Category: Nevin Manimala

Blood Cancer J. 2022 Apr 1;12(4):53. doi: 10.1038/s41408-022-00648-y.

ABSTRACT

The objective of this study is to examine the association between neighborhood socioeconomic status (nSES) and baseline allostatic load (AL) and clinical trial endpoints in patients enrolled in the E1A11 therapeutic trial in multiple myeloma (MM). Study endpoints were symptom burden (pain, fatigue, and bother) at baseline and 5.5 months, non-completion of induction therapy, overall survival (OS) and progression-free survival (PFS). Multivariable logistic and Cox regression examined associations between nSES, AL and patient outcomes. A 1-unit increase in baseline AL was associated with greater odds of high fatigue at baseline (adjusted OR [95% CI] = 1.21 [1.08-1.36]) and a worse OS (adjusted hazard ratio, [95% CI] = 1.21 [1.06-1.37]). High nSES was associated with worse baseline bother (middle OR = 4.22 [1.11-16.09] and high 4.49 [1.16-17.43]) compared to low nSES. There was no association between AL or nSES and symptom burden at 5.5 months, non-completion of induction therapy or PFS. Additionally, there was no association between nSES and OS. AL may have utility as a predictive marker for OS among patients with MM and may allow individualization of treatment. Future studies should standardize and validate AL patients with MM.

PMID:35365604 | DOI:10.1038/s41408-022-00648-y

BDJ Open. 2022 Apr 1;8(1):9. doi: 10.1038/s41405-022-00101-z.

ABSTRACT

OBJECTIVES: Understanding of lifelong control of disease processes associated with caries and its management is an essential part of dental education. This study evaluated the dental students’ knowledge of caries diagnosis and management using the International Caries Classification and Management System (ICCMS).

METHODS: A survey was conducted among undergraduate dental students at two dental schools, attending the sixth (centre 1) and seventh semester (centre 2), respectively. Medical histories, clinical images and radiographs of 12 patients were compiled as anonymous cases. For each case, a specific lesion was to be assessed. In addition, the students should determine the patient’s caries risk and select a treatment option. An expert report (consensus decision) was used as the reference standard. For statistical analysis, kappa statistics and binomial tests were used.

RESULTS: A total of 46 students participated in this study. The percentage of agreement of responses to the reference was: centre 1: 40.7-51.3%, centre 2: 57.9-67.9%. The corresponding Kappa values were: centre 1: 0.073-0.175, centre 2: 0.315-0.432. Overall, students tended to underestimate the codes compared to the reference standard (p < 0.001).

CONCLUSION: Introducing systematic content about caries diagnosis and management such as ICDAS and ICCMS in the learning objectives of undergraduate dental students can be proposed. However, in order to improve diagnosis and enable a more reliable choice of treatment options, attention should also be given to the way they are didactically taught.

PMID:35365612 | DOI:10.1038/s41405-022-00101-z

Wound Repair Regen. 2022 Apr 1. doi: 10.1111/wrr.13005. Online ahead of print.

ABSTRACT

The objective of this study was to develop a pilot physician driven patient pyoderma gangrenosum (PG) registry to summarise patient baseline demographics, PG-related medical history, treatments, and outcomes for patients with pyoderma gangrenosum. Standardised patient information was collected prospectively during clinical encounters between December 2019 and July 2021 at a single academic institution. Eligibility criteria for the study was a diagnosis of pyoderma gangrenosum determined by a PARACELSUS score of at least 10 for ulcerative patients. Main outcome measures included demographic data, PG related history and comorbidities, past and current treatments, healing outcomes, hospitalisations and recurrences of PG. The Pyoderma Gangrenosum Study (PYGAS) Registry currently includes 52 patients with 56 target lesions of four distinct PG subtypes (41 ulcerative, 12 peristomal, 2 vegetative and 1 bullous). For the 38 patients with 41 total ulcerative PG lesions, referrals to our institution most commonly came from dermatologists (42.1%). The median follow-up time in our initial registry was 5.5 months (95% CI = 4.1-11.5 months), with average time between follow-up visits at 1.1 months. These ulcers were most commonly treated with first-line systemic immunosuppressants (70.6%), such as corticosteroids or cyclosporine. Additional use of systemic immunomodulators at baseline visit was statistically significantly associated with healing (P = 0.048). This pilot study suggests that use of systemic immunomodulators has an impact on healing of PG patients. Wound care regimens are variable, and assessing their impact on treatment outcomes could be challenging. Standardisation of both wound care regimens and data collection in prospective clinical studies is necessary to assess their impact in PG treatment outcomes.

