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Effective bleeding control and symptom relief by lower dose regimens of continuous combined hormone replacement therapy: a randomized comparative dose-ranging study.

OBJECTIVES: We compared two different continuous combined hormone replacement therapy (HRT) regimens of estradiol valerate (E(2)V) and medroxyprogesterone acetate (MPA) with a combination of micronized estradiol (E(2)) and norethisterone acetate (NETA) to determine bleeding pattern, control of climacteric symptoms, lipid profile, endometrial and general safety in a 1-year multicenter study. METHODS: 440 postmenopausal women were randomized to three treatment groups to receive: 1 mg E(2)V+2.5 mg MPA; 1 mg E(2)V+5 mg MPA; or 2 mg of E(2)+1 mg NETA. After the first 6 months, the E(2)V dose was increased to 2 mg in both E(2)V/MPA groups. Information on bleeding was recorded on diaries by the women and intensity of climacteric symptoms was assessed using VAS scales. Physical and laboratory examinations, endometrial biopsy and vaginal ultrasonography were performed at baseline and follow-up visits. RESULTS: Significantly fewer bleeding days were experienced in the first 3 months by women taking E(2)V/MPA compared with women taking E(2)/NETA. When the dose of E(2)V was increased in the E(2)V/MPA groups, an increase in maximum bleeding intensity was observed in the group receiving 2.5 mg of MPA, but not in the group taking 5 mg of MPA. All dose combinations effectively relieved climacteric symptoms and beneficial effects on the lipid profile were seen after 6 months in all groups. Tolerability and endometrial safety were good and no cases of hyperplasia were observed. More women discontinued treatment prematurely in the E(2)/NETA group compared with either of the E(2)V/MPA groups. The overall continuation rates ranged from 70 to 86%. CONCLUSIONS: These results confirm that lower dose combinations of continuous combined HRT are usually sufficient to control symptoms or avoid breakthrough bleeding. However, if higher E(2)V dose is needed for symptom control, it should be combined with the higher dose of progestin (5 mg) to avoid bleeding disturbances. Flexible treatment regimens should be available for individualized HRT.

Aged↗

Hormonal replacement regimens and bleeding.

Hormone replacement therapy may increase the quality of life of postmenopausal women. Any regimen need to offer long-term endometrial safety. It is a standard to consider the co-administration of a sequential progestogen when estrogen replacement should be initiated in non-hysterectomized women. It is almost impossible to decide which combination of an estrogen and a progestogen seems to be optimal as individual tolerance of HRT may very well limit acceptability despite metabolic benefits and proven endometrial safety of a given combination. Several combinations of oral and transdermal estradiol or conjugated equine estrogens, oral progestogens, transdermal norethisterone acetate and levonorgestrel, and intrauterine levonorgestrel may achieve endometrial safety. It is noteworthy that there is no uniform correlation between the timing of onset of bleeding induced by any sequential estrogen and progestogen replacement and a certain pattern of histology. Therefore, although it is likely, there is no absolute reassurance that regular bleeding on or after day 11 of progestogen administration rules out abnormal histopathology. Transvaginal sonography seems not to be of pivotal importance to screen asymptomatic women on replacement therapy for detection of serious abnormal endometrial findings such as hyperplasia and endometrial cancer. Continuous combined hormone replacement therapy or the use of tibolone may be an alternative in postmenopausal women, who do not want any uterine bleedings after menopause. However, spottings or bleedings most often occur at the beginning of treatment. Vaginal administration of estriol and estradiol for urogenital symptoms of estrogen deficiency may stimulate the endometrium unintentionally. Available data suggest that use of oral estriol may be associated with endometrial hyperplasia and endometrial carcinoma relatively more often compared to sequential HRT. Raloxifene, a benzothiophene derivative acting as a selective estrogen receptor modulator approved for prevention of vertebral osteoporosis, rarely causes uterine bleeding. There is no ideal therapy available to suit women looking for a permanently bleed-free hormonal replacement therapy today.

Administration, Intravaginal↗

Abnormal vaginal bleeding in the nonpregnant patient.

