Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial.

Importance: Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies. Objective: To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure. Design, Setting, and Participants: A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19-related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021. Interventions: Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475). Main Outcomes and Measures: The primary outcome was a composite of tracheal intubation or mortality within 30 days. Results: The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, -8% [95% CI, -15% to -1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, -1% [95% CI, -8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group. Conclusions and Relevance: Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings. Trial Registration: isrctn.org Identifier: ISRCTN16912075.

Inflatable penile prosthesis outcomes after pelvic radiation.

INTRODUCTION Few studies have compared surgical outcomes after 3-piece inflatable penile prosthesis (IPP) surgery in patients exposed to pelvic radiation therapy (RT) compared to a radiation naïve control group. MATERIALS AND METHODS: A total of 715 consecutive patients underwent 3-piece IPP placement between 2007-2018. There were 101 men exposed to pelvic RT before or after IPP for a variety of malignancies and 153 men met inclusion criteria for the control group, which included men undergoing IPP surgery with a history of radical prostatectomy but no exposure to pelvic RT. RESULTS: Patients in the RT group had a higher body mass index (kg/m²) (28.7 versus 27.8, p = 0.003) and higher Charlson co-morbidity index score (6 versus 5; p < 0.001). At a median follow up of 5 years (IQR 2-8 years), there was an 18.4% surgical complication rate in the radiation group compared to 11.5% in the control group, though this was not statistically significant (p = 0.141). Timing of radiation, prior artificial urinary sphincter (AUS) status, co-implantation of an AUS, and brand of prosthesis were not associated with increased rate of complications. On multivariable logistic regression analysis, exposure to RT was not significantly associated with increased risks of complications (OR: 1.31; CI 0.55-3.12). CONCLUSIONS: This study shows no significant increase in risk of surgical complication in patients exposed to pelvic RT and supports the use of IPP in men with a history of RT and refractory erectile dysfunction.

Adapting to domiciliary non-invasive ventilation in chronic obstructive pulmonary disease: a qualitative interview study.

BACKGROUND: Domiciliary non-invasive ventilation may be used in palliative care of patients with chronic obstructive pulmonary disease, although there is uncertainty regarding effect on quality of life. AIM: Explore experiences of domiciliary non-invasive ventilation in chronic obstructive pulmonary disease, to understand decision-making processes and improve future palliative care. DESIGN: Qualitative interview study, based on constructivist grounded theory, and using the framework method for data management and analysis. PARTICIPANTS: 20 chronic obstructive pulmonary disease patients, 4 carers and 15 healthcare professionals. RESULTS: Most patients had very severe chronic obstructive pulmonary disease. Data were categorised into four domains - clinical, technical, socio-economic and experiential. Healthcare professionals felt uncertain regarding clinical evidence, emphasising social support and tolerance as deciding factors in non-invasive ventilation use. Conversely, patients reported symptomatic benefit, which generally outweighed negative experiences and led to continued use. Healthcare professionals felt that patients chose to be on non-invasive ventilation; however, most patients felt that they had no choice as healthcare professionals recommended non-invasive ventilation or their poor health mandated it. CONCLUSIONS: Our study identifies 'adapting to non-invasive ventilation' as the central process enabling long-term use in palliative care, although the way in which this is approached by healthcare professionals and patients does not always converge. We present ideas emerging from the data on potential interventions to improve patient experience and adaptation.

Utility of respiratory ward-based NIV in acidotic hypercapnic respiratory failure.

BACKGROUND AND OBJECTIVE: We sought to elicit predictors of in-hospital mortality for first and subsequent admissions with acidotic hypercapnic respiratory failure (AHRF) in a cohort of chronic obstructive pulmonary disease patients who have undergone ward-based non-invasive ventilation (NIV), and identify features associated with long-term survival. METHODS: Analysis of prospectively collected data at a single centre on patients undergoing NIV for AHRF between 2004 and 2009. Predictors of in-hospital mortality and intubation were sought by logistic regression and predictors of long-term survival by Cox regression. RESULTS: Initial pH exhibited a threshold effect for in-hospital mortality at pH 7.15. This relationship remained in patients undergoing their first episode of AHRF. In both first and subsequent admissions, a pH threshold of 7.25 at 4 h was associated with better prognosis (P = 0.02 and P = 0.04 respectively). In second or subsequent episodes of AHRF, mortality was lower and predicted only by age (P = 0.002) on multivariate analysis. CONCLUSIONS: NIV could be used on medical wards for patients with pH 7.16 or greater on their first admission, although more conservative values should continue to be used for those with a second or subsequent episodes of AHRF.

