Nevin Manimala

Clin Ther. 2021 Nov 15:S0149-2918(21)00434-3. doi: 10.1016/j.clinthera.2021.10.012. Online ahead of print.

ABSTRACT

PURPOSE: This study was conducted to examine and verify the use of saliva as an alternative matrix for monitoring phenytoin drug levels in patients with epilepsy. Drug concentrations are measured to evaluate whether a suitable drug level has been achieved to minimize the risk for toxicity, inadequate efficacy, or therapy resistance and compliance issues.

METHODS: Quantitative analysis was performed by using reverse-phase HPLC after sample pretreatment with acetonitrile. Seventy-eight patients who met the inclusion/exclusion criteria were examined in this study. Trough concentrations of both saliva and serum were taken at steady state.

FINDINGS: Of the 78 patients enrolled, only 11 (14.1%) had normal levels. Twenty-eight patients (35.9%) had subtherapeutic levels, and 39 (50%) had toxic levels. Simultaneously, salivary phenytoin levels were analyzed; only 13 patients (17.3%) had therapeutic levels, 25 patients (33.3%) had subtherapeutic levels, and 37 (49.3%) had toxic levels. Among the study population, most of the patients were aged 31 to 40 years (25.6%) followed by the age group 21 to 30 years (19.2%). The lowest percentage of patients were in the age groups 71 to 80 years and >80 years (1.3%) each. This study found a statistically significant relationship between free serum and salivary phenytoin levels (P < 0.001). A very weak and insignificant correlation was observed between serum/salivary phenytoin levels and sex/age of the study population. The results of the present study support the use of saliva as an alternative to serum/plasma for monitoring phenytoin therapy.

IMPLICATIONS: The free concentration of a drug represents the freely diffusible drug fraction, which is the therapeutically active form. Accordingly, the free drug concentration correlates to clinical efficacy and drug toxicity better than total concentration.

PMID:34794834 | DOI:10.1016/j.clinthera.2021.10.012

Clin Ther. 2021 Nov 15:S0149-2918(21)00410-0. doi: 10.1016/j.clinthera.2021.10.007. Online ahead of print.

ABSTRACT

PURPOSE: Currently available references provide evidence on the efficacy of probiotics strains but exclude product-specific information, making it challenging for health care professionals (HCPs) to provide consumers with suitable recommendations on probiotics. An online probiotics e-reference database was developed to assist HCPs in delivering evidence-based recommendations on probiotics to consumers. The usability and applicability of the database in health care practice were evaluated.

METHODS: Information on the efficacy of probiotics and probiotic products was collated using a PubMed literature search, and from local pharmacies and online supplement stores. A web database was compiled using various programming scripts and uploaded onto a web server. The database was beta-tested using an online self-administered questionnaire for community-based pharmacists, and responses were analyzed using descriptive statistics.

FINDINGS: The database comprised 584 clinical study excerpts, 449 probiotic products, and 1879 unique product-study links. Users can search for suitable probiotics based on their indication profile or for a specific probiotic product. Information provided includes the probiotic constituents, dosage regimen, and indications of the product, with supporting clinical evidence. Overall, all participants of the beta-test indicated that they were satisfied with the database and were willing to use it again (both, 13 participants [100%]). In addition, all participants indicated that they found the database intuitive to use and smooth functioning, without inconsistencies (both, 13 [100%]). The majority also indicated that they found the information provided to be clear, comprehensive, and useful in health care practice (12 [92.3%] each).

IMPLICATIONS: The probiotics e-reference database is an integrated resource that is user-friendly, and provides HCPs with ready access to clear and comprehensive information on probiotic products and clinical studies, so that HCPs can provide consumers with relevant and evidence-based recommendations on probiotics.

PMID:34794833 | DOI:10.1016/j.clinthera.2021.10.007

Dent Mater. 2021 Nov 15:S0109-5641(21)00285-2. doi: 10.1016/j.dental.2021.10.007. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the influence of filler geometry and viscosity of luting composites on marginal adhesive gap width (MGW) and occlusal surface height (OSH) of all-ceramic partial crowns.

METHODS: Forty-eight all-ceramic partial crowns (Celtra Duo, Dentsply) were created and divided into six groups (n = 8). Restorations were bonded using universal adhesive (Prime & Bond Active, Dentsply) in combination with low-viscosity composites (LV) containing amorphous fillers (Calibra Ceram, Dentsply) (LV-AF), heterogeneous fillers (Tetric EvoFlow, Ivoclar Vivadent) (LV-HF) vs. high-viscosity composites (HV) containing spherical fillers (Ceram.x, Dentsply) (HV-SF) or heterogeneous fillers (Tetric EvoCeram, Ivoclar Vivadent) (HV-HF). HV materials were used either with or without sonication. MGW [µm] was measured by SEM. Displacements of the restorations after luting, such as changes (Δ) in OSH [µm], tilting and rotation [°], were measured using a dial gauge and 3D-analytical software (OraCeck, Cyfex). Statistical analysis was by Mann-Whitney U-test and t-test with α = 0.05.

