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Abstract

Objectives

Diagnostic reasoning has been shown to be influenced by a prior similar patient case. However, it is unclear whether this process influences diagnostic error rates or whether clinicians at all experience levels are equally susceptible. The present study measured the influence of specific prior exposure and experience level on diagnostic accuracy.

Methods

To create the experience of prior exposure, participants (pre-clerkship medical students, emergency medicine residents, and faculty) first verified diagnoses of clinical vignettes. The influence of prior exposures was measured using equiprobable clinical vignettes; indicating two diagnoses. Participants diagnosed equiprobable cases that were: 1) matched to exposure cases (in one of three conditions: a) similar patient features, similar clinical features; b) dissimilar patient features, similar clinical features; c) similar patient features, dissimilar clinical features), or 2) not matched to any prior case (d) no exposure). A diagnosis consistent with a matched exposure case was scored correct. Cases with no prior exposure had no matched cases, hence validated the equiprobable design.

Results

Diagnosis A represented 47% of responses in condition d, but there was no influence of specific similarity of patient characteristics for Diagnosis A, F(3,712)=7.28, p=0.28 or Diagnosis B, F(3,712)=4.87, p=0.19. When re-scored based on matching both equiprobable diagnoses, accuracy was high, but favored faculty (n=40) 98%, and residents (n=39) 98% over medical students (n=32) 85%, F(2,712)=35.6, p<0.0001. Accuracy for medical students was 84, 87, 94, and 73% for conditions a–d, respectively, interaction F(2,712)=3.55, p<0.002.

Conclusions

The differential diagnosis of pre-clerkship medical students improved with prior exposure, but this was unrelated to specific case or patient features. The accuracy of medical residents and staff was not influenced by prior exposure.

Abstract

The present study was aimed to evaluate hematological and oxidative stress parameters in domestic dogs infested naturally (n=10) by Rhipicephalus sp. to compare with non-infested dogs (n=10). All blood samples were collected from brachial vein into tubes EDTA for the hematological analysis such as red blood cells (RBCs), white blood cells (WBCs), hemoglobin (HGB) and platelets (PLT). Serum was rapidly separated after centrifugation and stored at -20 °C until it was used for malondialdehyde (MDA) and 2,2’-Azinobis-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) inhibition measurements. HGB in non-infested dogs was significantly higher than in infested dogs (P<0.05). There was no significant difference in RBCs, WBCs and PLT between both groups (P>0.05). The mean of MDA concentration was high in infested dogs (0.92±0.62 nmol/ml) compared to non-infested dogs (0.75±0.25 nmol/ml). On the other hand, the percentage of ABTS inhibition was similar in both groups (P=0.71). High tick number seems significantly affected WBCs (P<0.0001) and HGB (P<0.001) in infested dogs. Concerning oxidative status, there was no significant differences (P>0.05) between low and high infested dogs, neither in the amount of MDA nor in the ABTS inhibition. In conclusion, infested dogs induced RBCs alterations, which coincided with the oxidative damage, as evidenced by MDA serum levels. Also, there was a relationship between the tick number in infested dogs and the hematological parameters.

Abstract

Ablepharon macrostomia syndrome (AMS) is a rare congenital disorder. To our knowledge, only 20 cases have been reported to date, and all in patients from Western countries. We report a case of AMS in a Thai patient, who presented at age 3 months with severe ectropion of both upper and lower eyelids, alopecia totalis, no palpable clitoris, and hypoplasia of both labia minora and labia majora. Trio whole exome sequencing analysis was performed, which revealed a heterozygous missense c.223G>A (p.Glu75Lys) variation in TWIST2. To our knowledge, this is the first reported case of AMS in a patient from Thailand and the first reported case of AMS in Asia.

Abstract

Background

Epidermal growth factor receptor (EGFR) sequence variants in patients from Myanmar have not yet been reported.

Objectives

To describe the molecular epidemiology of EGFR variants in patients from Myanmar with lung adenocarcinoma.

Methods

Histological diagnosis and categorization of biopsies collected from 66 patients (28–78 years) with lung cancer was conducted using a panel of antibodies including those to: TTF1, P40, synaptophysin, CK7, and napsin-A. Samples from patients with confirmed adenocarcinoma were tested for EGFR variants using a cobas EGFR Mutation Test kit and cobas z 480 System (Roche). We conducted a univariate analysis of categorical factors using a χ2 or Fisher exact test.