Development and Relevance of Hypercapnia in COPD.

Background: Identification of patients who may become hypercapnic, or develop acidotic hypercapnic respiratory failure (AHRF), is important in chronic obstructive pulmonary disease (COPD) to avoid hospital admission and select patients for use of home NIV. This study aimed to identify factors associated with presence and development of hypercapnia. Methods: 1224 patients, 637 with COPD and 587 with alpha 1 antitrypsin deficiency (AATD), from 4 previously established patient cohorts, were included in cross-sectional analyses of hypercapnia (PaCO2 ≥ 6.5 kPa or 48.8 mmHg), focusing on phenotypic features of COPD and mortality. Longitudinal associations of rising PaCO2 were also assessed. A second cohort of 160 COPD patients underwent sleep studies and 1-year follow-up, analysing in a similar way, incorporating additional information from their sleep studies if appropriate. Results: Hypercapnia was 15 times more common in usual COPD than AATD (p < 0.01) after adjustment for baseline differences by regression. Independent predictors of hypercapnia in COPD included FEV1 and current use of oxygen; these variables, together with lack of emphysema, explained 11% of variance in CO2. Increasing PaCO2 also associated with higher risk of death (p=0.03). 44/160 patients exhibited sleep disordered breathing. The sleep study cohort also showed an association of low FEV1 with hypercapnia. Prior hospital admission for AHRF was also clinically significant, being a feature of almost double the number of hypercapnic patients in both test and sleep study COPD cohorts. Conclusion: Lower FEV1 and prior AHRF are the main associations of hypercapnia in COPD, which carries a poor prognosis, particularly worsening over time.

Neurogenic bladder is an independent risk factor for complications associated with inflatable penile prosthesis implantation.

Men with neurogenic bladder (NGB) often have concomitant erectile dysfunction and may be considered for inflatable penile prosthesis (IPP) placement. However, it is unclear if NGB is a risk factor for complications associated with IPP placement. The aim of this study is to compare surgical outcomes after IPP placement in a contemporary cohort of patients with NGB to that of a non-neurogenic control group. To accomplish this, consecutive records of patients who underwent IPP implantation between 2007 and 2018 were retrospectively reviewed. Patients with a known neurologic lesion and documented NGB by clinical or urodynamic criteria were compared with a non-neurogenic control group of men with erectile dysfunction. We found that patients in the NGB cohort were younger (median age 48 vs. 62 years, p < 0.001) and less likely to void spontaneously prior to surgery (3% vs. 97%, p < 0.001). The most common cause for NGB was spinal cord injury (46%). There was a 24.3% overall rate of complication (infection, erosion, or mechanical failure) in the NGB cohort compared with a 7.5% rate in the non-neurogenic control group (p = 0.001). On multivariate logistic regression modeling, NGB (OR 3.47; 95% CI 1.13-10.71; p = 0.03) was independently associated with risk of IPP complication. First time penile prosthesis was associated with lower risk of IPP complication (OR 0.25 95% CI 0.09-0.71; p = 0.01). In conclusion, patients with NGB are at increased risk for complications after IPP placement. Patients should be counseled accordingly, and all efforts should be made to stabilize bladder function prior to surgery.

Quality Improvement Foley Project to Reduce Catheter-Related Trauma in a Large Community Hospital.

Indwelling catheter placement is a modifiable risk factor for urethral trauma. We implemented a multidisciplinary Foley Project protocol in June 2015, which consisted of a system-wide catheter education program, difficult urinary catheterization (DUC) algorithm, and skilled catheter nursing team to improve patient outcomes. A retrospective review of male DUC consults between June 2014 and September 2015 was performed. The preprotocol group includes consults received from June 2014 to May 2015. The postprotocol group includes consults received from June 2015 to September 2015. There were 74 patients in the preprotocol and 18 patients in the postprotocol group. The overall incidence rates of catheter-associated trauma during placement were 41.1% in the preprotocol and 5.9% in the postprotocol groups (p = .005). In the preprotocol group, 53.4% required a procedure by a urologist, whereas only 11.8% of patients in the postprotocol group required a procedure (p = .002). The Foley Project protocol reduced the frequency of catheter-associated trauma and procedures.

A Retrospective Comparative Outcomes and Cost Analysis of Office Based, Ultrasound Guided Renal Mass Biopsy Performed by Urologists and Standard Hospital Biopsies for Small Renal Masses.

