The serotonin transporter gene polymorphism is associated with the susceptibility and the pain severity in Idiopathic Trigeminal Neuralgia patients

Background

To investigate the possible association between the serotonin transporter gene (5-HTTLPR) and rs 25531 polymorphism and the susceptibility and the pain severity in Trigeminal Neuralgia patients.

Methods

A total of 244 TN patients and 280 age and sex matched healthy volunteer were recruited. 5-HTTLPR and rs 25531 genotyping were performed. All patients received the carbamazepine treatment and the treatment response was evaluated at 6 months.

Results

The genotype distribution of 5-HTTLPR between TN patients and controls were significantly different. The TN Patients had a higher prevalence of short-short genotype than controls. The short-short genotype carriers are also significantly associated with higher pain severity and poorer carbamazepine treatment response compared to the long-long genotype carriers. In contrast, the rs 25531 polymorphism was not associated with the susceptibility to TN, neither with the pain severity and the treat response to carbamazepine.

Conclusion

The 5-HTTLPR polymorphism is associated with the susceptibility to TN and pain severity of TN.     

The Relationship between Vascular Endothelial Growth Factor 1154G/A Polymorphism and Recurrent Implantation Failure

Objective

The aim of this study was to investigate the relationship between herpesvirus-associated ubiquitin-specific protease (HAUSP A/G, rs1529916), tumor protein p53 (TP53 Arg/Pro, rs1042522), leukemia inhibitory factor (LIF G/T, rs929271), glycoprotein 130 (gp130 A/T, rs1900173) and vascular endothelial growth factor (VEGF G/A, rs1570360) polymorphisms and recurrent implantation failure (RIF) in Brazilian women.

Subjects and Methods

A total of 120 women with RIF (i.e. those with ≥5 cleaved embryos transferred and a minimum of 2 failed in vitro fertilization/intracytoplasmic sperm injection attempts) were included. The control group involved 89 women who had experienced at least 1 live birth (without any infertility treatment). DNA was extracted from the peripheral blood of all participants, and the abovementioned single-nucleotide polymorphisms (SNPs) were genotyped by real-time polymerase chain reaction. The data were evaluated using Fisher''s test.

Results

A significant difference between the RIF and control groups was found in the VEGF gene where the GG genotype showed a 2.1-fold increased chance of not being included in the RIF group, while the presence of an A allele increased this risk 1.6-fold. No significant differences were found for the other polymorphisms.

Conclusion

This study showed an association between the VEGF -1154G/A polymorphism and RIF in Brazilian women.Key Words: Implantation failure, Single-nucleotide polymorphisms, Genetic biomarker, VEGF ߝ1154G/A, Infertility, Assisted reproduction     

Genetic Polymorphisms and Peritoneal Membrane Function

♦ Background:

Outcomes for peritoneal dialysis (PD) patients are affected by the characteristics of the peritoneal membrane, which may be determined by genetic variants. We carried out a systematic review of the literature to identify studies which assessed the association between genetic polymorphisms, peritoneal membrane solute transport, and clinical outcomes for PD patients.

♦ Methods:

The National Library of Medicine was searched using a variety of strategies. Studies which met our inclusion criteria were reviewed and data abstracted. Our outcomes of interest included: high transport status peritoneal membrane, risk for peritonitis, encapsulating peritoneal sclerosis (EPS), patient and technique survival. We combined data from studies which evaluated the same genetic polymorphism and the same outcome.

♦ Results:

We evaluated 18 relevant studies. All studies used a candidate gene approach. Gene polymorphisms in the interleukin (IL)-6 gene were associated with peritoneal membrane solute transport in several studies in different ethnic populations. Associations with solute transport and polymorphisms in endothelial nitric oxide synthase and receptor for advanced glycation end product genes were also identified. There was evidence of a genetic predisposition for peritonitis found in 2 studies, and for EPS in 1 study. Survival was found to be associated with a polymorphism in vascular endothelial growth factor and technique failure was associated with a polymorphism in the IL-1 receptor antagonist.

♦ Conclusions:

There is evidence that characteristics of the peritoneal membrane and clinical outcomes for PD patients have genetic determinants. The most consistent association was between IL-6 gene polymorphisms and peritoneal membrane solute transport.     

