Model risk scores may underestimate rate of biochemical recurrence in African American men with localized prostate cancer: a cohort analysis of over 3000 men.

INTRODUCTION: This study aims to determine if there is a difference in prostate cancer nomogram-adjusted risk of biochemical recurrence (BCR) and/or adverse pathology (AP) between African American (AAM) and Caucasian men (CM) undergoing radical prostatectomy (RP). METHODS: A retrospective review was performed of men undergoing RP in the Pennsylvania Urologic Regional Collaborative between 2015 and 2021. Cox proportional hazard regression models were used to compare the rate of BCR after RP, and logistic regression models were used to compare rates of AP after RP between CM and AAM, adjusting for the CAPRA, CAPRA-S, and MSKCC pre- and post-operative nomogram scores. RESULTS: Rates of BCR and AP after RP were analyzed from 3190 and 5029 men meeting inclusion criteria, respectively. The 2-year BCR-free survival was lower in AAM (72.5%) compared to CM (79.0%), with a hazard ratio (HR) of 1.38 (95% CI 1.16-1.63, p < 0.001). The rate of BCR was significantly greater in AAM compared to CM after adjustment for MSKCC pre-op (HR 1.29; 95% CI 1.08-1.53; p = 0.004), and post-op nomograms (HR 1.26; 95% CI 1.05-1.49; p < 0.001). There was a trend toward higher BCR rates among AAM after adjustment for CAPRA (HR 1.13; 95% CI 0.95-1.35; p = 0.17) and CAPRA-S nomograms (HR 1.11; 95% 0.93-1.32; p = 0.25), which did not reach statistical significance. The rate of AP was significantly greater in AAM compared to CM after adjusting for CAPRA (OR 1.28; 95% CI 1.10-1.50; p = 0.001) and MSKCC nomograms (OR 1.23; 95% CI 1.06-1.43; p = 0.007). CONCLUSION: This analysis of a large multicenter cohort provides further evidence that AAM may have higher rates of BCR and AP after RP than is predicted by CAPRA and MSKCC nomograms. Accordingly, AAM may benefit with closer post-operative surveillance and may be more likely to require salvage therapies.

Safety of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer and malignant ureteric obstruction.

OBJECTIVES: To determine whether patients with carcinoma invading bladder muscle (MIBC) and ureteric obstruction can safely receive cisplatin-based neoadjuvant chemotherapy (C-NAC), and to determine whether such patients require relief of obstruction with a ureteric stent or percutaneous nephrostomy prior to beginning C-NAC. PATIENTS AND METHODS: We performed a single-institution retrospective analysis of MIBC patients receiving C-NAC and falling into three groups: no ureteric obstruction (NO); relieved ureteric obstruction (RO); and unrelieved ureteric obstruction (URO). To address whether patients with obstruction can safely receive C-NAC, we compared patients with NO to those with RO, with the primary outcome of premature chemotherapy discontinuation. To investigate whether patients with obstruction should have the obstruction relieved prior to NAC, we compared RO to URO patients using a primary composite outcome of grade ≥ 3 adverse events, premature chemotherapy discontinuation, dose reduction, or dose interruption. The primary outcomes were compared using multivariable logistic regression. Sensitivity analyses were performed for the RO vs URO comparison, in which patients with only mild degrees of obstruction were excluded from the URO group. RESULTS: A total of 193 patients with NO, 49 with RO, and 35 with URO were analysed. There were no statistically significant differences between those with NO and those with RO in chemotherapy discontinuation (15% vs 22%; P = 0.3) or any secondary outcome. There was no statistically significant difference between those with RO and URO in the primary composite outcome (51% vs 53%; P = 1) or any secondary outcome. CONCLUSION: Patients with ureteric obstruction can safely receive C-NAC. Relief of obstruction was not associated with increased safety of C-NAC delivery.

A Multi-Institutional Experience with Robotic Vesicovaginal and Ureterovaginal Fistula Repair After Iatrogenic Injury.