INTRODUCTION: Renal mass biopsy is useful in the evaluation of small renal masses. We have previously reported that office based, ultrasound guided renal mass biopsy is safe, effective and feasible when performed by urologists. This study compares office based, ultrasound guided renal mass biopsy performed by urologists and hospital based renal mass biopsy. METHODS: We retrospectively studied 70 patients who underwent office based, ultrasound guided renal mass biopsy and 155 who underwent hospital based, ultrasound or computerized tomography guided renal mass biopsy for evaluation of a small renal mass (4.0 cm or less) between January 2010 and February 2016. RESULTS: A total of 70 patients underwent office based, ultrasound guided renal mass biopsy. Median age in this group was 69.5 years, median body mass index was 29.5 kg/m2 and 61.4% of the patients (43) were male. A total of 103 patients underwent hospital based, ultrasound guided biopsy. Median age in this group was 68.0 years, median body mass index was 29.3 kg/m2 and 53.4% of the patients (55) were male. Finally, 52 patients underwent hospital based, computerized tomography guided biopsy. Median age in this group was 69 years, median body mass index was 30.1 kg/m2 and 51.9% of the patients (27) were male. Median tumor size was 2.7 cm in patients undergoing office based, ultrasound guided renal mass biopsy, 2.2 cm in those undergoing hospital based, ultrasound guided biopsy and 2.1 cm in those undergoing hospital based, computerized tomography guided biopsy (p = 0.001). Renal cell carcinoma was found in 43 of 70 (61.4%), 74 of 103 (71.8%) and 33 of 52 (63.5%) respective biopsies. Respective diagnostic rates were 81.4% (57 of 70 cases), 88.3% (91 of 103) and 86.5% (45 of 52, p = 0.434). Concordance with surgical pathology was 97.7% (42 of 43 cases), 100% (35 of 35) and 100% (15 of 15), respectively. Complication rates were 4.3% (3 of 70 patients), 13.6% (14 of 103) and 13.5% (7 of 52), respectively (p = 0.096). Cost analysis revealed that when available, office based, ultrasound guided renal mass biopsy provides the health care system a total savings of approximately $46,011 yearly. CONCLUSIONS: Office based, ultrasound guided renal mass biopsy for small renal masses is a safe and efficacious option for select patients, and potentially offers greater convenience and availability as well as decreased health care costs.

Office-based Ultrasound-guided Renal Core Biopsy Is Safe and Efficacious in the Management of Small Renal Masses.

OBJECTIVE: To evaluate the safety and efficacy of ultrasound (US)-guided percutaneous renal mass biopsy (RMB) performed in the office setting by urologists. MATERIALS AND METHODS: This is a retrospective study involving patients who underwent office-based US-guided percutaneous RMB between April 2010 and October 2015. Baseline vital signs and US were performed prior to the procedure. Patients were then observed for 1 hour after the procedure and repeat vital signs and US were performed. Hemodynamically stable patients who did not develop hematoma were discharged. RESULTS: In 108 patients, 70 (64.8%) were male, median age was 69.5 years, and median mass size was 3.3 cm (interquartile range: 2.5-4.6). Biopsy yield was as follows: 72 (66.7%) had renal cell carcinoma, 14 (13.0%) had benign renal parenchyma, 11 (10.2%) had oncocytoma, 6 (5.6%) had angiomyolipoma, 2 (1.9%) had lymphoma, and 3 (2.8%) had other disease. The initial nondiagnostic rate was 14 of 108 (13.0%). There were 28 of 108 (25.9%) patients observed whereas 79 of 108 (73.2%) received surgery or ablative therapy. Final pathology was concordant with biopsy results in 66 of 68 (97.1%) cases. Three patients experienced a grade I Clavien-Dindo surgical complication, all of which were managed conservatively. CONCLUSION: Office-based US-guided RMB is safe and efficacious in the management of appropriately selected SRM. It potentially offers improved dynamic characterization of solid renal mass, greater convenience to patients, as well as cost savings. Further studies are needed to evaluate this promising technique.

Robot-Assisted Laparoscopic Nephroureterectomy for Transitional Cell Carcinoma of a Right Pelvic Kidney.

