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In the NLUTD patient with concomitant hematuria, recurrent urinary tract infections, or suspected anatomic anomaly e. This statement is supported by a systematic review Ismail with a serious risk of bias. Any patient with painless gross hematuria requires upper tract imaging i.

SCI patients have a slightly elevated risk of bladder cancer which is especially pronounced after 20 years of disease. In a systematic review of 15 studies encompassing , SCI patients, the only patient factor correlating with bladder cancer was the presence of gross hematuria. Patients with indwelling catheters or those who perform CIC are at risk of urinary tract irritation or catheter trauma as the source of bleeding, but this cannot be determined without cystoscopic investigation. Benign bladder lesions, urethral strictures, or calculi can also be the cause of bleeding and will be effectively diagnosed with a cystoscopy and receive the correct treatment.

Recurrent UTIs are not rare in NLUTD patients, but in this population they can be the result of anatomic defects in the bladder such as foreign bodies or bladder diverticula that can be diagnosed with cystoscopy. NLUTD patients with difficult urethral catheter passage or hematuria with catheterization can have urethral strictures or a false passage from catheter trauma, particularly in those patients with external sphincter spasm during catheter passage.

Cystoscopy can effectively diagnose these conditions and may prompt treatment of a stricture or a change in catheterization technique after careful observation of the patient performing CIC.

Alternatively, in the case that a urethral stricture is highly suspected as the cause of difficult catheter passage, a retrograde urethrogram can make the diagnosis of urethral strictures in male patients. The evidence base supporting statements nineteen and twenty are shared based on identified studies enrolling NLUTD patients using different bladder management strategies with subgroup analyses for those using indwelling catheters in several studies.

The evidence base is comprised of two systematic reviews Ismail , Cameron and four observational studies El-Masri , Hamid , Sammer , Hamid , which were limited only by a serious risk of bias. Patients with SCI are at higher risk than the general population for developing bladder cancer; however, this overall risk is only 0.

Half of the patients utilized indwelling catheters as a bladder management method making it a significant risk factor, along with smoking and recurrent UTIs. It has been suggested that surveillance cystoscopy in this population might be beneficial in the early detection of bladder cancer, given their higher risk, and might reduce overall morbidity and mortality.

However, although conceptually attractive, this notion has not yet been proven. A systematic review of nine studies has shown that cystoscopy and cytology are poor screening tests for bladder cancer in NLUTD patient.

Only one malignancy was found on screening, but many patients had benign inflammatory or metaplastic lesions that led to surgical biopsy and other investigations. None of these studies deemed routine cystoscopy as useful in the detection of bladder cancer. The difficulty in this population, who have more UTIs and catheter burden, is that the bladder is subject to irritation and subsequent inflammatory lesion e.

Routine cystoscopy leads to over detection of these benign lesions, which in turn leads to surgical biopsy and its inherent risk. In studies that looked closely at annual surveillance, patients were found to develop advanced symptomatic cancer between surveillance cystoscopy episodes making it a poor screening study.

This argument also applies to patients who underwent prior augmentation cystoplasty. Routine cystoscopy was performed on 92 patients who were at least ten years status-post prior bladder augmentation.

Screening cystoscopy did not identify any tumors and the only malignancy was diagnosed after cystoscopy was done for gross hematuria after a previously normal screening cystoscopy. In NLUTD patients with indwelling catheters, clinicians should perform interval physical examination of the catheter and the catheter site suprapubic or urethral.

This statement is informed by three observational studies Katsumi , Gao , Lavelle with a very serious risk of bias, plus evidence was downgraded for indirectness. Indwelling catheters are chronic foreign bodies present in the urinary tract and their site of entry is inherently at risk for complications. The urethra is at risk for catheter hypospadias i. The catheter itself can cause pressure necrosis of the tissue of the urethra or even the pubic bone over prolonged periods of time. Risk factors for this complication include individuals with decreased sensation in the perineal area, impaired cognition, larger catheter size, and patients who are seated for prolonged periods of time.