Objectives: To describe our multi-institutional experience with robotic repair of iatrogenic urogynecologic fistulae (UGF), including vesicovaginal fistulae (VVF) and ureterovaginal fistulae (UVF). Methods: We performed a retrospective review identifying patients who underwent robotic repair of VVF and UVF between January 2010 and May 2019. All patients failed conservative management with Foley catheter or upper tract drainage (ureteral stent and/or nephrostomy tube), respectively. Patient demographics and perioperative outcomes were analyzed. Success was defined as no vaginal leakage of urine postoperatively, in the absence of drains, catheters, or stents. Results: Of 34 patients, 22/34 (65%) had VVF and 12/34 (35%) had UVF repair. VVF etiology included radiation (1/22, 4.5%) and surgery (21/22, 95.5%). Four of 22 (18%) had undergone prior repair attempt. Median console time was 187 minutes (interquartile range [IQR]: 151-219), estimated blood loss (EBL) was 50 mL (IQR: 50-93), and median length of stay (LOS) was 1 day (IQR: 1-2). Two of 22 (9%) patients had a postoperative complication. At mean follow-up of 28.9 months, 20/22 (91%) VVF cases were clinically effective. UVF etiology was gynecologic surgery in all cases; 8/12 (67%) were left-sided, 4/12 (33%) were right-sided. None was repeat repairs. Two of 12 (17%) underwent ureteroureterostomy, and 10/12 (83%) had reimplant. Median console time was 160 minutes (IQR: 133-196), EBL was 50 mL (IQR: 50-112), and LOS was 1 day (IQR: 1-1). No complications were encountered. At mean follow-up of 29.3 months, 100% of UVF repairs were effective. Conclusions: Robotic repair of iatrogenic UGF may be effectively performed with low complication rates by experienced urologic surgeons.

Phenotyping nocturnal polyuria: circadian and age-related variations in diuresis rate, free water clearance and sodium clearance.

BACKGROUND: this study compares diuresis rate, sodium clearance and free water clearance (FWC) by age and time of day (nighttime vs. daytime) in subjects with and without nocturnal polyuria (NP) to determine whether these variables affect the phenotype of NP. METHODS: post hoc analysis of two prospective observational studies. Eight urine samples collected at 3-h intervals and a single blood sample were used to calculate daytime (10a/1p/4p/7p/10p) and nighttime (1a/4a/7a) diuresis rates, sodium clearance and FWC. Three mixed linear models were constructed for diuresis rate, sodium clearance and FWC using four predictor variables: NP status (present [nocturnal urine production >90 ml/h] vs. absent [≤90 ml/h]), time of day, age and study identification. RESULTS: subjects with NP experienced higher nighttime versus daytime diuresis rates, sodium clearance and FWC. Regardless of NP status, increased age was accompanied by an increase in the ratio of nighttime/daytime diuresis rate, nighttime sodium clearance and daytime sodium clearance. FWC showed a complex age effect, which was independent of time of day or NP status. CONCLUSIONS: age-related increases in nighttime/daytime diuresis rate, 24-h sodium clearance and 24-h FWC are not specific to subjects with NP. The age-related surge in either nocturnal sodium clearance or nocturnal FWC may represent the relevant substrate for behavioural or pharmacologic interventions targeting sodium diuresis or free water diuresis, respectively. Increases in FWC in older age groups may reflect impaired circadian rhythmicity of endogenous AVP or changes in responsiveness of the aged nephron to water clearance.

Racial/ethnicity differences in endorsing influential factors for prostate cancer treatment choice: An analysis of data from the personal patient profile-prostate (P3P) I and II trials.

OBJECTIVE: Rates and choice of treatment for localized prostate cancer vary according to race/ethnicity in American men. We hypothesized that there were group differences in influential values and preferences related to treatment decisions. METHODS: We analyzed samples from 2 multicenter, randomized trials of the Patient Profile-Prostate (P3P) I and II decision aid, first comparing the groups on other demographic and decisional variables using Chi-square tests. Stratified (P3P I vs. II) logistic regression was then used to assess the univariate association between race/ethnicity and endorsement of moderate-or-strong influence of 14 lifestyle factors, current or future symptoms, or important others on the decision. A multivariable stratified logistic regression with backward variable selection was used to further estimate the association between influential factors and race/ethnicity. RESULTS: There were 494 and 392 participants in P3P I and P3P II, respectively, with 40 Hispanic, 168 non-Hispanic black, 637 non-Hispanic white, 19 others and 6 missing. Age (P = 0.0001), education (P < 0.0001), marital status (P < 0.0001), income (P < 0.0001), Internet use for information (P < 0.0001) and decisional control preference were significantly different across racial/ethnic groups. In adjusted analyses, we saw racial/ethnic differences in the decisional influence of age (Non-Hispanic Black (NHB) vs. Non-Hispanic White (NHW) OR: 0.56 95%CI 0.38-0.85 P = 0.002), religion/spirituality (NHB vs. NHW OR: 3.2095%CI1.95-5.26, P < 0.0001), future bladder function (NHB vs. NHW OR: 0.5795%CI 0.35-0.90, P = 0.04), future ability to engage in recreation (NHB vs. NHW OR: 0.5495%CI 0.34-0.86, P = 0.02), and a story of a famous person with prostate cancer (NHB vs. NHW OR: 2,11 95%CI 1.30-3.43, P = 0.007). No interactions were found. CONCLUSION: Our results suggest racial/ethnic differences for influences underlying treatment choice. Better understanding these influences may help us present salient information about treatment options to patients and address disparities.