PMID:35363927 | DOI:10.1111/wrr.13005

Cogn Sci. 2022 Apr;46(4):e13121. doi: 10.1111/cogs.13121.

ABSTRACT

The extraction of cooccurrences between two events, A and B, is a central learning mechanism shared by all species capable of associative learning. Formally, the cooccurrence of events A and B appearing in a sequence is measured by the transitional probability (TP) between these events, and it corresponds to the probability of the second stimulus given the first (i.e., p(B|A)). In the present study, nonhuman primates (Guinea baboons, Papio papio) were exposed to a serial version of the XOR (i.e., exclusive-OR), in which they had to process sequences of three stimuli: A, B, and C. In this manipulation, first-order TPs (i.e., AB and BC) were uninformative due to their transitional probabilities being equal to .5 (i.e., p(B|A) = p(C|B) = .5), while second-order TPs were fully predictive of the upcoming stimulus (i.e., p(C|AB) = 1). In Experiment 1, we found that baboons were able to learn second-order TPs, while no learning occurred on first-order TPs. In Experiment 2, this pattern of results was replicated, and a final test ruled out an alternative interpretation in terms of proximity to the reward. These results indicate that a nonhuman primate species can learn a nonlinearly separable problem such as the XOR. They also provide fine-grained empirical data to test models of statistical learning on the interaction between the learning of different orders of TPs. Recent bioinspired models of associative learning are also introduced as promising alternatives to the modeling of statistical learning mechanisms.

PMID:35363923 | DOI:10.1111/cogs.13121

Biometrics. 2022 Apr 1. doi: 10.1111/biom.13639. Online ahead of print.

NO ABSTRACT

PMID:35363907 | DOI:10.1111/biom.13639

Cochrane Database Syst Rev. 2022 Apr 1;4:CD013846. doi: 10.1002/14651858.CD013846.pub2.

ABSTRACT

BACKGROUND: Patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in preterm infants. Cyclooxygenase inhibitors (COX-I) may prevent PDA-related complications. Controversy exists on which COX-I drug is the most effective and has the best safety profile in preterm infants.

OBJECTIVES: To compare the effectiveness and safety of prophylactic COX-I drugs and ‘no COXI prophylaxis’ in preterm infants using a Bayesian network meta-analysis (NMA).

SEARCH METHODS: Searches of Cochrane CENTRAL via Wiley, OVID MEDLINE and Embase via Elsevier were conducted on 9 December 2021. We conducted independent searches of clinical trial registries and conference abstracts; and scanned the reference lists of included trials and related systematic reviews.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) that enrolled preterm or low birth weight infants within the first 72 hours of birth without a prior clinical or echocardiographic diagnosis of PDA and compared prophylactic administration of indomethacin or ibuprofen or acetaminophen versus each other, placebo or no treatment.

DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal. We used the GRADE NMA approach to assess the certainty of evidence derived from the NMA for the following outcomes: severe intraventricular haemorrhage (IVH), mortality, surgical or interventional PDA closure, necrotizing enterocolitis (NEC), gastrointestinal perforation, chronic lung disease (CLD) and cerebral palsy (CP).