In women, the relatively short urethra and bladder neck gradually dilate over time, which can lead to urine leakage around the catheter.

A temporary solution is often to increase the catheter size, which only increases the pressure on the urethra, further exacerbating the problem. The urethra can become so dilated that the catheter balloon is expelled and a larger mL balloon is often employed. As with catheter upsizing, balloon upsizing also exacerbates the problem long-term. A larger balloon causes more bladder stimulation and spasms, often resulting in the larger balloon to be expelled as well.

Hence, neither increasing the size of the catheter nor balloon are recommended and rather an investigation of the cause of leakage is indicated. These urethral injuries can be repaired with urethroplasty if the tissue is amenable. Suprapubic catheters avoid urethral complications but can also erode through the abdominal wall if improperly secured. Granulation tissue can often occur around the suprapubic catheter site and can bleed and make tube changes more difficult.

This can be easily identified and treated in the office with topical silver nitrate application. In NLUTD patients with indwelling catheters who are at risk for upper and lower urinary tract calculi e.

The evidence base for this statement is comprised of four observational studies Guzelkucuk , Katsumi , Lavelle , Gao The studies were limited by an aggregate very serious risk of bias, plus evidence was downgraded for indirectness. NLUTD patients with indwelling catheters are at unique risk for stones because of the chronic presence of a foreign body in their urinary tract.

The catheter increases the risk of UTIs 90 and is a source of chronic bacteriuria, both of which are risk factors for bladder and upper tract calculi.

The catheter itself can serve as a nidus for biofilm and crystal formation. When the balloon is deflated for catheter changes, these shells of calculi are often left in the bladder to serve as a seed for bladder calculi formation. In addition, UTIs and bacteriuria from urease splitting organism can result in high urine pH, which precipitates urinary crystals. The advantage of detecting these stones when small is that very small stones can be irrigated in clinic, while those that are slightly larger can be managed with a simple cystolithalopaxy.

Cystoscopy only allows for assessment of the bladder and KUB is less sensitive for bladder stones compared to US. Any patient with an indwelling catheter falls under the moderate- or high-risk NLUTD category for long-term surveillance and requires surveillance based on their particular risk level Statement 14 and Statement This statement is supported by three observational studies Skelton , Tornic , Weglinski all reporting on the prevalence of asymptomatic bacteriuria and symptomatic UTI.

The studies carried an aggregate very serious risk of bias but evidence was not further downgraded. The rationale to screen asymptomatic NLUTD patients is to treat those with positive urine cultures with antibiotics, to reduce bacteriuria, and to prevent the development of a future symptomatic UTI.

However, the risk of developing a UTI in this patient population appears to be low enough to not justify treatment, thus eliminating the need for screening in the asymptomatic NLUTD population. Tornic et al. The statement is supported by four observational studies Tornic , Weglinki , Skelton , Waites with a very serious risk of bias but no further limitations. Antibiotic resistance is a significant problem in patients with NLUTD, given the high frequency of antibiotic use.

The unnecessary use of antibiotics, such as for treating asymptomatic bacteriuria, should be avoided at all costs. Treatment of asymptomatic bacteriuria in catheter-free patients with SCI is followed by early recurrence of the bacteriuria with more resistant strains.

The exception to treating asymptomatic bacteriuria in NLUTD patients is in patients who are pregnant and prior to urologic procedures, in which urothelial disruption or upper tract manipulation is anticipated.

Perioperative antimicrobial treatment or prophylaxis for contaminated or clean-contaminated procedures is a best practice. In NLUTD patients with signs and symptoms suggestive of a urinary tract infection, clinicians should obtain a urinalysis and urine culture. The evidence base is comprised of five observational studies Linsenmeyer , Massa , Ronco , Togan , Clark reporting on outcomes informing this statement.

