Protein-Protein interactive networks identified in bronchoalveolar lavage of severe compared to nonsevere asthma.

INTRODUCTION: Previous bronchoalveolar lavage fluid (BALF) proteomic analysis has evaluated limited numbers of subjects for only a few proteins of interest, which may differ between asthma and normal controls. Our objective was to examine a more comprehensive inflammatory biomarker panel in quantitative proteomic analysis for a large asthma cohort to identify molecular phenotypes distinguishing severe from nonsevere asthma. METHODS: Bronchoalveolar lavage fluid from 48 severe and 77 nonsevere adult asthma subjects were assessed for 75 inflammatory proteins, normalized to BALF total protein concentration. Validation of BALF differences was sought through equivalent protein analysis of autologous sputum. Subjects' data, stratified by asthma severity, were analysed by standard statistical tests, principal component analysis and 5 machine learning algorithms. RESULTS: The severe group had lower lung function and greater health care utilization. Significantly increased BALF proteins for severe asthma compared to nonsevere asthma were fibroblast growth factor 2 (FGF2), TGFα, IL1Ra, IL2, IL4, CCL8, CCL13 and CXCL7 and significantly decreased were platelet-derived growth factor a-a dimer (PDGFaa), vascular endothelial growth factor (VEGF), interleukin 5 (IL5), CCL17, CCL22, CXCL9 and CXCL10. Four protein differences were replicated in sputum. FGF2, PDGFaa and CXCL7 were independently identified by 5 machine learning algorithms as the most important variables for discriminating severe and nonsevere asthma. Increased and decreased proteins identified for the severe cluster showed significant protein-protein interactions for chemokine and cytokine signalling, growth factor activity, and eosinophil and neutrophil chemotaxis differing between subjects with severe and nonsevere asthma. CONCLUSION: These inflammatory protein results confirm altered airway remodelling and cytokine/chemokine activity recruiting leukocytes into the airways of severe compared to nonsevere asthma as important processes even in stable status.

Zio® XT Patches in Pediatrics During the COVID-19 Pandemic: Comparisons Between In-Person and Mail-Home Application.

The Zio® (Zio) XT Patch is a 14-day continuous ambulatory ECG monitor. During the Covid-19 pandemic, Zios were mailed directly to patients for self-application. The purpose of this study was to compare the percent artifact, a marker for quality, of in-clinic (IC) to mail-home (MH) applications in a pediatric population. A single-center, IRB-approved study of patients 0- < 21 years of age with Zios was studied for wear and artifact time filtered out based on iRhythm's proprietary algorithm. In total, 284 Zios were randomly selected and analyzed for total wear time and artifact. Of these, 149 were IC prior to 12/31/2019 and 135 MH patches prescribed after 1/1/2020. No significant difference was found for percent artifact between the IC (7.8%) and MH (8.3%) group. Average IC wear-time was 127 h compared to MH at 99 h (p = 0.02). In conclusion, application of Zio patches outside of the pediatric cardiology clinic offers equivalent artifact, a marker of quality, as those applied in clinic and should be consideration as a viable alternative.

Minimizing Device-Device Interactions Using Bipolar Pacemaker Leads in a Pediatric Patient.

Phrenic nerve injury can lead to a disruption of the autonomic nervous system (ANS) resulting in episodes of bradycardic arrest. Implanted diaphragmatic pacing has been used to overcome phrenic nerve paralysis, but these do not change the ANS. Therefore, patients with phrenic nerve paralysis may require the implantation of a permanent cardiac pacemaker to overcome bradycardic episodes. Having two electronic devices in the same patient may lead to device-device interaction (DDI). This can result in over-sensing leading to lack of pacing of either device. We present the case of a 17-year-old pediatric male with phrenic nerve injury who required implantation of both diaphragm and cardiac pacemaker. Intra-procedural interrogation of the cardiac pacemaker demonstrated DDI in unipolar mode, but not in bipolar. Thus, we demonstrated the safe utilization of multiple implantable electronic devices in the pediatric patient without device-device interaction.

Trends in Incidence and Outcomes of Clostridium difficile Colitis in Hospitalized Patients of Febrile Neutropenia: A Nationwide Analysis.

