Testing for marginal covariate effect when the subgroup size induced by the covariate is informative.

In many cluster-correlated data analyses, informative cluster size poses a challenge that can potentially introduce bias in statistical analyses. Different methodologies have been introduced in statistical literature to address this bias. In this study, we consider a complex form of informativeness where the number of observations corresponding to latent levels of a unit-level continuous covariate within a cluster is associated with the response variable. This type of informativeness has not been explored in prior research. We present a novel test statistic designed to evaluate the effect of the continuous covariate while accounting for the presence of informativeness. The covariate induces a continuum of latent subgroups within the clusters, and our test statistic is formulated by aggregating values from an established statistic that accounts for informative subgroup sizes when comparing group-specific marginal distributions. Through carefully designed simulations, we compare our test with four traditional methods commonly employed in the analysis of cluster-correlated data. Only our test maintains the size across all data-generating scenarios with informativeness. We illustrate the proposed method to test for marginal associations in periodontal data with this distinctive form of informativeness.

Multiblock partial least squares and rank aggregation: Applications to detection of bacteriophages associated with antimicrobial resistance in the presence of potential confounding factors.

Urban environments, characterized by bustling mass transit systems and high population density, host a complex web of microorganisms that impact microbial interactions. These urban microbiomes, influenced by diverse demographics and constant human movement, are vital for understanding microbial dynamics. We explore urban metagenomics, utilizing an extensive dataset from the Metagenomics & Metadesign of Subways & Urban Biomes (MetaSUB) consortium, and investigate antimicrobial resistance (AMR) patterns. In this pioneering research, we delve into the role of bacteriophages, or "phages"-viruses that prey on bacteria and can facilitate the exchange of antibiotic resistance genes (ARGs) through mechanisms like horizontal gene transfer (HGT). Despite their potential significance, existing literature lacks a consensus on their significance in ARG dissemination. We argue that they are an important consideration. We uncover that environmental variables, such as those on climate, demographics, and landscape, can obscure phage-resistome relationships. We adjust for these potential confounders and clarify these relationships across specific and overall antibiotic classes with precision, identifying several key phages. Leveraging machine learning tools and validating findings through clinical literature, we uncover novel associations, adding valuable insights to our comprehension of AMR development.

Bilateral Subdiaphragmatic Vagal Nerve Stimulation Using a Novel Waveform Decreases Body Weight, Food Consumption, Adiposity, and Activity in Obesity-Prone Rats.

INTRODUCTION: Obesity affects millions of Americans. The vagal nerves convey the degree of stomach fullness to the brain via afferent visceral fibers. Studies have found that vagal nerve stimulation (VNS) promotes reduced food intake, causes weight loss, and reduces cravings and appetite. METHODS: Here, we evaluate the efficacy of a novel stimulus waveform applied bilaterally to the subdiaphragmatic vagal nerve stimulation (sVNS) for almost 13 weeks. A stimulating cuff electrode was implanted in obesity-prone Sprague Dawley rats maintained on a high-fat diet. Body weight, food consumption, and daily movement were tracked over time and compared against three control groups: sham rats on a high-fat diet that were implanted with non-operational cuffs, rats on a high-fat diet that were not implanted, and rats on a standard diet that were not implanted. RESULTS: Results showed that rats on a high-fat diet that received sVNS attained a similar weight to rats on a standard diet due primarily to a reduction in daily caloric intake. Rats on a high-fat diet that received sVNS had significantly less body fat than other high-fat controls. Rats receiving sVNS also began moving a similar amount to rats on the standard diet. CONCLUSION: Results from this study suggest that bilateral subdiaphragmatic vagal nerve stimulation can alter the rate of growth of rats maintained on a high-fat diet through a reduction in daily caloric intake, returning their body weight to that which is similar to rats on a standard diet over approximately 13 weeks.

Pseudo-value regression of clustered multistate current status data with informative cluster sizes.

Multistate current status data presents a more severe form of censoring due to the single observation of study participants transitioning through a sequence of well-defined disease states at random inspection times. Moreover, these data may be clustered within specified groups, and informativeness of the cluster sizes may arise due to the existing latent relationship between the transition outcomes and the cluster sizes. Failure to adjust for this informativeness may lead to a biased inference. Motivated by a clinical study of periodontal disease, we propose an extension of the pseudo-value approach to estimate covariate effects on the state occupation probabilities for these clustered multistate current status data with informative cluster or intra-cluster group sizes. In our approach, the proposed pseudo-value technique initially computes marginal estimators of the state occupation probabilities utilizing nonparametric regression. Next, the estimating equations based on the corresponding pseudo-values are reweighted by functions of the cluster sizes to adjust for informativeness. We perform a variety of simulation studies to study the properties of our pseudo-value regression based on the nonparametric marginal estimators under different scenarios of informativeness. For illustration, the method is applied to the motivating periodontal disease dataset, which encapsulates the complex data-generation mechanism.

