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Specialised Register, CENTRAL, CDSR, MEDLINE, Ovid Embase and PsycINFO to 26 May 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of people aged 18 years or older of either sex and any ethnicity with clinically diagnosed panic disorder, with or without agoraphobia. We included trials that compared the effectiveness of antidepressants and benzodiazepines with each other or with a placebo.
DATA COLLECTION AND ANALYSIS
Two authors independently screened titles/abstracts and full texts, extracted data and assessed risk of bias. We analysed dichotomous data and continuous data as risk ratios (RRs), mean differences (MD) or standardised mean differences (SMD): response to treatment (i.e. substantial improvement from baseline as defined by the original investigators: dichotomous outcome), total number of dropouts due to any reason (as a proxy measure of treatment acceptability: dichotomous outcome), remission (i.e. satisfactory end state as defined by global judgement of the original investigators: dichotomous outcome), panic symptom scales and global judgement (continuous outcome), frequency of panic attacks (as recorded, for example, by a panic diary; continuous outcome), agoraphobia (dichotomous outcome). We assessed the certainty of evidence using threshold analyses.
MAIN RESULTS
Overall, we included 70 trials in this review. Sample sizes ranged between 5 and 445 participants in each arm, and the total sample size per study ranged from 10 to 1168. Thirty-five studies included sample sizes of over 100 participants. There is evidence from 48 RCTs (N = 10,118) that most medications are more effective in the response outcome than placebo. In particular, diazepam, alprazolam, clonazepam, paroxetine, venlafaxine, clomipramine, fluoxetine and adinazolam showed the strongest effect, with diazepam, alprazolam and clonazepam ranking as the most effective. We found heterogeneity in most of the comparisons, but our threshold analyses suggest that this is unlikely to impact the findings of the network meta-analysis. Results from 64 RCTs (N = 12,310) suggest that most medications are associated with either a reduced or similar risk of dropouts to placebo. Alprazolam and diazepam were associated with a lower dropout rate compared to placebo and were ranked as the most tolerated of all the medications examined. Thirty-two RCTs (N = 8569) were included in the remission outcome. Most medications were more effective than placebo, namely desipramine, fluoxetine, clonazepam, diazepam, fluvoxamine, imipramine, venlafaxine and paroxetine, and their effects were clinically meaningful. Amongst these medications, desipramine and alprazolam were ranked highest. Thirty-five RCTs (N = 8826) are included in the continuous outcome reduction in panic scale scores. Brofaromine, clonazepam and reboxetine had the strongest reductions in panic symptoms compared to placebo, but results were based on either one trial or very small trials. Forty-one RCTs (N = 7853) are included in the frequency of panic attack outcome. Only clonazepam and alprazolam showed a strong reduction in the frequency of panic attacks compared to placebo, and were ranked highest. Twenty-six RCTs (N = 7044) provided data for agoraphobia. The strongest reductions in agoraphobia symptoms were found for citalopram, reboxetine, escitalopram, clomipramine and diazepam, compared to placebo. For the pooled intervention classes, we examined the two primary outcomes (response and dropout). The classes of medication were: SSRIs, SNRIs, TCAs, MAOIs and BDZs. For the response outcome, all classes of medications examined were more effective than placebo. TCAs as a class ranked as the most effective, followed by BDZs and MAOIs. SSRIs as a class ranked fifth on average, while SNRIs were ranked lowest. When we compared classes of medication with each other for the response outcome, we found no difference between classes. Comparisons between MAOIs and TCAs and between BDZs and TCAs also suggested no differences between these medications, but the results were imprecise. For the dropout outcome, BDZs were the only class associated with a lower dropout compared to placebo and were ranked first in terms of tolerability. The other classes did not show any difference in dropouts compared to placebo. In terms of ranking, TCAs are on average second to BDZs, followed by SNRIs, then by SSRIs and lastly by MAOIs. BDZs were associated with lower dropout rates compared to SSRIs, SNRIs and TCAs. The quality of the studies comparing antidepressants with placebo was moderate, while the quality of the studies comparing BDZs with placebo and antidepressants was low.
