Nevin Manimala

Cochrane Database Syst Rev. 2021 Mar 21;3:CD012799. doi: 10.1002/14651858.CD012799.pub2.

ABSTRACT

BACKGROUND: Premature ejaculation (PE) is a common problem among men that occurs when ejaculation happens sooner than a man or his partner would like during sex; it may cause unhappiness and relationship problems. Selective serotonin re-uptake inhibitors (SSRIs), which are most commonly used as antidepressants are being used to treat this condition.

OBJECTIVES: To assess the effects of SSRIs in the treatment of PE in adult men.

SEARCH METHODS: We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, CINAHL), clinical trial registries, conference proceedings, and other sources of grey literature, up to 1 May 2020. We applied no restrictions on publication language or status.

SELECTION CRITERIA: We included only randomized controlled clinical trials (parallel group and cross-over trials) in which men with PE were administered SSRIs or placebo. We also considered ‘no treatment’ to be an eligible comparator but did not find any relevant studies.

DATA COLLECTION AND ANALYSIS: Two review authors independently classified and abstracted data from the included studies. Primary outcomes were participant-perceived change with treatment, satisfaction with intercourse and study withdrawal due to adverse events. Secondary outcomes included self-perceived control over ejaculation, participant distress about PE, adverse events and intravaginal ejaculatory latency time (IELT). We performed statistical analyses using a random-effects model. We rated the certainty of evidence according to GRADE.

MAIN RESULTS: We identified 31 studies in which 8254 participants were randomized to receiving either SSRIs or placebo. Primary outcomes: SSRI treatment probably improves self-perceived PE symptoms (defined as a rating of ‘better’ or ‘much better’) compared to placebo (risk ratio (RR) 1.92, 95% confidence interval (CI) 1.66 to 2.23; moderate-certainty evidence). Based on 220 participants per 1000 reporting improvement with placebo, this corresponds to 202 more men per 1000 (95% CI 145 more to 270 more) with improved symptoms with SSRIs. SSRI treatment probably improves satisfaction with intercourse compared to placebo (defined as a rating of ‘good’ or ‘very good’; RR 1.63, 95% CI 1.42 to 1.87; moderate-certainty evidence). Based on 278 participants per 1000 reporting improved satisfaction with placebo, this corresponds to 175 more (117 more to 242 more) per 1000 men with greater satisfaction with intercourse with SSRIs. SSRI treatment may increase treatment cessations due to adverse events compared to placebo (RR 3.80, 95% CI 2.61 to 5.51; low-certainty evidence). Based 11 study withdrawals per 1000 participants with placebo, this corresponds to 30 more men per 1000 (95% CI 17 more to 49 more) ceasing treatment due to adverse events with SSRIs. Secondary outcomes: SSRI treatment likely improve participants’ self-perceived control over ejaculation (defined as rating of ‘good’ or ‘very good’) compared to placebo (RR 2.29, 95% CI 1.72 to 3.05; moderate-certainty evidence). Assuming 132 per 1000 participants perceived at least good control, this corresponds to 170 more (95 more to 270 more) reporting at least good control with SSRIs. SSRI probably lessens distress (defined as rating of ‘a little bit’ or ‘not at all’) about PE (RR 1.54, 95% CI 1.26 to 1.88; moderate-certainty evidence). Based on 353 per 1000 participants reporting low levels of distress, this corresponds to 191 more men (92 more to 311 more) per 1000 reporting low levels of distress with SSRIs. SSRI treatment probably increases adverse events compared to placebo (RR 1.71, 95% CI 1.48 to 1.99; moderate-certainty evidence). Based on 243 adverse events per 1000 among men receiving placebo, this corresponds to 173 more (117 more to 241 more) men having an adverse event with SSRIs. SSRI treatment may increase IELT compared to placebo (mean difference (MD) 3.09 minutes longer, 95% CI 1.94 longer to 4.25 longer; low-certainty evidence).

AUTHORS’ CONCLUSIONS: SSRI treatment for PE appears to substantially improve a number of outcomes of direct patient importance such as symptom improvement, satisfaction with intercourse and perceived control over ejaculation when compared to placebo. Undesirable effects are a small increase in treatment withdrawals due to adverse events as well as substantially increased adverse event rates. Issues affecting the certainty of evidence of outcomes were study limitations and imprecision.

PMID:33745183 | DOI:10.1002/14651858.CD012799.pub2

Ground Water. 2021 Mar 21. doi: 10.1111/gwat.13094. Online ahead of print.