Risk of dementia following androgen deprivation therapy for treatment of prostate cancer.

BACKGROUND: Evidence for androgen deprivation therapy (ADT) and risk of dementia is both limited and mixed. We aimed to assess the association between ADT and risk of dementia among men with localized and locally advanced prostate cancer (PCa). METHODS: We conducted a retrospective cohort study using SEER-Medicare-linked data among 100,414 men aged ≥ 66 years and diagnosed with localized and locally advanced PCa (cT1-cT4) between 1992 and 2009. We excluded men with a history of stroke, dementia, or use of psychiatric services. Men were followed until death or administrative end of follow-up at 36 months. Inverse-probability weighted Fine-Gray models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for Alzheimer's, all-cause dementia, and use of psychiatric services by duration of pharmacologic ADT (0, 1-6, and ≥ 7 months). RESULTS: Among 100,414 men with PCa (median age 73 [IQR: 69-77] years; 84% white, 10% black), 38% (n = 37,911) received ADT within 6 months of diagnosis. Receipt of any pharmacologic ADT was associated with a 17% higher risk of all-cause dementia (HR 1.17, 95% CI 1.07-1.27), 23% higher risk of Alzheimer's (HR 1.23, 95% CI 1.11-1.37), and 10% higher risk of psychiatric services use, though the confidence interval included the null (HR 1.10, 95% CI 1.00-1.22). Longer duration of ADT (≥7 months) was associated with a 25% higher risk of all-cause dementia, 34% higher risk of Alzheimer's, and 9% higher risk of psychiatric services, compared with no ADT. CONCLUSIONS: Our study supports an association between pharmacologic ADT and higher risk of all-cause dementia, Alzheimer's, and use of psychiatric services among men with localized and locally advanced PCa.

Genomic classifiers for treatment selection in newly diagnosed prostate cancer.

OBJECTIVES: To review systematically the literature on genomic tests for prostate cancer (PCa) and to evaluate the current state of the evidence on their use in patients with newly diagnosed PCa. METHODS: We conducted a systematic review by searching PubMed, Embase, Cochrane Central and conference abstracts from the American Urological Association, published between 2010 and 2018. Studies evaluating Prolaris, Oncotype Dx and Decipher assays were assessed for inclusion by two authors. Studies were excluded if the results were derived from surgical specimens rather than biopsy specimens. A meta-analysis was not performed owing to significant variations in methodologies, definitions and outcome measures. RESULTS: A total of 729 articles were retrieved in our initial search. After removing duplicates (270) and excluding articles deemed not relevant (432), 21 full-text articles were deemed suitable for inclusion in the present analysis. The full-text articles comprised eight studies on Prolaris, eight studies on Oncotype Dx and five studies on Decipher. For each genomic test we extracted data regarding the risks of adverse pathology, biochemical recurrence, metastasis and PCa-specific mortality. CONCLUSION: The results of genomic tests that use biomarkers derived from prostate biopsy can be used in conjunction with clinicopathological variables to improve our ability to risk-stratify patients with newly diagnosed PCa. Additional data are needed on the impact of using these tests on long-term patient outcomes and their cost-effectiveness.

Periodontal status and bacteremia with oral viridans streptococci and coagulase negative staphylococci in allogeneic hematopoietic stem cell transplantation recipients: a prospective observational study.