MAIN RESULTS: We included 28 RCTs (3999 preterm infants). Nineteen RCTs (n = 2877) compared prophylactic indomethacin versus placebo/no treatment, 7 RCTs (n = 914) compared prophylactic ibuprofen versus placebo/no treatment and 2 RCTs (n = 208) compared prophylactic acetaminophen versus placebo/no treatment. Nine RCTs were judged to have high risk of bias in one or more domains.We identified two ongoing trials on prophylactic acetaminophen. Bayesian random-effects NMA demonstrated that prophylactic indomethacin probably led to a small reduction in severe IVH (network RR 0.66, 95% Credible Intervals [CrI] 0.49 to 0.87; absolute risk difference [ARD] 43 fewer [95% CrI, 65 fewer to 16 fewer] per 1000; median rank 2, 95% CrI 1-3; moderate-certainty), a moderate reduction in mortality (network RR 0.85, 95% CrI 0.64 to 1.1; ARD 24 fewer [95% CrI, 58 fewer to 16 more] per 1000; median rank 2, 95% CrI 1-4; moderate-certainty) and surgical PDA closure (network RR 0.40, 95% CrI 0.14 to 0.66; ARD 52 fewer [95% CrI, 75 fewer to 30 fewer] per 1000; median rank 2, 95% CrI 1-2; moderate-certainty) compared to placebo. Prophylactic indomethacin resulted in trivial difference in NEC (network RR 0.76, 95% CrI 0.35 to 1.2; ARD 16 fewer [95% CrI, 42 fewer to 13 more] per 1000; median rank 2, 95% CrI 1-3; high-certainty), gastrointestinal perforation (network RR 0.92, 95% CrI 0.11 to 3.9; ARD 4 fewer [95% CrI, 42 fewer to 137 more] per 1000; median rank 1, 95% CrI 1-3; moderate-certainty) or CP (network RR 0.97, 95% CrI 0.44 to 2.1; ARD 3 fewer [95% CrI, 62 fewer to 121 more] per 1000; median rank 2, 95% CrI 1-3; low-certainty) and may result in a small increase in CLD (network RR 1.10, 95% CrI 0.93 to 1.3; ARD 36 more [95% CrI, 25 fewer to 108 more] per 1000; median rank 3, 95% CrI 1-3; low-certainty). Prophylactic ibuprofen probably led to a small reduction in severe IVH (network RR 0.69, 95% CrI 0.41 to 1.14; ARD 39 fewer [95% CrI, 75 fewer to 18 more] per 1000; median rank 2, 95% CrI 1-4; moderate-certainty) and moderate reduction in surgical PDA closure (network RR 0.24, 95% CrI 0.06 to 0.64; ARD 66 fewer [95% CrI, from 82 fewer to 31 fewer] per 1000; median rank 1, 95% CrI 1-2; moderate-certainty) compared to placebo. Prophylactic ibuprofen may result in moderate reduction in mortality (network RR 0.83, 95% CrI 0.57 to 1.2; ARD 27 fewer [95% CrI, from 69 fewer to 32 more] per 1000; median rank 2, 95% CrI 1-4; low-certainty) and leads to trivial difference in NEC (network RR 0.73, 95% CrI 0.31 to 1.4; ARD 18 fewer [95% CrI, from 45 fewer to 26 more] per 1000; median rank 1, 95% CrI 1-3; high-certainty), or CLD (network RR 1.00, 95% CrI 0.83 to 1.3; ARD 0 fewer [95% CrI, from 61 fewer to 108 more] per 1000; median rank 2, 95% CrI 1-3; low-certainty). The evidence is very uncertain on effect of ibuprofen on gastrointestinal perforation (network RR 2.6, 95% CrI 0.42 to 20.0; ARD 76 more [95% CrI, from 27 fewer to 897 more] per 1000; median rank 3, 95% CrI 1-3; very low-certainty). The evidence is very uncertain on the effect of prophylactic acetaminophen on severe IVH (network RR 1.17, 95% CrI 0.04 to 55.2; ARD 22 more [95% CrI, from 122 fewer to 1000 more] per 1000; median rank 4, 95% CrI 1-4; very low-certainty), mortality (network RR 0.49, 95% CrI 0.16 to 1.4; ARD 82 fewer [95% CrI, from 135 fewer to 64 more] per 1000; median rank 1, 95% CrI 1-4; very low-certainty), or CP (network RR 0.36, 95% CrI 0.01 to 6.3; ARD 70 fewer [95% CrI, from 109 fewer to 583 more] per 1000; median rank 1, 95% CrI 1-3; very low-certainty). In summary, based on ranking statistics, both indomethacin and ibuprofen were equally effective (median ranks 2 respectively) in reducing severe IVH and mortality. Ibuprofen (median rank 1) was more effective than indomethacin in reducing surgical PDA ligation (median rank 2). However, no statistically-significant differences were observed between the COX-I drugs for any of the relevant outcomes.