Diagnosing external ventricular drain-related ventriculitis by means of local inflammatory response: soluble triggering receptor expressed on myeloid cells-1

Introduction

External ventricular drainage (EVD)-related ventriculitis is one of the most severe complications associated with the use of EVDs. Establishing an early and certain diagnosis can be difficult in critically ill patients. We performed this prospective study to evaluate the usefulness of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) determination in cerebrospinal fluid (CSF) in the diagnosis of ventriculitis.

Methods

A prospective observational study was conducted of 73 consecutive patients with EVD. Samples of CSF for culture, cytobiochemical analysis and sTREM-1 determination were extracted three times a week. Ventriculitis diagnosis required a combination of microbiological, cytobiochemical and clinical criteria.

Results

Seventy-three consecutive patients were included. EVD-related ventriculitis was diagnosed in six patients and EVD-colonization in ten patients. Patients without clinical or microbiological findings were considered controls. The median CSF sTREM-1 was 4,320 pg/ml (interquartile range (IQR): 2,987 to 4,886) versus 266 pg/ml (118 to 689); P <0.001. There were no differences when comparing colonized-patients and controls. The best cut-off sTREM-1 value for the diagnosis of ventriculitis was 2,388.79 pg/ml (sensitivity 100%, specificity 98.5%, positive predictive value 85.71%, negative predictive value 100%). CSF proteins, glucose and the ratio CSF/serum glucose were also significantly different (P = 0.001). Serum biomarkers were not useful to diagnose EVD-related infection. These results were confirmed by a case–control study with ventriculitis patients (cases) and non-ventriculitis (control subjects) matched by age, comorbidities, severity scales and EVD duration (P = 0.004).

Conclusions

CSF sTREM-1 was useful in the diagnosis of ventriculitis, in a similar measure to classical CSF parameters. Furthermore, CSF sTREM-1 could prove the diagnosis in uncertain cases and discriminate between EVD-colonization and infection.     

Continuous regional arterial infusion for acute pancreatitis: a propensity score analysis using a nationwide administrative database

Introduction

Although continuous regional arterial infusion (CRAI) of a protease inhibitor and an antibiotic may be effective in patients with severe acute pancreatitis, CRAI has not yet been validated in large patient populations. We therefore evaluated the effectiveness of CRAI based on data from a national administrative database covering 1,032 Japanese hospitals.

Methods

In-hospital mortality, length of stay and costs were compared in the CRAI and non-CRAI groups, using propensity score analysis to adjust for treatment selection bias.

Results

A total of 17,415 eligible patients with acute pancreatitis were identified between 1 July and 30 September 2011, including 287 (1.6%) patients who underwent CRAI. One-to-one propensity-score matching generated 207 pairs with well-balanced baseline characteristics. In-hospital mortality rates were similar in the CRAI and non-CRAI groups (7.7% vs. 8.7%; odds ratio, 0.88; 95% confidence interval, 0.44–1.78, P = 0.720). CRAI was associated with significantly longer median hospital stay (29 vs. 18 days, P < 0.001), significantly higher median total cost (21,800 vs. 12,600 United States dollars, P < 0.001), and a higher rate of interventions for infectious complications, such as endoscopic/surgical necrosectomy or percutaneous drainage (2.9% vs. 0.5%, P = 0.061).

Conclusions

CRAI was not effective in reducing in-hospital mortality rate in patients with acute pancreatitis, but was associated with longer hospital stay and higher costs. Randomized controlled trials in large numbers of patients are required to further evaluate CRAI for this indication.     

Transcription Factor 7-Like 2 (TCF7L2) Polymorphism and Hyperglycemia in an Adult Italian Population-Based Cohort

OBJECTIVE

To assess whether TCF7L2 polymorphism has a role in the deterioration of glycemic control.

RESEARCH DESIGN AND METHODS

Metabolic variables were evaluated at baseline and after 6-year follow-up in 1,480 Caucasian subjects from a population-based cohort.