RESULTS: MGW (p = 0.002) and tilting (p = 0.001) were significantly smaller with LV (228.0 ± 112.35 µm; 0.89 ± 1.25°) than with HV (338.1 ± 97.26 µm; 1.95 ± 1.26°). Sonication had no effect on MGW in HV-HF (332.32 ± 91.39 µm) and HV-SF (343.85 ± 105.48 µm; p = 0.74). Sonication decreased ΔOSH by ~50% with HV-SF (64.21 ± 27.90 µm) but remained unchanged with HV-HF (39.06 ± 14.08 µm; p = 0.004). There was no difference in rotation between HV (0.82 ± 0.81°) and LV (0.61 ± 0.74°; p = 0.29). The LV-AF and LV-HF groups showed no statistical differences in MGW, ΔOSH, tilting or rotation (p > 0.05).

SIGNIFICANCE: Irrespective of filler geometry and insertion technique, the use of high-viscosity composites for the adhesive cementation of modern all-ceramic partial crowns increases displacement, marginal misfit and occlusal surface height.

PMID:34794829 | DOI:10.1016/j.dental.2021.10.007

J Psychiatr Res. 2021 Nov 9:S0022-3956(21)00668-3. doi: 10.1016/j.jpsychires.2021.11.019. Online ahead of print.

ABSTRACT

Gilles de la Tourette Syndrome (GTS) is a multifactorial neurodevelopmental disorder characterized by tics and multiple comorbidities. The pathophysiology is not yet fully understood, but both environmental and genetic risk factors seem to be involved. Twin studies provide important knowledge on genetic factors. We assessed the concordance of GTS and chronic tic disorders (CTD) in monozygotic (MZ) twins, and examined tic severity, symptoms of obsessive-compulsive disorder (OCD), attention deficit/hyperactivity disorder and autism spectrum disorder. Twin pairs, where at least one twin was diagnosed with any tic disorder, were identified through Danish Twin Registry, Psychiatric Central Registry, Danish National Patient Registry and National Tourette Clinic, Copenhagen University Hospital, Herlev. Zygosity was tested with single-nucleotide polymorphism (SNP) genotyping and clinical assessment was done with validated tools. 14 MZ twin pairs were included: five were discordant. Seven twin pairs were concordant for GTS, and for two pairs one twin had GTS and the other CTD. Among the twins with CTD or GTS, 50% had at least one comorbidity, which is higher than in background populations. The GTS + OCD-phenotype was significantly more frequent among GTS-concordant than among discordant twins. No statistically significant differences were found between the GTS-concordant and discordant twin pairs regarding tic severity or comorbidities. Thorough clinical assessment and SNP-based genotyping are important when conducting clinical twin studies. We found high concordance of GTS and CTD, which supports the notion that both disorders have common genetic risk factors. Further studies with larger cohorts including dizygotic twins are warranted for more conclusive results.

PMID:34794811 | DOI:10.1016/j.jpsychires.2021.11.019

Air Med J. 2021 Nov-Dec;40(6):427-430. doi: 10.1016/j.amj.2021.07.008. Epub 2021 Aug 30.

ABSTRACT

OBJECTIVE: Since the introduction of video laryngoscopy (VL) as a technique for orotracheal intubation, its use has become widespread among prehospital providers. However, little information is available about the efficacy and success of VL compared with direct laryngoscopy (DL) in the helicopter emergency medical services (HEMS) setting. The objective of this study was to investigate whether VL or DL increased successful first-pass orotracheal intubations and overall intubation success by HEMS providers.

DESIGN: A retrospective chart review was performed on adults intubated by a HEMS program from January 2015 to July 2017. All orotracheal intubations with at least 1 attempt were included. Excluded were emergent cricothyrotomies, nonintubated patients, and those intubated before HEMS care.

RESULTS: DL accounted for 21 intubations, whereas VL was used for 150 intubations. Nineteen of 21 (90.5%) DL intubations were successful on first pass, whereas 127 of 150 (84.7%) VL intubations were successful on first pass. The overall success rate was 90.5% for DL and 92.7% for VL. For both first-pass and overall success rates, the differences between modalities were not statistically significant. DL and VL had nearly identical complication rates, with hypoxia being the primary complication in both groups.

CONCLUSION: No statistically significant difference was found in the first-pass rate, the overall success rate, or complications between DL and VL.

PMID:34794783 | DOI:10.1016/j.amj.2021.07.008

Air Med J. 2021 Nov-Dec;40(6):415-418. doi: 10.1016/j.amj.2021.08.003. Epub 2021 Sep 3.