AIM: This study was aimed to investigate whether any association could be found between the presence of an inflamed and infected periodontium (e.g., gingivitis and periodontitis) and the development of bacteremia during neutropenia following allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: Eighteen patients underwent a periodontal examination before HSCT. Patients were classified as periodontally healthy [all periodontal pocket depths (PPD) ≤ 4 mm and bleeding on probing (BOP) ≤ 10%) or as having gingivitis/periodontitis (PPD ≥ 4 mm and BOP > 10%]. Oral mucositis (OM) was scored using the daily mucositis score. Blood cultures were taken at least twice weekly. RESULTS: Five patients were periodontally healthy, while 13 patients had gingivitis or periodontitis. Twelve patients (67%) developed bacteremia during neutropenia, of which 11 patients (61%) had one or more episodes of bacteremia due to coagulase-negative staphylococci (CONS, most often Staphylococcus epidermidis) or to oral viridans streptococci (OVS), or both. Patients with gingivitis/periodontitis more often had bacteremia than those with a healthy periodontium (p = 0.047), and BOP was associated with bacteremia (p = 0.049). All patients developed ulcerative OM, but its severity and duration were not associated with bacteremia. OM duration and the length of stay in the hospital were strongly correlated (R = 0.835, p ≤ 0.001). CONCLUSION: This study indicates that periodontal infections may contribute to the risk of developing OVS and CONS bacteremia during neutropenia following HSCT. While our results point to the importance of periodontal evaluation and management before HSCT, further studies on periodontal contribution to systemic infectious complications are warranted.

Review of current literature and implications of RANKL inhibitors for oral health care providers.

Bisphosphonates (BPs) were the first class of drugs commonly used to prevent skeletal-related events (SRE) in patients with osteoporosis, multiple myeloma (MM), or solid tumors with metastases to bone. A new alternative class of agents, receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors, are now available for use in these indications and have the potential to replace intravenous BPs. This paper presents a review of the current literature on denosumab and its association with osteonecrosis of the jaw (ONJ). Denosumab is a RANKL inhibitor that has recently been approved for the prevention of SRE for the same indications as BPs except for MM. Although the overall frequency of denosumab-related ONJ may be similar or higher than estimates of the occurrence rate of bisphosphonate-related ONJ, evidence continues to support appropriate planning and preventive care can reduce the likelihood of adverse effects, including osteonecrosis.

The effects of osteoclast modifiers on the oral cavity: a review for prescribers.

PURPOSE OF REVIEW: Osteonecrosis of the jaw associated with therapeutic osteoclast modifiers is a rare but serious event. The consequences of osteonecrosis can be devastating despite current treatment. With the increase in diversity of agents and significant increase in the prevalence of osteoclast modifiers prescribed by oncologists understanding diagnosis and management of osteoclast modifiers-related osteonecrosis of the jaws (OMRONJ) is necessary. The risk of osteonecrosis when osteoclast modifiers are used for management of osteoporosis is much less than osteoclast modifiers used in the oncology setting. A basic understanding of the oral exam and current management will lead to more effective communication and more effective prevention of devastating OMRONJ. RECENT FINDINGS: An indistinguishable rate of ONJ seen with new therapeutic agents is becoming apparent and relevant preventive therapy and counseling of the patient is indicated. Currently there is no comprehensive clinical guideline that unifies oncologists and oral health providers in the prevention and management of OMRONJ. SUMMARY: Communication and proper planning with each patient's provider is the most effective strategy to prevent OMRONJ. A team composed of an oncologist, oral and maxillofacial surgeon and dentist competent in managing this condition is necessary. An understanding of the cause and development of OMRONJ can give the prescriber an improved perspective to communicate with oral health professional colleagues. Current guidelines emphasize the need for dental management prior to the use of osteoclast modifiers for the prevention and management of osteonecrosis of the jaw.

Management of bisphosphonate-associated osteonecrosis: pentoxifylline and tocopherol in addition to antimicrobial therapy. An initial case series.

BACKGROUND: Studies of the use of pentoxifylline and α-tocopherol in osteoradionecrosis of the jaw have suggested their efficacy in this condition. We report an initial case series of pentoxifylline and α-tocopherol for patients with bisphosphonate-associated osteonecrosis (BON). METHODS: Six cases referred for management of BON were provided pentoxifylline and α-tocopherol in addition to antimicrobial therapy, and followed for a mean of 10 months. RESULTS: A 74% decrease in area of bony exposure and symptom control was achieved in these cases. DISCUSSION: Pentoxifylline with α-tocopherol may represent a strategy for management of BON. Controlled trials in cases of BON appear warranted.

