Use of Open Claims vs Closed Claims in Health Outcomes Research.

Background: Closed claims are frequently used in outcomes research studies. Lately, the availability of open claims has increased the possibility of obtaining information faster and on a larger scale. However, because of the possibility of missing claims and duplications, these data sets have not been highly utilized in medical research. Objective: To compare frequently used healthcare utilization measures between closed claims and open claims to analyze if the possibility of missing claims in open claims data creates a downward bias in the estimates. Methods: We identified 18 different diseases using 2022 data from 2 closed claims data sets (MarketScan® and PharMetrics® Plus) and 1 open claims database (Kythera). After applying an algorithm that removes possible duplications from open claims data, we compared healthcare utilizations such as inpatient, emergency department, and outpatient use and length of stay among these 3 data sets. We applied standardized differences to compare the medians for each outcome. Results: The sample size of the open claims data sets was 10 to 65 times larger than closed claims data sets depending on disease type. For each disease, the estimates of healthcare utilization were similar between the open claims and closed claims data. The difference was statistically insignificant. Conclusions: Open claims data with a bigger sample size and more current available information provide essential advantages for healthcare outcomes research studies. Therefore, especially for new medications and rare diseases, open claims data can provide information much earlier than closed claims, which usually have a time lag of 6 to 8 months.

Hyperthermia alters neurobehavior by affecting cell proliferation and neuronal survival in young male rats.

Maintenance of body temperature within physiological range is critical for the fetal and neonatal development. Hyperthermia is one of the most frequently encountered pediatric complaints and may cause neurological disorders due to neuronal injury. In this study, we aimed to investigate the effects of hyperthermia on behavioral alterations, neuronal survival, apoptosis, and cell proliferation in young male Sprague-Dawley rats. Twenty-one 13-day-old rats were randomly divided into three groups (n = 7 per group). Body temperature was increased to 39°C and 41°C in a hyperthermia induction chamber for 30 min, whereas the animals in control group were maintained at 36°C. Twenty-four hours after hyperthermia, animals were subjected to the open field test, elevated-O-maze test, and grip strength test to assess the locomotor activity, anxiety, and motor function. Neuronal survival, apoptosis, and cell proliferation were investigated in cortex, hippocampal dentate gyrus (DG) and CA1 regions, and corpus callosum (CC). Decreased locomotor activity and motor function and increased anxiety were observed in the hyperthermia groups, and these were more pronounced in the 41°C group. Neuronal survival was significantly decreased in DG, CA1, and CC in the hyperthermia groups (**p < 0.01). Apoptosis was significantly induced in cortex, DG, and CC of the animals exposed to heat (*p < 0.05). In addition, cell proliferation positivity decreased significantly only in DG and CC of the animals exposed to heat (*p < 0.05). Our results suggest that neurobehavioral deficits caused by hyperthermia may be due to the increased apoptosis and neuronal cell death and decreased cell proliferation in the brain of postnatal developing rats.

Polychlorinated biphenyls and organochlorine pesticides in breast milk samples and their correlation with dietary and reproductive factors in lactating mothers in Istanbul.

Persistent organic pollutants (POPs) continue to threaten the environment and human health. We have investigated levels of polychlorinated biphenyls (PCBs) and organochlorinated pesticides (OCPs) in breast milk samples. A questionnaire was also obtained from the study participants. A total of 48 healthy lactating mothers (mean age: 29.5±0.8 years) living in Istanbul volunteered to participate in this study. High-resolution analyses of several OCPs and PCB congeners were done by gas chromatography. The levels of seven major PCB congeners (28, 52, 101, 118, 138, 153, and 180) and eight OCPs (α-benzenehexachloride, ß-benzenehexachloride, δ-benzenehexachloride, hexachlorobenzene (HCB), and 2,4'-dichlorodiphenyldichloroethylene (2,4DDE), 4,4'-dichlorodiphenyldichloroethylene (4,4DDE), 2,4'-dichlorodiphenyltrichloroethane (2,4DDT), and 4,4'-dichlorodiphenyltrichloroethane (4,4DDT)) were determined. The analysis showed that the highest levels of PCBs were observed in PCB 52 (22.99±8.78 ng/g lipid), PCB 101 (12.22±7.8 ng/g lipid), PCB 28 (11.44±5.16 ng/g lipid), and PCB 153 (1.70±0.74 ng/g lipid). The highest OCPs detected were 4,4DDT (3.33±2.05 ng/g lipid) and 4,4DDE (0.86 ± 0.39 ng/g lipid), and the lowest was observed in HCB (0.016 ± 0.01 ng/g lipid). Our findings show that traces of PCBs and OCPs are still present in breast milk of lactating women living in Istanbul, and these pollutants decline in multipara women compared to primipara mothers. We also suggest that breast milk is a useful and representative biological tool for human biomonitoring of POPs.