Vaginal bleeding is a common complaint in most emergency departments. Abnormal vaginal bleeding causes many patients a great deal of stress and inconvenience. Although treatment of most cases is straightforward, vaginal bleeding can herald serious occult disease including cancer, coagulopathy, and systemic illness. Vaginal bleeding can also be the initial complaint in patients suffering sexual abuse or trauma. From an emergency medicine perspective, vaginal bleeding should be approached in terms of whether the patient is stable or not. Subsequent evaluation should exclude or treat problems that might cause the patient's condition to deteriorate. The emergency physician is able to provide initial therapy for most causes of vaginal bleeding, and in most cases the patient must be referred to a gynecologist for further evaluation and treatment.

Adolescent↗

Gastrointestinal bleeding, angiodysplasia, cardiovascular disease, and acquired von Willebrand syndrome.

Recent evidence points to isolated deficiency of the largest multimers of von Willebrand factor (VWF)-known as von Willebrand syndrome type 2A (VWS-2A)-as a risk factor for bleeding from gastrointestinal (GI) angiodysplasia. This disorder is not widely recognized, perhaps because most patients do not exhibit generalized hemostatic impairment (bleeding is generally restricted to GI angiodysplasia) and because all but the largest multimers of VWF remain detectable in the plasma (thus, routine screening tests for VWS-2A are usually normal). The "Rosetta stone" for elucidating this syndrome was the enigma of Heyde's syndrome (aortic stenosis plus bleeding GI angiodysplasia), particularly the striking observation that aortic valve replacement generally cures GI bleeding and that preoperative deficiency of the largest VWF multimers undergoes long-term normalization after valve replacement. We critically review the evidence implicating VWS-2A as a risk factor for bleeding GI angiodysplasia. We hypothesize that VWS-2A secondary to cardiovascular disease other than severe aortic stenosis, such as peripheral arterial occlusive disease, could explain why elderly patients often develop recurrent GI bleeding or iron deficiency anemia from GI angiodysplasia.

Angiodysplasia↗

Surgical management of gastrointestinal bleeding.

Severe gastrointestinal bleeding has historically been a clinical problem primarily under the purview of the general surgeon. Diagnostic advances made as the result of newer technologies, such as fiberoptic and video endoscopy, selective visceral arteriography, and nuclear scintigraphy, have permitted more accurate and targeted operations. More importantly, they have led to safe, effective nonoperative therapeutic interventions that have obviated the need for surgery in many patients. Today, most gastrointestinal bleeding episodes are initially managed by endoscopic or angiographic control measures. Such interventions are often definitive in obtaining hemostasis. Even temporary cessation or attenuation of massive bleeding in an unstable patient permits a safer, more controlled operative procedure by allowing an adequate period of preoperative resuscitation. Despite the less frequent need for surgical intervention, traditional operative approaches, such as suture ligation, lesion or organ excision, vagotomy, portasystemic anastomosis, and devascularization procedures, continue to be life-saving in many instances. The proliferation of laparoscopic surgery has fostered the application of minimally invasive techniques to highly selected patients with gastrointestinal bleeding. Intraoperative endoscopy has greatly facilitated the accuracy of laparoscopic surgery by endoscopic localization of bleeding lesions requiring excision. It is anticipated that the evolving technologies pertinent to the diagnosis and management of gastrointestinal bleeding will continue to promote collaboration and cooperation between gastroenterologists, radiologists, and surgeons.

Clinical Trials as Topic↗

Acute gastrointestinal bleeding in the intensive care unit. The intensivist's perspective.

Gastrointestinal (GI) hemorrhage is a common and potentially lethal medical emergency that is a common cause for intensive care unit admission. The intensivist plays an important role as a member of the medical team managing the patient with GI bleeding who is at high risk because of severe bleeding, comorbidity, or the presence of endoscopic stigmata of recent hemorrhage. This article presents the intensivist's approach to GI hemorrhage in initial patient assessment, triage, resuscitation, specialist consultation, diagnostic evaluation, and medical therapy. This article focuses on types of GI bleeding of particular concern to the intensivist, including esophageal variceal bleeding, stress-related GI bleeding, and GI bleeding associated with myocardial infarcation.

Acute Disease↗

Ultrasonographic detection of asymptomatic endometrial cancer in postmenopausal patients offers no prognostic advantage over symptomatic disease discovered by uterine bleeding.

