Absence Of Associated Symptoms Research Articles

"The Fever Is Still There!": Workup and Management of Prolonged Fever.

Fever is one of the most common chief complaints that brings pediatric patients to seek medical care. Although fever is, in most cases, a physiologic response to a pathogen that has alerted the immune system, prolonged fever can be challenging to work up for the treating pediatrician. In addition to assessing causes of fever, pediatricians must also address the fears that many caregivers may have surrounding elevations in body temperature and provide education as to when fever becomes a concern. Fever can be classified by its duration as well as the presence or absence of associated symptoms. Fever without a source is defined as a fever that has been present for 1 week without a clear cause. Fever of unknown origin is a fever that has been present daily for 8 days or more without an apparent source. This article will walk through considerations for a clinician evaluating a pediatric patient with prolonged fever. [Pediatr Ann. 2023;52(4):e124-e126.].

Intravenous ibuprofen for acute treatment of migraine: A double-blind, randomized, placebo-controlled pilot study.

To evaluate the efficacy and safety of intravenous (IV) Ibuprofen for acute treatment of migraine. IV nonsteroidal anti-inflammatory drugs (NSAIDs) are an alternative to oral NSAIDs, especially in patients with severe migraine who have emesis or gastroparesis. To date, only three IV NSAIDs (ketorolac, ibuprofen, and meloxicam) are available in the United States for use in moderate and severe pain, but no placebo-controlled trial is available for migraine. We performed a single-center, double-blind, randomized, placebo-controlled pilot study to evaluate the efficacy and safety of IV ibuprofen as an acute treatment of migraine (NCT01230411). Individuals with episodic migraine were screened at the Jefferson Headache Center. Qualified subjects were treated for migraine attacks within 2-72h following the headache onset with either 800mg of IV ibuprofen or placebo in 250ml saline bolus. Migraine pain intensity (4-point Likert scale) and associated symptoms were assessed at predetermined time points (0.25, 0.5, 1, 1.5, 2, 4, 8, 24h). The primary endpoint was pain relief at 2h after infusion. Important secondary endpoints included pain freedom at 2h, sustained relief over 24h, use of rescue therapy, and absence of associated symptoms. Adverse events (AEs) were also collected. Seventy-four participants were enrolled between 2011 and 2017. Forty-four subjects (female 33/44; 75.0%) with mean (SD) age 41.0 (11.2) 11.2 years came for the treatment. All treated subjects (n=44) were included in the analysis. Among them, 23 were randomized to receive IV ibuprofen. Both groups were demographically similar except for longer migraine duration (i.e., years lived with disease) in the active treatment than in the placebo group. At 2h posttreatment, pain relief was found in 74% (17/23) and 48% (10/21) after IV ibuprofen and placebo, respectively (odds ratio [OR] 3.12, 95% CI: 0.88-11.0; p=0.078). Other secondary endpoints at 2 and 24h were not significant. The longitudinal repeated-measures analysis within 2h on ibuprofen treatment showed significant pain relief (OR 2.47, 95% CI 1.08-5.7; p=0.033) and absence of associated symptoms: photophobia (OR 4.0, 95% CI 1.57-10.3; p=0.004), phonophobia (OR 3.12, 95% CI 1.16-8.4; p=0.025), and osmophobia (OR 3.45, 95% CI 1.01-11.8; p=0.048). AEs were observed in seven subjects in both groups, with arm pain being the most common. No serious AE was reported. This study did not meet the primary endpoint but showed pain relief and elimination of several associated symptoms within 2h on repeated-measures analysis. Although limited by small sample size and high placebo response, our results indicate that IV ibuprofen may be a safe and effective option for acute treatment of migraine, but more extensive studies are necessary.