Across the outcomes, studies carried a very serious risk of bias plus for evidence was downgraded in the inconsistency domain for studies reporting on accuracy of predicting a UTI based on symptoms. The classic symptoms of UTI seen in able-bodied patients such as dysuria, urgency, and frequency may be seen in NLUTD patients with intact lower urinary sensation; however, these symptoms are often not applicable to many patients with NLUTD due to changes in lower urinary tract sensation and altered modes of bladder management.

In addition, the signs and symptoms suggestive of UTI can be impacted by the specific neurologic disorder causing NLUTD, the severity of the neurologic disorder, the degree of alteration of bladder sensation and type of bladder management volitional void versus IC versus indwelling catheter. Due to these many variables, there are no signs and symptoms alone that are adequately specific and sensitive enough to predict the presence of a UTI in all patients with NLUTD.

Due to these challenges, the Panel recommends that patients with signs and symptoms suggestive of a UTI should have a UA and urine culture, allowing for optimal diagnosis and the ability to use culture-specific antibiotics when treating a UTI in NLUTD patients.

Linsenmayer and Oakley evaluated the accuracy of predicting UTI based on symptoms in a prospective case series of consecutive SCI patients male; at T6 or higher. Patients presented to the urology clinic with complaints of a UTI over a nine-month period. UTI was defined as a new onset of clinical signs and symptoms e. In addition, the authors found that the type of bladder management had no impact on whether patients with SCI were able to predict the presence of a UTI based on symptoms alone.

Massa et al. This study was part of a larger trial evaluating the effectiveness of hydrophilic catheters in patients with chronic SCI injured for at least six months and recurrent UTI. During the three-month period, participants completed a monthly UTI signs and symptoms questionnaire i.

The authors found that patients were much better at predicting when they did not have a UTI versus when they did have a UTI. The authors also evaluated individual signs and symptoms to identify their predictive values alone. The presence of urinary leukocytes had the highest sensitivity Cloudy urine had the second highest positive predictive value Ronco et al.

Patients were divided into two groups: symptomatic UTI episodes; patients and asymptomatic UTI episodes; patients. Asymptomatic UTI had the same culture criteria without any of the above signs and symptoms.

There was no clinical sign or symptom that was diagnostic of UTI. Their conclusion was that these signs and symptoms, in isolation, were not optimal for a diagnosis of UTI. They also found that fever was not associated with more concerning urinary findings and speculated this could be related to various other causes of infection leading to fever. This data illustrates the challenges of diagnosing UTI with symptoms alone in the NLUTD population, especially in those patients with altered and decreased sensation.

Without standard normal UTI symptoms, clinicians often rely on non-specific symptoms such as increased spasticity, abdominal discomfort, malaise, and increased symptoms of AD. All these symptoms can be secondary to UTI; however, these symptoms can also be caused by a variety of other conditions not related to UTI.

However, AD symptoms could also be secondary to bladder distention, bladder or kidney stones, constipation, hemorrhoids, and pressure ulcers. Thus, it is very important to obtain a UA and urine culture to optimally obtain a diagnosis of UTI in this patient population. However, it can also be unclear as to how to interpret culture results in patients with NLUTD who manage their bladder by a variety of methods.

In addition, the IDSA did not advocate using pyuria to determine whether antibiotics should be administered; however, they did state that if pyuria was absent another cause of symptoms, other than UTI, should be sought. Finally, another argument for obtaining a urine culture is the ability to treat a UTI with culture-specific antibiotics and the importance of antibiotic stewardship.

This is especially applicable to patients with NLUTD who may be at greater risk of harboring resistant organisms. Changes included positive to negative culture, negative to positive culture, and a change in organism in a positive culture. Clark and Welk reviewed urine culture results over a two-year period of patients with NLUTD at a tertiary care urology clinic.