ABSTRACT

Groundwater is one of the major valuable water resources for the use of communities, agriculture and industries. In the present study, we have developed three novel hybrid Artificial Intelligence (AI) models which is a combination of Modified RealAdaBoost (MRAB), Bagging (BA), and Rotation Forest (RF) ensembles with Functional Tree (FT) base classifier for the Groundwater Potential Mapping (GPM) in the basaltic terrain at DakLak province, Highland Centre, Vietnam. Based on the literature survey, these proposed hybrid AI models are new and have not been used in the GPM of an area. Geospatial techniques were used and geo-hydrological data of 130 groundwater wells and 12 topographical and geo-environmental factors were used in the model studies. One-R Attribute Evaluation (ORAE) feature selection method was used for the selection of relevant input parameters for the development of AI models. Performance of these models was evaluated using various statistical measures including Area Under the receiver operation Curve (AUC). Results indicated that though all the hybrid models developed in this study enhanced the goodness-of-fit and prediction accuracy, but MRAB-FT (AUC=0.742) model outperformed RF-FT (AUC=0.736), BA-FT (AUC=0.714) and single FT (AUC=0.674) models. Therefore, the MRAB-FT model can be considered as a promising AI hybrid technique for the accurate GPM. Accurate mapping of the groundwater potential zones will help in adequately recharging the aquifer for optimum use of groundwater resources by maintaining the balance between consumption and exploitation.

PMID:33745148 | DOI:10.1111/gwat.13094

J Clin Periodontol. 2021 Mar 21. doi: 10.1111/jcpe.13451. Online ahead of print.

ABSTRACT

BACKGROUND: Outcome discrepancies between protocols and respective publications represent a concerning bias. The purpose of this study was to assess the prevalence of selective outcome reporting (SOR) in root coverage randomized clinical trials (RCTs).

METHODS: Published root coverage RCTs (July 2005 to March 2020) were included if a corresponding protocol could be identified in a public registry. Discrepancies between protocol and its correspondent publication(s) were compared regarding primary and secondary outcomes and other study characteristics. Associations between trial characteristics and SOR were evaluated.

RESULTS: Forty four studies (54 publications) were included. The majority of studies (77.3%) were retrospectively registered. SOR was frequent (40.9% of trials) and consisted of primary outcome downgrade (22.7%); secondary outcome upgrade (11.4%); new primary outcome introduced in publication (25%); protocol primary outcome omitted from publication (13.6%) and discrepancy in primary outcome timing (18.2%). SOR was unclear in 20.5% of studies and favoured statistical significance in 12 studies (27.3%). SOR was significantly associated with study significance (p < 0.001) and unclear outcome definition in the publication (p < 0.001). Only a third (32.8%) of primary outcomes were completely defined.

CONCLUSIONS: The present study identified high prevalence of SOR in root coverage RCTs.

PMID:33745136 | DOI:10.1111/jcpe.13451

Ground Water. 2021 Mar 21. doi: 10.1111/gwat.13096. Online ahead of print.

ABSTRACT

Mass balance calculations and hydrodynamics of groundwater flow suggest that the solutes in brines of the coastal sabkha aquifer from the Emirate of Abu Dhabi are derived largely from ascending geologic brines into the sabkha from the underlying formations. Solute interpretation for the ascending brine model was based on two independent but secondary lines of evidence (solute ratios and solute fluxes). In the current study, direct primary evidence for this ascending brine model was provided through analyses of δ⁸¹ Br, δ³⁷ Cl, and ⁸⁷ Sr/⁸⁶ Sr. Different solute histories of geologic brine and seawater provide an “isotopic fingerprint” that can uniquely distinguish between the two possible sources. Samples from the coastal sabkha aquifer of Abu Dhabi were determined to have a mean δ⁸¹ Br of 1.17‰ that is statistically equal, at the 95% confidence level, to the mean of 1.11‰ observed in the underlying geologic brine and statistically different than seawater. Similarly, the δ³⁷ Cl in sabkha brine has a mean of 0.25‰ and is statistically equal to a mean of 0.21‰ in the underlying geologic brines at the 95 % confidence level and statistically different from seawater. Also, dissolved strontium isotope data are consistent with the ascending brine model and even with the complex set of processes in the sabkha the variance in strontium isotope results is similar to the geologic brine. These observations provide primary direct evidence consistent that the major source of these solutes (and presumably others in the aquifer) is from discharging geologic brines, not from adjacent seawater.

PMID:33745130 | DOI:10.1111/gwat.13096

Eur Cell Mater. 2021 Mar 21;41:388-400. doi: 10.22203/eCM.v041a25.