AUTHORS' CONCLUSIONS
In terms of efficacy, SSRIs, SNRIs (venlafaxine), TCAs, MAOIs and BDZs may be effective, with little difference between classes. However, it is important to note that the reliability of these findings may be limited due to the overall low quality of the studies, with all having unclear or high risk of bias across multiple domains. Within classes, some differences emerged. For example, amongst the SSRIs paroxetine and fluoxetine seem to have stronger evidence of efficacy than sertraline. Benzodiazepines appear to have a small but significant advantage in terms of tolerability (incidence of dropouts) over other classes.
Topics: Adult; Humans; Panic Disorder; Selective Serotonin Reuptake Inhibitors; Paroxetine; Fluoxetine; Venlafaxine Hydrochloride; Serotonin and Noradrenaline Reuptake Inhibitors; Alprazolam; Clomipramine; Reboxetine; Clonazepam; Desipramine; Network Meta-Analysis; Antidepressive Agents; Antidepressive Agents, Tricyclic; Benzodiazepines; Diazepam
PubMed: 38014714
DOI: 10.1002/14651858.CD012729.pub3 -
Advances in Therapy Oct 2021Hot flushes/flashes (HFs) or other vasomotor symptoms affect between 45 and 97% of women during menopause. Hormone replacement therapy (HRT) is effective at alleviating... (Review)
Review
Neurokinin 3 Receptor Antagonists Compared With Serotonin Norepinephrine Reuptake Inhibitors for Non-Hormonal Treatment of Menopausal Hot Flushes: A Systematic Qualitative Review.
INTRODUCTION
Hot flushes/flashes (HFs) or other vasomotor symptoms affect between 45 and 97% of women during menopause. Hormone replacement therapy (HRT) is effective at alleviating menopausal symptoms, but some women cannot or prefer not to take HRT. Since current non-hormonal options have suboptimal efficacy/tolerability, there is a pressing need for an effective, well-tolerated alternative. The neurokinin 3 receptor (NK3R) has recently been implicated in the generation of menopausal HFs and represents a novel therapeutic target to ameliorate HF symptoms. This review aims to assess if NK3R antagonists (NK3Ras) are more effective than Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)-currently a common choice for non-hormonal treatment of menopausal HFs.
METHODS
Studies were identified after systematically searching Ovid MEDLINE and EMBASE databases based on PRISMA guidelines. Trial quality and bias were assessed. Key efficacy outcomes (HF frequency, HF severity and number of night-time awakenings/night-sweats) and selected safety outcomes were extracted and analysed.
RESULTS
Seven SNRI and four NK3Ra placebo-controlled randomised trials (plus four follow-up reports) were included in this review. NK3Ra administration resulted in a larger reduction from baseline in HF frequency, HF severity and night-sweats compared to SNRIs. Five of seven SNRI trials showed a reduction in HF frequency that was statistically significant (by 48-67% from baseline at weeks 8 or 12) whereas all NK3Ra trials showed a statistically significant reduction in HF frequency (by 62-93% from baseline at weeks 2, 4 or 12). While SNRI trials reported poor tolerability, particularly nausea, NK3Ra trials reported good tolerability overall, although two trials reported elevation in transaminases.
CONCLUSION
NK3Ras trials show encouraging efficacy and tolerability/safety. Completion of phase 3 NK3Ra trials are required to confirm efficacy and uphold safety/tolerability data but phase 2 results suggest that NK3Ras are more effective than SNRIs for non-hormonal treatment of menopausal HFs.
Topics: Female; Humans; Menopause; Norepinephrine; Receptors, Neurokinin-3; Serotonin; Selective Serotonin Reuptake Inhibitors
PubMed: 34514552
DOI: 10.1007/s12325-021-01900-w -
The Cochrane Database of Systematic... Mar 2020Approximately 80% of breast cancers amongst premenopausal women are hormone receptor-positive. Adjuvant endocrine therapy is an integral component of care for hormone... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Approximately 80% of breast cancers amongst premenopausal women are hormone receptor-positive. Adjuvant endocrine therapy is an integral component of care for hormone receptor-positive breast cancer and in premenopausal women includes oestrogen receptor blockade with tamoxifen, temporary suppression of ovarian oestrogen synthesis by luteinising hormone releasing hormone (LHRH) agonists, and permanent interruption of ovarian oestrogen synthesis with oophorectomy or radiotherapy. Recent international consensus statements recommend single-agent tamoxifen or aromatase inhibitors with ovarian function suppression (OFS) as the current standard adjuvant endocrine therapy for premenopausal women (often preceded by chemotherapy). This review examined the role of adding OFS to another treatment (i.e. chemotherapy, endocrine therapy, or both) or comparing OFS to no further adjuvant treatment.