Assessment of Mandibular Movement Monitoring With Machine Learning Analysis for the Diagnosis of Obstructive Sleep Apnea

Given the high prevalence of obstructive sleep apnea (OSA), there is a need for simpler and automated diagnostic approaches. To evaluate whether mandibular movement (MM) monitoring during sleep coupled with an automated analysis by machine learning is appropriate for OSA diagnosis. Diagnostic study of adults undergoing overnight in-laboratory polysomnography (PSG) as the reference method compared with simultaneous MM monitoring at a sleep clinic in an academic institution (Sleep Laboratory, Centre Hospitalier Universitaire Université Catholique de Louvain Namur Site Sainte-Elisabeth, Namur, Belgium). Patients with suspected OSA were enrolled from July 5, 2017, to October 31, 2018. Obstructive sleep apnea diagnosis required either evoking signs or symptoms or related medical or psychiatric comorbidities coupled with a PSG-derived respiratory disturbance index (PSG-RDI) of at least 5 events/h. A PSG-RDI of at least 15 events/h satisfied the diagnosis criteria even in the absence of associated symptoms or comorbidities. Patients who did not meet these criteria were classified as not having OSA. Agreement analysis and diagnostic performance were assessed by Bland-Altman plot comparing PSG-RDI and the Sunrise system RDI (Sr-RDI) with diagnosis threshold optimization via receiver operating characteristic curves, allowing for evaluation of the device sensitivity and specificity in detecting OSA at 5 events/h and 15 events/h. Among 376 consecutive adults with suspected OSA, the mean (SD) age was 49.7 (13.2) years, the mean (SD) body mass index was 31.0 (7.1), and 207 (55.1%) were men. Reliable agreement was found between PSG-RDI and Sr-RDI in patients without OSA (n = 46; mean difference, 1.31; 95% CI, -1.05 to 3.66 events/h) and in patients with OSA with a PSG-RDI of at least 5 events/h with symptoms (n = 107; mean difference, -0.69; 95% CI, -3.77 to 2.38 events/h). An Sr-RDI underestimation of -11.74 (95% CI, -20.83 to -2.67) events/h in patients with OSA with a PSG-RDI of at least 15 events/h was detected and corrected by optimization of the Sunrise system diagnostic threshold. The Sr-RDI showed diagnostic capability, with areas under the receiver operating characteristic curve of 0.95 (95% CI, 0.92-0.96) and 0.93 (95% CI, 0.90-0.93) for corresponding PSG-RDIs of 5 events/h and 15 events/h, respectively. At the 2 optimal cutoffs of 7.63 events/h and 12.65 events/h, Sr-RDI had accuracy of 0.92 (95% CI, 0.90-0.94) and 0.88 (95% CI, 0.86-0.90) as well as posttest probabilities of 0.99 (95% CI, 0.99-0.99) and 0.89 (95% CI, 0.88-0.91) at PSG-RDIs of at least 5 events/h and at least 15 events/h, respectively, corresponding to positive likelihood ratios of 14.86 (95% CI, 9.86-30.12) and 5.63 (95% CI, 4.92-7.27), respectively. Automatic analysis of MM patterns provided reliable performance in RDI calculation. The use of this index in OSA diagnosis appears to be promising.

Menstrual History-Taking at Annual Well Visits for AdolescentGirls.

To determine the rates at which primary care providers elicit menstrual histories from adolescent girls at well visits. Retrospective chart review. The departments of Pediatrics, Adolescent Medicine, and Family Medicine of Cooper University Healthcare from January 1, 2010 to June 1,2016. Women aged 12-21years who were seen for a well visit in the described setting. None. We searched physician well visit notes for documentation of the following aspects of menstrual history: menarche, last menstrual period, usual length of cycle, and the presence or absence of associated symptoms (such as pain and cramps). The presence or absence of each aspect was recorded in a binary fashion in a deidentified data set. A total of 954 unique charts were analyzed: 415 from Adolescent Medicine, 289 from Family Medicine, and 250 from General Pediatrics at Cooper University Healthcare. Adolescent Medicine was 6.44 times more likely to take a complete menstrual history than Family Medicine (P<.0001) and 5.80 times more likely than Pediatrics (P<.0001). There was no statistical difference between Pediatrics and Family Medicine (odds ratio, 0.55; P=.3150). Menstrual history-taking is often incomplete and can vary between departments, even within the same institution. These results indicate opportunities to raise awareness about the importance of a complete menstrual history and to develop quality improvement initiatives to increase documentation of the complete menstrual history.