Adjusting for informative cluster size in pseudo-value-based regression approaches with clustered time to event data.

Informative cluster size (ICS) arises in situations with clustered data where a latent relationship exists between the number of participants in a cluster and the outcome measures. Although this phenomenon has been sporadically reported in the statistical literature for nearly two decades now, further exploration is needed in certain statistical methodologies to avoid potentially misleading inferences. For inference about population quantities without covariates, inverse cluster size reweightings are often employed to adjust for ICS. Further, to study the effect of covariates on disease progression described by a multistate model, the pseudo-value regression technique has gained popularity in time-to-event data analysis. We seek to answer the question: "How to apply pseudo-value regression to clustered time-to-event data when cluster size is informative?" ICS adjustment by the reweighting method can be performed in two steps; estimation of marginal functions of the multistate model and fitting the estimating equations based on pseudo-value responses, leading to four possible strategies. We present theoretical arguments and thorough simulation experiments to ascertain the correct strategy for adjusting for ICS. A further extension of our methodology is implemented to include informativeness induced by the intracluster group size. We demonstrate the methods in two real-world applications: (i) to determine predictors of tooth survival in a periodontal study and (ii) to identify indicators of ambulatory recovery in spinal cord injury patients who participated in locomotor-training rehabilitation.

Ureterocele as a cause of chronic intractable abdominal pain.

A ureterocele is a submucosal, cystic dilation of the terminal ureter, either congenital or acquired, as it enters the bladder. It is a rare clinical entity that can be entirely asymptomatic and present as an incidental finding or can manifest in the form of distressing symptoms such as unremitting abdominal pain, haematuria, obstructive uropathy, to name a few. The authors present a case of abdominal pain in a 43-year-old woman who was presumptively attributed to various clinical entities and was finally referred to the chronic pain clinic. The patient underwent numerous diagnostic tests, psychological evaluations and therapeutic interventions, including surgeries, over the years that failed to mitigate her symptoms until urologic imaging reported intravesical ureterocele as the underlying disorder. The case report entails the diagnostic challenge faced by the authors along with the clinical characteristics of ureterocele.

Metagenomic Geolocation Prediction Using an Adaptive Ensemble Classifier.

Microbiome samples harvested from urban environments can be informative in predicting the geographic location of unknown samples. The idea that different cities may have geographically disparate microbial signatures can be utilized to predict the geographical location based on city-specific microbiome samples. We implemented this idea first; by utilizing standard bioinformatics procedures to pre-process the raw metagenomics samples provided by the CAMDA organizers. We trained several component classifiers and a robust ensemble classifier with data generated from taxonomy-dependent and taxonomy-free approaches. Also, we implemented class weighting and an optimal oversampling technique to overcome the class imbalance in the primary data. In each instance, we observed that the component classifiers performed differently, whereas the ensemble classifier consistently yielded optimal performance. Finally, we predicted the source cities of mystery samples provided by the organizers. Our results highlight the unreliability of restricting the classification of metagenomic samples to source origins to a single classification algorithm. By combining several component classifiers via the ensemble approach, we obtained classification results that were as good as the best-performing component classifier.

Paresthesia-Free Dorsal Root Ganglion Stimulation: An ACCURATE Study Sub-Analysis.

INTRODUCTION: ACCURATE, a randomized controlled trial comparing dorsal root ganglion (DRG) stimulation to spinal cord stimulation, showed that DRG stimulation is a safe and effective therapy in individuals with lower extremity chronic pain due to complex regional pain syndrome (CRPS) type I or II. Investigators noted that DRG stimulation programming could be adjusted to minimize, or eliminate, the feeling of paresthesia while maintaining adequate pain relief. The present study explores treatment outcomes for DRG subjects who were paresthesia-free vs. those who experienced the sensation of paresthesia, as well as the factors that predicted paresthesia-free analgesia. METHODS: A retrospective analysis of therapy outcomes was conducted for 61 subjects in the ACCURATE study who received a permanent DRG neurostimulator. Outcomes of subjects who were paresthesia-free were compared to those who experienced paresthesia-present therapy at 1, 3, 6, 9, and 12-month follow-ups. Predictor variables for the presence or absence of paresthesias with DRG stimulation were also explored. RESULTS: The percentage of subjects with paresthesia-free pain relief increased from 16.4% at 1-month to 38.3% at 12-months. Paresthesia-free subjects generally had similar or better outcomes for pain severity, pain interference, quality of life, and mood state as subjects with paresthesia-present stimulation. Factors that increased the odds of a subject feeling paresthesia were higher stimulation amplitudes and frequencies, number of implanted leads, and younger age. CONCLUSIONS: Some DRG subjects achieved effective paresthesia-free analgesia in the ACCURATE trial. This supports the observation that paresthesia is not synonymous with pain relief or required for optimal analgesia with DRG stimulation.