Of the 81 individuals with at least two positive cultures, there was Interestingly, antibiotic sensitivity concordance was higher than what was seen for the specific bacterial organism ciprofloxacin: This illustrates the importance of checking prior culture results if empiric antibiotics are to be started once a UA and culture have been obtained, but not yet resulted, in NLUTD patients with signs and symptoms of a UTI.

In NLUTD patients with a febrile urinary tract infection, clinicians should order upper tract imaging if:. In addition, the potential alteration of normal sensation may impact signs and symptoms, such as flank or abdominal pain, that would normally inform the caregiver of a potentially more dangerous condition.

If there is a high degree of suspicion for a UTI then empiric antibiotics should be initiated with the antibiotic changed, if needed, based on the culture result. The clinician may choose an antibiotic based on a recent, prior culture, if available. The need for appropriate radiographic assessment in these patients is still required, even if they have an appropriate response to antibiotics. Therefore, it is imperative that patients continue to be risk stratified see Table 3 and evaluated appropriately based on their level of risk.

In NLUTD patients with a suspected urinary tract infection and an indwelling catheter, clinicians should obtain the urine culture specimen after changing the catheter and after allowing for urine accumulation while plugging the catheter. Urine should not be obtained from the extension tubing or collection bag. IDSA recommends obtaining urine specimens aseptically through the catheter port in patients with short-term indwelling catheterization and suspected UTI.

Due to concerns related to biofilm possibly impacting the adequate assessment of the urine, the recommendation from the IDSA is to obtain urine for culture from a freshly placed catheter. In addition, it is specifically stated that urine should not be obtained from the drainage bag.

The studies that support this statement are older and primarily evaluated elderly patients who managed their bladder with chronic indwelling catheters for a variety of reasons; these were not studies that specifically evaluated the topic in NLUTD patients. Bergqvist et al. Fourteen of the specimens were negative, which correlated between both techniques.

However, when bacteriuria was identified, there was a lack of agreement in 12 of 36 specimens. The concern was that specimens obtained via a chronically placed catheter were not optimal and the authors recommended suprapubic bladder aspiration when obtaining urine in patients with a chronic indwelling catheter. While suprapubic aspiration is not the recommendation of the Panel, this does speak to the potential benefit of obtaining urine for culture from a newly placed catheter over one that has not been changed.

Two other studies focused on the concept of placement of a new catheter to obtain urine in patients with chronic indwelling catheters which reflects present day practice.

Grahn et al. A catheter specimen was obtained via needle aspiration from the distal end of the catheter that had not been changed for at least 30 days; the bladder specimen was obtained from the end of a freshly placed catheter that was clamped for 30 minutes.

There was a difference in 22 of 41 isolated bacterial strains in 17 of 20 patients. There were 17 instances where the CFU count from the catheter exceeded the quantity of the same strain in the bladder by at least tenfold. Tenney et al. In NLUTD patients with recurrent urinary tract infections, clinicians should evaluate the upper and lower urinary tracts with imaging and cystoscopy. Similar to the evaluation of hematuria, it is considered good clinical practice to evaluate both the upper and lower urinary tracts for sources of recurrent UTI.

Imaging is needed for examining the upper urinary tracts. The risks of direct visualization via ureteroscopy far outweighs the benefit in this situation and is not recommended. Contrast studies are not required in the initial evaluation. Since the risks of lower urinary tract evaluation via cystoscopy are low, it is a necessary part of the evaluation of recurrent UTIs.

In NLUTD patients with recurrent urinary tract infections and an unremarkable evaluation of the upper and lower urinary tract, clinicians may perform urodynamic evaluation. For each outcome, studies carried a very serious risk of bias and evidence was further downgraded for indirectness. Lapides hypothesized in that reduced blood flow to the bladder is a risk factor for UTI.