First Report of Grapevine Latent Viroid Infecting Grapevine (Vitis vinifera) in Italy

Grapevine latent viroid (GLVd) is a new viroid recently discovered in grapevines (Vitis vinifera L.) of the variety Thompson Seedless, located in Xinjiang, China (Zhang et al. 2014), proposed as a new species in the genus Apscaviroid. It contains the typical structural elements of the other apscaviroids, i.e., circular genomic RNA able to assume a rod-like conformation, central and terminal conserved regions, poly-purine stretch in the pathogenicity associated P domain (Di Serio et al., 2017). Autonomous replication of GLVd in grapevine and absence of associated symptoms were confirmed by bioassays with infectious in vitro transcripts (Zhang et al. 2014). Up to now, the presence of GLVd has been reported only in grapevine of the variety Thompson Seedless grown in China (Zhang et al. 2014) and in Vitis sp. collected in South Korea (GenBank accession no. LC163596.1, unpublished). In July 2015, a survey based on next generation sequencing (NGS) of small RNAs of the grapevine collection Grinzane-Cavour, located in Piedmont, Italy, was carried out in order to investigate the grapevine virome. Bioinformatic analyses highlighted the presence of GLVd in a pool of 10 plants collected during the survey. A unique contig of 271 bp, a genome coverage of 82.6%, and an identity of 98.16% with the GLVd reference genome (KR605505.1) was obtained. This contig represented 822 (0.01%) of total reads, similar to the read percentages observed for other viroids detected by NGS (Candresse et al. 2017). The presence of GLVd as well as its circularity was confirmed by RT-PCR, using the pair of adjacent primers of opposite polarity GLVd-252F (5′-GCTCTCCAACGCCCTAA-3′) and GLVd-251R (5′-ACCATTAGTCCGCACGA-3′), mapping to positions 252-268 and 235-251 of the GLVd reference (KR605505.1), respectively (Zhang et al. 2014), which amplify the full-length monomeric cDNA of the viroid. GLVd was detected in four out of the 10 plants belonging to the sequenced pool: three plants from three Vitis vinifera L. cultivars (Adissi, Rkatsiteli, and Katta Kourgan), originally from Armenia, Georgia, and Uzbekistan, respectively, and one plant from V. riparia (cv. Gloire de Montpellier), originally from North America. A 330-bp genome sequence was obtained from the V. vinifera cultivar Katta Kourgan by RT-PCR amplification, cloning in the pCR-Blunt II-TOPO plasmid by Zero Blunt TOPO PCR Cloning Kit (Life Technologies, Carlsbad, CA) and Sanger sequencing. The sequence (MG770884) showed 99% identity and a single base insertion (+C226) when compared with the sequence assembled from the Illumina data, possibly reflecting sequence heterogeneity in the GLVd population. The new GLVd genomic sequence showed 97% identity with both the type sequences KR605505.1 (Chinese isolate) and LC163596.1 (Korean isolate), analogous to the sequence identity (97%) between the Chinese and Korean isolates. To the best of our knowledge, this is the first report of GLVd in Europe. As previously reported, no obvious symptoms were observed in the GLVd infected plants; however, the elicitation of symptoms related to environmental changes or mixed infections with other grapevine-infecting viruses cannot be excluded (Szychowski et al. 1995). Moreover, the recent characterization of viromes associated to apparently healthy host populations has raised the question of the possible biological/ecological role of asymptomatic viral entities (Roossinck and Bazan 2017). Further studies will be useful to better elucidate these aspects.

Clinicopathological, Biochemical, and Sonographic Features of Thyroid Nodule Predictive of Malignancy among Adult Filipino Patients in a Tertiary Hospital in the Philippines.