RESULTS

At baseline, T-allele carriers showed significantly lower BMI and homeostasis model assessment for β-cell function (HOMA-B) values and higher fasting glycemia and diabetes prevalence. At follow-up, fasting glucose and HOMA-B index were increased and reduced, respectively, in carriers of the T-allele. Incident impaired fasting glucose (IFG) and incident diabetes were 5.7, 10.7, 16.9% and 1.6, 1.7, 3.0% in the CC, CT, and TT genotypes, respectively. In a multiple logistic regression model, the association between incident IFG and the T-allele was significant (odds ratio [OR] 2.08 [95% CI 1.35–3.20] and 3.56 [2.11–5.98] in CT and TT genotypes, respectively).

CONCLUSIONS

The T-allele of TCF7L2 rs7903146 polymorphism was independently associated with increasing fasting glucose values toward hyperglycemia in the follow-up.Among the variety of TCF7L2 polymorphisms correlating with type 2 diabetes, the single nucleotide polymorphism (SNP) rs7903146 has shown the strongest association with the disease (1). We investigated the association of the SNP rs7903146 with 1) type 2 diabetes or 2) impaired fasting glucose (IFG) or 3) the metabolic syndrome (MS) in an adult Italian population-based cohort both cross-sectionally and after 6-year follow-up.     

Genetic association and gene expression studies suggest that genetic variants in the SYNE1 and TNF genes are related to menstrual migraine

Background

Menstrual migraine (MM) encompasses pure menstrual migraine (PMM) and menstrually-related migraine (MRM). This study was aimed at investigating genetic variants that are potentially related to MM, specifically undertaking genotyping and mRNA expression analysis of the ESR1, PGR, SYNE1 and TNF genes in MM cases and non-migraine controls.

Methods

A total of 37 variants distributed across 14 genes were genotyped in 437 DNA samples (282 cases and 155 controls). In addition levels of gene expression were determined in 74 cDNA samples (41 cases and 33 controls). Association and correlation analysis were performed using Plink and RStudio.

Results

SNPs rs3093664 and rs9371601 in TNF and SYNE1 genes respectively, were significantly associated with migraine in the MM population (p = 0.008; p = 0.009 respectively). Analysis of qPCR results found no significant difference in levels of gene expression between cases and controls. However, we found a significant correlation between the expression of ESR1 and SYNE1, ESR1 and PGR and TNF and SYNE1 in samples taken during the follicular phase of the menstrual cycle.

Conclusions

Our results show that SNPs rs9371601 and rs3093664 in the SYNE1 and TNF genes respectively, are associated with MM. The present study also provides strong evidence to support the correlation of ESR1, PGR, SYNE1 and TNF gene expression in MM.     

Interactions Among Related Genes of Renin-Angiotensin System Associated With Type 2 Diabetes

OBJECTIVE

To explore the association between epistasis among related genes of the renin-angiotensin system (RAS) and type 2 diabetes.

RESEARCH DESIGN AND METHODS

Gene polymorphisms were genotyped in 394 type 2 diabetic patients and 418 healthy control subjects in this case-control study. We used the multifactor dimensionality reduction method to identify gene-gene interactions.

RESULTS

No single locus was associated with type 2 diabetes, except for the insert/deletion (I/D) polymorphism of the ACE gene in female subjects. In multi-locus analyses, in male subjects the model of rs2106809 (ACE2), rs220721 (Mas), rs699 (AGT), and I/D (ACE) was significant (P = 0.043). This combination was associated with a 4.00 times (95% CI 2.51–6.38; P < 0.0001) greater prevalence of type 2 diabetes. In female subjects, the model of rs2106809 (ACE2), I/D (ACE), and rs1403543 (AGTR2) was significant (P = 0.012). This three-locus combination was associated with a 2.76 times (1.91–3.97; P < 0.0001) greater prevalence of type 2 diabetes.

CONCLUSIONS

Interactions among RAS-related genes were associated with type 2 diabetes in a Chinese population.Over the past few years, a number of new genetic loci associated with type 2 diabetes have been uncovered based on genome-wide association scans. Investigations into gene-gene interactions, however, are uncommon because the method is computationally challenging (1). In type 2 diabetes, attempts to elucidate possible epistasis have provided only a few examples (2–4).Recently, studies have supported the idea that using our understanding of biology, including that of cytokine networks and hormone systems, may help guide analysis of epistasis (5,6). Clinical evidence suggests that the renin-angiotensin system (RAS) is associated with the etiology of type 2 diabetes (7–9). However, the influence of genetic interaction within the RAS on type 2 diabetes susceptibility is still unknown. The aim of our study was to explore the contribution of epistasis among RAS-related genes.     