INTRODUCTION: Clostridium difficile infection (CDI) has been attracting attention lately as the most common hospital acquired infection. Patients with neutropenia because of malignancy seem to be at an increased risk for developing CDI. There is currently limited data that assesses the national burden and outcomes of CDI in Febrile Neutropenia (FN). METHODS: We analyzed the National Inpatient Sample (NIS) database for all subjects with discharge diagnosis of FN with or without CDI (ICD-9 codes 288.00, 288.03,780.60, and 008.45) as primary or secondary diagnosis during the period from 2008 to 2014. All analyses were performed with SAS, version 9.4 (SAS Institute). RESULTS: From 2008 to 2014 there were total 19422 discharges of FN patients with CDI. There was a rising incidence of CDI in patients with FN from 4.11% (in 2008) to 5.83% (in 2014). The In-hospital mortality showed a decreasing trend from 7.79% (in 2008) to 5.32% (in 2014), likely because of improvements in diagnostics and treatment. The overall mortality (6.37% vs. 4.61%), length of stay >5 days (76.45% vs. 50.98%), hospital charges >50,000 dollars (64.43% vs. 40.29%), colectomy and colostomy (0.35% vs. 0.15%), and discharge to skilled nursing facility (10.47% vs. 6.43%) was significantly more in FN patients with CDI versus without CDI over 7 years (2008 to 2014). Age above 65 years, Hispanic race, hematological malignancies, urban hospital settings, and sepsis were significant predictors of mortality in febrile neutropenia patients with CDI. DISCUSSION: Despite the significant decrease in mortality, the incidence of CDI is rising in hospitalized FN patients with underlying hematological malignancies. Risk factor modification, with the best possible empiric antibiotic regimen is imperative for reducing mortality and health care costs in this cohort.

Development of a patient and institutional-based model for estimation of operative times for robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium.

OBJECTIVES: To design a methodology to predict operative times for robot-assisted radical cystectomy (RARC) based on variation in institutional, patient, and disease characteristics to help in operating room scheduling and quality control. PATIENTS AND METHODS: The model included preoperative variables and therefore can be used for prediction of surgical times: institutional volume, age, gender, body mass index, American Society of Anesthesiologists score, history of prior surgery and radiation, clinical stage, neoadjuvant chemotherapy, type, technique of diversion, and the extent of lymph node dissection. A conditional inference tree method was used to fit a binary decision tree predicting operative time. Permutation tests were performed to determine the variables having the strongest association with surgical time. The data were split at the value of this variable resulting in the largest difference in means for the surgical time across the split. This process was repeated recursively on the resultant data sets until the permutation tests showed no significant association with operative time. RESULTS: In all, 2 134 procedures were included. The variable most strongly associated with surgical time was type of diversion, with ileal conduits being 70 min shorter (P < 0.001). Amongst patients who received neobladders, the type of lymph node dissection was also strongly associated with surgical time. Amongst ileal conduit patients, institutional surgeon volume (>66 RARCs) was important, with those with a higher volume being 55 min shorter (P < 0.001). The regression tree output was in the form of box plots that show the median and ranges of surgical times according to the patient, disease, and institutional characteristics. CONCLUSION: We developed a method to estimate operative times for RARC based on patient, disease, and institutional metrics that can help operating room scheduling for RARC.

Evaluation of robotic and laparoscopic partial nephrectomy for small renal tumours (T1a).

OBJECTIVE: To compare laparoscopic partial nephrectomy (LPN) with robotic PN (RPN) using meta-analytical techniques, since there has been a rise in the incidence of small renal masses (SRM; <4 cm) minimally invasive approaches are becoming more popular in dealing with such pathologies. MATERIALS AND METHODS: A systematic review of the literature was performed to identify studies comparing LPN and RPN. Comparative studies evaluating RPN and LPN that fulfilled the inclusion criteria were selected. Data on preoperative, operative (operative time, estimated blood loss [EBL], and warm ischaemia time [WIT]), postoperative (length of stay [LOS]) variables and complications were collected. A meta-analysis using random effect model was performed. A further Bland-Altman analysis of some of the operative variables was done to compare their reproducibility and mean difference in techniques. RESULTS: Six studies matched the selection criteria. In all, 256 patients were analysed (40% RPN and 60% LPN). There was no significant different in EBL (P = 0.12, 95% confidence interval [CI] -12.01 to 104.26). Similarly, there was no significant different in WIT between the groups (P = 0.23, 95% CI -15.22 to 3.70). Also, LOS (P = 0.22, 95% CI -0.38 to 0.09) and overall postoperative complication rates were not significantly different between the groups (P = 0.84, 95% CI -0.05 to 0.06). CONCLUSIONS: Despite multiple studies reporting better perioperative variables for RPN, the present study found no significant differences between RPN and LPN. This has implications for both the surgeon and the patient. Lack of randomised controlled trials in addition to a lack of long-term oncological data for RPN are current limitations.