BackgroundThyroid nodules may harbor cancer in 5% to 15% of cases. Specific clinical and sonographic features predictive of malignancy have been investigated in various populations, but due to differences in epidemiology, risk factors and iodine nutrition status, these predictors may not be valid in the Philippines. This study determined the clinicopathological, biochemical, and sonographic features of thyroid nodules predictive of malignancy among adult Filipino patients at the University of the Philippines-Philippine General Hospital (UP-PGH).MethodsWe reviewed the medical records of Filipino patients ≥19 years of age who underwent thyroid surgery in UP-PGH from 2008 to 2011.ResultsA total of 837 of 1,670 patients (50.1%) were enrolled in the study, which included 417 benign and 420 malignant tumors. The mean age at diagnosis was 38±11 years, with female predominance. Multiple logistic regression analysis showed that the presence of a hard or firm nodule (odds ratio [OR], 58.8, P<0.001; OR, 12.8, P<0.001), presence of microcalcifications (OR, 11.1; P<0.001), irregular margins on ultrasound (OR, 4.5; P<0.001), and absence of associated symptoms (OR, 2.3; P<0.002) increased significantly the likelihood of thyroid malignancy.ConclusionSimilar to international data, the absence of associated symptoms, firm to hard thyroid nodules, and the presence of microcalcifications and irregular margins were significant predictors of thyroid malignancy.

Total Migraine Freedom, a Potential Primary Endpoint to Assess Acute Treatment in Migraine: Comparison to the Current FDA Requirement Using the Complete Rizatriptan Study Database

To examine total migraine freedom (TMF), defined as pain freedom and absence of associated symptoms, using rizatriptan clinical trial data and to explore advantages of TMF as a single primary composite efficacy endpoint. The FDA has set a higher regulatory hurdle for registration of new migraine agents requiring both pain freedom (or relief) and absence of each associated symptom (phonophobia, photophobia, and nausea). Twelve studies representing phase III + efficacy/safety studies of rizatriptan 10 mg in adults treating migraine were included in the meta-analysis. The percentage of patients achieving TMF at 2 hours by study and combined by treatment group was summarized by treatment paradigm (early/mild pain, moderate/severe, menstrual migraine). To demonstrate the impact of the strict migraine regulatory hurdle on clinical trial design and to compare it to TMF, simulation via bootstrap sampling was used. Odds ratios (rizatriptan vs placebo, all P < .001) for TMF were 6.2 (95% CI: [4.9, 7.7]) for moderate/severe, 2.7 (95% CI: [1.8, 4.0]) for menstrual, and 3.1 (95% CI: [2.4, 4.0]) for early/mild. Most with moderate/severe migraine reported photophobia and/or phonophobia at baseline, but only half had nausea. Simulation results showed a substantial loss of power analyzing absence of pain and each symptom compared with the composite TMF endpoint across all treatment paradigms. Rizatriptan 10 mg was superior to placebo in achieving TMF at 2 hours post-dose across all treatment paradigms. Given that the majority of patients with migraine do not exhibit all 3 associated symptoms, the TMF endpoint has significant advantages vs establishing efficacy on pain and each symptom individually.

Out-of-hospital cardiac arrest caused by transient left ventricular apical ballooning syndrome

We describe a case of out-of-hospital cardiac arrest due to ventricular fibrillation in a patient with transient left ventricular apical ballooning syndrome. Our report confirms that left ventricular apical ballooning may have the same complications of myocardial infarction, adding the early ventricular fibrillation to the previous findings of left ventricular wall rupture, ventricular arrhythmias during hospitalization and complete atrio-ventricular block. Moreover, left ventricular apical ballooning may have different and unusual clinical onsets, including sudden cardiac death due to ventricular tachyarrhythmias in the absence of associated symptoms. Therefore, in our opinion left ventricular apical ballooning may be considered as a possible cause of sudden death in otherwise healthy women.