OBJECTIVES
To assess effects of OFS for treatment of premenopausal women with hormone receptor-positive early breast cancer.
SEARCH METHODS
For this review update, we searched the Specialised Register of the Cochrane Breast Cancer Group, MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov on 26 September 2019. We screened the reference lists of related articles, contacted trial authors, and applied no language restrictions.
SELECTION CRITERIA
We included all randomised trials assessing any method of OFS, that is, oophorectomy, radiation-induced ovarian ablation, or LHRH agonists, as adjuvant treatment for premenopausal women with early-stage breast cancer. We included studies that compared (1) OFS versus observation, (2) OFS + chemotherapy versus chemotherapy, (3) OFS + tamoxifen versus tamoxifen, and (4) OFS + chemotherapy + tamoxifen versus chemotherapy + tamoxifen.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed risk of bias and certainty of evidence using the GRADE approach. Hazard ratios (HRs) were derived for time-to-event outcomes, and meta-analysis was performed using a fixed-effect model. The primary outcome measures were overall survival (OS) and disease-free survival (DFS). Toxicity, contralateral breast cancer, and second malignancy were represented as risk ratios (RRs), and quality of life data were extracted when provided.
MAIN RESULTS
This review update included 15 studies involving 11,538 premenopausal women with hormone receptor-positive early breast cancer; these studies were conducted from 1978 to 2014. Some of these treatments are not current standard of care, and early studies did not assess HER2 receptor status. Studies tested OFS versus observation (one study), OFS plus chemotherapy versus chemotherapy (six studies), OFS plus tamoxifen versus tamoxifen (six studies), and OFS plus chemotherapy and tamoxifen versus chemotherapy and tamoxifen (two studies). Of those studies that reported the chemotherapy regimen, an estimated 72% of women received an anthracycline. The results described below relate to the overall comparison of OFS versus no OFS. High-certainty evidence shows that adding OFS to treatment resulted in a reduction in mortality (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.78 to 0.94; 11 studies; 10,374 women; 1933 reported events). This treatment effect was seen when OFS was added to observation, to tamoxifen, or to chemotherapy and tamoxifen. The effect on mortality was not observed when OFS was added to chemotherapy without tamoxifen therapy (HR 0.95, 95% CI 0.82 to 1.09; 5 studies; 3087 women; median follow-up: range 7.7 to 12.1 years). The addition of OFS resulted in improved DFS (HR 0.83, 95% CI 0.77 to 0.90; 10 studies; 8899 women; 2757 reported events; high-certainty evidence). The DFS treatment effect persisted when OFS was added to observation, to tamoxifen, and to chemotherapy and tamoxifen. The effect on DFS was reduced when OFS was added to chemotherapy without tamoxifen therapy (HR 0.90, 95% CI 0.79 to 1.01; 5 studies; 2450 women). Heterogeneity was low to moderate across studies for DFS and OS (respectively). Evidence suggests that adding OFS slightly increases the incidence of hot flushes (grade 3/4 or any grade; risk ratio (RR) 1.60, 95% CI 1.41 to 1.82; 6 studies; 5581 women; low-certainty evidence, as this may have been under-reported in these studies). Two other studies that could not be included in the meta-analysis reported a higher number of hot flushes in the OFS group than in the no-OFS group. Seven studies involving 5354 women collected information related to mood; however this information was reported as grade 3 or 4 depression, anxiety, or neuropsychiatric symptoms, or symptoms were reported without the grade. Two studies reported an increase in depression, anxiety, and neuropsychiatric symptoms in the OFS group compared to the no-OFS group, and five studies indicated an increase in anxiety in both treatment groups (but no difference between groups) or no difference overall in symptoms over time or between treatment groups. A single study reported bone health as osteoporosis (defined as T score < -2.5); this limited evidence suggests that OFS increases the risk of osteoporosis compared to no-OFS at median follow-up of 5.6 years (RR 1.16, 95% CI 1.10 to 28.82; 2011 women; low-certainty evidence). Adding OFS to treatment likely reduces the risk of contralateral breast cancer (HR 0.75, 95% CI 0.57 to 0.97; 9 studies; 9138 women; moderate-certainty evidence). Quality of life was assessed in five studies; four studies used validated tools, and the fifth study provided no information on how data were collected. Two studies reported worse quality of life indicators (i.e. vaginal dryness, day and night sweats) for women receiving OFS compared to those in the no-OFS group. The other two studies indicated worsening of symptoms (e.g. vasomotor, gynaecological, vaginal dryness, decline in sexual interest, bone and joint pain, weight gain); however these side effects were reported in both OFS and no-OFS groups. The study that did not use a validated quality of life tool described no considerable differences between groups.