Nerve growth factor (NGF): a potential urinary biomarker for overactive bladder syndrome (OAB)?

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The search for a biomarker in overactive bladder syndrome (OAB) is an emerging field of interest, as bladder dysfunction is a common complaint that causes significant morbidity. A biomarker may give us insight as a diagnostic tool, and also inform us about how severe the condition is, how it may progress and how it may best be treated. The protein of interest here is nerve growth factor (NGF) and it has been shown to be a dynamic molecule in the bladder of patients with OAB. Urinary levels have been seen to rise in patients with OAB and fall in those who respond to treatment. However, there have also been many studies that examine this trend in numerous other conditions, e.g. interstitial cystitis, bladder outflow obstruction, renal stone disease and patients with neurological impairment after stroke. As a result the specificity of this as a potential urinary biomarker for OAB is questioned. This is a review of published studies, which discusses the pros and cons of NGF as a potential urinary biomarker. The evidence is examined and the studies are summarised together in a Table. Questions remain about the reliability, practicality and specificity of NGF as a biomarker for OAB. These questions need to be addressed by further studies that could clarify the points raised. OBJECTIVE: To review the current literature on the use of urinary nerve growth factor (NGF) as a potential biomarker for overactive bladder syndrome (OAB). METHOD: A comprehensive electronic literature search was conducted using the PubMed database to identify publications relating to urinary NGF. RESULTS: There are a growing number of publications that have measured urinary NGF levels in different types of bladder dysfunction. These range from OAB, bladder pain syndrome, idiopathic and neurogenic detrusor overactivity, bladder oversensitivity and bladder outflow obstruction. Urinary NGF levels do appear to be raised in these pathological states when compared with healthy control samples. In patients with OAB, these raised urinary NGF levels appear to also reduce after successful treatment with antimuscarinics and botulinum toxin A, which indicates a potential use in monitoring responses to treatment. However, raised levels are not limited to OAB, which questions its specificity. Urinary NGF measurements are performed with an enzyme-linked immunosorbent assay using polyclonal antibodies to NGF. The technique requires standardisation, and the different antibodies to NGF require validating. Also a definition of what is the 'normal' range of NGF in urine is still required before it can be used as a diagnostic and prognostic tool. CONCLUSIONS: Whilst the evidence for an increased urinary NGF in OAB appears convincing, many questions about its validity remain including: specificity, sensitivity, cost- and time-effectiveness. Many criteria for what constitutes a biomarker still need to be evaluated and met before this molecule can be considered for this role.

Prevalence and antimicrobial susceptibility of Acinetobacter spp. in a tertiary care hospital in Peshawar: a cross-sectional study.