Similar improvements in UTI incidence were noted after sacral deafferentation and bladder augmentation in NLUTD patients that also showed improved bladder capacity and pressures. This would theoretically result in turbulent flow and urinary stasis, potentially resulting in a higher bacterial colony count primarily and secondarily increasing the UTI risk due to elevated PVR and VUR.

In NLUTD patients who manage their bladder with an indwelling catheter, clinicians should not use daily antibiotic prophylaxis to prevent urinary tract infection. The statement is informed by a systematic review Morton of fifteen studies using multiple bladder management and was limited by a serious risk of bias. Although antibiotics reduce or delay the onset of bacteriuria and UTI in chronically catheterized patients, many experts and guideline panels discourage prophylactic antibiotic use, primarily because of the development of antibiotic resistance.

A systematic review by Morton et al. While the majority of studies reviewed did focus on patients managing their bladder with CIC, studies that evaluated outcomes in patients managing their bladder with an indwelling catheter were included.

The conclusion from the systematic review was that antimicrobial prophylaxis did not significantly decrease symptomatic infections in patients with spinal cord dysfunction. In addition, approximately a two-fold increase in antimicrobial-resistant bacteria was seen. In NLUTD patients who manage their bladders with clean intermittent catheterization and do not have recurrent urinary tract infections, clinicians should not use daily antibiotic prophylaxis.

Included studies carried an aggregate serious risk of bias but evidence was not downgraded for any other domain. This recommendation was largely based on the strength of two systematic reviews that did not find evidence to support the use of prophylactic antibiotics for patients with NLUTD who manage their bladder with CIC and do not have issues with recurrent UTI.

Morton et al. However, antibiotic prophylaxis did not significantly decrease the rate of symptomatic UTIs and resulted in an approximate 2-fold increase in bacterial resistance. The type of bladder management used by the patients in these various studies included both CIC and indwelling catheter; the majority were using CIC. A subsequent systematic review, published in , evaluated a variety of outcomes related to the use of antibiotic prophylaxis. This analysis included three cross-over trials and one parallel group trial.

There were some differences regarding patient population including pediatric patients and UTI definition. One study reported fewer UTIs in the control group and one study noted fewer UTIs in the group of patients on antibiotic prophylaxis.

An additional study evaluated differences between febrile and afebrile UTI the only study to report outcomes in this manner and reported antibiotic prophylaxis resulted in less afebrile UTIs, but did not have an impact on febrile UTIs. The final conclusion of the systematic review was that there was not adequate evidence to make recommendations to this practice.

What is unclear is if antibiotic prophylaxis would be beneficial in patients who manage their bladder with CIC and have recurrent UTIs.

Fisher et al. Half of the cohort received once-daily antibiotic over a month period. Patients on antibiotic prophylaxis were less likely to have a symptomatic, antibiotic-treated UTI; 1. Clinicians may recommend pelvic floor muscle training for appropriately selected patients with NLUTD, particularly those with multiple sclerosis or cerebrovascular accident, to improve urinary symptoms and quality of life measures. The evidence base informing this statement is comprised of two systematic reviews Thomas , Block , one RCT Thomas , and one observational study Xia reporting one urinary symptoms and quality of life.

Across the outcomes of interest, the aggregate risk of bias was serious, and evidence was downgraded for inconsistency of results across the studies reporting on quality of life domains. Various types of behavioral and physiotherapeutic approaches have been employed for managing symptoms associated with NLUTD. Although limited with regards to statistical power, data suggests non-invasive interventions, which are associated with minimal side effects, may be offered and are of particular benefit to select patients.

In general, pelvic floor exercise reliably enhances strength and endurance of pelvic floor muscles across diverse patient groups. Improvements in the pelvic floor musculature were associated with reduction of LUTS and may be correlated with improvements on various QoL questionnaires. All intervention effects were maintained at 24 weeks follow-up. Similar improvements in frequency and episodes of urgency incontinence were seen across both groups. All pelvic floor enhancements were maintained during an additional six months of follow up.