Efficacy of oral naratriptan in the treatment of menstrually related migraine

The aim of this study was to investigate the efficacy of orally administered 2.5 mg naratriptan in the treatment of menstrually related migraine (MRM). A high percentage of women suffering from migraine report increased frequency of attacks in association with menstruation that may be more severe, of longer duration and more difficult to treat than at other times. This was a phase IIIb, randomized, double-blind, placebo-controlled clinical trial. Subjects were given either 2.5 mg naratriptan or placebo to treat a single MRM episode, defined as starting between days -2 and +4 relative to the start of menstruation. The primary efficacy measure was the percentage of subjects who were free of pain 4 h after treatment, the absence of pain at 30 min, 1 and 2 h being secondary efficacy measures. Other secondary measures were the absence of associated symptoms, sustained headache relief 24 h after a single dose of the study medication, recourse to a second dose of study medication or escape medication, pain intensity 4-24 h after first treatment, the ability to carry out work or daily activities, and patient satisfaction. Adverse events were also monitored. A total of 275 women were enrolled in the trial and 229 (115 naratriptan group, 114 placebo group) provided data on the effects of the study medication on MRM. A higher percentage of subjects in the naratriptan group (58%) reported complete pain relief 4 h after medication than in the placebo group (30%) (P<0.001). Significant differences between the naratriptan and placebo groups and in favor of naratriptan were also found for: total pain relief at 2 h (P=0.004), sustained pain-free response within 4-24 h (P<0.001), absence of all associated symptoms at 2 and 4 h (P=0.004), ability to work and carry out daily activities at 2 h (P=0.036), and patient overall satisfaction (P<0.001). Three adverse events were recorded that might potentially be attributable to naratriptan. Naratriptan given orally at a dose of 2.5 mg is effective in the acute treatment of MRM as early as 2 h after treatment.

Éducation thérapeutique du patient : vers une démarche raisonnée

Heel pain is a very common foot disease. Varieties of names such as plantar fasciitis, jogger's heel, tennis heal, policeman's heel are used to describe it. Mechanical factors are the most common etiology of heel pain. Common causes of hell pain includes: Plantar Fasciitis, Heel Spur, Sever's Disease, Heel bump, Achilles Tendinopathy, Heel neuritis, Heel bursitis. The diagnosis is mostly based on clinical examination. Normally, the location of the pain and the absence of associated symptoms indicating a systemic disease strongly suggest the diagnosis. Several therapies exist including rest, physical therapy, stretching, and change in footwear, arch supports, orthotics, night splints, anti-inflammatory agents, and surgery. Almost all patients respond to conservative nonsurgical therapy. Surgery is the last treatment option if all other treatments had failed. Rest, ice, massage, the use of correct exercise and complying with a doctor's advice all play important part in helping to recover from this hell pain condition, but getting good quality, suitable shoes with the appropriate amount of support for the whole foot is the most important.

Neurofibromatosis Type 1 in a Pediatric Population: Ste-Justine's Experience

To date, few pediatric series of neurofibromatosis type 1 (NF-1) have been described in the literature even though it is the most frequently encountered phakomatosis. We reviewed 987 charts of pediatric patients with a presumptive diagnosis of NF-1 who were evaluated at Ste-Justine hospital from January 1, 1991 to July 31, 2002. Patients who presented with two or more cardinal criteria were diagnosed with NF-1. Clinical and laboratory data were retrospectively collected, including: demographics, neuroimaging and presence or absence of associated symptoms or signs of NF-1. A total of 279 patients were diagnosed with NF-1. The mean age at diagnosis was 3.4 years. Ninety-nine percent of the patients had café au lait spots and 47% had a first degree relative with NF-1. Almost 60 percent (59.6%) of those seen by an ophthalmologist had Lisch nodules. Optic glioma was found in in 14.7%, cutaneous neurofibromas in 38.4%, plexiform neurofibromas in 24.7%, neurofibrosarcoma in 1.8%, learning disabilities in 39%, attention deficit disorder in 40.5%, osseous dysplasias in 7.2%, pseudoarthrosis in 3.6%, precocious puberty in 3.2% and short stature in 17.9%. Magnetic resonance, when performed, showed hyperintense T2 lesions in 87.1% of cases. The mean period of follow-up was 7.4 years. Neurofibromatosis type 1 is a multisystemic disorder associated with increased risk of malignancy. It can be diagnosed at a very young age and clinical follow-up is advised. To our knowledge, this is the largest single center study of NF-1 in a pediatric population.