AUTHORS’ CONCLUSIONS: Prophylactic indomethacin probably results in a small reduction in severe IVH and moderate reduction in mortality and surgical PDA closure (moderate-certainty), may result in a small increase in CLD (low-certainty) and results in trivial differences in NEC (high-certainty), gastrointestinal perforation (moderate-certainty) and cerebral palsy (low-certainty). Prophylactic ibuprofen probably results in a small reduction in severe IVH and moderate reduction in surgical PDA closure (moderate-certainty), may result in a moderate reduction in mortality (low-certainty) and trivial differences in CLD (low-certainty) and NEC (high-certainty). The evidence is very uncertain about the effect of acetaminophen on any of the clinically-relevant outcomes.

PMID:35363893 | DOI:10.1002/14651858.CD013846.pub2

Mycoses. 2022 Apr 1. doi: 10.1111/myc.13440. Online ahead of print.

ABSTRACT

Cryptococcosis is a common opportunistic infection associated with HIV/AIDS. The present review systematically describes the clinical and biological aspects of cryptococcosis in the Democratic Republic of Congo (DRC) and estimates its 2020 burden in people living with HIV (PLHIV). Following PRISMA guidelines, we searched online databases for records of cryptococcosis/Cryptococcus spp. in the DRC. Meta-analysis was then performed to estimate summary statistics and the corresponding 95% confidence intervals (CI). A total of 30 studies were included. These included 1,018 cryptococcosis patients, including 80.8% with NMC and predominantly immunocompromised due to HIV/AIDS (97.6%). The NMC mean prevalence was estimated at 9.63% (95% CI: 5.99-14.07). More than one in two patients (52.7%) under treatment died. Monotherapy with fluconazole was the main treatment administered (80.6%). Furthermore, we estimate that about 9,265 (95% CI: 5,763-13,537) PLHIV had cryptococcosis in 2020, in DRC; of which about 4,883 (95% CI: 3,037-7,134) would have died in the same year. Among isolates in all included studies, 74 strains have been characterized. Of these, 82.4% concerned Cryptococcus neoformans sensu lato (s.l) (exclusively of serotype A and mostly of molecular types VNI and VNII) and 17.6% concerned Cryptotoccus gattii s.l (belonging to serotype B and molecular type VGI). Cryptococcosis remains common with an unacceptably high mortality rate. A large number of PLHIV affected by and dying from cryptococcosis in 2020 demonstrates its heavy burden among the Congolese PLHIV. To mitigate this burden, it is important to improve the quality and accessibility of care for all PLHIV.

PMID:35363896 | DOI:10.1111/myc.13440

Am J Hypertens. 2022 Apr 1:hpac043. doi: 10.1093/ajh/hpac043. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to investigate the association of pulse pressure (PP) with the cardio-cerebrovascular disease (CCVD) risk and all-cause mortality according to blood pressure level using Korean national cohort data.

METHODS: This study was retrospectively designed and based on the Korean National Health Insurance Service-National Health Screening Cohort. Participants aged 40 to 69 years at baseline were categorized into normal, elevated, stage 1, and stage 2 groups according to blood pressure. Each group was further classified into five groups separated by 10-mmHg increments in PP. The primary composite outcome was defined as CCVDs and all-cause mortality. Cox proportional hazards regression models were adopted after stepwise adjustment for confounders to investigate the composite outcome.

RESULTS: During the follow-up period (median follow-up period, 12.0 years), the primary composite outcome occurred in 18,444 (15.0%) of 122,783 men and 10,096 (11.4%) of 88,550 women. After complete adjustment for confounders, in the stage 1 hypertensive men, the hazard ratio (HR) (95% confidence intervals [CIs]) of the 31-40, 41-50, 51-60, and >60 mmHg PP groups were 1.112 (1.013-1.221), 1.035 (0.942-1.137), 1.009 (0.907-1.123), and 1.324 (1.130-1.551) in comparison with the ≤30 mmHg PP group. In the stage 2 hypertensive men, the HRs (95% CIs) were 1.069 (0.949-1.204), 1.059 (0.940-1.192), 1.123 (0.999-1.263), and 1.202 (1.061-1.358) compared to the ≤30 mmHg PP group. However, these associations were not significant in women.