ABSTRACT

OBJECTIVE: Hospital mergers have made interhospital transfers necessary in the consolidation of medical services. Physicians must make decisions on the level of interfacility transport modalities (ITMs). We sought to assess physician knowledge of and comfort with ITMs.

METHODS: A survey was e-mailed to 2,510 physicians in a health care system. Participation was voluntary and anonymous. The mean and median Likert values were calculated overall. Similar calculations were performed for emergency medicine physicians (EMPs) and critical care physicians (CCPs). These calculations were compared with those for noncritical care physicians (NCCPs) using the t-test and Mann-Whitney test.

RESULTS: Of the 181 physicians who responded, 169 physicians identified a specialty. Sixty-nine were EMPs/CCPs, whereas 100 were NCCPs. The mean and median Likert values were statistically significantly higher for EMPs/CCPs compared with NCCPs (P < .0001) in the areas of knowledge of ITMs, comfort in choosing ITMs, and knowledge in choosing ground versus air critical care transport (CCT). The most important factor for using ground or air CCT was patient stability. Sixty percent believed air CCT to be faster than ground.

CONCLUSION: EMPs/CCPs seem to be more comfortable with ITMs than NCCPs. Further research should evaluate whether educational interventions lead to a more appropriate use of ITMs.

PMID:34794781 | DOI:10.1016/j.amj.2021.08.003

Taiwan J Obstet Gynecol. 2021 Nov;60(6):1072-1077. doi: 10.1016/j.tjog.2021.09.019.

ABSTRACT

OBJECTIVE: Considering the clinical evidence of BRAF inhibitors that can treat melanoma patients successfully, we aimed to investigate the status of BRAF mutations of primary mucinous ovarian carcinomas (MOC) in Taiwanese women, and apply the emerging paradigm classification of BRAF mutation groups.

MATERIALS AND METHODS: 20 archived primary MOC samples were analyzed. The BRAF mutations of activation segment (exon 15), CR3 (conserved regions 3), kinase domain of the BRAF gene were analyzed using the highly sensitive BRAF mutant enriched kit (FemtoPath®) with Sanger sequencing method. Additionally, we extended our prior reported data of HER2 aberrations and KRAS mutation into this study in order to compare with the status of BRAF mutation.

RESULTS: Of them (n = 20), 16 (80%) harbored BRAF missense mutations. Their mutation profile and case number (n) were categorized as (1) class I: V600E (n=1), V600M (n = 1); (2) class II: A598V (n = 1), T599I (n = 10); (3) class III: none (n = 0); and (4) unclassified variants: S602F (n = 2), T599I/S602F (n = 1). The BRAF S602F is novel. The prevalence of BRAF mutation is significantly higher than either HER2 mutation (80% vs. 35%; p = 0.022) or HER2 amplification (80% vs. 35%; p = 0.022). However, the mutation rates of BRAF and KRAS were not significantly different (80% vs. 60%; p = 0.289).

CONCLUSION: Activating BRAF mutation, HER2 amplification, HER2 mutation and KRAS mutation were not mutually exclusive. However, they may even have a synergistic effect in tumorigenesis. BRAF mutation is not uncommon in primary MOC of Taiwanese. The BRAF mutant (T599I) stands the majority. We suggested that there was a lower potential response to the existing V600 BRAF inhibitors, but may be responsive to dual BRAF plus MEK inhibitors or single MEK inhibitor. Further studies are warranted to investigate the clinical benefits of newly targeted therapy in recurrent or advanced stage primary MOC patients carrying different classes of BRAF mutation.

PMID:34794740 | DOI:10.1016/j.tjog.2021.09.019

Taiwan J Obstet Gynecol. 2021 Nov;60(6):1043-1046. doi: 10.1016/j.tjog.2021.09.001. Epub 2021 Sep 9.

ABSTRACT

OBJECTIVES: Aim of this study is to evaluate the prognosis of pregnant women having SARS-CoV-2 infection and investigate whether there was a difference in perinatal outcomes between pregnant women who had SARS-CoV-2 infection and those who did not.

MATERIALS AND METHODS: This prospective observational study was conducted with 116 singleton pregnancies. Cases enrolling in the study were divided into two groups. While those in the first group had a history of SARS-CoV-2 infection (n = 46) the second group consisted of healthy pregnant women (n = 70).