ABSTRACT

For spinal load and muscle force estimation as well as for numerical model and experimental setup validation, data on human intradiscal pressure are essential. Therefore, the aim of the present meta-analysis was to summarise all in vitro measurements of human intradiscal pressure performed under defined boundary conditions, i.e. without external loading (intrinsic pressure), under axial loading (compression, traction, shear) and under single-planar bending loading (flexion, extension, lateral bending, axial rotation). Data were evaluated based on segmental level and normalised to force and moment. Regression analysis was performed to investigate coefficients of determination and statistical significance of relationships between intradiscal pressure and segmental level for the single loading conditions. 35 studies fulfilled the inclusion criteria, from which a total of 451 data points were collected for the meta-analysis. High coefficients of determination were found in axial compression (r2 = 0.875) and flexion (r2 = 0.781), while being low for intrinsic pressure (r2 = 0.266) and lateral bending (r2 = 0.385), all showing significant regression fitting (p < 0.01). Intradiscal pressure decreases from the upper cervical spine to the sacrum in all loading conditions, considering the same amount of loading for all segmental levels, while the intrinsic pressure exhibits a minimum of the regression curve in the mid-thoracic spine. Apart from its potential for numerical and experimental model validation, this dataset may help to understand the load distribution along the human spine.

PMID:33745125 | DOI:10.22203/eCM.v041a25

Clin Oral Investig. 2021 Mar 21. doi: 10.1007/s00784-021-03896-7. Online ahead of print.

ABSTRACT

OBJECTIVES: The present case series aimed to examine lip repositioning surgery (LRS) outcomes related to changes in external and internal upper lip (UL) dimensions, utilizing both conventional clinical and novel radiographic approaches.

MATERIALS AND METHODS: Patients (n = 13) diagnosed with hypermobile UL (>8-mm mobility during smile) and excessive gingival display (≥4-mm) were included and assessed at baseline and 6 months postoperatively. Clinical parameters at rest included total lip and internal lip length (vestibular depth). At maximum smile included total lip, philtrum (ergotrid), and vermilion lengths. Cephalometric parameters included anterior maxillary height; lip length; nasolabial angle; anteroposterior lip thickness; internal lip length (vestibular depth); and vestibular fornix position (using novel approach employing radiopaque marker). Linear mixed-effect models, Pearson’s correlation, and linear regression were used for statistical analyses.

RESULTS: LRS did not affect total UL length at rest (p = 0.418). It resulted in significant internal UL length decrease (-3.8 ± 2.1 mm, p < 0.001) and significant increases of vermilion length (1.9 ± 1.0 mm, p < 0.001) and anteroposterior lip thickness (0.7 ± 0.7 mm, p = 0.002). The clinical and radiographic measurements of total UL length at rest (r ≥ 0.734) and of internal UL length (r ≥ 0.737), and the two radiographic assessments of vestibular depth (r = 0.842), were strongly correlated.

CONCLUSIONS: LRS resulted in significant decrease of vestibular depth/internal UL length and in significant increases of UL vertical vermilion length and UL anteroposterior thickness, without affecting total UL length at rest.

CLINICAL RELEVANCE: The documented lip dimensional outcomes should help practitioners when treatment-planning LRS and counseling patients seeking treatment for hypermobile UL.

PMID:33745100 | DOI:10.1007/s00784-021-03896-7

Clin Rheumatol. 2021 Mar 20. doi: 10.1007/s10067-021-05680-0. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the frequency of glutathione S-transferase (GST), catalase, and SOD2 genetic polymorphisms and their correlation with SLE.

METHODS: A total of 290 females (patients = 151; controls= 139) were recruited. Multiplex PCR was performed for genotyping GSTM1 and GSTT1 genes, whereas real-time qPCR was used for determination of SNPs: CAT C262T, SOD2 C47T, GSTP1 A313G and GSTP1 IVS6 -C16T.

RESULTS: Thiol levels are decreased in SLE patients (p<0.001), while MDA levels were significantly higher (p<0.001) and those carrying the polymorphisms had higher rates of oxidative stress. Patients with double null deletion GSTT1^null/GSTM1^null had a frequency almost five times higher than the controls (p<0.001, OR 4.81, CI 1.98-12.11). SLE patients had a lower wild-type frequency of SOD2^CC allele compared to controls (12.4% vs 27.3%). Statistical significances were observed on the association between the GSTT1^null and GSTM1^null with SOD2^mut (p<0.001, OR 0.15, CI 0.05-0.47), with GSTP1 A303G (p=0.012, OR 0.19, CI 0.05-0.69), and with GSTP1 IVS6 (p=0.008, OR 0.14, CI 0.03-0.63). The same was observed between SOD2 C47T with GSTP1 A303G (p=0.09, OR 0.27, CI 0.09-0.74) and GSTP1 IVS6 (p=0.036, OR 0.41, CI 0.18-0.92).