AUTHORS' CONCLUSIONS
This review found evidence that supports adding OFS for premenopausal women with early, hormone receptor-positive breast cancers. The benefit of OFS persisted when compared to observation, and when added to endocrine therapy (tamoxifen) or chemotherapy and endocrine therapy (tamoxifen). The decision to use OFS may depend on the overall risk assessment based on tumour and patient characteristics, and may follow consideration of all side effects that occur with the addition of OFS.
Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Gonadotropin-Releasing Hormone; Humans; Premenopause; Randomized Controlled Trials as Topic; Survival Analysis; Tamoxifen; Treatment Outcome
PubMed: 32141074
DOI: 10.1002/14651858.CD013538 -
The Cochrane Database of Systematic... May 2022The World Health Organization (WHO) End TB Strategy stresses universal access to drug susceptibility testing (DST). DST determines whether Mycobacterium tuberculosis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The World Health Organization (WHO) End TB Strategy stresses universal access to drug susceptibility testing (DST). DST determines whether Mycobacterium tuberculosis bacteria are susceptible or resistant to drugs. Xpert MTB/XDR is a rapid nucleic acid amplification test for detection of tuberculosis and drug resistance in one test suitable for use in peripheral and intermediate level laboratories. In specimens where tuberculosis is detected by Xpert MTB/XDR, Xpert MTB/XDR can also detect resistance to isoniazid, fluoroquinolones, ethionamide, and amikacin.
OBJECTIVES
To assess the diagnostic accuracy of Xpert MTB/XDR for pulmonary tuberculosis in people with presumptive pulmonary tuberculosis (having signs and symptoms suggestive of tuberculosis, including cough, fever, weight loss, night sweats). To assess the diagnostic accuracy of Xpert MTB/XDR for resistance to isoniazid, fluoroquinolones, ethionamide, and amikacin in people with tuberculosis detected by Xpert MTB/XDR, irrespective of rifampicin resistance (whether or not rifampicin resistance status was known) and with known rifampicin resistance.
SEARCH METHODS
We searched multiple databases to 23 September 2021. We limited searches to 2015 onwards as Xpert MTB/XDR was launched in 2020.
SELECTION CRITERIA
Diagnostic accuracy studies using sputum in adults with presumptive or confirmed pulmonary tuberculosis. Reference standards were culture (pulmonary tuberculosis detection); phenotypic DST (pDST), genotypic DST (gDST),composite (pDST and gDST) (drug resistance detection).
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed reports for eligibility and extracted data using a standardized form. For multicentre studies, we anticipated variability in the type and frequency of mutations associated with resistance to a given drug at the different centres and considered each centre as an independent study cohort for quality assessment and analysis. We assessed methodological quality with QUADAS-2, judging risk of bias separately for each target condition and reference standard. For pulmonary tuberculosis detection, owing to heterogeneity in participant characteristics and observed specificity estimates, we reported a range of sensitivity and specificity estimates and did not perform a meta-analysis. For drug resistance detection, we performed meta-analyses by reference standard using bivariate random-effects models. Using GRADE, we assessed certainty of evidence of Xpert MTB/XDR accuracy for detection of resistance to isoniazid and fluoroquinolones in people irrespective of rifampicin resistance and to ethionamide and amikacin in people with known rifampicin resistance, reflecting real-world situations. We used pDST, except for ethionamide resistance where we considered gDST a better reference standard.