The aim of this study was to investigate whether endometrial carcinoma (EC) screening by transvaginal sonography (TVS) has a prognostic advantage over symptomatic EC. In a retrospective study, 190 postmenopausal patients with symptomatic EC and 123 asymptomatic patients with suspicious endometrium detected by TVS were analysed regarding clinical, socio-economic and histopathological findings. Total bleeding time and the International Federation of Gynecology and Obstetrics (FIGO) tumour stage were evaluated with respect to their effect on survival. In 123 asymptomatic patients with suspicious endometrium, 16 (13%) EC, 61 (50%) polyps, 21 (17%) hyperplasias, 23 (19%) atrophias, 1 (0.8%) myoma and 1 (0.8%) metastasis were found. TVS findings in asymptomatic patients resulted in unnecessary operations, which were associated with considerable costs totalling at least 116256. Compared with screened asymptomatic patients, symptomatic patients were significantly (P<0.05) older, more frequently obese, and hypertensive, had a larger proportion of cases living in rural areas and visited their gynaecologists rarely. The bleeding time of symptomatic patients strongly correlated with the tumour stage (P<0.0001). Depending on the bleeding time, the 5-year disease-free survival and overall survival rates were 77% and 86% (no bleeding), 83% and 98% (<8 weeks), 74% and 90% (8-16 weeks), and 62% and 69% (>16 weeks), respectively. The corresponding tumour stage-related data for disease-free and overall survival were 100% (Ia; both rates), 87% and 95% (Ib), 66% and 93% (Ic), 63% and 78% (II) and 36% (III/IV; both rates), respectively. Postmenopausal vaginal bleeding represents an early symptom of EC, but it is not always perceived as problematic by the patients. There is no prognostic advantage for screened compared with symptomatic patients, who had bleeding of shorter than 8 weeks. Moreover, patients who are at a high risk for EC tend to avoid TVS screening. Finally, endometrial screening often results in unnecessary operations, which are associated with increased morbidity and costs.

Aged↗

Helicobacter pylori and upper gastrointestinal bleed in heart valve surgery.

OBJECTIVE: This study was designed to evaluate objectively the incidence of Helicobacter pylori infection and upper gastrointestinal (GI) bleeding in patients following heart valve replacement surgery. Since the discovery of Helicobacter pylori, its association with gastritis, peptic ulceration and upper GI bleed have been extensively studied. Anticoagulation of patients with mechanical heart valve prostheses is a prerequisite for the prevention of valve thrombosis and thrombo-embolic events. However anticoagulation can have its complications, notably that of upper GI bleeding. METHODS: Patients were assessed in routine postoperative outpatient clinics following cardiac valve replacement surgery. This assessment comprised initially of a questionnaire reflecting the symptomatology of upper GI bleeding and its subsequent management. With informed consent, a small sample of blood was obtained by stilette. The Helicobacter pylori status was assessed by measuring the presence of antibodies (immunoglobins) to Helicobacter pylori in a commercially available test kit, the Rapid Helisal Test. In this preliminary study 150 consecutive patients were scrutinised and their responses to the questionnaire were collected and compared with the Helisal test. RESULTS: From the 150 patients studied, 37 patients were found to be positive to the Helisal test for Helicobacter pylori infection, representing 24.6% of all the cohorts. Of these 37 patients, eight gave a positive history of upper GI bleed; five requiring hospital admission with three requiring urgent upper GI endoscopy. Although these eight patients represent only 4.4% of the total group, it is significant to note that this represents 21.6% of those patients found to be Helicobacter pylori positive. There were no GI complications in any of those tested negative. There was an increasing incidence of Helicobacter pylori infection in the older age group of patients. CONCLUSIONS: Helicobacter pylori infection is a common infection with serious consequences in heart valve surgery. For those requiring anticoagulation, the incidence of serious consequential upper GI bleed is significantly higher in the presence of this infection. Preoperative or immediate postoperative eradication of the organism is mandatory in those patients requiring indefinite anticoagulation.

Adult↗

Management of acute bleeding per rectum.