CONCLUSIONS: The deletion GSTT1^null/GSTM1^null may contribute to the increased of the oxidative stress in SLE patients. Isolated GSTP1 and CAT polymorphisms do not seem to influence the increased oxidative stress, neither SLE clinical manifestations. SOD2 47^CT/TT allele may have greater oxidative stress due to structural change in the protein and decreased H₂O₂ production. The combination of polymorphic genes may be involved in the pathogenesis of the disease. Key points • Major question of our paper: Many studies have shown that the antioxidant status levels are decreased in patients with SLE, especially in severe stages of disease. We believe that this paper will be of interest to the readership of your journal had the involvement of polymorphisms and mutations in several genes that contribute to the genetic etiology of SLE, suggesting that these may influence the mechanisms of disease. • Our results. Thiol level was significantly (p<.001) lower and MDA level significantly increased (p<.001) among SLE patients. Those carrying the polymorphisms had higher rates of oxidative stress. SLE Patients had a frequency almost five times higher of double null deletion GSTT1null/GSTM1null than the controls. SLE Patients had a lower wild type frequency of SOD2CC allele compared to controls (12.4% vs 27.3%). We believed the deletion GSTT1null/GSTM1null may contribute to the increased of the oxidative stress in SLE patients while carriers of the mutant SOD2 47CT/TT allele may have greater oxidative stress due to structural change in the protein and decreased H2O2 production. The combination of polymorphic genes may be involved in the pathogenesis of the disease. • Implications of our results: Evidence for the involvement of genetic factors in severe clinical to lupus is compelling. This manuscript shows genetic insights in pathogenic pathways that may lead to severe clinical implications to LES. Therefore, it is necessary to understand their impact on overall disease pathogenesis and prognosis in these patients. We understand from general consensus about environmental factors can modify disease, however, maybe just in individuals who have a permissive genetic background. Even that no single gene predisposes some individuals to LES, we believe the genetic factors described in this manuscript are important elements in susceptibility to severe clinical to LES.

PMID:33745084 | DOI:10.1007/s10067-021-05680-0

J Assist Reprod Genet. 2021 Mar 20. doi: 10.1007/s10815-021-02149-6. Online ahead of print.

ABSTRACT

PURPOSE: To characterize the demographic differences between infertile/sub-fertile women who utilized infertility services vs. those that do not.

METHODS: A retrospective analysis of cross-sectional data obtained during the 2011-2013, 2013-2015, and 2015-2017 cycles of National Survey for Family Growth from interviews administered in home for randomly selected participants by a National Center of Health Statistics (NCHS) surveyor was used to analyze married, divorced, or women with long-term partners who reported difficulty having biological children (sub-fertile/infertile women). Demographic differences such as formal marital status, education, race, and religion were compared between women who presented for infertility care vs. those that did not. The primary outcome measure was presenting for infertility evaluation and subsequently utilizing infertility services. Healthcare utilization trends such as having a usual place of care and insurance status were also included as exposures of interest in the analysis.

RESULTS: Of the 12,456 women included in the analysis 1770 (15.3%) had used infertility services and 1011 (8.3%) said it would be difficult for them to have a child but had not accessed infertility services. On univariate analysis, compared to women who used infertility services, untreated women had lower average household incomes (295.3 vs. 229.8% of the federal poverty line respectively). Untreated women also had lower levels of education and were more likely to be divorced or never have married. In terms of health status, unevaluated women were less likely to have a usual place for healthcare (87.3%) as compared to women presenting for fertility care (91.9%) (p = 0.004). When examining insurance status, 23.3% of unevaluated women were uninsured as compared to 8.3% of evaluated women. On multivariate analysis, infertile women without insurance were at 0.37 odds of utilizing infertility care compared to women with insurance.

CONCLUSIONS: Demographic factors are associated with the utilization of infertility care. Insurance status is a significant predictor of whether or not infertile women will access treatment. Data from the three most recent NSFG surveys along with prior analyses demonstrate the need for expanded insurance coverage in order to address the socioeconomic disparities between infertile women who are accessing services vs. those that are not.

