The effect of soft cervical collars on persistent neck pain in patients with whiplash injury

Thirty-five male patients, aged 34-79 yr, with definite rheumatoid arthritis (RA) were recruited from out-patient clinics and randomized to receive monthly injections of testosterone enanthate 250 mg or placebo as an adjunct therapy for 9 months. Endpoints included disease activity parameters and bone mineral density (BMD). At baseline, there were negative correlations between the ESR and serum testosterone (r = -0.42, P < 0.01) and BMD (hip, r = -0.65, P < 0.01). A total of 29.6% of all patients had at least one vertebral fracture, most having multiple fractures. Back pain, however, was not more prevalent in fracture patients (55% vs 50%). Disease activity was significantly higher in the fracture group (joint score P < 0.05, rheumatoid factor P < 0.01). Thirty patients completed the trial, 15 receiving testosterone and 15 receiving placebo. There were significant rises in serum testosterone, dihydrotestosterone and oestradiol in the treatment group. There was no significant effect of treatment on disease activity overall, five patients receiving testosterone underwent a "flare'. Differences in mean BMD following testosterone or placebo were non-significant (spine: +1.2% vs -1.1%; femur: -0.3% vs +0.3%). There was no suggestion of a positive effect of testosterone on disease activity in men with RA.     

Specific vocalized complaints in whiplash and minor head injury patients

BACKGROUND: Serum FSH levels rise with increasing age in normal women, particularly as they enter the menopausal transition and progress to the postmenopausal state. The contributions of decreasing levels of inhibin-A (INH-A) and inhibin-B (INH-B) to this rise are presently unclear, as there are no reports of dimeric INH levels in relation to menopausal status. The present study was undertaken in order to provide preliminary data on relationships amongst the dimeric inhibins, oestradiol (E2) and FSH in normal subjects of defined menopausal status. METHODS: Single serum samples were obtained between cycle days 3 and 8 in regularly cycling women, or at random in those with irregular cycles or amenorrhoea, in 110 women, aged 48-59 years, in the third year of a prospective longitudinal study of the menopausal transition, 'The Melbourne Women's Mid-Life Health Project'. Samples were assayed for FSH, E2, INH-A, INH-B and immunoreactive inhibin (IR-INH) and results were analysed following logarithmic transformation. Undetectable values were assigned the limit of sensitivity of the respective assays. The relationships between hormones were evaluated as a function of menopausal stage. The latter was assigned as Stage 1, premenopausal (no reported change in menstrual cycle pattern), Stage 2, early peri-menopausal (reported change in menstrual cycle frequency in the preceding year with a bleed in the preceding 3 months), Stage 3, late peri-menopausal (no menses in the preceding 3-11 months) and Stage 4, postmenopausal (no menses in the preceding 12 months). RESULTS: The hormone concentrations in premenopausal subjects (geometric means, FSH 13.5 IU/l, E2 306 pmol/l, IR-INH 217 U/l, INH-A 96 ng/l, and INH-B 48 ng/l) were used as reference points for the other stages of menopausal status. Early peri-menopausal subjects had significantly lower levels of IR-INH (147 U/l) and INH-B (13.5 ng/l) in the presence of a small, statistically nonsignificant rise in FSH (to 21.4 U/l) and no significant change in E2 or INH-A. In late peri-menopausal subjects, IR-INH fell to 76 U/l, INH-A fell to 4.2 ng/l, whilst INH-B was not significantly different at 14 ng/l. FSH had risen significantly to 72.21 U/l. Oestradiol also fell significantly to 89 pmol/l. In the postmenopausal subjects there were no further significant changes in the peptide hormones or FSH, but E2 fell further to 41 pmol/l. There was a significant (P < 0.05) inverse correlation between FSH and E2 (R = -0.78), FSH and IR-INH (R = -0.66), FSH and INH-A (R = -0.53), FSH and INH-B (R = -0.29) while IR-INH and either INH-A or INH-B were positively correlated (R = +0.57 and +0.35, respectively). The data are consistent with negative feedback roles for both dimeric inhibins and E2 as contributors to the regulation of FSH secretion as menopausal status changes. CONCLUSIONS: The major significant endocrine event in women in the early peri-menopausal phase of the menopausal transition is a substantial fall in the circulating levels of inhibin-B with no significant change in inhibin-A or oestradiol. Progression to late peri-menopausal status is accompanied by a marked fall in inhibin-A and oestradiol and a rise in FSH without further change in inhibin-B. Inhibin-B, a marker of follicle number, is a significant factor in the endocrinology of the menopausal transition.     