Doxepin rinse for management of mucositis pain in patients with cancer: one week follow-up of topical therapy.

This study assessed the effectiveness of oral doxepin rinse for mucositis-related pain management in patients following 1 week of repeated dosing. Patients with oral mucositis due to head and neck radiation therapy or hematopoietic stem cell transplant (HSCT) were recruited to participate in a 1-week follow-up study. Subjects who gave informed consent rinsed with doxepin (5 ml) during the initial visit and were then told to use doxepin rinse over the next week as needed, three to six times per day, and return for a follow-up visit. At each visit, mucositis was scored using the Oral Mucositis Assessment Scale and oral pain was assessed using a visual analogue scale before and after rinsing. The use of a systemic analgesic was recorded, and side effects were documented. At the follow-up visit, subjects were also asked to retrospectively report average pain scores they experienced over the past week, 5 and 15 minutes following rinse. Nine subjects were enrolled in the study. Statistically significant reductions in pain scores were reported for 2 hours following doxepin rinse during the initial visit (p < .05). Patients recalled that their pain significantly dropped within 5 minutes of rinsing over the week of repeated dosing (p < .05). At the follow-up visit, subjects reported statistically significant pain reduction 5 minutes after doxepin rinsing (p < .05). These results indicate that doxepin rinsing continues to produce reduced intensity of pain levels over a 1-week span of repeated dosing.

A survey of the current approaches to diagnosis and management of oral premalignant lesions.

BACKGROUND: Early diagnosis of oral premalignant lesions (OPLs) and oral squamous cell carcinoma facilitates treatment with less aggressive approaches and results in a better prognosis. The authors conducted a study to identify current practices in the diagnosis and management of these oral lesions by oral medicine professionals. METHODS: The authors sent a questionnaire to 176 diplomates of the American Board of Oral Medicine and asked them to complete the questionnaires and return them by mail. RESULTS: The initial clinical approach taken by most of the responders included visual examination, elimination of possible local causes and two-week follow-up. Adjuvant clinical tests included toluidine blue, oral brush biopsy and exfoliative cytology. If there was no clinical improvement after two weeks, most responders recommended that a biopsy be performed. Induration, red component, nonhomogeneous surface and ulceration were characteristics of lesions that increased the responders' decisions to perform a biopsy. Lesion symptoms and location also contributed to their decisions to perform a biopsy. Follow-up more frequently than twice a year was recommended for red lesions, lesions with histologically confirmed dysplasia or both. Most clinicians recommend a biopsy during follow-up of an OPL whenever the lesion changes in appearance. CONCLUSIONS: The findings of this survey may provide background for initial guidelines to be used by oral practitioners to diagnose and manage OPL. Clinicians' awareness of the complexity of OPL diagnosis and management is important, and referral to an experienced provider is recommended.

A survey of National Cancer Institute-designated comprehensive cancer centers' oral health supportive care practices and resources in the USA.

BACKGROUND: The oral complications and morbidity resulting from overall cancer therapy utilizing radiation, chemotherapy, and/or stem cell transplantation can have significant impact on a patient's health, quality of life, cost of care, and cancer management. There has been minimal health services research focusing on the status of medically necessary, oral supportive services at US cancer centers. METHODS: A pre-tested, survey questionnaire was distributed to the directors of National Cancer Institute (NCI)-designated comprehensive cancer centers to assess each institution's resource availability and clinical practices, as it relates to the prevention and management of oral complications during cancer treatment. RESULTS: Sixteen of the 39 comprehensive cancer centers responded to the survey. Of the respondents, 56% of the centers did not have a dental department. The sites of delivery of oral supportive care services range from the provision of in-house dental care to community-based, private practice sites. No standard protocols were in place for either oral preventive care or for supportive services for oral complications during or after cancer therapy. Fifty percent of the responding comprehensive cancer centers reported orally focused research and/or clinical trial activities. CONCLUSIONS: Comprehensive cancer care must include an oral care component, particularly for those cancer patients who are at high risk for oral complications. This requires a functional team of oral care providers collaborating closely within the oncology team. Considering the number of cancer patients receiving aggressive oncologic treatment that may result in oral toxicity, the impact of oral conditions on a compromised host, and the potential lack of appropriate resources and healthcare personnel to manage these complications, future research efforts are needed to identify the strengths and weaknesses of present oral supportive care delivery systems at both NCI-designated cancer centers and community-based oncology practices.