BACKGROUND: Nephroureterectomy is the standard of care for transitional cell carcinoma (TCC) involving the upper urinary tract. However, few published case reports exist describing the surgical treatment of ectopic kidneys with TCC. Surgical removal of a pelvic kidney can be complicated by aberrant vasculature supply, a tortuous ureter and abutting anatomical structures. Thus, it is necessary to determine the most appropriate surgical technique for treatment of pelvic kidneys with suspected malignancy. CASE PRESENTATION: A 65-year-old female who presented with hematuria and lower abdominal pain was found to have a right pelvic kidney with a heterogeneous mass on computed tomography (CT) urogram. A robot-assisted laparoscopic nephroureterectomy of the right pelvic kidney was performed. Histopathological analysis revealed high-grade TCC with microscopic extension through the muscularis propria of the renal pelvis and superficially into the renal parenchyma. CONCLUSION: This case demonstrates the successful use of robot-assisted laparoscopic nephroureterectomy in the treatment of a pelvic kidney with TCC. Preoperative CT angiography is critical to define vascular anatomy and to prevent significant blood loss and damage to surrounding structures during surgery. This case was presented because TCC of a pelvic kidney is a rare occurrence and the use of robot-assisted nephroureterectomy for treatment of this disease is novel.

The effect of domiciliary noninvasive ventilation on clinical outcomes in stable and recently hospitalized patients with COPD: a systematic review and meta-analysis.

INTRODUCTION: Noninvasive ventilation (NIV) improves survival among patients with hypercapnic respiratory failure in hospital, but evidence for its use in domiciliary settings is limited. A patient's underlying risk of having an exacerbation may affect any potential benefit that can be gained from domiciliary NIV. This is the first comprehensive systematic review to stratify patients based on a proxy for exacerbation risk: patients in a stable state and those immediately post-exacerbation hospitalization. METHODS: A systematic review of nonrandomized and randomized controlled trials (RCTs) was undertaken in order to compare the relative effectiveness of different types of domiciliary NIV and usual care on hospital admissions, mortality, and health-related quality of life. Standard systematic review methods were used for identifying studies (until September 2014), quality appraisal, and synthesis. Data were presented in forest plots and pooled where appropriate using random-effects meta-analysis. RESULTS: Thirty-one studies were included. For stable patients, there was no evidence of a survival benefit from NIV (relative risk [RR] 0.88 [0.55, 1.43], I2=60.4%, n=7 RCTs), but there was a possible trend toward fewer hospitalizations (weighted mean difference -0.46 [-1.02, 0.09], I2=59.2%, n=5 RCTs) and improved health-related quality of life. For posthospital patients, survival benefit could not be demonstrated within the three RCTs (RR 0.89 [0.53, 1.49], I2=25.1%), although there was evidence of benefit from four non-RCTs (RR 0.45 [0.32, 0.65], I2=0%). Effects on hospitalizations were inconsistent. Post hoc analyses suggested that NIV-related improvements in hypercapnia were associated with reduced hospital admissions across both populations. Little data were available comparing different types of NIV. CONCLUSION: The effectiveness of domiciliary NIV remains uncertain; however, some patients may benefit. Further research is required to identify these patients and to explore the relevance of improvements in hypercapnia in influencing clinical outcomes. Optimum time points for commencing domiciliary NIV and equipment settings need to be established.

Innovative use of intravesical tacrolimus for hemorrhagic radiation cystitis.

Hemorrhagic cystitis is a rare and severe late complication of pelvic radiation, and there is no regulatory-approved drug treatment. We present an 81-year-old man with a history of localized prostate cancer, which was treated with external beam radiation therapy and subsequently developed severe hemorrhagic radiation cystitis for which he has failed several treatments. We present the novel use of intravesical tacrolimus for the treatment of refractory radiation cystitis and gross hematuria. The patient tolerated the treatment well, and it resulted in the resolution of his gross hematuria without further consideration for formalin instillation or cystectomy and diversion. Intravesical tacrolimus is a safe, minimally invasive, and promising treatment option for radiation hemorrhagic cystitis.