RESULTS: Emergency Cesarean section was performed on three SARS-CoV-2 infected pregnancies (30, 33 and 34 gestational weeks). Intensive care unit admission was required for all three cases after delivery and two of them died. Among the pregnancies that had an infection in the third trimester, 71.4% (n = 20) of them had delivery in 14 days after diagnosis and 17.4% (n = 8) of their newborns were followed up at newborn intensive care unit. Overall, only one newborn had a positive swab test result for SARS-CoV-2. There was no statistically significant difference between groups regarding their delivery week (37.02 ± 5.85 vs 38.5 ± 2.33). Similarly, there was no significant difference between groups, concerning mean age, parity, and birth weight (P = 0.707, P = 0.092, P = 0.334; P < 0.05). Furthermore, the difference between SARS-CoV-2 infected pregnancies that were followed up as inpatient or outpatient with respect to the delivery week and birth weight was not significant (p > 0.05). Also, APGAR 5 scores of hospitalized women (9.3 ± 1.1) were found to be lower than the outpatient group (9.8 ± 0.8) (P = 0.043; p < 0.05).

CONCLUSION: No significant difference was detected between groups in terms of the delivery week, birth weight, and APGAR scores. The inpatient group was found to have lower APGAR 5 scores.

PMID:34794735 | DOI:10.1016/j.tjog.2021.09.001

Taiwan J Obstet Gynecol. 2021 Nov;60(6):1038-1042. doi: 10.1016/j.tjog.2021.09.015.

ABSTRACT

OBJECTIVE: Oligohydramnios is defined as amniotic fluid index in ultrasonographic measurement is less than 5 percentile according to gestational age, the amniotic fluid volume is ≤ 5 cm, or if the single deepest dial is < 2 cm. The condition of oligohydramnios that not with fetal structural/chromosomal abnormalities, intrauterine growth retardation, intrauterine infection and maternal disease is described as isolated oligohydramnios (IO). The aim of this study is to examine whether oxidative stress and reactive oxygen species (ROS) have a place in the pathophysiology of IO.

MATERIALS AND METHODS: In this prospective case-control study, a total of 126 participants were included. The patient group consisted of 65 patients who were diagnosed IO, and the control group consisted of 61 healthy normal pregnants. Native thiol (-SH), total thiol (-SH + -SS), dynamic disulfide (-SS), IMA values from maternal serum were measured and compared between groups.

RESULTS: Maternal serum -SH and -SH + -SS values were significantly lower in the IO group than in the control group (409.47 ± 55.36 μmol/L vs. 437.40 ± 48.68 μmol/L, p = 0.03 and 457.40 ± 63.01 μmol/L vs. 484.59 ± 52.75 μmol/L, p = 0.01). In the IO group when -SS/-SH and -SS/-SH + -SS ratio was found to be statistically significantly higher than control group (5.84 ± 1.1 vs 5.41 ± 0.71, p = 0.01 and 5.2 ± 0.88 vs 4.8 ± 0.58, p = 0.01), -SH/-SH + -SS ratio was significantly lower (89.56 ± 1.7 vs 90.24 ± 1.16, p = 0.01). There was no significant difference in terms of -SS value (p = 0.66). IMA value was significantly higher in the IO group than control group (0.76 ± 0.10 ABSU vs 0.68 ± 0.06, p < 0.01). It is seen as a result of ROC analysis that -SH, -SH + -SS, -SS/-SH, -SS/-SH + -SS, -SH/-SH + -SS and IMA values have a diagnostic value for IO (p < 0.05).

CONCLUSION: The thiol/disulfide balance shifted towards oxidative stress in IO compared to control group. So oxidative stress and ROS have a place in the pathophysiology of IO.

PMID:34794734 | DOI:10.1016/j.tjog.2021.09.015

J Am Dent Assoc. 2021 Nov 15:S0002-8177(21)00513-4. doi: 10.1016/j.adaj.2021.08.004. Online ahead of print.

ABSTRACT

BACKGROUND: The authors undertook a prospective study to determine whether kidney transplant recipients had an increased risk of developing complications, such as local acute infection, alveolitis, increased bleeding, pain, and delayed healing, after tooth extraction.

METHODS: The authors selected patients who underwent kidney transplants more than 6 months ago (study group) and patients who had not (control group) older than 18 years who needed to undergo extraction of erupted teeth. The same oral surgeon performed all tooth extractions while the patients were under local anesthesia. Another blind researcher examined the patients 3, 7, and 21 days after tooth extraction. The first end point was occurrence of complications (local acute infection, alveolitis, increased bleeding), and the second end point was socket reepithelialization on day 21.

RESULTS: Forty-five tooth extractions were performed on 38 study group participants and 61 on 57 control group participants. There was no statistical difference between the groups regarding the incidence of any complication or delayed socket epithelialization.

CONCLUSIONS: The results of this pilot study suggest that there is no difference in postoperative healing after tooth extractions between stable kidney transplant patients and control patients.

PRACTICAL IMPLICATIONS: This is the first prospective study assessing the frequency of postoperative complications after tooth extraction in kidney transplant recipients. This clinical trial was registered at ClinicalTrials.gov. The registration number is NCT02547753.

PMID:34794682 | DOI:10.1016/j.adaj.2021.08.004