MRI of cerebrum and cervical columna within two days after whiplash neck sprain injury

The present study was undertaken to evaluate if MRI within 2 days of a motor vehicle accident could reveal pathology of importance for understanding long-term disability after whiplash neck-sprain injuries. As part of a prospective study cervical and cerebral MRI was performed on 40 neck sprain patients with whiplash injury after car accidents. The imaging was done within 2 days of the injury to make sure that any neck muscle bleeding, oedema or other soft tissue injuries could be detected. The MRI findings from the patients were both correlated to reported symptoms 6 months after the accident and compared to a control group of 20 volunteers. The MRI of both brain and neck revealed no significant differences between the patients and the control group. When the patients were grouped according to the main MRI findings at intake and compared according to the development of subjective symptoms reported by the patients, the only significant difference was more headaches at 6 months in the groups with disk pathology or spondylosis when compared to the group with no pathology. In conclusion, MRI within 2 days of the whiplash neck-sprain injury could not detect pathology connected to the injury nor predict symptom development and outcome.     

Adrenocortical function in patients with active pulmonary tuberculosis

STUDY OBJECTIVE: To assess adrenal function in patients with acute pleuropulmonary tuberculosis (APT) and compare it with that function in patients with community-acquired pneumonia (CAP). PATIENTS: Over a period of 6 months all consecutive patients 18 years of age or older with newly diagnosed APT and CAP were entered into the study. MEASUREMENTS: The whole patients had the following investigations: 1) Serum Na+, K+ and glucose concentrations 2) Systolic and diastolic blood pressures. 3) An ultrasonographic study of the adrenal glands. 4) A standard ACTH stimulation test. RESULTS: There was no significative difference in the serum cortisol level between the two groups at any time of the ACTH stimulation test (basal, 30 and 60 minutes), neither when taking into account the increments between basal and 60 minutes after stimulation serum cortisol levels. All patients in both groups had normal ACTH stimulation test with a peak stimulated cortisol level at 60 minutes > 504 nmol/L. CONCLUSIONS: We did not find evidence of adrenal cortical dysfunction in patients with acute pleuropulmonary tuberculosis or with community-acquired pneumonia in our hospital.     

Technetium-99m-MAG3 renal studies in spinal cord injury patients: normal range, reproducibility, and change as a function of duration and level of injury

The normal range, reproducibility, and change as a function of duration and level of injury for Tc-99m-MAG3 renal studies were quantitated in spinal cord injury (SCI) patients. METHODS: Five SCI patients without evidence of renal disease in each of four groups: less than 2 months, 2-12 months, 1-2 years, and greater than 2 years from time of injury, were each studied twice. There were at least two patients with paraplegia and two with tetraplegia in each group. Renal clearance (camera based method), percent function in each kidney, time of peak renal parenchymal activity, and half time of parenchymal activity following the peak were evaluated. The peak and half times were determined with regions of interest (ROIs) over the entire kidney and over just the cortex. All results were compared to normal ranges previously established in normal subjects of the same age range using the same methodology. RESULTS: Renal clearance in the less than 2 month SCI patients was not significantly different from normal subjects in either paraplegic or in tetraplegic individuals. However, clearance in tetraplegics was increased by 28.5% at 2-12 month, increased by 50.6% at 1-2 years, and decreased by 25.9% at greater than 2 years compared to normal subjects (all P < 0.02). Clearance in those with paraplegia showed a similar, but less marked, trend (P = NS). The time of peak parenchymal activity when measured with cortical ROIs did not vary among patient groups or level of injury, but was increased compared to normal subjects (P < 0.05). The percent function in each kidney and half time following the peak were symmetrical, did not differ among patient groups or with level of injury, and did not differ from normal subjects. The parenchymal peak time was significantly shorter with cortical rather than renal ROIs in all patient groups (P < 0.05). In serial studies in the same patient the percent standard deviation in total renal clearance was less than between single studies in different patients, but the decrease was significant for only the right kidney (P < 0.03), and the decrease was not as great as in normal subjects. In addition, the percent standard deviation for percent function in each kidney was significantly less than the percent standard deviations in single studies (P < 0.02). There were no significant differences between intra- and interpatient studies for any other parameter. CONCLUSION: We conclude that: (1) renal clearance measured with Tc-99m-MAG3 in tetraplegic patients increases significantly during the first 2 years following injury and decreases significantly thereafter; there is a similar, but much less marked, trend in paraplegics, (2) parenchymal peak times with cortical ROIs occur later for SCI patients than for normal subjects, and (3) there is more intrapatient variation in total renal clearance and percent renal clearance on a side in SCI patients than in normal subjects suggesting that it may be harder to study SCI patients reproducibly. These findings should be taken into account when performing and interpreting Tc-99m-MAG3 renal studies in SCI patients.     