BACKGROUND: Bleeding per rectum is a common indication for acute hospital admissions to the colorectal department. The frequencies of aetiologies in Singapore are different from those in Western populations. A retrospective analysis of the demography, pathology and management of acute bleeding per rectum was performed to determine the outcome and difference in aetiology from the West. METHODS: During the 1-year period from 1 October 1995 to 30 September 1996, 547 patients were admitted to Singapore General Hospital form the emergency department for acute bleeding per rectum. There were 377 males and 170 females; the mean age was 42 years (range, 15-97 years). RESULTS: Of the patients admitted, 87% wer admitted due to perianal conditions diagnosed at bedside proctoscopy, where haemorrhoids mad up 94%. One percent bled from the upper gastrointestinal tract, while 12% bled from colorectal pathology. Massive bleeding form the colorectum was uncommon. Less than one third of the 47 patients required blood transfusions. Colonoscopy was the most useful diagnostic tool for bleeding from the colorectum. The more common colonic pathologies were diverticular disease (33%), adenomas (18%), and malignancy (26%), accounting for the majority of acute patient admissions. Colonic causes of bleeding were less common and were most stable. There were differences in the frequencies of aetiologies in our population compared ot Western populations. Understanding the common pathologies and outcomes guides the management fo our patients.

Adolescent↗

Emergency endometrial resection in women with acute, severe uterine bleeding.

STUDY OBJECTIVE: To evaluate the efficacy and safety of endometrial hysteroscopic resection in the treatment of severe uterine bleeding. DESIGN: Pilot feasibility study (Canadian Task Force classification II-2). SETTING: Department of gynecology at a general hospital. PATIENTS: Twenty-six women with severe uterine bleeding. INTERVENTION: Hysteroscopic transcervical endometrial resection under general anesthesia. MEASUREMENTS AND MAIN RESULTS: Bleeding had a benign organic cause in 25 women. One endometrial carcinoma was detected in endometrial chips in a postmenopausal woman and was managed with hysterectomy. Fifteen cycling women experienced complete remission of uterine bleeding; one underwent hysterectomy during follow-up. Atrophic endometrium was present in nine menopausal women during follow up. CONCLUSION: Endometrial transcervical resection was effective in controlling heavy bleeding, preventing future episodes of severe bleeding, and avoiding further medical or surgical treatment during 19 months of follow-up.

Electrocoagulation↗

Evaluation of Uterine Blood Loss with Bleeding and Visual Analog Scales

Measurements of uterine blood loss are important when comparing treatments for prolonged and excessive bleeding. We tested two methods of quantifying uterine blood loss in 110 women (age &gte;18 yrs) who were evaluated for uterine bleeding: a new bleeding scale and a visual analog scale. The bleeding scale measured the amount of flow from none to prolonged, excessive, and disabling. Data were analyzed by covariance, stepwise regression analysis, and factor analysis. Patient and physician visual analog scales were highly correlated. The patients rated themselves higher (worse) by 2 mm. The bleeding scale was more correlated with the physician scale than with the patient scale. The amount of flow most heavily weighted the visual scale, and clot size and activity most heavily weighted the bleeding scale. Duration of flow and anemia affected summary scores.

Journal Article↗

An association between imaging and acute posttraumatic ear bleeding with trismus.

OBJECTIVES: Computed tomography findings for each of 94 patients with unilateral ear bleeding and trismus correlated with either comminuted temporal bone fracture (26 cases) or bilateral temporomandibular joint fracture (68 cases). STUDY DESIGN: Ninety-four patients with post-traumatic unilateral ear bleeding and 10 asymptomatic adults underwent coronal computed tomography examinations of their temporomandibular joints. Of these, 26 patients with intact temporomandibular joints underwent axial computed tomography of the temporal bones. For 23 of the 94 symptomatic patients, computed tomography was the final imaging procedure; for the other 71 symptomatic patients, it was the first imaging procedure. Quantifications of the radiation dose and the per-patient cost of imaging were performed. Measurement of the maximal mandibular movements in vertical and horizontal directions was performed clinically in the 10 asymptomatic adult control subjects and in the 94 patients with trismus and ear bleeding. RESULTS: Ten control subjects had maximal opening values of 40 mm or more, and horizontal movement exceeded 24 mm. In 68 symptomatic patients, coronal computed tomography demonstrated bilateral fracture: there was bilateral high condylar fracture in 35 patients, and there was ipsilateral to the bleeding high condylar fracture with contralateral subcondylar fracture dislocation in 33 patients. Axial computed tomography scans in 26 symptomatic patients with intact temporomandibular joints demonstrated comminuted petrous bone fracture ipsilateral to the ear bleeding. CONCLUSIONS: Patients with post-traumatic ear bleeding associated with trismus should first be evaluated by computed tomography. Any other initial procedure doubles the radiation dose as well as the cost of the imaging.