Some subscales on various QoL measures also improved significantly. Two of the available published systematic reviews concluded there was no definitive evidence for any particular pelvic floor intervention; , the third review concluded that in patients with MS, behavioral therapy interventions improve QoL and reduce incontinence episodes but this review inappropriately pooled dissimilar trials in the meta-analysis.

Clinicians may recommend antimuscarinics, or beta-3 adrenergic receptor agonists, or a combination of both, to improve bladder storage parameters in NLUTD patients. Clinicians may recommend alpha-blockers to improve voiding parameters in NLUTD patients who spontaneously void. The aggregate risk of bias across the studies reporting on outcomes informing this statement was serious plus evidence was downgraded for inconsistency of results and imprecision in the reported outcomes.

Statement 34 is informed by two RCTs Abrams , Sung and one observational study Gomes reporting on voiding parameters. The risk of bias for studies reporting on the parameters was serious and evidence was further downgraded for imprecision.

The Panel acknowledges and appreciates recent attention to the potential risks of long-term treatment with anticholinergic agents with regards to cognitive impairment and dementia. There exists conflicting literature regarding the actual association and risk profile, with overall low-certainty evidence.

In selected NLUTD patients, use of alternative agents less likely to cross the blood-brain barrier without demonstrated cognitive risk may be appropriate. Additional evidence suggests that the use of alpha-blockers combined with antimuscarinics can ameliorate symptoms across several etiologies of NLUTD in the setting of relatively minor AEs.

Emerging, and therefore less robust, evidence exists for use of the more recently approved beta-3 agonist, in the NLUTD population.

Six of the 21 included studies were RCTs, crossovers, or randomized designs that compared active treatments. Half of these trials included sample sizes likely to provide adequate statistical power; however, most trials demonstrated a high or unclear risk of bias. In addition, the RCTs administered a range of medications e.

Consequently, there is insufficient high-quality evidence for particular medications in specific patient categories over clinically relevant periods of time.

The remaining observational studies generally reported findings consistent with the RCTs but follow up durations were limited, and patient groups were diverse. Published systematic reviews addressing use of oral medications in NLUTD patients highlight similar methodological issues, including a relative absence of long-term follow-up data, lack of sufficient evidence for particular patient groups or medications, and relative absence of consistent reporting of outcomes using validated and standardized measures.

Madersbacher et al. Flexible dose studies, which resulted in higher doses, appeared to improve efficacy without decreasing tolerability. The most frequently reported AE was dry mouth with higher rates reported for oxybutynin IR compared to trospium, tolterodine, and propiverine. Higher medication doses were not necessarily associated with higher rates of AEs, but studies that administered combinations of medications generally reported higher AE rates.

Overall, this systematic review indicated that the available literature was limited in quality by relatively short follow-up durations, small sample sizes in many studies with inadequate statistical power, lack of consideration for clinically important outcomes i.

Other AE rates were statistically similar between active treatment and placebo groups. Stothers et al. The authors concluded that standardized tools were infrequently used and obtaining data relevant to specific types of NLUTD patients, particularly SCI patients, requires the use of standardized urodynamics methodology, standardized urinary tract terminology, bladder diaries, the American Spinal Injury Association impairment scale, and symptom scores validated in SCI patients.

Although the Panel concurs that class-specific administration may be employed by clinicians across NLUTD pathologies, several explicit conditions may display benefit more than others with regards to individual medical therapy. These disease-specific concerns are detailed below. Alpha-blockers Tamsulosin. Of the original patients, completed the one-year open label extension. The primary outcome was maximum urethral pressure. During the randomized phase, the active treatment groups had greater MUP decreases Patients had a mean change of Voided volume increased significantly for the 0.

In addition, during the randomized phase, incontinence episode frequency and pad utilization improved for the 0. During the open label phase, QoL scores on patient reported questionnaires improved significantly compared to baseline. AEs were generally transient; the most frequently reported were dizziness, abnormal ejaculation, and fatigue. During the randomized phase, more patients discontinued for AEs in the placebo group 4. During the open label extension, 9.