Incidence of narcotic abuse during pregnancy in northwestern Ontario: Three-year prospective cohort study

Objective

To document the incidence and outcomes of narcotic use during pregnancy in northwestern Ontario.

Design

Three-year prospective cohort study.

Setting

Sioux Lookout and surrounding communities in northwestern Ontario.

Participants

A total of 1206 consecutive births in a catchment area of 28 000 First Nations patients.

Main outcome measures

Incidence of narcotic use, and maternal and neonatal outcomes.

Results

Incidence of narcotic use in pregnancy has risen to 28.6% (P < .001) and incidence of neonatal abstinence syndrome has fallen to 18.0% of narcotic-exposed births (P = .003). Daily intravenous drug use is now a common pattern of abuse.

Conclusion

Narcotic abuse in pregnancy has dramatically increased in northwestern Ontario. Neonatal outcomes have improved as a result of a family medicine–based prenatal and obstetric program that includes a narcotic replacement and tapering program.     

TEST-RETEST RELIABILITY OF TWO CLINICAL TESTS FOR THE ASSESSMENT OF HIP ABDUCTOR ENDURANCE IN HEALTHY FEMALES

Background

Substantial deficits in performance of hip abductor in patients with common lower extremity injuries are reported in literature. Therefore, assessing hip abductor endurance might be of major importance for clinicians and researchers.

Purposes

The purpose of this study was to examine the test-retest reliability of two hip abductor endurance tests in healthy females. Learning effect, systematic difference in the rate of perceived exertion and relationship between endurance performance and some clinical characteristics of participants were also investigated.

Design

Observational study, with a test-retest design.

Methods

Thirty-six healthy females, aged 18-30 years, were recruited. In two identical assessment sessions, the participants performed an isometric hip abductor strength test and two different hip abductor endurance tests

Results

Isometric and dynamic endurance tests demonstrated good test-retest reliability (intraclass correlation coefficients (ICC) = 0.73 and 0.78, respectively). The standard errors of measurement (SEM) and the minimal detectable changes (MDC) were, respectively, 19.8 and 54.9 seconds for isometric endurance test and 21.2 and 58.7 repetitions for dynamic endurance test. Moderate correlation between both endurance tests (r = 0.60, p = 0.0001) and weak correlation between dynamic endurance test and strength (r = 0.44, p = 0.008) were found.

Conclusions

The results of the present study demonstrate good test-retest reliability of two non-instrumented clinical tests of hip abductor endurance in healthy females.

Level of evidence

2b     

The 372 T/C genetic polymorphism of TIMP-1 is associated with serum levels of TIMP-1 and survival in patients with severe sepsis

Introduction

Previous studies have found higher circulating levels of tissue inhibitor of matrix metalloproteinase (TIMP)-1 in nonsurviving septic patients than in surviving septic patients, and an association between the 372 T/C genetic polymorphism of TIMP-1 and the risk of developing certain diseases. However, the relationship between genetic polymorphisms of TIMP-1, circulating TIMP-1 levels and survival in patients with severe sepsis has not been examined, and this was the objective of the study.

Methods

This multicentre, prospective, observational study was carried out in six Spanish ICUs. We determined the 372 T/C genetic polymorphism of TIMP-1 (rs4898), serum levels of TIMP-1, matrix metalloproteinase (MMP)-9, MMP-10, TNFα, IL-10 and plasma plasminogen activator inhibitor-1 (PAI-1). Survival at 30 days from ICU admission was the endpoint assessed. The association between continuous variables was carried out using Spearman''s rank correlation coefficient or Spearman''s rho coefficient. Multivariate logistic regression analysis was applied to determine the association between the 372 T/C genetic polymorphism and survival 30 days from ICU admission.