Acute Disease↗

Clinical impact of push enteroscopy in patients with gastrointestinal bleeding of unknown origin.

BACKGROUND & AIMS: Despite the frequent use of push enteroscopy (PE), little is known of its clinical impact. The aim of this study was to evaluate the impact of PE on diagnostic and therapeutic management of patients with gastrointestinal bleeding of unknown origin. METHODS: Seventy-five consecutive patients (mean age, 56 y) referred for PE were included in this 1-year prospective study. Indications for PE were overt bleeding in 46 patients (61%) and iron-deficiency anemia in 29 patients (39%). Before the procedure, the prescribing physicians were asked to fill out a questionnaire listing the theoretical patient management plan (diagnostic procedures and/or treatment) as if PE were not available. One month after PE, the same physicians were asked about: (1) diagnostic procedures performed after PE, (2) the final diagnosis, and (3) their opinion of the usefulness of PE in clinical management. The clinical impact of PE on diagnostic and/or therapeutic management was assessed by 3 study physicians. RESULTS: Responses to the 2 questionnaires were obtained for all patients. The diagnostic yield of PE was 32% (24 of 75). The clinical impact of PE (changes in diagnostic and/or therapeutic management) was 55% (n = 41). PE was perceived as helpful by the prescribing physicians in 55% of cases. PE tended to influence patient management more in cases of overt bleeding than in cases of occult bleeding (63% vs. 41%; P = 0.06). CONCLUSIONS: PE influenced the clinical management of more than half the patients with GI bleeding of unknown origin, and was particularly useful in patients with overt bleeding.

Adolescent↗

A negative rapid urease test is unreliable for exclusion of Helicobacter pylori infection during acute phase of ulcer bleeding. A prospective case control study.

BACKGROUND: The reliability of the rapid urease test has not been proven in patients with peptic ulcer bleeding. Some studies show bad diagnostic results with the rapid urease test for gastrointestinal bleeding. AIMS: To evaluate the efficacy of the rapid urease test in patients with bleeding gastric or duodenal ulcers. PATIENTS AND METHODS: A total of 96 patients with acute peptic ulcer bleeding without proton pump inhibitor or antibiotic therapy within the last 14 days before bleeding were included into the study. During index endoscopy, specimens for histological and rapid urease test were obtained from the antrum and corpus mucosa of the stomach. Patients were also investigated by the 13C-urea breath test. Diagnostic quality parameters were calculated with the histology and the 13C-urea breath test as reference and compared with a matched control group with uncomplicated ulcers. RESULTS: The sensitivity of the rapid urease test was 80% and the specificity 100% compared to histology and 13C-urea breath test. The negative predictive value was 75%. These values were statistically significantly different from those of the control group (sensitivity 96%, specificity 100%, negative predictive value 88%). CONCLUSION: The exclusive use of the rapid urease test cannot be recommended in patients with peptic ulcer bleeding.

Adult↗

One-week antibiotics versus maintenance acid suppression therapy for Helicobacter pylori-associated peptic ulcer bleeding.

Bleeding peptic ulcer is the most important cause of upper gastrointestinal bleeding. Our aim was to compare the effect of anti-Helicobacter therapy with maintenance treatment of H2-receptor antagonist in the prevention of relapses of ulcer and bleeding. Patients with bleeding duodenal or gastric ulcers and H. pylori infection were randomized to receive either a one-week course of triple therapy with bismuth subcitrate, metronidazole, and tetracycline plus ranitidine or a six-week course of ranitidine 300 mg/day. After the ulcers healed, the antibiotic-treated patients were not given any medication, whereas the ranitidine-treated patients continued to receive a maintenance dose of 150 mg/day. One hundred twenty-six patients were randomized to receive anti-Helicobacter therapy and 124 patients to receive long-term ranitidine. H. pylori eradication was achieved in 98.2% in those who received triple therapy and 6.1% in those who received ranitidine (P < 0.0001). At the six-week follow-up, ulcer healing was documented in 88.2% in those who received triple therapy and 86.1% in those who received ranitidine (P = 0.639). Recurrent ulcer developed in nine of the ranitidine-treated patients and three of them presented with recurrent upper gastrointestinal bleeding. One patient in the antibiotic group developed recurrent ulcer without rebleeding (P = 0.01). It is concluded that eradication of H. pylori is sufficient for the prevention of recurrent bleeding ulcers.