Blood count values and ratios for predicting sleep apnea in obese children.

OBJECTIVES: To detect whether the mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are contributing factors in the diagnosis and severity of sleep apnea in obese children. INTRODUCTION: Obesity is a public health problem, and its prevalence increases daily. Although PSG is the gold standard test in the investigation of sleep apnea, the application of this test requires equipment, personnel, time, and cost. There is no simple laboratory test for diagnosing and determining the severity of sleep apnea. Recently, MPV, NLR, and PLR, known as the inflammatory markers in CBC test parameters, have been investigated in some studies. We aim to investigate whether these parameters could provide a method for diagnosing and determining the severity of OSAS in obese children. METHODS: Clinical records of 180 patients were evaluated. All subjects had venous blood samples collected from the antecubital vein in the morning, after an overnight fasting, one day before PSG. Hemoglobin, RDW, MPV, PLT, platelet distribution width (PDW), and WBC count were measured. After anthropometric and laboratory analysis, 127 obese children were assessed for sleep study. Eighty-three patients who met the required polysomnographic criteria were divided into three groups as follows: group A [non-OSAS, apnea-plus-hypopnea index (AHI) < 1], groupB (1 ≤ AHI < 5), and groupC (AHI ≥ 5). RESULTS: Total recording time, total sleep time, sleep efficiency, REM, and NREM sleep stage latency values were not statistically significant among groups. However, the number of awakenings, AHI, oxygen desaturation events, mean oxygen saturation, lowest oxygen saturation, average desaturation, and snoring time values had significant difference among the groups. There was no statistically significant difference among the groups in terms of WBC, Hemoglobin, platelets, PDW, neutrophil, and lymphocyte values. However, RDW values showed a statistically significant difference between groups A and C. Although there was no statistically significant difference of MPV values among groups, NLR and PLR values were statistically significant between groups A and C. CONCLUSION: According to our study, NLR, PLR, and RDW were found to be significantly higher in children whose AHI was ≥5 than in children from the other groups. However, no correlation was found between MPV levels and OSAS in children.

Comparison of intraperitoneal and intratesticular ozone therapy for the treatment of testicular ischemia-reperfusion injury in rats.

We compare the efficacy of intratesticular ozone therapy with intraperitoneal ozone therapy in an experimental rat model. For this purpose, 24 rats were divided into four groups including sham-operated, torsion/detorsion, torsion/detorsion plus intraperitoneal ozone (O-IP), and torsion/detorsion plus intratesticular ozone (O-IT). The O-IP ozone group received a 4 mg kg-1 intraperitoneal injection of ozone, and the O-IT group received the same injection epididymally. At 4 h after detorsion, the rats were sacrificed and orchiectomy materials were assessed histopathologically. Spermatogenesis in the seminiferous tubules and damage to the Sertoli cells were histopathologically evaluated in the testes using the Johnsen scoring system. i-NOS and e-NOS activities in the testis tissue were also evaluated. Torsion-detorsion caused a decreased Johnsen score and increased apoptosis of spermatogonial and Sertoli cells. Ozone injection prevented increases in Johnsen score and i-NOS level. e-NOS level of the O-IP group was significantly lower than that of the O-IP group, and i-NOS level of the O-IT group was significantly lower than that of the O-IP group. Local ozone therapy is more effective than systemic ozone therapy at improving IRI-related testicular torsion. Our study is the first to show that the efficacy of intratesticular implementation of ozone therapy is higher than that of intraperitoneal ozone therapy.

Association between gene polymorphisms in TIM1, TSLP, IL18R1 and childhood asthma in Turkish population.