Results

Of 275 patients with severe sepsis, 80 had genotype CC, 55 had genotype CT and 140 had genotype TT of the 372 T/C genetic polymorphism of TIMP-1. Patients with the T allele showed higher serum levels of TIMP-1 than patients without the T allele (P = 0.004). Multiple logistic regression analysis showed that the T allele was associated with higher mortality at 30 days (odds ratio = 2.08; 95% confidence interval = 1.06 to 4.09; P = 0.03). Survival analysis showed that patients with the T allele presented lower 30-day survival than patients without the T allele (χ² = 5.77; P = 0.016). We found an association between TIMP-1 levels and levels of MMP-9 (ρ = -0.19; P = 0.002), MMP-10 (ρ = 0.55; P <0.001), TNFα (ρ = 0.56; P <0.001), IL-10 (ρ = 0.48; P <0.001) and PAI-1 (ρ = 0.49; P <0.001).

Conclusion

The novel findings of our study are that septic patients with the T allele in the 372 T/C genetic polymorphism of TIMP-1 showed higher serum TIMP-1 levels and lower survival rate. The determination of the 372 T/C genetic polymorphism of TIMP-1 thus has prognostic implications and could help in the selection of patients who may benefit from modulation of the MMP/TIMP balance.     

COMPARISON OF ECCENTRIC AND CONCENTRIC EXERCISE INTERVENTIONS IN ADULTS WITH SUBACROMIAL IMPINGEMENT SYNDROME

Background

Researchers have demonstrated moderate evidence for the use of exercise in the treatment of subacromial impingement syndrome (SAIS). Recent evidence also supports eccentric exercise for patients with lower extremity and wrist tendinopathies. However, only a few investigators have examined the effects of eccentric exercise on patients with rotator cuff tendinopathy.

Purpose

To compare the effectiveness of an eccentric progressive resistance exercise (PRE) intervention to a concentric PRE intervention in adults with SAIS.

Study Design

Randomized Clinical Trial

Methods

Thirty‐four participants with SAIS were randomized into concentric (n = 16, mean age: 48.6 ± 14.6 years) and eccentric (n = 18, mean age: 50.1 ± 16.9 years) exercise groups. Supervised rotator cuff and scapular PRE''s were performed twice a week for eight weeks. A daily home program of shoulder stretching and active range of motion (AROM) exercises was performed by both groups. The outcome measures of the Disabilities of the Arm, Shoulder, and Hand (DASH) score, pain‐free arm scapular plane elevation AROM, pain‐free shoulder abduction and external rotation (ER) strength were assessed at baseline, week five, and week eight of the study.

Results

Four separate 2x3 ANOVAs with repeated measures showed no significant difference in any outcome measure between the two groups over time. However, all participants made significant improvements in all outcome measures from baseline to week five (p <  0.0125). Significant improvements also were found from week five to week eight (p < 0.0125) for all outcome measures except scapular plane elevation AROM.

Conclusion

Both eccentric and concentric PRE programs resulted in improved function, AROM, and strength in patients with SAIS. However, no difference was found between the two exercise modes, suggesting that therapists may use exercises that utilize either exercise mode in their treatment of SAIS.

Level of evidence

Therapy, level 1b     

Bi-allelic and tri-allelic 5-HTTLPR polymorphisms and triptan non-response in cluster headache

Background

Triptans are only effective in terminating cluster headache (CH) attacks in 70-80% of patients. Pharmacogenetic aspects of the serotonin metabolism, specifically variation in the 5-HTTLPR may be involved.

Methods

Genetic association study in a well-defined cohort of 148 CH patients with information on drug response to triptans. CH was diagnosed according to the criteria of the International Headache Society. Genotypes of the 43-bp insdel (rs4795541) and A > G (rs25531) polymorphisms in the 5-HTTLPR promoter region were detected by restriction fragment length polymorphism analysis. We used logistic regression analysis to investigate the association between bi-allelic and tri-allelic genotypes and triptan non-response with genotype models.

Results

Mean age at study entry among patients was 44.6 ± 10.5 years, 77.7% were men. The genotype distribution both for the bi-allelic and the tri-allelic polymorphism was in Hardy-Weinberg equilibrium. We did not find an association of the bi-allelic polymorphism with triptan non-response. While the effect estimates for the S variant of the tri-allelic polymorphisms suggested increased odds of triptan non-response in CH patients (multivariable-adjusted odds ratio [95% confidence interval]: L*L* genotype—reference; L*S* genotype—1.33 [0.53-3.32]; S*S* genotype—1.46 [0.54-3.98]), the results were not statistically significant.