PMID:33745082 | DOI:10.1007/s10815-021-02149-6

J Cancer Res Clin Oncol. 2021 Mar 21. doi: 10.1007/s00432-021-03591-w. Online ahead of print.

ABSTRACT

PURPOSE: There is uncertainty regarding the role of adding immune checkpoint inhibitors (ICIs) to neoadjuvant chemotherapy (NACT) in early-stage triple-negative breast cancer (TNBC).

METHODS: We identified randomized controlled trials (RCTs) comparing ICIs combined with NACT to NACT in early-stage TNBC. Efficacy outcomes included pathological complete response (pCR) and event-free survival (EFS). Toxicity data included any grade 3/4 adverse events (AEs), serious AEs, AEs leading to death, common and meaningful AEs associated with chemotherapy and immune-related AEs. Odds ratio (ORs), hazard ratios (HR) and their respective 95% confidence intervals (CI) for efficacy and toxicity were extracted and pooled in a meta-analysis. Differences in the odds for pCR between programmed death ligand 1 (PD-L1) status and between PD-L1 and PD-1 inhibitors were also assessed.

RESULTS: Five RCTs comprising 2,075 patients were analyzed. Compared to NACT alone, combination of ICIs and NACT significantly improved pCR (OR 1.75, 95% CI 1.25-2.47, p = 0.001) and EFS (HR 0.66, 95% CI 0.48-0.91, p = 0.01). Magnitude of effect on pCR was similar between PD-L1-positive and PD-L1-negative tumors (p for the subgroup difference = 0.80) and between PD-L1 and PD-1 inhibitors (p = 0.27). The combination treatment resulted in higher odds of any grade 3/4 AEs (OR 1.31, p = 0.02) and serious AEs (OR 1.84, p = 0.006), with no statistically significant difference in AEs leading to death (OR 1.67, p = 0.51). Higher magnitude of toxicity was observed for immune-related AEs.

CONCLUSION: Combination of ICIs and NACT were associated with improved outcome in early-stage TNBC while increasing toxicity significantly. Longer follow-up is desired to better understand the risk and benefit ratio of this combination.

PMID:33745080 | DOI:10.1007/s00432-021-03591-w

Environ Sci Pollut Res Int. 2021 Mar 20. doi: 10.1007/s11356-021-13343-5. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFASs) are used in a wide range of products and have been found ubiquitously in our indoor environment, and there is evidence that exposure to PFAS can lead to adverse endocrine effects, such as thyroid hormone disruption. Pet cats have a high dust intake due to their grooming behavior and have been shown to be a suitable sentinel species for assessment of toddler’s exposure. Here we used paired household dust (n=46) and cat serum (n=27) samples to establish whether dust is a relevant exposure pathway to PFASs. An analytical method for PFAS analysis was optimized using a low volume of cat serum samples, combining solid-phase extraction and online sample cleanup. Dust was extracted with methanol by sonication and cleaned up by addition of active carbon. In total, 27 PFASs were analyzed by liquid chromatography/mass spectrometry analysis. The correlation between PFAS levels in dust and serum, serum lipids and thyroid hormone levels, and PFAS levels in dust between different rooms were statistically evaluated. PFOS and PFDA could be quantified in all cat serum samples (median 2300 pg/mL and 430 pg/mL, respectively), followed by PFOA (median 1100 pg/mL), quantified in 96% of the samples. The levels of 6:2 and 8:2 diPAPs were determined in 65% and 92% of the serum samples, respectively, and were an order of magnitude lower (1.4-160 pg/mL). Household dust on the other hand was dominated by 6:2 and 8:2 diPAPs, with a median of 65 ng/g dust and 49 ng/g dust, respectively. PFOS (median 13 ng/g dust) and PFOA (median 9 ng/g dust) were quantified in 93% of the dust samples. Only eight PFASs were detected (>LOD) in at least 50% of the samples of both matrices and could be paired. Significant correlations between cat serum and dust were found for PFOA (r_S=0.32, p<0.049) and PFUnDA (r_S=0.55, p<0.001). Significant positive correlations were found between serum total thyroxine (r_S=0.11, p<0.05) and PFNA and between serum cholesterol and PFHpA (r_S=0.46, p<0.01), PFUnDA (r_S=0.40, p<0.05), PFDoDA (r_S=0.44, p<0.01), and sum PFAS (r_S=0.48, p<0.01). In conclusion, this study confirmed that dust is a relevant exposure pathway for the ingestion of some PFASs for cats, and the serum levels of PFASs could be of relevance for the cat’s health.

PMID:33745045 | DOI:10.1007/s11356-021-13343-5