MAIN RESULTS
We included two multicentre studies from high multidrug-resistant/rifampicin-resistant tuberculosis burden countries, reporting on six independent study cohorts, involving 1228 participants for pulmonary tuberculosis detection and 1141 participants for drug resistance detection. The proportion of participants with rifampicin resistance in the two studies was 47.9% and 80.9%. For tuberculosis detection, we judged high risk of bias for patient selection owing to selective recruitment. For ethionamide resistance detection, we judged high risk of bias for the reference standard, both pDST and gDST, though we considered gDST a better reference standard. Pulmonary tuberculosis detection - Xpert MTB/XDR sensitivity range, 98.3% (96.1 to 99.5) to 98.9% (96.2 to 99.9) and specificity range, 22.5% (14.3 to 32.6) to 100.0% (86.3 to 100.0); median prevalence of pulmonary tuberculosis 91.3%, (interquartile range, 89.3% to 91.8%), (2 studies; 1 study reported on 2 cohorts, 1228 participants; very low-certainty evidence, sensitivity and specificity). Drug resistance detection People irrespective of rifampicin resistance - Isoniazid resistance: Xpert MTB/XDR summary sensitivity and specificity (95% confidence interval (CI)) were 94.2% (87.5 to 97.4) and 98.5% (92.6 to 99.7) against pDST, (6 cohorts, 1083 participants, moderate-certainty evidence, sensitivity and specificity). - Fluoroquinolone resistance: Xpert MTB/XDR summary sensitivity and specificity were 93.2% (88.1 to 96.2) and 98.0% (90.8 to 99.6) against pDST, (6 cohorts, 1021 participants; high-certainty evidence, sensitivity; moderate-certainty evidence, specificity). People with known rifampicin resistance - Ethionamide resistance: Xpert MTB/XDR summary sensitivity and specificity were 98.0% (74.2 to 99.9) and 99.7% (83.5 to 100.0) against gDST, (4 cohorts, 434 participants; very low-certainty evidence, sensitivity and specificity). - Amikacin resistance: Xpert MTB/XDR summary sensitivity and specificity were 86.1% (75.0 to 92.7) and 98.9% (93.0 to 99.8) against pDST, (4 cohorts, 490 participants; low-certainty evidence, sensitivity; high-certainty evidence, specificity). Of 1000 people with pulmonary tuberculosis, detected as tuberculosis by Xpert MTB/XDR: - where 50 have isoniazid resistance, 61 would have an Xpert MTB/XDR result indicating isoniazid resistance: of these, 14/61 (23%) would not have isoniazid resistance (FP); 939 (of 1000 people) would have a result indicating the absence of isoniazid resistance: of these, 3/939 (0%) would have isoniazid resistance (FN). - where 50 have fluoroquinolone resistance, 66 would have an Xpert MTB/XDR result indicating fluoroquinolone resistance: of these, 19/66 (29%) would not have fluoroquinolone resistance (FP); 934 would have a result indicating the absence of fluoroquinolone resistance: of these, 3/934 (0%) would have fluoroquinolone resistance (FN). - where 300 have ethionamide resistance, 296 would have an Xpert MTB/XDR result indicating ethionamide resistance: of these, 2/296 (1%) would not have ethionamide resistance (FP); 704 would have a result indicating the absence of ethionamide resistance: of these, 6/704 (1%) would have ethionamide resistance (FN). - where 135 have amikacin resistance, 126 would have an Xpert MTB/XDR result indicating amikacin resistance: of these, 10/126 (8%) would not have amikacin resistance (FP); 874 would have a result indicating the absence of amikacin resistance: of these, 19/874 (2%) would have amikacin resistance (FN).
AUTHORS' CONCLUSIONS
Review findings suggest that, in people determined by Xpert MTB/XDR to be tuberculosis-positive, Xpert MTB/XDR provides accurate results for detection of isoniazid and fluoroquinolone resistance and can assist with selection of an optimised treatment regimen. Given that Xpert MTB/XDR targets a limited number of resistance variants in specific genes, the test may perform differently in different settings. Findings in this review should be interpreted with caution. Sensitivity for detection of ethionamide resistance was based only on Xpert MTB/XDR detection of mutations in the inhA promoter region, a known limitation. High risk of bias limits our confidence in Xpert MTB/XDR accuracy for pulmonary tuberculosis. Xpert MTB/XDR's impact will depend on its ability to detect tuberculosis (required for DST), prevalence of resistance to a given drug, health care infrastructure, and access to other tests.