Gastric myoelectrical activity in patients with cervical spinal cord injury

OBJECTIVE: Dyspeptic symptoms are common in patients with cervical spinal cord injury (SCI). The supraspinal control of sympathetic innervation to the stomach is interrupted in these patients. Gastric emptying has been reported to be delayed in some patients with cervical SCI. Gastric myoelectrical activity is known to regulate gastric motility and is correlated with gastric emptying. The change in gastric myoelectrical activity after cervical SCI is unknown; our aim was to investigate it. METHODS: The study was performed in 12 cervical SCI patients and 14 healthy controls. Gastric myoelectrical activity was recorded using surface electrogastrography for 30 min in the fasting state and 1 h after a standard test meal. Spectral analysis was performed to compute the following parameters from the electrogastrogram; investigated were the percentage of 2-4 cycles/min (cpm) slow waves, the instability coefficient (IC) of the dominant frequency, the postprandial increment of dominant frequency (deltaF), and its power (deltaP). RESULTS: In both fasting and fed states, regular and stable gastric slow waves were observed in both the control group and patients with cervical SCI. The percentage of normal 2-4 cpm slow waves (preprandial, 80.7+/-3.6% vs 91.5+/-3.7%, p > 0.05; postprandial, 82.0+/-4.4% vs 87.2+/-4.2%, p > 0.05) and IC (preprandial, 0.19+/-0.04% vs 0.28+/-0.05%; postprandial, 0.24+/-0.04% vs 0.27+/-0.02%, p > 0.05) were not significantly different between the two groups. The dominant frequency and its power were also similar between the two groups, no matter whether in the fast (frequency, 2.92+/-0.3 vs 2.93+/-0.06 cpm; power, 30.05+/-1.29 vs 29.08+/-1.23 dB, p > 0.05) or fed (frequency, 3.17+/-0.07 vs 3.02+/-0.06 cpm; power, 32.55+/-0.90 vs 32.07+/-1.18 dB,p > 0.05) state. The postprandial response measured by deltaF (0.25+/-0.09 vs 0.09+/-0.07 cpm, p > 0.05) and deltaP (2.52+/-1.10 vs 2.24+/-1.20 dB, p > 0.05) were also similar between the two groups. CONCLUSION: Gastric myoelectrical activity was not altered after cervical SCI.     

Integration of auditory and kinesthetic information in motion: Alterations in Parkinson's disease.

The main aim in this work was to study the interaction between auditory and kinesthetic stimuli and its influence on motion control. The study was performed on healthy subjects and patients with Parkinson's disease (PD). Thirty-five right-handed volunteers (young, PD, and age-matched healthy participants, and PD-patients) were studied with three different motor tasks (slow cyclic movements, fast cyclic movements, and slow continuous movements) and under the action of kinesthetic stimuli and sounds at different beat rates. The action of kinesthesia was evaluated by comparing real movements with virtual movements (movements imaged but not executed). The fast cyclic task was accelerated by kinesthetic but not by auditory stimuli. The slow cyclic task changed with the beat rate of sounds but not with kinesthetic stimuli. The slow continuous task showed an integrated response to both sensorial modalities. These data show that the influence of the multisensory integration on motion changes with the motor task and that some motor patterns are modulated by the simultaneous action of auditory and kinesthetic information, a cross-modal integration that was different in PD-patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pentoxifylline stimulates various sperm motion parameters and cervical mucus penetrability in patients with asthenozoospermia

The Yugoslavia Prospective Study of environmental lead exposure has studied the associations between exposure to lead and pregnancy outcomes; childhood neuropsychological, behavioral, and physical development; and hematologic, renal, and cardiovascular function. The cohort comprises 577 children born to women recruited at midpregnancy in two towns in Kosovo, Yugoslavia; one town is the site of a lead smelter, refinery, and battery plant and the other is 25 miles away and relatively unexposed. A sample of these children has been followed at 6-month intervals through 7.5 years of age. Blood lead concentrations ranged from 1 to 70 microg/dl. Exposure to lead was not associated with adverse pregnancy outcomes. Exposure was associated with modest decrements in intelligence, small increases in blood pressure, higher risks of proteinuria, small increases in behavior problems, and perturbed hematopoiesis. Only at low level exposures (i.e., <16 microg/dl) were small associations with decreased height found. We discuss methodological problems that may hinder causal interpretation of these data, namely, use of blood lead concentration as an exposure measure, confounding, and town-specific associations. We conclude that while reported associations are small, collectively they lend support to the notion that lead is a toxicant with numerous adverse health effects.     