Results

Histological types were adenocarcinoma (61%, 40/66), squamous cell carcinoma (24%, 16/66), neuroendocrine carcinoma (9%, 6/66), undifferentiated carcinoma (2%, 1/66), adenosquamous carcinoma (2%, 1/66), small cell anaplastic carcinoma (2%, 1/66), and pleomorphic sarcoma (2%, 1/66). EGFR variants were detected in 15 of 40 (38%) cases of adenocarcinoma. Among them, 6 patients (40%) had an exon 19 deletion, another 6 (40%) had exon 21 substitutions, 1 (7%) had exon 20 insertion S768I, and 2 (13%) had compound variations (1 of exon 21 L858R and exon 18 G719X, and 1 of exon 20 S768I and exon 18 G719X). Although limited by small sample size, no significant association was found between the variants and factors including family cancer history, age group, sex, ethnicity, or occupation. However, there was a strong significant association between never-smokers and EGFR variants (P = 0.008).

Conclusion

Knowledge of EGFR variants in patients from Myanmar is encouraging for their effective cancer treatment.

Abstract

Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) is a sophisticated transcription factor that is particularly important in the inflammatory response, but it regulates more than 400 individual and dependent genes for parts of the apoptotic, angiogenic, and proliferative, differentiative, and cell adhesion pathways. NF-κB function is directly inhibited by the binding of inhibitor of κB (IκB), and the imbalance between NF-κB and IκB has been linked to the development and progression of cancer and a variety of inflammatory disorders. These observations might broaden the horizon of current knowledge, particularly on the pathogenesis of inflammatory diseases considering the roles of NF-κB and IκB. In this context, we focus this narrative review on a comparative discussion of our findings with other literature regarding variations of NFKB1 and NFKB1A and their association with susceptibility to widespread inflammatory disorders (such as atherosclerosis, morbid obesity, Behçet syndrome, Graves disease, Hashimoto disease) and common cancers (such as gliomas).

Abstract

Objectives

Electronic alert systems to identify potential sepsis in children presenting to the emergency department (ED) often either alert too frequently or fail to detect earlier stages of decompensation where timely treatment might prevent serious outcomes.

Methods

We created a predictive tool that continuously monitors our hospital’s electronic health record during ED visits. The tool incorporates new standards for normal/abnormal vital signs based on data from ∼1.2 million children at 169 hospitals. Eighty-two gold standard (GS) sepsis cases arising within 48 h were identified through retrospective chart review of cases sampled from 35,586 ED visits during 2012 and 2014–2015. An additional 1,027 cases with high severity of illness (SOI) based on 3 M’s All Patient Refined – Diagnosis-Related Groups (APR-DRG) were identified from these and 26,026 additional visits during 2017. An iterative process assigned weights to main factors and interactions significantly associated with GS cases, creating an overall “score” that maximized the sensitivity for GS cases and positive predictive value for high SOI outcomes.

Results

Tool implementation began August 2017; subsequent improvements resulted in 77% sensitivity for identifying GS sepsis within 48 h, 22.5% positive predictive value for major/extreme SOI outcomes, and 2% overall firing rate of ED patients. The incidence of high-severity outcomes increased rapidly with tool score. Admitted alert positive patients were hospitalized nearly twice as long as alert negative patients.

Conclusions

Our ED-based electronic tool combines high sensitivity in predicting GS sepsis, high predictive value for physiologic decompensation, and a low firing rate. The tool can help optimize critical treatments for these high-risk children.

Abstract

Background

In patients with phenylketonuria, the central nervous system is adversely affected by noncompliance with diet. The levels of phenylalanine and many different amino acids (AAs) in the plasma of patients with phenylketonuria can be measured simultaneously.

Objectives

To measure the blood plasma levels of neurotransmitter AAs in a cohort of patients in Sanliurfa province, Turkey, with phenylketonuria for use as a support parameter for the follow-up of patients.

Methods

The phenylketonurics that we followed (n = 100) were divided into 2 groups according to their compliance with their dietary treatment. Plasma AA analysis results of phenylketonurics were compared with those of healthy children in a control group (n = 50).

Results

In the diet incompliant group (n = 56), the mean levels of γ-aminobutyric acid (GABA; 0.96 ± 1.07 μmol/L) and glycine (305.1 ± 105.19 μmol/L) were significantly higher than those in the diet compliant group (n = 44; GABA P = 0.005, glycine P < 0.001) and in the control group (GABA and glycine P < 0.001), whereas the mean levels of glutamic acid (39.01 ± 22.94 μmol/L) and asparagine (39.3 ± 16.89 μmol/L) were lower (P < 0.001) in the diet incompliant group. A positive correlation was observed between the levels of phenylalanine and GABA and glycine. A negative relationship was found between the levels of phenylalanine and glutamic acid and asparagine.