Acinetobacter spp. have been a primary cause of nosocomial infections worldwide, causing significant morbidity and mortality, especially in Pakistan. The purpose of this study was to investigate the trend of antimicrobial resistance over a 5-year period in a tertiary care hospital in Pakistan. Methods: A retrospective cross-sectional study regarding the occurrence and antimicrobial resistance of Acinetobacter spp. recovered from clinical specimens that were referred to the Pathology Laboratory of Northwest General Hospital, Peshawar. The data from 2014 to 2019 was recorded and analyzed by the laboratory. Sociodemographic characteristics and laboratory record data was analyzed using SPSS, version 25. A chi-square test was applied to see the significance. Results: Of 59 483 clinical samples, Acinetobacter baumannii strains were detected in 114 of them. The majority of the clinical samples were from blood (89.5%) followed by sputum (7.9%), wound swab (1.8%), and bone marrow (0.9%). A. baumannii has been found in 52 men (67.53%) and 28 women (75.67%), with an overall risk of 0.669 times. In 76 men (98.70%), sensitivity for ertapenem (99.1), colistin (96.49), and tigecycline (78.9%) were also observed which indicated the potential viability of these drugs to treat multidrug-resistant (MDR) Acinetobacter infections. The male-to-female risk ratio was 0.98 for colistin and 0.71 for amikacin. Conclusion: Increased frequency of MDR supports the need for continuous surveillance to determine the prevalence and evolution of MDR Acinetobacter spp. in Pakistan. Colistin, tigecyclines, and ertapenem remain the possible line of drugs to treat MDR Acinetobacter.

Differences in treatment and outcomes among patients with ST-segment elevation myocardial infarction with and without standard modifiable risk factors: a systematic review and meta-analysis.

There are limited data available on outcomes and pathophysiology behind ST-segment elevation myocardial infarction (STEMI) in populations without standard modifiable risk factors (SMuRFs). The authors carried out this meta-analysis to understand the differences in treatment and outcomes of STEMI patients with and without SMuRFs. Methods: A systematic database search was performed for relevant studies. Studies reporting desired outcomes among STEMI patients with and without SMuRFs were selected based on predefined criteria in the study protocol (PROSPERO: CRD42022341389). Two reviewers independently screened titles and abstracts using Covidence. Full texts of the selected studies were independently reviewed to confirm eligibility. Data were extracted from all eligible studies via a full-text review of the primary article for qualitative and quantitative analysis. In-hospital mortality following the first episode of STEMI was the primary outcome, with major adverse cardiovascular events (MACE), repeat myocardial infarction (MI), cardiogenic shock, heart failure, and stroke as secondary outcomes of interest. Odds ratio (OR) with a 95% CI was used to estimate the effect. Results: A total of 2135 studies were identified from database search, six studies with 521 150 patients with the first STEMI episode were included in the analysis. The authors found higher in-hospital mortality (OR: 1.43; CI: 1.40-1.47) and cardiogenic shock (OR: 1.59; 95% CI: 1.55-1.63) in the SMuRF-less group with no differences in MACE, recurrent MI, major bleeding, heart failure, and stroke. There were lower prescriptions of statin (OR: 0.62; CI: 0.42-0.91) and Angiotensin converting enzyme inhibitor /Angiotensin II receptor blocker (OR: 0.49; CI: 0.28-0.87) at discharge in SMuRF-less patients. There was no difference in procedures like coronary artery bypass graft, percutaneous coronary intervention, and thrombolysis. Conclusion: In the SMuRF-less STEMI patients, higher in-hospital mortality and treatment discrepancies were noted at discharge.

Breath biomarkers of insulin resistance in pre-diabetic Hispanic adolescents with obesity.

Insulin resistance (IR) affects a quarter of the world's adult population and is a major factor in the pathogenesis of cardio-metabolic disease. In this pilot study, we implemented a non-invasive breathomics approach, combined with random forest machine learning, to investigate metabolic markers from obese pre-diabetic Hispanic adolescents as indicators of abnormal metabolic regulation. Using the ReCIVA breathalyzer device for breath collection, we have identified a signature of 10 breath metabolites (breath-IR model), which correlates with Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (R = 0.95, p < 0.001). A strong correlation was also observed between the breath-IR model and the blood glycemic profile (fasting insulin R = 0.91, p < 0.001 and fasting glucose R = 0.80, p < 0.001). Among tentatively identified metabolites, limonene, undecane, and 2,7-dimethyl-undecane, significantly cluster individuals based on HOMA-IR (p = 0.003, p = 0.002, and p < 0.001, respectively). Our breath-IR model differentiates between adolescents with and without IR with an AUC-ROC curve of 0.87, after cross-validation. Identification of a breath signature indicative of IR shows utility of exhaled breath metabolomics for assessing systemic metabolic dysregulation. A simple and non-invasive breath-based test has potential as a diagnostic tool for monitoring IR progression, allowing for earlier detection of IR and implementation of early interventions to prevent onset of type 2 diabetes mellitus.