Topics: Adult; Amikacin; Antibiotics, Antitubercular; Drug Resistance, Bacterial; Ethionamide; Fluoroquinolones; Humans; Isoniazid; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Rifampin; Sensitivity and Specificity; Tuberculosis, Lymph Node; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary
PubMed: 35583175
DOI: 10.1002/14651858.CD014841.pub2 -
International Journal of Cosmetic... Aug 2023Sweating is the human body's thermoregulation system but also results in unpleasant body odour which can diminish the self-confidence of people. There has been continued... (Review)
Review
Sweating is the human body's thermoregulation system but also results in unpleasant body odour which can diminish the self-confidence of people. There has been continued research in finding solutions to reduce both sweating and body odour. Sweating is a result of increased sweat flow and malodour results from certain bacteria and ecological factors such as eating habits. Research on deodorant development focuses on inhibiting the growth of malodour-forming bacteria using antimicrobial agents, whereas research on antiperspirant synthesis focuses on technologies reducing the sweat flow, which not only reduces body odour but also improves people's appearance. Antiperspirant's technology is based on the use of aluminium salts which can form a gel plug at sweat pores, obstructing the sweat fluid from arising onto the skin surface. In this paper, we perform a systematic review on the recent progress in the development of novel antiperspirant and deodorant active ingredients that are alcohol-free, paraben-free, and naturally derived. Several studies have been reported on the alternative class of actives that can potentially be used for antiperspirant and body odour treatment including deodorizing fabric, bacterial, and plant extracts. However, a significant challenge is to understand how the gel-plugs of antiperspirant actives are formed in sweat pores and how to deliver long-lasting antiperspirant and deodorant benefits.
Topics: Humans; Antiperspirants; Deodorants; Body Odor; Sweating; Sweat Glands
PubMed: 36896776
DOI: 10.1111/ics.12852 -
Archives of Dermatological Research Oct 2023Sweating is a physiologic mechanism of human thermoregulation. Hyperhidrosis is defined as a somatic disorder where the sweating is exaggerated in an exact area because... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sweating is a physiologic mechanism of human thermoregulation. Hyperhidrosis is defined as a somatic disorder where the sweating is exaggerated in an exact area because the sweat glands are hyperfunctioning. It negatively affects the quality of life of the patients. We aim to investigate patient satisfaction and the effectiveness of oxybutynin in treating hyperhidrosis.
METHODS
We prospectively registered the protocol of this systematic review and meta-analysis on PROSPERO (CRD 42022342667). This systematic review and meta-analysis were reported according to the PRISMA statement guidelines. We searched three electronic databases (PubMed, Scopus, Web of Science) from inception until June 2, 2022, using MeSH terms. We include studies comparing patients with hyperhidrosis who received oxybutynin or a placebo. We assessed the risk of bias using the Cochrane risk of bias assessment tool (ROB2) for randomized controlled trials. The risk ratio was calculated for categorical variables, and the mean difference was calculated for continuous variables using the random effect model with 95% confidence intervals (CI).
RESULTS
Six studies were included in the meta-analysis, with a total of 293 patients. In all studies, patients were assigned to receive either Oxybutynin or Placebo. Oxybutynin represented an HDSS improvement (RR = 1.68 95% CI [1.21, 2.33], p = 0.002). It also can improve the quality of life. There is no difference between oxybutynin and placebo regarding dry mouth (RR = 1.68 95% CI [1.21, 2.33], p = 0.002).
CONCLUSION
Our study suggests that using oxybutynin as a treatment for hyperhidrosis is significant and needs to be highlighted for clinicians. However, more clinical trials are needed to grasp the optimum benefit.
Topics: Humans; Treatment Outcome; Quality of Life; Randomized Controlled Trials as Topic; Hyperhidrosis
PubMed: 36869926
DOI: 10.1007/s00403-023-02587-5 -
Sports Medicine (Auckland, N.Z.) Jul 2023Heat adaptation regimes are used to prepare athletes for exercise in hot conditions to limit a decrement in exercise performance. However, the heat adaptation literature... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Heat adaptation regimes are used to prepare athletes for exercise in hot conditions to limit a decrement in exercise performance. However, the heat adaptation literature mostly focuses on males, and consequently, current heat adaptation guidelines may not be optimal for females when accounting for the biological and phenotypical differences between sexes.
OBJECTIVES
We aimed to examine: (1) the effects of heat adaptation on physiological adaptations in females; (2) the impact of heat adaptation on performance test outcomes in the heat; and (3) the impact of various moderators, including duration (minutes and/or days), total heat dose (°Cmin), exercise intensity (kcalmin), total energy expended (kcal), frequency of heat exposures and training status on the physiological adaptations in the heat.