The cost-effectiveness of domiciliary non-invasive ventilation in patients with end-stage chronic obstructive pulmonary disease: a systematic review and economic evaluation.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic progressive lung disease characterised by non-reversible airflow obstruction. Exacerbations are a key cause of morbidity and mortality and place a considerable burden on health-care systems. While there is evidence that patients benefit from non-invasive ventilation (NIV) in hospital during an acute exacerbation, evidence supporting home use for more stable COPD patients is limited. In the U.K., domiciliary NIV is considered on health economic grounds in patients after three hospital admissions for acute hypercapnic respiratory failure. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of domiciliary NIV by systematic review and economic evaluation. DATA SOURCES: Bibliographic databases, conference proceedings and ongoing trial registries up to September 2014. METHODS: Standard systematic review methods were used for identifying relevant clinical effectiveness and cost-effectiveness studies assessing NIV compared with usual care or comparing different types of NIV. Risk of bias was assessed using Cochrane guidelines and relevant economic checklists. Results for primary effectiveness outcomes (mortality, hospitalisations, exacerbations and quality of life) were presented, where possible, in forest plots. A speculative Markov decision model was developed to compare the cost-effectiveness of domiciliary NIV with usual care from a UK perspective for post-hospital and more stable populations separately. RESULTS: Thirty-one controlled effectiveness studies were identified, which report a variety of outcomes. For stable patients, a modest volume of evidence found no benefit from domiciliary NIV for survival and some non-significant beneficial trends for hospitalisations and quality of life. For post-hospital patients, no benefit from NIV could be shown in terms of survival (from randomised controlled trials) and findings for hospital admissions were inconsistent and based on limited evidence. No conclusions could be drawn regarding potential benefit from different types of NIV. No cost-effectiveness studies of domiciliary NIV were identified. Economic modelling suggested that NIV may be cost-effective in a stable population at a threshold of £30,000 per quality-adjusted life-year (QALY) gained (incremental cost-effectiveness ratio £28,162), but this is associated with uncertainty. In the case of the post-hospital population, results for three separate base cases ranged from usual care dominating to NIV being cost-effective, with an incremental cost-effectiveness ratio of less than £10,000 per QALY gained. All estimates were sensitive to effectiveness estimates, length of benefit from NIV (currently unknown) and some costs. Modelling suggested that reductions in the rate of hospital admissions per patient per year of 24% and 15% in the stable and post-hospital populations, respectively, are required for NIV to be cost-effective. LIMITATIONS: Evidence on key clinical outcomes remains limited, particularly quality-of-life and long-term (> 2 years) effects. Economic modelling should be viewed as speculative because of uncertainty around effect estimates, baseline risks, length of benefit of NIV and limited quality-of-life/utility data. CONCLUSIONS: The cost-effectiveness of domiciliary NIV remains uncertain and the findings in this report are sensitive to emergent data. Further evidence is required to identify patients most likely to benefit from domiciliary NIV and to establish optimum time points for starting NIV and equipment settings. FUTURE WORK RECOMMENDATIONS: The results from this report will need to be re-examined in the light of any new trial results, particularly in terms of reducing the uncertainty in the economic model. Any new randomised controlled trials should consider including a sham non-invasive ventilation arm and/or a higher- and lower-pressure arm. Individual participant data analyses may help to determine whether or not there are any patient characteristics or equipment settings that are predictive of a benefit of NIV and to establish optimum time points for starting (and potentially discounting) NIV. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012003286. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Protocol for a systematic review and economic evaluation of the clinical and cost-effectiveness of non-hospital-based non-invasive ventilation (NIV) in patients with stable end-stage COPD with hypercapnic respiratory failure.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) remains a significant public health burden. Non-invasive ventilation (NIV) is a method of supported breathing used as standard care for acutely unwell patients in hospital with COPD, but there is uncertainty around the potential benefits of using NIV in the treatment of stable patients in a non-hospital setting. This is a protocol for systematic reviews of the clinical and cost-effectiveness of NIV in this context, being undertaken in support of a model based economic evaluation. METHODS/DESIGN: Standard systematic review methods aimed at minimising bias will be employed for study identification, selection and data extraction for both the clinical and economic systematic reviews. Bibliographic databases (for example MEDLINE, EMBASE) and ongoing trials registers will be searched from 1980 onwards. The search strategy will combine terms for the population with those for the intervention. Studies will be selected for review if the population includes adult patients with COPD and hypercapnic respiratory failure, however defined. Systematic reviews, randomised controlled trials and observational studies (with n >1) will be included, and quality assessment will be tailored to the different study designs. The primary outcome measures of interest are survival, quality of life, and healthcare utilisations (hospitalisation and Accident and Emergency attendances). Meta-analyses will be undertaken where clinical and methodological homogeneity exists, supported by predefined subgroup analyses where appropriate. A systematic review of the evidence on the cost-effectiveness of non-hospital NIV will be completed, and a model-based cost-utility analysis undertaken to determine the cost-effectiveness of non-hospital-based NIV compared with standard care. DISCUSSION: These reviews will attempt to clarify the clinical effectiveness of non-hospital NIV in COPD patients as well as the cost-effectiveness. The findings may indicate whether NIV in a non-hospital setting should be considered more routinely in this patient group, and what the likely cost implications will be. PROSPERO REGISTRATION: 2012:CRD42012003286.