Conclusions

Data from our study do not indicate a role of bi-allelic and tri-allelic genotypes of the 5-HTTLPR polymorphism in triptan non-response in CH.     

Development and Testing of Self-Management Scale for PD Patients

♦ Objectives:

To develop and evaluate the self-management scale for peritoneal dialysis (PD) patients.

♦ Methods:

The item pool was formulated based on literature reviews and in-depth interviews. An initial scale containing five factors and 44 items was constructed through two rounds of Delphi expert consultation and a preliminary test. A total of 313 PD patients from the Jiangsu-Zhejiang-Shanghai area were surveyed to test the reliability and validity of the scale.

♦ Results:

Five factors, namely solution bag replacement, troubleshooting during operation, diet management, complication monitoring, emotion management and return to social life, were extracted by exploratory factor analysis: the 28 items could explain 64.567% of the total variance; the content validity index was 0.963; the Cronbach’s α coefficient and split-half coefficient were 0.926 and 0.960 respectively; and test-retest reliability was 0.937.

♦ Conclusion:

The scale has been proved to be a reliable and valid tool which allows PD nurses to evaluate the self-management ability of PD patients. The evaluation outcomes can serve as a basis for individualized nursing plans and interventions so as to provide highly effective nursing care.     

Sonography of the optic nerve sheath beyond the hyperacute stage of intracerebral hemorrhage

Purpose

To evaluate the feasibility and utility of serial measuring of the optic nerve sheath diameter beyond the hyperacute and acute stage of intracerebral hemorrhage (ICH).

Methods

Four patients with extensive ICH in the left basal ganglia were followed using ultrasound (US) and cerebral CT scans.

Results

Optic nerve sheath diameter values assessed beyond the acute stage of ICH showed a high correlation (ρ = 0.84, p = 0.0022) with midline shift of the third ventricle seen on CT scans.

Conclusions

Optic nerve sonography can be useful to evaluate patients with extensive ICH beyond the acute stage and help monitoring clinical evolution in these patients, when ICP monitoring is not feasible.     

Testing for Rewards: A Pilot Study to Improve Type 1 Diabetes Management in Adolescents

OBJECTIVE

To evaluate the effectiveness of monetary reinforcement to increase the frequency of self-monitoring blood glucose (SMBG).

RESEARCH DESIGN AND METHODS

Ten adolescents with poorly controlled diabetes enrolled in a 12-week program in which they earned monetary reinforcers based on SMBG frequency ($0.10 per test, with bonuses for ≥4 tests per day, and $251.40 maximum).

RESULTS

SMBG increased from 1.8 ± 1.0 to 4.9 ± 1.0 tests per day (P < 0.001) with 90% completing four or more tests per day. Mean A1C fell from 9.3 ± 0.9% to 8.4 ± 1.5% (P = 0.05). Adolescents and parents reported high satisfaction with procedures.

CONCLUSIONS

Reinforcing adolescents for SMBG may increase testing and improve A1C.     

Carriage of Mutant Dihydrofolate Reductase and Dihydropteroate Synthase Genes among Plasmodium falciparum Isolates Recovered from Pregnant Women with Asymptomatic Infection in Lagos,Nigeria

Objective

To assess N51I, C59R and S108N polymorphisms of dihydrofolate reductase (dhfr) and A437G and K540E of dihydropteroate synthase (dhps) genes of P. falciparum isolates recovered from pregnant women with asymptomatic malaria in a coastal setting in Nigeria.

Subjects and Methods

A total of 107 consenting and consecutively enrolled pregnant women (mean age ± standard deviation, 26.6 ± 4.5 years) attending antenatal care at the Iru/Victoria Island Primary Health Centre, Lagos, were screened for peripheral malaria by microscopy, by a histidine-rich protein-2-based rapid diagnostic test (RDT) and by polymerase chain reaction (PCR) using finger-pricked and dot blood samples. DNA was extracted from the blood and used for dhfr and dhps gene polymorphism analyses by PCR and restriction fragment length polymorphism. The sociodemographic and parasite data obtained were analysed.