Conclusions

A relationship exists between the levels of plasma phenylalanine in a cohort of phenylketonurics in Sanliurfa province, Turkey, and the levels of some excitatory and inhibitory AAs. Excitatory and inhibitory AA levels in plasma may be used as support parameters in the follow-up of patients with phenylketonuria.

Abstract

Background

Neonatal jaundice and elevated levels of liver enzymes are found in infants with breast milk jaundice (BMJ).

Objectives

To determine the prevalence and duration of elevated serum levels of liver enzymes in Thai infants with BMJ.

Methods

We conducted a prospective study of Thai infants with BMJ, excluding those with pathological causes of jaundice. We measured the serum levels of total bilirubin (TB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT); followed infants with elevated levels; and estimated the time for levels to become normal using Kaplan–Meier analysis.

Results

We included 42 infants (median age: 17.5 days) with BMJ, and elevated serum levels of at least 1 enzyme were found in 27 (64%) infants. We excluded 4 (10%) infants because they did not continue to be exclusively breastfed, 17 (40%) were lost to follow-up, and 21 (50%) completed the study. We found that 19 (45%) of the 42 infants had elevated GGT, 11 (26%) had elevated ALT, and 9 (21%) each had elevated AST and ALP levels. The median time for enzyme levels to normalize was 291 days (95% confidence interval [CI], 109.8 to 472.2) for ALT, 240 days (95% CI, 139.0 to 340.9) for AST, 184 days (95% CI, 4.4 to 363.6) for ALP, 120 days (95% CI, 74.6 to 164.5) for TB, and 63 days (95% CI, 61.44 to 64.6) for GGT. Infants were otherwise healthy during the follow-up.

Conclusion

The prevalence of elevated serum levels of liver enzymes in Thai infants was unexpectedly high, but the levels became normal spontaneously despite continued breastfeeding, which endorses a “watchful waiting” strategy in managing asymptomatic infants with BMJ.

Abstract

Objectives

While the need to address patients’ social determinants of health (SDoH) is widely recognized, less is known about physicians’ actual clinical problem-solving when it comes to SDoH. Do physicians include SDoH in their assessment strategy? Are SDoH incorporated into their diagnostic thinking and if so, do they document as part of their clinical reasoning? And do physicians directly address SDoH in their “solution” (treatment plan)?

Methods

We used Unannounced Standardized Patients (USPs) to assess internal medicine residents’ clinical problem solving in response to a patient with asthma exacerbation and concern that her moldy apartment is contributing to symptoms – a case designed to represent a clear and direct link between a social determinant and patient health. Residents’ clinical practices were assessed through a post-visit checklist and systematic chart review. Patterns of clinical problem solving were identified and then explored, in depth, through review of USP comments and history of present illness (HPI) and treatment plan documentation.

Results

Residents fell into three groups when it came to clinical problem-solving around a housing trigger for asthma: those who failed to ask about housing and therefore did not uncover mold as a potential trigger (neglectors – 21%; 14/68); those who asked about housing in negative ways that prevented disclosure and response (negative elicitors – 24%, 16/68); and those who elicited and explored the mold issue (full elicitors – 56%; 28/68). Of the full elicitors 53% took no further action, 26% only documented the mold; and 21% provided resources/referral. In-depth review of USP comments/explanations and residents’ notes (HPI, treatment plan) revealed possible influences on clinical problem solving. Failure to ask about housing was associated with both contextual factors (rushed visit) and interpersonal skills (not fully engaging with patient) and with possible differences in attention (“known” vs. unknown/new triggers, usual symptoms vs. changes, not attending to relocation, etc.,). Use of close-ended questions often made it difficult for the patient to share mold concerns. Negative responses to sharing of housing information led to missing mold entirely or to the patient not realizing that the physician agreed with her concerns about mold. Residents who fully elicited the mold situation but did not take action seemed to either lack knowledge or feel that action on SDoH was outside their realm of responsibility. Those that took direct action to help the patient address mold appeared to be motivated by an enhanced sense of urgency.

Conclusions

Findings provide unique insight into residents’ problem solving processes including external influences (e.g., time, distractions), the role of core communication and interpersonal skills (eliciting information, creating opportunities for patients to voice concerns, sharing clinical thinking with patients), how traditional cognitive biases operate in practice (premature closure, tunneling, and ascertainment bias), and the ways in which beliefs about expectancies and scope of practice may color clinical problem-solving strategies for addressing SDoH.