Dolor torácico en urgencias de pediatría: un proceso habitualmente benigno

To describe the characteristics and management of the children aged less than 14 years presenting to the pediatric emergency department with chest pain. Retrospective review of all the patients who presented to the pediatric emergency department with chest pain from 15 January 2001 to 14 January 2002. Families received a follow-up telephone call inquiring about the patient's outcome. The Mann-Whitney U test was used for non-parametric data and the Chi-square test with Yates' correction and Fisher's exact test were used for categorical data. Statistical significance was set at p<0.05. In 2001, 161 children presented with chest pain, representing 0.34% of the total number of consultations. Less than half of these patients (48%) had associated symptoms. Physical examination revealed abnormalities in 63% of the patients (39.1%). The most common finding was pain on palpation of the chest wall. Additional diagnostic tests were performed in 129 patients (80%). These included 116 radiographs, 62 electrocardiograms and nine miscellaneous tests. Abnormalities were found in seven chest radiographs. Only one child was admitted to hospital with pneumonia. The most common discharge diagnoses were idiopathic and/or musculoskeletal chest pain in 139 patients, pain of respiratory origin in 14 patients, gastrointestinal disorders in one patient, cardiac problems in one patient and other morbid processes in nine patients. Children with associated symptoms were more likely to receive a diagnosis other than nonspecific chest pain (28% vs 3.2% in children without other symptoms; relative risk: 8.66). Outpatient treatment included analgesics in 105 patients (65.2%). Only two children (1.2%) returned for reevaluation and no important findings were detected. Telephone follow-up was carried out in 117 children (72.6%). The pain lasted for less than 24 hours in 52 patients (32.2%). Thirty percent of the patients missed at least one day of school because of chest pain. Chest pain is an infrequent chief complaint in our setting and, in the absence of associated symptoms, is not generally associated with serious disorders. The decision to use complementary diagnostic tests should be individualized to each patient.

Rizatriptan 5 mg for the Acute Treatment of Migraine in Adolescents: A Randomized, Double‐Blind, Placebo‐Controlled Study

To investigate the tolerability and efficacy of rizatriptan 5 mg in adolescent migraineurs. Randomized, double-blind, placebo-controlled study. Patients aged 12 to 17 years received rizatriptan 5 mg (n = 149) or placebo (n = 147) for a moderate or severe headache and for up to two recurrences. Headache severity, presence or absence of associated symptoms, and functional disability were assessed over a 4-hour postdose period, and any adverse events were recorded. The primary efficacy measure was pain-free status at 2 hours postdose. Rizatriptan 5 mg was well tolerated. The most commonly reported adverse events (all with incidence of 5% or less) among patients receiving rizatriptan were dry mouth, dizziness, asthenia/fatigue, nausea, and somnolence. The percentage of patients pain-free at 2 hours was 32% for rizatriptan 5 mg versus 28% for placebo (P=.474). The percentage of patients with pain relief (reduction of predose pain intensity to mild or none) at 2 hours was 66% for rizatriptan versus 56% for placebo (P=.079). Placebo response rates were higher than those typically observed in previous studies of rizatriptan in adults. Compared with placebo, rizatriptan significantly improved functional disability at 1.5 and 2 hours, and nausea at 1 and 1.5 hours. Post hoc analysis showed a significant benefit of rizatriptan versus placebo in the percentage of patients who had pain relief when their migraine attacks were treated on weekends (65% versus 36%, P=.046) compared with weekdays (66% versus 61%, P=.365), and the weekend placebo response rate was similar to that seen in adults. Rizatriptan 5 mg was well tolerated and effective on some measures when used in adolescents for the treatment of a migraine attack.

Haemorrhoids--objective measurement of proctoscopic appearances.

The proctoscopic diagnosis of haemorrhoids may be influenced by the surgeon's knowledge of the presence or absence of associated symptoms. In this study, an observer with no knowledge of the history, was used to check the surgeon's proctoscopic findings in 12 asymptomatic controls, and 24 symptomatic patients on 2 occasions, the latter group undergoing McGivney rubber band ligation. There was very good correlation between the findings of the surgeon and the observer, indicating a lack of 'historical bias'. The documentation method designed to allow this comparison proved sufficiently accurate and reproducible to enable a correlation between haemorrhoidal mass and symptoms. Relief of symptoms after treatment correlated well with an objective reduction in haemorrhoidal mass.