Results

Of the 107 patients, 34 (31.8%), 46 (43%) and 40 (37.4%) were found to be P. falciparum infected using microscopy, RDT and corrected RDT-PCR, respectively (p < 0.05). The prevalence of P. falciparum isolates with mutant and mixed genotypes of dhfr at codons 51, 59 and 108 was 70, 75 and 80%, respectively, and the triple mutation in the homozygous form was 35%. The prevalence of the homozygous quintuple dhfr plus dhps mutant was 5%, while that of the P. falciparum isolates with mutant or mixed genotypes of dhps at codons 437 and 540 was 37.5 and 22.5%, respectively.

Conclusion

This study revealed the emergence of the K540E mutation among the parasite population in Lagos. However, it supports the implementation of the intermittent preventive treatment of malaria during pregnancy with sulphadoxine-pyrimethamine with continuous effectiveness monitoring in the study area.Key Words: Sulphadoxine-pyrimethamine resistance, Asymptomatic malaria, Dihydrofolate reductase gene, Dihydropteroate synthase gene, Single-nucleotide mutations, Pregnant women, Nigeria     

Monomicrobial Necrotizing Fasciitis Caused by Aeromonas hydrophila and Klebsiella pneumoniae

Objective

To compare specific characteristics and clinical outcomes of monomicrobial necrotizing fasciitis caused by Aeromonas hydrophila and Klebsiella pneumoniae.

Material and Methods

Cases of monomicrobial necrotizing fasciitis caused by A. hydrophila (n = 11) and K. pneumoniae (n = 7) over an 8-year period were retrospectively reviewed. Differences in mortality, patient characteristics, clinical presentations, and laboratory data were compared between the A. hydrophila and the K. pneumoniae groups.

Results

The clinical signs and symptoms at the time of presentation did not differ significantly (p > 0.05) between the two groups. The A. hydrophila group had a significantly shorter interval between contact and admission (1.55 ± 0.52 vs. 5.14 ± 2.12 days, p < 0.001) and significant lower total white blood cell counts (10,245 ± 5,828 vs. 19,014 ± 11,370 cells/mm³, p < 0.045) than the K. pneumoniae group in the emergency room. Hepatic dysfunction was associated with mortality in patients with A. hydrophila infection, while diabetes mellitus was associated with mortality in patients with K. pneumoniae infection. Overall, 5 (45.5%) patients in the A. hydrophila group and 3 (42.8%) in the K. pneumoniae group died.

Conclusion

The initial clinical course of A. hydrophila monomicrobial necrotizing fasciitis was characterized by more rapidly progressive disease than that of the K. pneumoniae infection. Patients with hepatic dysfunction and necrotizing fasciitis should be suspected of having A. hydrophila infection, and diabetic patients with necrotizing fasciitis should be suspected of having K. pneumoniae infection initially.Key Words: Necrotizing fasciitis, Aeromonas hydrophila, Klebsiella pneumoniae     

IRS1 Genotype Modulates Metabolic Syndrome Reversion in Response to 2-Year Weight-Loss Diet Intervention: The POUNDS LOST trial

OBJECTIVE

Genetic variants near IRS1 are associated with features of the metabolic syndrome (MetS). We examined whether genetic variants near IRS1 might modulate the effects of diets varying in fat content on the MetS status in a 2-year weight-loss trial.

RESEARCH DESIGN AND METHODS

Two variants near IRS1, rs1522813 and rs2943641, were genotyped in 738 overweight/obese adults (age 60 ± 9 years; BMI 32.7 ± 3.9 kg/m²) randomly assigned to one of four weight-loss diets (a deficit of 750 kcal/day of caloric intake from baseline) varying in macronutrient contents for 2 years. We compared MetS status of high-fat (40% of caloric intake; n = 370) and low-fat (20% caloric intake; n = 368) diet groups differentiated by genotypes (rs1522813 A-allele carriers and noncarriers and rs2943641T-allele carriers and noncarriers).

RESULTS

Among rs1522813 A-allele carriers, the reversion rates of the MetS were higher in the high-fat diet group than those in the low-fat diet group over the 2-year intervention (P = 0.002), while no significant difference between diet groups was observed among noncarriers (P = 0.27). The genetic modulation on dietary effect was independent of weight changes. The odds ratio (OR) for the 2-year reversion of the MetS was 2.88 (95% CI 1.25–6.67) comparing the high-fat and low-fat diets among rs1522813 A-allele carriers, while the corresponding OR was 0.83 (0.36–1.92) in noncarriers. The variant rs2943641 was not observed to modulate dietary effects on the MetS status.