Endovascular Intravascular Lithotripsy in the Treatment of Calcific Common Femoral Artery Disease: A Case Series With an 18-Month Follow-Up.

BACKGROUND: Intravascular lithotripsy (IVL) is a novel endovascular treatment for calcified common femoral artery disease (CFA). Data on midterm effectiveness for clinically driven target lesions revascularization (CD-TLR) is lacking. This study investigated CD-TLR during 18-month follow-up in patients requiring IVL for CFA disease treatment. METHODS: In a single-center retrospective cohort study, electronic medical record of patients undergoing IVL for CFA disease from January 2018 to March 2020 were reviewed. Primary outcome was CD-TLR estimated by Kaplan-Meier method during 18-month follow-up. Univariate logistic regression was used to compare differences in CD-TLR by the type of adjunct therapy used. RESULTS: Among 54 CFA lesions in 50 patients, mean age (SD) was 75(8) years, gender and race were predominantly male (74%, n = 37) and white (94%, n = 47), respectively. Rutherford class III claudication was most common (70%, n = 35) with mean ABI of 0.66 (0.26) and mean angiographic stenosis of 77% (13%). Adjunct use of drug-coated balloon (DCB) angioplasty was 83% (n = 45) and atherectomy was 39% (n = 21). Residual angiographic stenosis was <30% in all cases. Complications included dissection requiring stent placement (2%, n = 1). After 18-months, 18% (n = 9) died unrelated to procedural complications and 6% (n = 3) were lost to follow-up. 18-month cumulative freedom from CD-TLR was 80.6% (95% CI: 69.1%, 92%). Univariate logistic regression did not reveal a statistically significant difference in CD-TLR with type of adjunct therapy used (p > 0.05). CONCLUSION: IVL with adjunct use of DCB and/or atherectomy is safe and effective in treatment of calcified CFA disease. Randomized studies are required to confirm these findings.

DNA nanotechnology for nucleic acid analysis: DX motif-based sensor.

A light on the tiles: A sensor that fluoresces in the presence of specific nucleic acids was designed and characterized. The sensor uses a molecular beacon probe and three adaptor strands to form a five-stranded assembly, a DX-tile, with a specific analyte. This sensor is a highly selective and affordable tool for the real-time analysis of DNA and RNA.

Proceedings of the North American Society of Head and Neck Pathology, Baltimore, MD, March 17, 2021: The Mistakes I Made When I Stepped Out of My Neck of the Woods.

Rapidly growing, symptomatic, non-hematological, malignant neck masses are unusual in young adults. We report a case of a 34-year-old African American male with sickle cell trait who presented with a large left supraclavicular/cervical mass comprising of poorly differentiated malignant epithelial cells consistent with metastatic carcinoma of unknown origin. Upon immunohistochemistry, the tumor showed loss of INI1 (BAF47) and retained PAX-8 expression. After extensive clinical and radiological work-up the primary tumor was found to be a 2.6 cm renal medullary carcinoma. This case highlights the role of multidisciplinary approach to the diagnosis of a neck mass and to understanding that certain genetically-defined tumors can occur at and metastasize to any site.

Type-2 Diabetes as a Risk Factor for Severe COVID-19 Infection.

The current outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed coronavirus disease 2019 (COVID-19), has generated a notable challenge for diabetic patients. Overall, people with diabetes have a higher risk of developing different infectious diseases and demonstrate increased mortality. Type 2 diabetes mellitus (T2DM) is a significant risk factor for COVID-19 progression and its severity, poor prognosis, and increased mortality. How diabetes contributes to COVID-19 severity is unclear; however, it may be correlated with the effects of hyperglycemia on systemic inflammatory responses and immune system dysfunction. Using the envelope spike glycoprotein SARS-CoV-2, COVID-19 binds to angiotensin-converting enzyme 2 (ACE2) receptors, a key protein expressed in metabolic organs and tissues such as pancreatic islets. Therefore, it has been suggested that diabetic patients are more susceptible to severe SARS-CoV-2 infections, as glucose metabolism impairments complicate the pathophysiology of COVID-19 disease in these patients. In this review, we provide insight into the COVID-19 disease complications relevant to diabetes and try to focus on the present data and growing concepts surrounding SARS-CoV-2 infections in T2DM patients.