Nutcracker Syndrome-An Unusual Case of Chronic Left Upper Abdominal Pain: A Case Report.

A 38-year-old woman presented with a chief complaint of sharp, achy left upper abdominal pain with radiation to the left flank. This pain started approximately one-and-a-half years before she consulted with a pain specialist. Although an extensive workup was completed, no organic cause was established as the cause of her pain. After undergoing successful fluoroscopically guided celiac plexus blocks, an abdominal magnetic resonance imaging scan was obtained that revealed nutcracker phenomenon. The patient was evaluated by an urologist and underwent renal autotransplantation. The patient subsequently had complete relief of her pain.

A Rare Case of Transverse Sinus Venous Thrombosis Simulating Postdural Puncture Headache After Cervical Epidural Injection.

Postdural puncture headache (PDPH) is a feared complication related to epidural steroid injections. We report a unique case in which all subjective and objective findings indicated the diagnosis of PDPH. However, the patient failed appropriate conservative and interventional management. Therapeutic failure prompted further investigation to establish the correct diagnosis of cerebral venous sinus thrombosis. Cerebral venous sinus thrombosis is a rare, difficult to diagnose, but potentially lethal disorder with nonspecific and variable clinical presentations, including headache and focal neurological deficits. Performing magnetic resonance imaging and magnetic resonance venogram should be considered early, especially in patients who fail to respond to standard interventions for PDPH.

Functional and patient-reported outcomes in symptomatic lumbar spinal stenosis following percutaneous decompression.

BACKGROUND: Neurogenic claudication due to symptomatic lumbar spinal stenosis (LSS) is a painful condition causing significant functional disability. While the cause of LSS is multifactorial, thickened ligamentum flavum (LF) accounts for up to 85% of spinal canal narrowing. mild percutaneous lumbar decompression allows debulking of the hypertrophic LF while avoiding the morbidities frequently associated with more invasive surgical procedures. METHODS: In this prospective case series study, consecutive LSS patients presenting with neurogenic claudication were treated with percutaneous lumbar decompression. Efficacy was evaluated using the Pain Disability Index (PDI) and Roland-Morris Disability Questionnaire. Pre- and postprocedure Standing Time, Walking Distance, and Visual Analog Score (VAS) were also monitored. Significant device- or procedure-related adverse events were reported. RESULTS: The mild procedure was successfully performed on forty patients. At twelve months, both PDI and Roland-Morris showed significant improvement of 22.6 points (ANOVA, P<0.0001) and 7.7 points (ANOVA, P<0.0001), respectively. Walking Distance, Standing Time, and VAS improvements were also statistically significant, increasing from 246 to 3,956 feet (ANOVA, P<0.0001), 8 to 56 minutes (ANOVA, P<0.0001), and 7.1 to 3.6 points (ANOVA, P<0.0001), respectively. Tukey HSD test found improvement in all 5-outcome measures to be significant from baseline at each follow-up interval. No significant device- or procedure-related adverse events were reported. CONCLUSION: This study demonstrated significant functional improvement as well as decreased disability secondary to neurogenic claudication after mild procedure. Safety, cost-effectiveness, and quality-of-life outcomes are best compared with comprehensive medical management in a randomized controlled fashion and, where ethical, to open lumbar decompression surgery.

Gender rather than choice of intermediate duration opioids affects emergence after craniotomy for large intracranial tumors.