CONCLUSIONS: Hypertensive men with an increased PP have an increased risk of CCVDs and all-cause mortality.

PMID:35363861 | DOI:10.1093/ajh/hpac043

Cryo Letters. 2021 Jul-Aug;42(4):227-232.

ABSTRACT

BACKGROUND: Biodiversity conservation by germplasm maintenance by cryobanks is an accepted way of saving species. The edible fish Glossogobius giuris is reported to be threatened in India and needs rehabilitation measures to improve their numbers in natural waters.

OBJECTIVE: To investigate the standardization of cryoprotectants for the preservation of male gametes of this species.

MATERIALS AND METHODS: Four different cryoprotectants were used: DMSO, glycerol, ethylene glycol and methanol. Different combinations of diluents and milt were processed inside a cold handling unit at -5 degree C and stored for the short-term.

RESULTS: Prior to exposure to cryoprotectants, the motility of fresh sperm was 98.3 ± 2.5%. After 10 min equilibration at room temperature in 7.5 % glycerol, sperm motility was 95.6 1.5%, and 93 , 3.2% after 180 min at -5 degree C in this cryoprotectant. In contrast, motility was 65C3% after equilibration in 12.5 % methanol, and survivability fell to 30.7 0.9% after 180 min storage at -5 degree C. Analysis by Bonferroni and Holm Multiple Comparison showed highly significant variations between the effect of methanol and the other cryoprotectants. There was a statistically significant fall in motility when using methanol compared to glycerol.

CONCLUSION: Glycerol provides greater protection to spermatozoa during cold storage at -5 degree C, possibly as a result of its membrane stabilizing power.

PMID:35363842

PLoS One. 2022 Apr 1;17(4):e0265971. doi: 10.1371/journal.pone.0265971. eCollection 2022.

ABSTRACT

Intravenous regional limb perfusions (RLP) are widely used in equine medicine to treat distal limb infections, including synovial sepsis. RLPs are generally deemed successful if the peak antibiotic concentration (Cmax) in the sampled synovial structure is at least 8-10 times the minimum inhibitory concentration (MIC) for the bacteria of interest. Despite extensive experimentation and widespread clinical use, the optimal technique for performing a successful perfusion remains unclear. The objective of this meta-analysis was to examine the effect of technique on synovial concentrations of antibiotic and to assess under which conditions Cmax:MIC ≥ 10. A literature search including the terms “horse”, “equine”, and “regional limb perfusion” between 1990 and 2021 was performed. Cmax (μg/ml) and measures of dispersion were extracted from studies and Cmax:MIC was calculated for sensitive and resistant bacteria. Variables included in the analysis included synovial structure sampled, antibiotic dose, tourniquet location, tourniquet duration, general anesthesia versus standing sedation, perfusate volume, tourniquet type, and the concurrent use of local analgesia. Mixed effects meta-regression was performed, and variables significantly associated with the outcome on univariable analysis were added to a multivariable meta-regression model in a step-wise manner. Sensitivity analyses were performed to assess the robustness of our findings. Thirty-six studies with 123 arms (permutations of dose, route, location and timing) were included. Cmax:MIC ranged from 1 to 348 for sensitive bacteria and 0.25 to 87 for resistant bacteria, with mean (SD) time to peak concentration (Tmax) of 29.0 (8.8) minutes. Meta-analyses generated summary values (θ) of 42.8 x MIC and 10.7 x MIC for susceptible and resistant bacteria, respectively, though because of high heterogeneity among studies (I2 = 98.8), these summary variables were not considered reliable. Meta-regression showed that the only variables for which there were statistically significant differences in outcome were the type of tourniquet and the concurrent use of local analgesia: perfusions performed with a wide rubber tourniquet and perfusions performed with the addition of local analgesia achieved significantly greater concentrations of antibiotic. The majority of arms achieved Cmax:MIC ≥ 10 for sensitive bacteria but not resistant bacteria. Our results suggest that wide rubber tourniquets and concurrent local analgesia should be strongly considered for use in RLP and that adequate therapeutic concentrations (Cmax:MIC ≥ 10) are often achieved across a variety of techniques for susceptible but not resistant pathogens.

PMID:35363825 | DOI:10.1371/journal.pone.0265971