UNLABELLED: Many immunologic and inflammatory mechanisms play a role in asthma etiology. The aim of this study was to investigate the susceptibility of asthma patients in the Turkish population with demonstrating genes for polymorphisms in TIM1, TSLP and IL18R1. All of the genomic DNA samples were isolated from blood samples according to a standard salting-out protocol. DNA samples were stored at -20°C until the genotype analysis was performed. rs3806933 (TSLP -847 C > T) and TIM1 -416G > C were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The rs3806933 (TSLP -847 C > T) was genotyped by PCR using our new primers and HphI restriction enzyme digestion. rs2287033 (IL18R1 c. 1270+150 A > G), rs3213733 (IL18R1 c. 626-196 G > T), and rs3771166 (IL18R1- c. 302+1694 C > T) were genotyped using SYBR green dye based real time PCR assay. RESULTS: The allele frequencies of 5 SNPs in TSLP, TIM-1, and IL18R1 genes were determined in 139 asthmatic patients and 126 healthy controls of in Turkish population. The investigated SNPs are as follows; rs3806933 (TSLP -847 C > T), TIM1 -416G > C, rs2287033 (IL18R1 c. 1270+150 A > G), rs3213733 (IL18R1 c. 626-196 G > T), and rs3771166 (IL18R1- c. 302+1694 C > T). Results suggest that IL18R1 c. 626-196 G > T (rs3213733) and TIM1 -416G > C are significantly associated with asthma in patients in Turkish population. Patients with AA genotypes of rs2287033 (IL18R1 c. 1270+150 A > G), have significantly less total serum IgE levels when compared with patients having GG or GA genotypes (p < 0.012; 381.77±239.46 vs 557.52±549.96, respectively). CONCLUSION: This study showed that IL18R1 c. 626 -196 G > T (rs3213733) and TIM1 -416G > C are significantly associated with asthma patients in Turkish population.

Efficacy of prophylactic fluconazole therapy in decreasing the incidence of Candida infections in extremely low birth weight preterm infants.

OBJECTIVE: Systemic fungal infections are major causes of morbidity and mortality, and are associated with significant neurodevelopmental impairment in premature infants. Our objective was to evaluate the efficacy of fluconazole prophylaxis in prevention of systemic fungal infections among preterm infants. STUDY DESIGN: This observational pre-post cohort study was performed in preterm infants with a birth weight of < 1,000 g who were given prophylactic fluconazole starting on the first postnatal day at a dose of 3 mg/kg twice a week. These infants were compared with preterm infants who were not given prophylaxis. RESULTS: Prophylaxis group consisted of 90 infants and control group consisted of 107 infants. Systemic fungal infection was observed in five patients (4.7%) in the control group while no fungal infection was detected in the prophylaxis group (p = 0.03). There were no significant differences between two groups in terms of demographic features, maternal and neonatal risk factors, and all-cause mortality rates. No adverse reactions were seen during the prophylaxis period. CONCLUSIONS: We suggest that intravenous fluconazole prophylaxis at a dose of 3 mg/kg twice a week is a safe and effective strategy for decreasing systemic fungal infections even in neonatal intensive care units with low rates of invasive Candida infection.

Effects of heat stress on endocrine functions & behaviour in the pre-pubertal rat.

BACKGROUND & OBJECTIVES: Heat stress related hyperthermia may cause damage to various organ systems. There are very few studies on the effects of hyperthermia on the endocrine system. We therefore, investigated effects of exogenously induced hyperthermia on adrenal, testicular and thyroid functions and behavioural alterations in pre-pubertal male Sprague-Dawley rats. METHODS: Three groups of 30-day old rats (n=7 per group) were used. Body temperature was increased to 39 °C (Group I) and 41 °C (Group II) in a hyperthermia induction chamber for 30 min. The rats in the Group III served as control (36 °C). All animals received saline and were decapitated 48 h after the experiments. Serum free triiodothyronin (fT3), free thyroxine (fT4), total testosterone and dehydroepiandrosterone sulphate (DHEA-S) levels were determined by chemiluminescence assay, and corticosterone by enzyme immunoassay. Testes, pituitary and adrenal glands were dissected out and processed for histopathological examination. To assess activity and anxiety of the animals, the open field test and elevated-0-maze test, respectively, were used in all groups 24 h before (day 29) and after (day 31) hyperthermia induction. RESULTS: Serum corticosterone levels (3.22 ± 1.3) were significantly reduced in the 39 °C (1.3 ± 0.9) and 41 °C (1.09 ± 0.7) hyperthermia groups (P<0.01) compared to controls. Serum levels of thyroid hormones did not significantly differ among the groups. DHEA-S and testosterone values were below the limit of detection in all groups. Histopathological examination revealed that there was mild hydropic degeneration in the pituitary and adrenal glands. Apoptotic germ cells were seen in the seminiferous tubules of pre-pubertal male rats exposed to hyperthermia (41 °C). Progression time in the open field test was significantly decreased and anxiety test scores increased in animals exposed to 39 °C compared to the control group (P<0.01). These parameters were more pronounced in the 41 °C hyperthermia group. INTERPRETATION & CONCLUSIONS: Our results show that heat exposure-induced stress may cause delayed reduction in serum corticosterone levels which may be associated with behavioural deficits in pre-pubertal male rats.