BACKGROUND: Opioid-based anesthetic techniques are commonly used during neurosurgical procedures. In the present randomized prospective study, we studied emergence after 4 anesthetic regimens combining intermediate duration opioids with isoflurane and nitrous oxide (N(2)O), in patients undergoing craniotomy for large (> 30 mm diameter with intracranial mass effect) intracranial tumors. METHODS: One hundred seven patients were randomized into 4 groups: Group A: fentanyl (≤ 5 µg/kg) + isoflurane (≤ 1 minimum alveolar concentration [MAC]), Group B: sufentanil (1-2 µg/kg plus infusion) + isoflurane (≤ 0.5 MAC), Group C: sufentanil (2 µg/kg bolus only) + isoflurane (≤ 1 MAC), and Group D: alfentanil (100 µg/kg plus infusion) + isoflurane (≤ 0.5 MAC). Boluses were administered as divided doses during induction, laryngoscopy, head pinning, and incision. Blood pressure was controlled at ±25% of baseline levels. All infusions were discontinued at the start of dural closure. Emergence was assessed using a mini-neurologic examination consisting of 7 questions. Groups were compared on time to emergence using survival analysis methods. RESULTS: The groups did not differ regarding extubation time, which occurred at a median of 4 to 6 minutes across groups after discontinuing N(2)O. The median emergence time ranged from 15 to 22.5 minutes and did not differ among groups. However, across all groups more women had emerged by 30 minutes compared with men (83% vs 57%, P â€Š=  .002). The median emergence time in women was found to be significantly shorter (0-15 minutes) than in men (15-30 minutes) (P â€Š=  .012). CONCLUSIONS: No between-group differences in emergence time were observed; the study was stopped early because of evidence that no differences were likely to be found if the study were continued. However, in a post hoc analysis, female gender was associated with faster emergence.

Prevalence of acne keloidalis nuchae in Nigerians.

BACKGROUND: The prevalence of acne keloidalis nuchae (AKN), a chronic inflammatory process of the hair follicles resulting in keloidal papules and plaques at the nape of the neck, is increasing in our environment. METHODS: A prospective hospital-based observational study was conducted at the adult medical dermatologic outpatient department of Irrua specialist teaching hospital, Edo State, Nigeria. All patients referred to the dermatology clinic with symptoms and signs of AKN were recruited. RESULTS: Thirty patients presented to the adult dermatologic unit with AKN over a period of 22 months, giving a gross incidence of 9.4% of dermatologic consultations. The common etiologic factor was secondary to trauma from an electric razor whilst having a haircut, followed by spread of keloid from the beard area. CONCLUSIONS: Minimization of trauma during hair cutting or shaving and personalization of haircare instruments may reduce the recently increased incidence of this condition in our environment.

Continuous femoral nerve analgesia after unilateral total knee arthroplasty: stimulating versus nonstimulating catheters.

BACKGROUND: Continuous femoral analgesia provides extended pain relief and improved functional recovery for total knee arthroplasty (TKA). Stimulating catheters may allow more accurate placement of catheters. METHODS: We performed a randomized prospective study to investigate the use of stimulating catheters versus nonstimulating catheters in 41 patients undergoing TKA. All patients received i.v. patient-controlled anesthesia for supplementary pain relief. The principal aim of the trial was to examine whether a stimulating catheter allowed the use of lesser amounts of local anesthetics than a nonstimulating catheter. The additional variables we examined included postoperative pain scores, opioid use, side effects, and acute functional orthopedic outcomes. RESULTS: Analgesia was satisfactory in both groups, but there were no statistically significant differences in the amount of ropivacaine administered; the median amount of ropivacaine given to patients in the stimulating catheter group was 8.2 mL/h vs 8.8 mL/h for patients with nonstimulating catheters, P = 0.26 (median difference -0.6; 95% confidence interval, -2.3 to 0.6). No significant differences between the treatment groups were noted for the amount of fentanyl dispensed by the i.v. patient-controlled anesthesia, numeric pain rating scale scores, acute functional orthopedic outcomes, side effects, or amounts of oral opioids consumed. CONCLUSION: The use of stimulating catheters in continuous femoral nerve blocks for TKA does not offer significant benefits over traditional nonstimulating catheters.

Metastatic malignant insulinoma in a patient with type 2 diabetes mellitus: case presentation and literature review.

OBJECTIVE: To describe the occurrence of metastatic malignant insulinoma in a patient with preexisting type 2 diabetes mellitus. METHODS: We present a detailed case report, with clinical, biochemical, and imaging findings, and summarize the data from 21 similar cases in the literature. RESULTS: The occurrence of malignant insulinoma in a patient with preexisting diabetes is very rare and thus can be a diagnostic challenge. In our patient with type 2 diabetes, endogenous hyperinsulinism was confirmed by demonstrating elevated insulin and C-peptide levels during hypoglycemic episodes in the absence of sulfonylurea on a blood screen. Abdominal computed tomographic scan and magnetic resonance imaging revealed a pancreatic mass as well as metastatic lesions in the liver. The pancreatic mass was removed and confirmed to be a malignant insulinoma. This procedure was followed by disappearance of the hypoglycemic episodes as well as the diabetes for a few months. On follow-up, however, more metastatic lesions appeared in conjunction with a protracted course of hypoglycemia that necessitated treatment with antihypoglycemic agents and, 3 years after the initial surgical intervention, culminated in the death of the patient. CONCLUSION: Our patient is one of the few subjects known to have a malignant insulinoma in conjunction with preexisting diabetes. A high degree of suspicion for the presence of an insulinoma should be maintained when unexplained hypoglycemic episodes occur in a patient with previously stable diabetes.