HVD-LSTM based recognition of epileptic seizures and normal human activity.

In this paper, we detect the occurrence of epileptic seizures in patients as well as activities namely stand, walk, and exercise in healthy persons, leveraging EEG (electroencephalogram) signals. Using Hilbert vibration decomposition (HVD) on non-linear and non-stationary EEG signal, we obtain multiple monocomponents varying in terms of amplitude and frequency. After decomposition, we extract features from the monocomponent matrix of the EEG signals. The instantaneous amplitude of the HVD monocomponents varies because of the motion artifacts present in EEG signals. Hence, the acquired statistical features from the instantaneous amplitude help in identifying the epileptic seizures and the normal human activities. The features selected by correlation-based Q-score are classified using an LSTM (Long Short Term Memory) based deep learning model in which the feature-based weight update maximizes the classification accuracy. For epilepsy diagnosis using the Bonn dataset and activity recognition leveraging our Sensor Networks Research Lab (SNRL) data, we achieve testing classification accuracies of 96.00% and 83.30% respectively through our proposed method.

Breath can discriminate tuberculosis from other lower respiratory illness in children.

Pediatric tuberculosis (TB) remains a global health crisis. Despite progress, pediatric patients remain difficult to diagnose, with approximately half of all childhood TB patients lacking bacterial confirmation. In this pilot study (n = 31), we identify a 4-compound breathprint and subsequent machine learning model that accurately classifies children with confirmed TB (n = 10) from children with another lower respiratory tract infection (LRTI) (n = 10) with a sensitivity of 80% and specificity of 100% observed across cross validation folds. Importantly, we demonstrate that the breathprint identified an additional nine of eleven patients who had unconfirmed clinical TB and whose symptoms improved while treated for TB. While more work is necessary to validate the utility of using patient breath to diagnose pediatric TB, it shows promise as a triage instrument or paired as part of an aggregate diagnostic scheme.

Prevalence and molecular diagnosis of Trypanosoma evansi in Nili-Ravi buffalo (Bubalus bubalis) in different districts of Punjab (Pakistan).

The prevalence of Trypanosoma evansi was investigated in 1,250 Nili-Ravi buffaloes of mixed age and sex by polymerase chain reaction (PCR) for the first time in Pakistan. DNA of the trypanosomes was isolated with TRIREAGENT®. The assay was employed using primers ESAG 6/7, specific for a 237-bp fragment from T. evansi genomic DNA. The samples were screened for the presence of T. evansi also by stained thin smear. Forty-four (3.5%) samples were positive by microscopy, while 97 (7.7%) samples were identified by PCR, indicating the high sensitivity of PCR for surveying the disease in epidemiological studies.

Application of the Kano model to determine quality attributes of patient's care at the primary healthcare centers of the Ministry of Health in Saudi Arabia, 2019.

BACKGROUND: Patient satisfaction is the ultimate goal in any healthcare system. Together with other traditional quality indicators, patient satisfaction must be addressed to improve the quality of health care. The strategic objectives of the Ministry of Health (MOH) formulated by the Saudi National Transformation Program are to improve the quality of healthcare services, expand privatization of governmental services, and create an attractive environment for both local and international investors. The objective of this study was to apply Kano model to determine quality attributes of patient care at primary healthcare centers in Saudi Arabia. MATERIALS AND METHODS: This cross-sectional study was conducted at primary healthcare centers (PHCs) under the MOH in Saudi Arabia between October 2018 and February 2019. Study included all Saudi adult patients aged 18 years or older attending the selected PHCs of MOH. Patients who had difficulty in comprehending were excluded. Data was collected by using a structured questionnaire based on the Kano model for the assessment of patients' expectations of the quality of care and provided services. Data was entered and analysed using SPSS. Chi-square test and t-test were used to test for statistical significance. RESULTS: The study included a total of 243 patients from 10 PHCs, 51% from consulting PHCs and 49% from nonconsulting PHCs. Response rate was 97.2%, and 44.9% respondents were males. Of the 18 attributes chosen for our study, 14 were one-dimensional, three belonged to the attractive type, and one was indifferent type. The top three one-dimensional attributes were "friendliness and respectfulness of the clinic receptionist," "friendliness and respectfulness of the nurses and laboratory staff," and "care and attention of the doctor". CONCLUSION: The investors and policymakers need to turn their attention to assisting in the privatization of governmental services by creating a good climate for both local and international investors.