Although the AEs precipitating discontinuation were not specified, the authors conclude that long-term tamsulosin is well-tolerated and improves bladder storage and emptying in SCI patients. Terazosin Perkash administered up to 5 mg daily in 28 male SCI patients for approximately 10 days. Three patients discontinued the medication for AEs of syncope, lethargy, and rash. An observational study employing one month of 5 mg terazosin administration in 22 SCI patients demonstrated improved bladder compliance with a significant mean pressure decrease of 36 cm H 2 O.

Of the four patients with AD, three experienced cessation of symptoms while using terazosin. Most patients reported reduced incontinence episodes with complete resolution of incontinence reported by four patients.

Ten patients continued to utilize terazosin after study conclusion with continued efficacy at a mean of 7. Five patients withdrew from the study for AEs including syncope and peripheral edema. Antimuscarinics Trospium. AEs were minor i. One observational study administered 10 mg solifenacin to 35 SCI patients with neurogenic detrusor overactivity NDO for 13 months.

Eight patients discontinued for lack of efficacy; two patients discontinued for intolerable AEs. All patients were allowed to titrate the dose, and all chose a final effective dosage of greater than 10 mg, with four patients taking the maximum of 30 mg per day. MCC increased significantly from to mL. Frequency 24 hours decreased from 12 to 8 voids and incontinence episodes per week decreased significantly from 13 to 6 episodes. Two patients in different treatment groups withdrew from the study for intolerable AEs i.

Similar AEs reported by five additional patients were graded mild to moderate. AEs were not systematically evaluated but 30 of the 97 patients on two medications reported experiencing dry mouth. The Panel appreciates that many practitioners will employ combination therapy with anticholinergic and beta-3 adrenergic receptor agonists based upon data from non-neurogenic OAB patients.

Beta 3 adrenergic receptor agonist Mirabegron. One observational study reported on effects of mirabegron initiated at 25 mg daily and increased to 50 mg after two weeks in 15 SCI patients with NDO followed for 7 weeks. AEs were minimal and included worsening incontinence and constipation. Systematic reviews have confirmed clinical improvements with beta-3 adrenergic receptor agonists for NLUTD. MS patients The administration of antimuscarinics can increase MCC and voided volume and reduce frequency, nocturia, incontinence events, urgency episodes, and urgency severity with generally minor AEs.

Antimuscarinics Oxybutynin compared to propantheline. Gajewski et al. MCC improved significantly more in the oxybutynin group mL than the propantheline group 35 mL. Although AEs in general were mild to moderate and experienced by most patients, approximately one-quarter of patients in each group withdrew from the study for severe AEs.

Thirty MS patients were administered solifenacin 5 — 10 mg daily and followed for two months. Of the 30 patients, 20 chose to continue the medication after study completion. Antimuscarinics Solifenacin. The randomized phase was followed by an eight-week open label extension in which all patients received active drug. Twenty-four-hour frequency improved significantly in the randomized phase with solifenacin but not placebo.

During the open label extension, significant decreases occurred in incontinence and nocturia episodes. There is currently no implemented hard cap on the total supply of Ether. This triple-point asset definition forms the bedrock of the Ethereum ecosystem. It also shows how ETH is analogous to key assets in traditional economies.

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More default shortcuts [74]. Support for text watermarks. Partial text and picture watermarks. This is not possible on Chromebooks as there is no app, Word for the web cannot do watermarks. Some formatting features are supported, e. No tdf , extension: TradutorLibreText. Yes [76]. No, extension: Sun Weblog Publisher outdated. Yes [77]. Line Focus removes removes distractions feature in MS Word. Yes [78]. No [79] [80]. No [81]. Yes [82]. OpenFormula standard.

