Lumbar Puncture Ordering and Results in the Pediatric Population: A Promising Data Source for Surveillance Systems

Background: The Centers for Disease Control and Prevention is incorporating laboratory data into real-time surveillance systems. When normal patterns of laboratory test orders and results are modeled, aberrations can be detected. Because many test orders are available electronically well before results, atypical patterns of test ordering may signal outbreaks.
Objectives: The authors sought to characterize baseline patterns in the ordering and early results of lumbar punctures, motivated by the possibility of using these data for real-time surveillance for early detection of meningitis or encephalitis outbreaks.
Methods: Retrospective cohorts of pediatric emergency department patients at a single hospital (1993–2003) and from the National Hospital and Ambulatory Medical Care Survey (1992–2000) were used for analysis.
Results: Test ordering exhibits seasonal patterns, with monthly peaks in January and August (p < 0.0001). For the hospital cohort, the rate of cerebrospinal fluid pleocytosis exhibits seasonal patterns (p < 0.0001), with a peak from August to October. This is strongly associated with the rate and pattern of clinical neurologic disease (p < 0.0001). A long-term secular decline in daily test ordering is evident, dropping from 5.3 to 2.9 in the hospital sample, and from 371.8 to 185.3 in the national sample (p < 0.001). The long-term rate of pleocytosis has declined (p < 0.0001), though the yield of testing for pleocytosis has improved (p = 0.0104).
Conclusions: Laboratory test patterns correspond with those of clinical disease and are a promising source of surveillance data. Using such data for real-time monitoring requires specific adjustments for patient age, periodicities, and secular trends.     

GJB2 mutations: passage through Iran

Hereditary hearing loss (HHL) is a very common disorder. When inherited in an autosomal recessive manner, it typically presents as an isolated finding. Interestingly and unexpectedly, in spite of extreme heterogeneity, mutations in one gene, GJB2, are the most common cause of congenital severe-to-profound deafness in many different populations. In this study, we assessed the contributions made by GJB2 mutations and chromosome 13 g.1777179_2085947del (the deletion more commonly known as del (GJB6-D13S1830) that includes a portion of GJB6 and is hereafter called Delta(GJB6-D13S1830)) to the autosomal recessive non-syndromic deafness (ARNSD) genetic load in Iran. Probands from 664 different nuclear families were investigated. GJB2-related deafness was found in 111 families (16.7%). The carrier frequency of the 35delG mutation showed a geographic variation that is supported by studies in neighboring countries. Delta(GJB6-D13S1830) was not found. Our prevalence data for GJB2-related deafness reveal a geographic pattern that mirrors the south-to-north European gradient and supports a founder effect in southeastern Europe.     

Evaluation of the effect of cognitive behavioral therapy on tocophobia: A systematic review and meta-analysis

Non-medical approaches including cognitive behavioral therapy (CBT) have been proposed for the management of tocophobia. A new method of performing CBT is through internet. The aim of this systematic review and meta-analysis was to evaluate the effect of internet-based and traditional CBT on tocophobia. A literature search was conducted on qualitative and quantitative articles from 2000 to 2019 in Pubmed, Scopus, Web of Science and Cochrane databases using search terms referring to tocophobia and CBT. Identified articles were screened in two steps; 1) title and abstract and 2) full text screening. The quality of the quantitative and qualitative studies was assessed using the quality criteria proposed by the Cochrane Collaboration and Jonna Briggs Institute (JBI) checklist respectively. Out of the 382 relevant studies, 9 studies were eligible for the review. A high level of heterogeneity was observed in the studies (I² = 94%, P < 0.001). The meta-analysis showed that both internet-based, and traditional CBT were effective in reducing tocophobia. CBT was more effective in interventions in the Middle Eastern compared to European countries. More than five CBT sessions could significantly reduce tocophobia. Healthcare providers and midwives should have basic knowledge on physiological interventions to reduce tocophobia.     