CONCLUSIONS

Our data suggest that high-fat weight-loss diets might be more effective in the management of the MetS compared with low-fat diets among individuals with the A-allele of the rs1522813 variant near IRS1.The metabolic syndrome (MetS) is a constellation of metabolic abnormalities including abdominal obesity, dyslipidemia (low HDL cholesterol levels, and hypertriglyceridemia), elevated blood pressure, and hyperglycemia (1). It has been well-documented that the MetS increases the risk of diabetes, cardiovascular disease, and all-cause mortality (2). Several clinical trials have suggested that dietary intervention is an effective way to manage the MetS (3–9), though a specific therapeutic diet for the MetS remains to be determined. We have previously shown that weight-loss diets varying in macronutrient components had similar effectiveness in reducing the prevalence of the MetS in a 2-year randomized clinical trial, the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial (10).Genetic factors may play an important role in the development of the MetS. Insulin receptor substrate 1 (IRS1), encoded by the IRS1 gene, plays a key role in the insulin signaling pathway (11–13). Recent genome-wide association studies have identified common genetic variants near the IRS1 gene associated with multiple features of the MetS, such as insulin resistance, abdominal obesity, and dyslipidemia, as well as risk of diabetes and coronary heart disease (14–17). Moreover, our previous gene–diet interaction analysis has shown that the genetic variant rs2943641 near IRS1 might modulate the effect of diets varying in fat content on weight loss and the improvement of insulin resistance (18). Thus, we hypothesized that genetic variation near IRS1 may also modify the effect of weight-loss diets varying in fat content on the MetS status.In the current study, we genotyped another genetic variant, rs1522813, for which occurrence is independent of the previously investigated genetic variant rs2943641 (r² < 0.01) and is also near IRS1, and compared the effects of the high-fat and low-fat diets on the reversion of the MetS according to genotypes of the two variants over a 2-year intervention in 738 overweight or obese adults from the POUNDS LOST trial.     

Real-Time Continuous Glucose Monitoring Significantly Reduces Severe Hypoglycemia in Hypoglycemia-Unaware Patients With Type 1 Diabetes

OBJECTIVE

To evaluate the effect of continuous glucose monitoring (CGM) on the frequency of severe hypoglycemia (SH) in patients with established hypoglycemia unawareness.

RESEARCH DESIGN AND METHODS

We conducted a retrospective audit of 35 patients with type 1 diabetes and problematic hypoglycemia unawareness, despite optimized medical therapy (continuous subcutaneous insulin infusion/multiple daily insulin injections), who used CGM for >1 year.

RESULTS

Over a 1-year follow-up period, the median rates of SH were reduced from 4.0 (interquartile range [IQR] 0.75–7.25) episodes/patient-year to 0.0 (0.0–1.25) episodes/patient-year (P < 0.001), and the mean (±SD) rates were reduced from 8.1 ± 13 to 0.6 ± 1.2 episodes/year (P = 0.005). HbA_1c was reduced from 8.1 ± 1.2% to 7.6 ± 1.0% over the year (P = 0.005). The mean Gold score, measured in 19 patients, did not change: 5.1 ± 1.5 vs. 5.2 ± 1.9 (P = 0.67).

CONCLUSIONS

In a specialist experienced insulin pump center, in carefully selected patients, CGM reduced SH while improving HbA_1c but failed to restore hypoglycemia awareness.Although real-time continuous glucose monitoring (CGM) has been shown in randomized controlled trials to improve glycemic control and mild-to-moderate hypoglycemia, studies to date have not shown convincing reductions in severe hypoglycemia (SH) (1,2). Clinically, CGM may benefit patients with impaired awareness of hypoglycemia (IAH), who have an increased risk of SH (3), by alerting them to impending hypoglycemia, and thus providing them with “technological” awareness to replace the loss of their “physiological” awareness. In our clinical service, across two associated tertiary hospitals, we have obtained case-specific funding for CGM for 35 patients with type 1 diabetes, IAH, and problematic hypoglycemia limiting daily activities during intensified insulin therapy. This audit evaluates outcomes at 1 year to see whether the use of CGM can reduce SH or improve awareness.