Effect of short-term Pritikin diet therapy on the metabolic syndrome.

The Pritikin Program (Aventura, FL) involves the use of a very-low-fat, low-sodium, high-fiber diet and exercise to decrease the risk of coronary heart disease (CHD). This study evaluated the effect of short-term Pritikin therapy on the metabolic risk factors for CHD in patients with the metabolic syndrome. Sixty-seven subjects who had the metabolic syndrome and attended the Pritikin Longevity Center & Spa for 12-15 days were studied. Short-term Pritikin therapy improved most CHD risk factors: body mass index decreased by 3% (P<.001); systolic and diastolic blood pressure, and serum glucose and low-density lipoprotein cholesterol concentrations decreased by 10%-15% (P<.001); serum triglyceride concentration decreased by 36% (P<.001); and 37% of subjects no longer met National Cholesterol Education Program criteria for the metabolic syndrome. Serum high-density lipoprotein cholesterol, however, decreased by 3% (P<.05). These data demonstrate that brief treatment with a very-low-fat, low-sodium, high-fiber diet and regular exercise simultaneously improves multiple CHD risk factors in patients with the metabolic syndrome.

"Renal dose" dopamine is associated with the risk of new-onset atrial fibrillation after cardiac surgery.

OBJECTIVE: "Renal dose" dopamine (rDA; 1-3 microg/kg per min) is administered to patients after cardiac surgery to preserve or improve renal function. Many of these patients develop new-onset postoperative atrial fibrillation or atrial flutter (pAF) that could be related to rDA administration. The objective of this investigation was to determine whether there was an association between rDA and new-onset pAF in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CABG). SETTING: Research hospital. SUBJECTS: The study population consisted of 1,731 patients undergoing CABG. INTERVENTIONS: CABG with and without rDA. DESIGN: After approval by the institutional review board, a retrospective study using the Cardiothoracic Anesthesia Patient Registry was undertaken to determine the association between rDA and pAF in patients undergoing CABG. Patients with a documented history of atrial fibrillation, those who required inotrope use during or after surgery, and those having valve surgery were excluded. MEASUREMENTS AND MAIN RESULTS: One-thousand seven-hundred thirty-one patients undergoing CABG during the period of January 1, 2000, through June 30, 2002, were the study population; of these, 15.0% (260/1,731) developed pAF. The incidence of pAF was 23.3 % (41/176) among patients who received rDA and 14.1% (219/1,555) among those who did not receive rDA. In the multivariable logistic regression model, patient age, gender, chronic obstructive pulmonary disease or asthma, and rDA were associated with pAF (p < .01). Receipt of rDA increased the odds of developing pAF by 74%, independent of the effect of other variables. CONCLUSIONS: Renal-dose dopamine is associated with a 1.74 odds ratio of pAF developing after CABG.

The comparative hemodynamic effects of methohexital and remifentanil in electroconvulsive therapy.

Remifentanil is a short acting opioid frequently used to supplement general anesthesia for brief procedures. Narcotic agents are known for their ability to blunt autonomic responses to stimuli such as laryngoscopy and intubation and do not alter seizure threshold. We hypothesized that the combination of remifentanil and methohexital for induction would produce favorable suppression of sympathetic response during electroconvulsive therapy (ECT). With Institutional Review Board approval and informed consent, patients were enrolled in a prospective, randomized, double-blind, crossover study of methohexital alone versus remifentanil with an adjuvant of low-dose methohexital. One hundred ten ECT treatments were evaluated and subjects were treated in an alternating fashion with one of two induction protocols: Methohexital alone in an 80-100 mg IV bolus or remifentanil 500 mcg IV bolus combined with methohexital 40 mg IV. Bilateral ECT was performed in standard fashion and systolic blood pressure and heart rate were recorded throughout the procedure. No significant differences were found in baseline hemodynamic values between the two groups. Heart rate was significantly lower in the remifentanil group versus methohexital group at one minute post-induction and just prior to ECT stimulus. Pre-ECT systolic blood pressure was not significantly different between the two groups. Heart rate remained lower in the remifentanil group at all measured timepoints during the treatment and continuously for five minutes after the seizure. Systolic blood pressure was significantly lower at one minute following the end of seizure and five minutes after end of seizure. Remifentanil's short duration of action, favorable side effect profile, potential proconvulsant activity and ability to suppress hemodynamic response make it a potential novel drug for ECT induction.