Adult↗

[Oesophageal and fundic variceal bleeding].

Oesophageal and fundic varices belong to the most frequent complications of cirrhosis and portal hypertension. Due to their significant morbidity and mortality, bleedings from oesophageal or fundic varices represent a challenge for the emergency medical team as well as for the gastroenterologist. The patient with a variceal bleeding should be accurately monitored and his/her hemodynamic parameters should be maintained stable with the administration of plasma expanders and blood units when indicated. An antibiotic prophylaxis in this setting--norfloxacin or ceftriaxon--has been demonstrated to significantly reduce morbidity and mortality. Additionally, the early administration of vasoactive compounds, such as terlipressin, somatostatin or octreotide, is associated with beneficial effects in reducing the bleeding. An upper gastrointestinal endoscopy should be generally performed within the first twelve hours from the beginning of the bleeding in order to obtain an accurate diagnosis and to provide an adequate treatment. Endoscopic procedures to control the bleeding include the rubber band ligation, the treatment of the varix with a sclerosing agent or the injection of tissue glue into the varix. In case of recurrent bleeding, beyond the above methods, different techniques, such as the transjugular porto-caval shunt, surgical shunt procedures, as well as embolisation of splanchnic blood vessels, represent additional therapeutic options. However, they are associated with very high mortality rates and their indication has to be discussed case by case by an interdisciplinary team of experts. Future therapies include the optimisation and the improvement of the current medical and endoscopic armamentarium, as well as the application of treatments to novel targets, such as the coagulation cascade.

Critical Care↗

Somatostatin analogue improves survival in conscious cirrhotic rats subjected to gastrointestinal bleeding.

1. The continuing doubt concerning the value of vasoconstrictive therapy for gastrointestinal bleeding may be related to the complexity of clinical trials in such a situation. 2. The effect of SM 201-995, a somatostatin analogue, was investigated in conscious cirrhotic rats before, during and after experimental bleeding from the portal territory. 3. Before haemorrhage, somatostatin analogue (8 micrograms h-1 kg-1 body weight, intravenously) produced a significant decrease in portal pressure (17%), whereas a placebo (saline) lacked significant effect. 4. The rats were then subjected to spontaneous bleeding, by disconnection of the portal catheter from the pressure gauge, for a 5 min period. At the end of the haemorrhage, haemodynamic parameters did not significantly differ between the group receiving somatostatin analogue and that receiving placebo. 5. Fifteen minutes after the end of the bleeding period, portal pressure was significantly lower in rats receiving somatostatin analogue [8.5 +/- 0.5 mmHg (1.13 +/- 0.07 kPa), mean +/- SEM] than in rats receiving placebo [11.0 +/- 1.1 mmHg (1.50 +/- 0.15 kPa)]. 6. The volume of blood lost and mortality were significantly lower in the group treated with somatostatin analogue (2.3 +/- 0.1 ml/100 g body weight and 8%, respectively) than in the group receiving placebo (3.0 +/- 0.1 ml/100 g body weight and 50%, respectively). 7. These results demonstrate, in an experimental model, the beneficial effect of somatostatin analogue for the treatment of gastrointestinal bleeding due to portal hypertension. They suggest that administration of this substance should be started as soon as possible after the beginning of haemorrhage and continued after the cessation of bleeding.

Animals↗

A new experimental approach to assessment of velopharyngeal adequacy: nasal manometric bleed testing.

A new experimental method for assessment of velopharyngeal adequacy/inadequacy, using nasal manometric pressure readings for three types of speech conditions under controlled incremental bleed conditions, is described. Cleft palate speakers (N = 30) tended to have higher nasal pressure readings than non-flect palate speakers (N = 56), with or without bleed conditions. Reduction in nasal pressure under controlled incremental bleed for non-cleft palate speakers and cleft palate adequate (CPA) speakers is compatible with an aerodynamic quadratic equation. Unlike cleft palate inadequate (CPI) speakers, non-cleft palate speakers and CPA speakers exhibit similar ability to achieve 0 cm nasal monometric pressure under a bleed bore diameter of 4 mm for a circular bleed orifice. Results for cleft palate marginal (CPM) speakers are less conclusive. Reliability of nasal manometric bleed testing was limitedly tested but not conclusively established in the present report. Further study of reliability and validity is necessary.

Adolescent↗