Oral doxepin rinse: the analgesic effect and duration of pain reduction in patients with oral mucositis due to cancer therapy.

This research expands on our prior study, in which we assessed pain reduction after topical doxepin rinse in patients with oral mucositis resulting from cancer and cancer therapy. We continued to enroll patients with painful oral mucositis attributable solely to cancer therapy and performed further analysis on the duration of pain reduction. Fifty-one patients with oral mucositis were enrolled. Mucositis was scored and oral pain was assessed with a visual analog scale before doxepin oral rinse (5 mg/mL) and at regular intervals up to 4 h after rinsing. Of those who reported pain reduction, 95% did so within 15 min of rinsing with doxepin. In the total sample, the average patient reported a 70% maximum decrease in pain (P < 0.0001). Recurrence of pain was slow and at the conclusion of the study 19 patients (37%) still reported a reduction from baseline pain. With this censored data we used Cox-proportional hazards to determine what variables best explained longer duration of pain reduction. Our final model determined that more severe baseline pain, worse mucosal erythema score, or a larger relative maximum reduction in pain were all associated with a slower rate of pain recurrence after oral rinsing (all P < 0.01).

Cancer-related oral health care services and resources: a survey of oral and dental care in Canadian cancer centres.

PURPOSE: Prevention and management of oral complications of cancer and cancer therapy will improve oral function and quality of life, and reduce morbidity and the cost of care. Oral assessment, and oral and dental care have been strongly recommended before cancer therapy and should be continued during and after cancer therapy. The purpose of this survey was to assess the resources available for oral care in Canadian cancer centres. METHODS: Provincial cancer centres were assessed by questionnaire to determine the resources available for oral care in these facilities. RESULTS: Wide variability in oral and dental care of patients with cancer across Canada and a lack of documented standards of care were reported. Very few cancer centres had institutionally supported dental staff to support the oral care of patients with cancer, and few had dental treatment capability on site. The majority of centres managed oral care needs in the community with the patient's prior dentist. CONCLUSIONS: We recommend that national guidelines be developed for medically necessary oral and dental care for patients with cancer.

The efficacy of pilocarpine and bethanechol upon saliva production in cancer patients with hyposalivation following radiation therapy.

PURPOSE: Pilocarpine and bethanechol have been reported as potentially effective sialogogues for xerostomic patients. The purpose of the present study was to compare the efficacy of bethanechol to that of pilocarpine in patients with dry mouth following cancer therapy. STUDY DESIGN: Patients with documented hyposalivation were provided pilocarpine or bethanechol for 2-3 weeks in an open-label randomized crossover study. Baseline and weekly whole resting saliva (WRS) and whole stimulated saliva (WSS) were obtained for 5 minutes. Subjective response and side effects were recorded. RESULTS: Forty-two xerostomic patients who had received radiation therapy to the head and neck participated. The increase in the WRS and WSS with each medication independently was limited. Statistically significant increase in WRS was seen for both medications when all patients using either agent were analyzed, but no statistically significant increase in WSS was found.Twenty-seven patients completed the crossover protocol. No significant difference in the effect was noted between each of the 2 drugs whether they were prescribed as the first or second drug in the crossover. Statistically significant improvement in subjective report of saliva production/mouth wetness was seen for patients on either medication. This study suggests that subjective improvement in symptoms of dry mouth may be related to resting saliva production, and not to stimulated saliva production. No statistically significant differences in adverse side effects were reported between the medications prescribed. The most common side effects were minor and included frequent urination, dizziness, and increased sweating. CONCLUSIONS: The findings indicate that head and neck radiation-treated patients with established hyposalivation will respond minimally to systemic sialagogues and while they may experience an increase in resting saliva little change in stimulated saliva may occur. It is not known whether relatively small increases in saliva are beneficial in maintaining oral health; however, subjective improvement suggests improved quality of life. While it is not known if prolonged use of a sialagogue will have increased effects, the limited increase in saliva seen following the second drug of the crossover suggests that prolonged use of a sialagogue may further increase saliva production.