Lack of ocular side effects after 2 years of topical steroids for allergic rhinitis.

PURPOSE: The aim of this study was to investigate ocular side effects in children with allergic rhinitis taking chronic intermittent nasal corticosteroids. METHODS: The study group included 150 children who had used intermittent intranasal budesonide for more than 2 years for allergic rhinitis. Ninety patients who were newly diagnosed as having allergic rhinitis without any treatment comprised the control group. Central corneal thickness, Schirmer test results, visual acuity, intraocular pressure, cataract formation, keratometry, and tear break-up time were compared in the two groups. RESULTS: The ages of the 150 study patients (85 boys) were between 8 and 15 years. The average age (± standard error of the mean [SEM]) was 11.7 ± 0.7 years and the mean (± SEM) steroid dosage used was 93.3 ± 7.0 µg daily with 42.2 ± 3.2 g total steroid use during treatment. The ages of the 90 control patients (54 boys) were between 7 and 15 years. There was no statistically significant difference between the study and control groups according to ocular findings (P > .05). Eye functions including cataract formation, corneal ectasia, ocular hypertension or glaucoma, and dry eye were not observed in any of the patients in the study group and were not correlated with total steroid dosage (r = 0.125, P = .447). CONCLUSION: A 2-year treatment of children with allergic rhinitis prescribed intermittent intranasal budesonide at an average daily dose of approximately 100 µg is not associated with ocular side effects such as cataract, glaucoma, corneal ectasia, and abnormal tear function.

Rosiglitazone, peroxisome proliferator receptor-gamma agonist, ameliorates gentamicin-induced nephrotoxicity in rats.

Nephrotoxicity is a major complication of gentamicin (GEN), which is widely used in the treatment of severe gram-negative infections. Reactive oxygen spaces (ROS) are important mediators of gentamicin-induced nephrotoxicity. Peroxisome proliferator-activated receptors (PPARs) have different activities including antioxidant properties. This study was performed to investigate the protective role of PPAR-γ agonist against GEN-induced nephrotoxicity. Male Wistar Albino rats were randomly divided into the following four groups, each of which consisted of six animals: (1) control; (2) intraperitoneally injected with GEN for 14 consecutive days (100 mg/kg/day); (3) treatment with rosiglitazone (RSG) via nasogastric gavage (10 mg/kg/daily for 14 days); (4) treatment with GEN + RSG combination for 14 day. Rats were decapitated on the 15th day and kidneys were removed. Urine was collected for every 24 h for the determination of daily urine volume. Urea, creatinine, Na(+) and K(+) levels were measured in blood. Malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (NO) levels along with glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) activities were determined in the renal tissue. Changes in body weight were recorded. GEN treatment was found to cause nephrotoxicity as evidenced by elevation of serum urea and creatinine levels. Renal impairment was also assessed by the renal histology. The significant decrease in GSH and increases in MDA and NO levels as well as a decrease in GSH-Px, CAT, and SOD activities indicated that GEN-induced renal damage was mediated through oxidative reactions. On the other hand, RSG administration protected kidney tissue against GEN-induced and free radical-mediated oxidative renal damage in rats.

Melatonin prevents acetaminophen-induced nephrotoxicity in rats.

Nephrotoxicity is a major complication of acetaminophen (APAP), a widely used analgesic and antipyretic drug, and there is no specific treatment for APAP-induced renal damage. It has been reported that reactive oxygen metabolites or free radicals are important mediators of APAP toxicity. In this study, the protective role of melatonin (MLT) on APAP-induced nephrotoxicity was investigated in rats. For this purpose, nephrotoxicity was induced in male Wistar albino rats by intraperitoneal (i.p.) administration of a single dose of 1,000 mg/kg APAP. Some of these rats also received i.p. melatonin (10 mg/kg) 20 min after administration of APAP. The rats were sacrificed 24 h after administration of APAP. Urea and creatinine levels were measured in the blood, and levels of malondialdehyde (MDA) and glutathione (GSH), and glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) activity were determined in renal tissue. Serum urea and creatinine levels increased significantly as a result of APAP nephrotoxicity. A significant increase in MDA and decreases in GSH level and GSH-Px, CAT, and SOD activity indicated that APAP-induced renal damage was mediated through oxidative stress. Significant beneficial changes were noted in serum and tissue oxidative stress indicators in rats treated with MLT. These biochemical observations were supplemented by histopathological examination of kidney sections, which revealed that MLT also reduced the severity of APAP-induced histological alterations in the kidney. These results indicate that administration of APAP causes oxidative stress to renal tissue and that MLT protects against the oxidative damage associated with APAP.