Largely supported. Copy of cells is kept for pasting, even if the user does other tasks like typing or inserting cells. No [83]. Support for Numbers v [84] , see also this comparison. Jumbo spreadsheets supported since LO 7. Limited support [86]. Inserted image cannot be resized nor cropped, usability issues. Add-on, not activated by default.

Additional features: Histogram, Random number generation, Rank and percentiles, and some more detailed options. No tdf , tdf , tdf Selection of some pre-set chart styles and layouts. No tdf regarding DAX functions. No tdf , tdf , tdf , tdf , tdf Yes [87]. Data types from online sources: geography, stocks, organization, location, zip code, university, space, satellite, element, chemistry, food, exercise, movie, characters, medical, body, media, nature, activities, other Not available in MS Office sales versions [89] , [90].

Extended set of forecast functions based on exponential smoothing algorithm. Forecast functions and forecast charts based on exponential smoothing algorithm not supported in macOS version. Multi-threaded calculation [91]. Multi-threaded import of XLSX documents. Parallel formula compiling on the CPU.

Multithreading is work in progress: tdf , [94] , Presentation “Making Calc Calculate in Parallel”. Starting in Excel , the following features use multi-core processors: saving a file, opening a file, refreshing a PivotTable for external data sources, except OLAP and SharePoint , sorting a cell table, sorting a PivotTable, and auto-sizing a column.

LET function. Yes Flow charts and organizational charts supported in rental version, not supported in MS Office sales versions. Yes [97]. Supported [98] , [99]. Yes List of Regular Expressions. Independent window. Cannot be moved outside the application window. Yes tdf No []. Possibility to switch between function names in local language and English. Export of comments according to PDF specification.

No Only available: Inverting colors for negative values. Yes not available on Windows, see tdf More detailed: Number formats: more flexible use of “Format Code” for custom adjustments, leading zeroes, language setting, percentages without percentage sign, thousands separator for percentages; Font: overligning of text, relief embossed, engraved , outline, shadow, underline of individual words, spacing settings, kerning; Borders: shadow, spacing to contents; Protection: hide cells when printing.

Less features. Number format “Boolean value”. Engineering notation. Natural language number format spelling out numbers in various languages. Easy work around for missing US zip code and US phone number formats. Partial Engineering notation via custom formats.

Partial Using work-arounds. No reverse icon order tdf Customization of icon sets, e. Partial Styles supported, Cell Format not supported. Partial tdf , tdf , tdf Less default shortcuts [] , tdf , tdf , tdf More default shortcuts [] , [] , []. Yes []. No only manually. No, basic workaround [] tdf No via extension GeOOo.

Map charts and ” 3D Maps “. No, workarounds [] , [] tdf Yes Quick analysis feature and visual summaries, trends, and patterns. Some of these features “Ideas in Excel” supported in rental version, not supported in MS Office sales versions; quick analysis feature not supported on macOS. Some partial workarounds suggested here tdf c1. No, extension: EuroOffice Sparkline.

Background color bugs regarding pattern tdf and gradient tdf Extension: Hatch Patterns for Cells. Background color, pattern, gradient.

No removed feature since MS Office For Android smartphones only , but with additional features for Excel and Word. Not supported in macOS version. Via external programs. Directly in the program. Partial support of document themes in Impress: [] [].

Supported Not supported in MS Office sales version. Supported Not supported in macOS sales version []. No tdf , solution: smArt extension. Some features only available in rental vesion []. Supported with Bluetooth pen or Surface pen. Using digital pen as a slide-show clicker Not supported in macOS version.

Support for Keynote v []. Supported on Windows. No support for embedding fonts in PowerPoint on macOS, although displayed. Limited editing, has been a GSOC project [].

Powerful editing. Less default shortcuts []. More default shortcuts [] , [].

 

EndNote X7/X8/X9/20 Windows: Install Word CWYW – EndNote X7相关专题

 

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