Improvement in quality of life after botulinum toxin-A injections for idiopathic detrusor overactivity: results from a randomized double-blind placebo-controlled trial.

OBJECTIVE To determine whether botulinum toxin-A (BTX-A) treatment has an effect on the quality of life (QoL) of patients with overactive bladder (OAB) refractory to anticholinergics. PATIENTS AND METHODS This was a single centre, randomized, double-blind, placebo-controlled trial. Participants were men and women with idiopathic detrusor overactivity (IDO). Participants were randomised to receive either 200 U of BTX-A (Botox(R), Allergan Inc., Irvine, CA, USA; n = 16) or placebo (n = 18) via a trigone-sparing flexible cystoscopic technique. QoL was assessed using the King's Health Questionnaire (KHQ) at baseline and at 4 and 12 weeks, after injection. At 12 weeks patients were 'unblinded' and a further open-label follow-up in the BTX-A group occurred at 24 weeks. The changes in the subdomains of the KHQ were assessed over the study period. RESULTS Overall QoL was significantly improved in the BTX-A treated patients compared with placebo in the blinded part of the study. When analysing the KHQ subdomains, 'Incontinence Impact', 'Emotions', 'Physical Limitations', 'Social Limitations' and 'Severity Measures' were significantly improved in those that received BTX-A compared with placebo. The 'Symptom Severity' domain was also significantly improved at 4 weeks but not at 12 weeks. At 12 weeks 'Role Limitations' also became statistically significant in favour of BTX-A. The open-label extension study suggested these benefits last for at least 24 weeks. CONCLUSIONS BTX-A bladder injections at 200 U appear to improve QoL in patients with OAB symptoms and IDO refractory to anticholinergics for at least 24 weeks. As well as the improvement seen in clinical parameters with this form of therapy, perhaps of more importance to the patient, is the improvement in QoL.

Assessment of urodynamic and detrusor contractility variables in patients with overactive bladder syndrome treated with botulinum toxin-A: is incomplete bladder emptying predictable?

OBJECTIVE: To assess whether incomplete bladder emptying and the need for clean intermittent self-catheterization (CISC) is predictable, by analysing urodynamic and detrusor contractility variables in patients treated with botulinum toxin-A (BTX-A) for refractory idiopathic detrusor overactivity (IDO). PATIENTS AND METHODS: Sixty-seven patients (mean age 50.3) with IDO, from two centres, had bladder injections of 200 U BTX-A. Patients with difficulty in emptying their bladder and/or persistent overactive bladder symptoms, with postvoid residual volumes (PVR) of >150 mL after treatment were started on CISC. Urodynamics were conducted at baseline, 4 and 12-16 weeks after injection with BTX-A. Detrusor contractility was assessed using the projected isovolumetric pressure (PIP1) in women and bladder contractility index (BCI) in men. RESULTS: There were improvements in the mean maximum cystometric capacity, bladder compliance and maximum detrusor pressures during filling cystometry after BTX-A injections. The PVR was significantly increased at 4 but not at 12 weeks. Nineteen patients required CISC and when compared with those not needing CISC their pretreatment maximum flow rate (15 vs 22 mL/s, P = 0.003), PIP1 (43 vs 58, P = 0.02) and BCI (113 vs 180, P = 0.001) were lower. Receiver operator characteristic curve analysis suggested that a PIP1 of < or =50 in women (sensitivity 0.83; specificity 0.70; area under the curve 0.822) and BCI < or =120 (sensitivity 0.7; specificity 0.79; area 0.879) might predict the need for CISC. CONCLUSION: The maximum flow rate, PIP1 and BCI were significantly lower in patients who required CISC after BTX-A treatment than in those who did not. A PIP1 of < or =50 in women and a BCI of < or =120 might be predictive of a need for CISC in this setting, and might help when counselling patients.