METHODS
SPORTDiscus, MEDLINE Complete and Embase databases were searched to December 2022. Random-effects meta-analyses for resting and exercise core temperature, skin temperature, heart rate, sweat rate, plasma volume and performance tests in the heat were completed using Stata Statistical Software: Release 17. Sub-group meta-analyses were performed to explore the effect of duration, total heat dose, exercise intensity, total energy expended, frequency of heat exposure and training status on resting and exercise core temperature, skin temperature, heart rate and sweat rate. An explorative meta-regression was conducted to determine the effects of physiological adaptations on performance test outcomes in the heat following heat adaptation.
RESULTS
Thirty studies were included in the systematic review; 22 studies were meta-analysed. After heat adaptation, a reduction in resting core temperature (effect size [ES] = - 0.45; 95% confidence interval [CI] - 0.69, - 0.22; p < 0.001), exercise core temperature (ES = - 0.81; 95% CI - 1.01, - 0.60; p < 0.001), skin temperature (ES = - 0.64; 95% CI - 0.79, - 0.48; p < 0.001), heart rate (ES = - 0.60; 95% CI - 0.74, - 0.45; p < 0.001) and an increase in sweat rate (ES = 0.53; 95% CI 0.21, 0.85; p = 0.001) were identified in females. There was no change in plasma volume (ES = - 0.03; 95% CI - 0.31, 0.25; p = 0.835), whilst performance test outcomes were improved following heat adaptation (ES = 1.00; 95% CI 0.56, 1.45; p < 0.001). Across all moderators, physiological adaptations were more consistently observed following durations of 451-900 min and/or 8-14 days, exercise intensity ≥ 3.5 kcalmin, total energy expended ≥ 3038 kcal, consecutive (daily) frequency and total heat dose ≥ 23,000 °Cmin. The magnitude of change in performance test outcomes in the heat was associated with a reduction in heart rate following heat adaptation (standardised mean difference = - 10 beatsmin; 95% CI - 19, - 1; p = 0.031).
CONCLUSIONS
Heat adaptation regimes induce physiological adaptations beneficial to thermoregulation and performance test outcomes in the heat in females. Sport coaches and applied sport practitioners can utilise the framework developed in this review to design and implement heat adaptation strategies for females.
Topics: Male; Humans; Female; Hot Temperature; Thermotolerance; Adaptation, Physiological; Exercise; Body Temperature Regulation
PubMed: 37222863
DOI: 10.1007/s40279-023-01831-2 -
Journal of Indian Prosthodontic Society 2021This systematic review aims to identify and interpret results of studies that evaluated the changes in the color stability of maxillofacial prosthetic materials due to... (Meta-Analysis)
Meta-Analysis Review
AIM
This systematic review aims to identify and interpret results of studies that evaluated the changes in the color stability of maxillofacial prosthetic materials due to chemical instability of silicones and pigments and the effect of exposure to environmental conditions and aging factors on the same.
SETTINGS AND DESIGN
This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines (PRISMA).
MATERIALS AND METHODS
Relevant articles written in English only, before November 15, 2019, were identified using an electronic search in the PubMed/Medline conducted to identify pertinent articles. The relevancy of the articles was verified by screening the title, abstract, and full text, if they met the inclusion criteria. A total of 42 articles satisfied the criteria, from which data were extracted for qualitative synthesis. This review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO registration number CRD42019124562).
STATISTICAL ANALYSIS USED
Since considerable data heterogenicity was present in all studies except the ones on incorporation of TiO2 for which meta-analysis using random effects model was performed.
RESULTS
The database search resulted in 234 studies, of which 202 articles were excluded due to lack of relevance, duplication, and unavailability of data. The remaining 32 fulltext articles were assessed for eligibility, out of which 2 articles were excluded. Twelve articles were yielded by manual search. A total of 42 studies were included in the present systematic review. Due to heterogeneous data, meta-analysis could be only carried out with the effect of TiO nano particle on color stability.
CONCLUSIONS
Although there has been extensive amount of research in this field, an ideal maxillofacial silicone exhibiting good color stability in various human and environmental aging conditions is yet to be identified. Human and environmental aging conditions have an adverse effect on the color stability and addition of TiO nano particle seems to improve the same.
Topics: Humans; Silicone Elastomers
PubMed: 33938863
DOI: 10.4103/jips.jips_253_19