Development of an immune function assay by measuring intracellular adenosine triphosphate (iATP) levels in mitogen-stimulated CD4+ T lymphocytes

We developed an immune function assay for monitoring CD4+ T cells activity based on changes in intracellular adenosine triphosphate (iATP) levels after phytohemagglutinin (PHA) stimulation. Blood samples were obtained from 40 healthy subjects and 30 RTRs and incubated with 5 µg/mL of PHA for 15–18 hr at 37°C and 5% CO₂. Afterward, the CD4+ T cells were separated by antibody-coated magnetic beads and lysed. Then, iATP content in unstimulated and stimulated conditions was measured by luciferin-luciferase reaction using a log-log standard curve. The iATP levels showed significant increase in CD4+ T cells in both healthy persons (mean: 550 ± 142 ng/mL vs. 109 ± 54 ng/mL) and RTRs (mean: 394 ± 160 ng/mL vs. 52 ± 37 ng/mL) after PHA stimulation (P < 0.001). However, the iATP production in RTRs was significantly lower than that in healthy individuals; both prior to and after stimulation with PHA (P < 0.001). No gender-specific difference in iATP production was observed between women and men subjects. This rapid and low-cost assay reflects the degree of immune cell function through assessment of CD4+ T cells activation. Thus, it can be used for evaluation of immune system status in immunodeficient individuals as well as in immunosuppressed transplant recipients who needs drug adjustment.     

Adenosine kinase deficiency: expanding the clinical spectrum and evaluating therapeutic options

Background

Adenosine kinase deficiency is a recently described defect affecting methionine metabolism with a severe clinical phenotype comprising mainly neurological and hepatic impairment and dysmorphism.

Methods

Clinical data of 11 additional patients from eight families with adenosine kinase deficiency were gathered through a retrospective questionnaire. Two liver biopsies of one patient were systematically evaluated.

Results

The main clinical symptoms are mild to severe liver dysfunction with neonatal onset, muscular hypotonia, global developmental retardation and dysmorphism (especially frontal bossing). Hepatic involvement is not a constant finding. Most patients have epilepsy and recurrent hypoglycemia due to hyperinsulinism. Major biochemical findings are intermittent hypermethioninemia, increased S-adenosylmethionine and S-adenosylhomocysteine in plasma and increased adenosine in urine. S-adenosylmethionine and S-adenosylhomocysteine are the most reliable biochemical markers. The major histological finding was pronounced microvesicular hepatic steatosis. Therapeutic trials with a methionine restricted diet indicate a potential beneficial effect on biochemical and clinical parameters in four patients and hyperinsulinism was responsive to diazoxide in two patients.

Conclusion

Adenosine kinase deficiency is a severe inborn error at the cross-road of methionine and adenosine metabolism that mainly causes dysmorphism, brain and liver symptoms, but also recurrent hypoglycemia. The clinical phenotype varies from an exclusively neurological to a multi-organ manifestation. Methionine-restricted diet should be considered as a therapeutic option.

     

Spinal Manipulation for Subacute and Chronic Lumbar Radiculopathy: A Randomized Controlled Trial

ObjectiveWe evaluated the efficacy of spinal manipulation for the management of nonacute lumbar radiculopathy.MethodsIn a university hospital we performed a randomized controlled trial with 2 parallel arms. Patients (n = 44) with unilateral radicular low back pain lasting more than 4 weeks were randomly allocated to manipulation and control groups. The primary outcome was the intensity of the low back pain on a visual analog scale. The secondary outcome was the Oswestry Disability Questionnaire score. We also measured spinal ranges of motion. The assessments were carried out at the baseline, immediately after intervention, and at 3 months’ follow-up. All patients underwent physiotherapy. The manipulation group received three sessions of manipulation therapy 1 week apart. For manipulation, we used Robert Maigne's technique.ResultsBoth groups experienced a decrease in back and leg pain significantly (all P ≤ 0.003). However, only the manipulation group showed significantly favorable results in the Oswestry scores (P < 0.001), and the straight leg raise test (P = 0.001). All ranges of motion increased significantly with manipulation (all P < 0.001), but the control group showed favorable results only in right and left rotations and in extension (all P < 0.001). Between-group analyses showed significantly better outcomes for manipulation in all measurements (all P ≤ 0.009) with large effect sizes.ConclusionSpinal manipulation improves the results of physiotherapy over a period of 3 months for patients with subacute or chronic lumbar radiculopathy.