Assessment of executive function in patients with mild traumatic brain injury

BACKGROUND: The nature of functional deficit after mild traumatic brain injury (TBI) defined by Glasgow Coma Score of 13-15 is not fully described. This study explored the sensitivity of several neuropsychological tests to identify sequelae of mild traumatic brain injury (TBI). METHODS: Eleven adult patients with mild TBI admitted to a Level 1 trauma center were studied. The battery of tests included the Wechsler Intelligence Scale for Children -Revised: Mazes Subtest, Trails A and B, the Boston Naming Test, The Multilingual Aphasia Examination: Controlled Oral Word Association Test, and the Paced Auditory Serial Addition Task. RESULTS: Control subjects performed significantly better than patients with mild TBI on Trails A and B, the Controlled Oral Word Association Test, and Paced Auditory Serial Addition Task (subtests 2-4). No significant differences in performances between patients and controls was found for the Wechsler Intelligence Scale for Children -Revised: Mazes Subtest, Boston Naming Test, and Paced Auditory Serial Addition Task Subtest 1. CONCLUSION: The results suggest that tests of specific frontal lobe executive functions are valuable in diagnosing and monitoring recovery from mild TBI.     

Clinical features of transurethral anterior sphincterotomy and urological management of patients with cervical spinal cord injury

BACKGROUND: The ideal urological management for the patients with cervical spinal cord injury (CSCI) is to obtain catheter free urination and to prevent urinary tract complications. We have evaluated cases that had undergone transurethral anterior sphincterotomy from the view-point of the operative indications and the efficacy. METHODS: We carried out sphincterotomy 166 times on 133 male patients with CSCI in our Center. Before the operations were performed, all patients suffered from urinary incontinence, and they were unable to catheterize themselves for low level activity of daily life. Before and after the operation, their detrusor functions with sphincter reactions were assessed by urodynamic study. In principle we have followed up these cases by cystogram combined with cystometry, cystogram and excretory-pyelography or abdominal ultrasonography. RESULTS: In post-operative evaluations, more than 80% of cases attained hypotonic detrusor contractions and residual urine was significantly decreased. In long term follow-up, 96% of patients had obtained catheter free urination and about 85% of patients had no urinary tract complications, such as bladder deformity, vesicoureteral reflux, or hydronephrosis, with the exception of common unavoidable urinary infections. About 20% of cases had to be re-operated upon, and some cases showed hypertonic detrusor contractions or detrusor-sphincter-dyssynnergia during follow-up. CONCLUSION: The operative indications of sphincterotomy should be decided when the CSCI patients is unable to perform self-catheterization, and when due to the dysfunction of the urethral sphincter, these patients suffered from voiding difficulties or autonomic dysreflexia, or when the urinary tract complications might occur. In the majority of cases the aims of the sphincterotomy were achieved but some cases underwent another operation or had recurrent dysfunction of the urethral sphincter, indicating the need for careful follow-up.     

Spectrum of sequelae after whiplash injury. Localization and development in relation to the clinical picture

Neck sprain, a common sequela of motor vehicle trauma, is characterised by soft tissue lesions in the facet joints (the capsule), cervical discs (the annulus), ligaments, muscles, and sometimes in the nerve roots or the central nervous system. The cardinal manifestation of whiplash injury is neck pain, which may arise from any innervated part of the injured joints or muscles except the disc nucleus, the articular surface of facet joints, or the flaval ligaments. Pain may be referred to the skin or muscles via the respective sensory nerves. The tissue lesions, together with post-traumatic nerve root degeneration or medullary compression, may give rise to the complex neck sprain syndrome. Localisation of the source of symptoms by means of meticulous physical examination, MRI (magnetic resonance imaging), or accurately sited local anaesthetic injections is described in the article, and operative and multimodal rehabilitation procedures are discussed.     

Hip and ankle range of motion in elite classical ballet dancers and controls

Use of herbal remedies from medicinal plants (bush medicines) was studied in 622 people with diabetes mellitus attending 17 government health centers on the island of Trinidad, Trinidad and Tobago. Bush medicines were used by 42% of patients surveyed and were used for diabetes by 24%. Bush medicine use was more frequent in Afro-Trinidadians and in those of mixed ethnicity than in Indo-Trinidadians, and was also more prevalent in those with lower educational attainment. Most patients using bush medicines (214/264, or 81%) reported gathering the plants themselves, and 107/264 (41%) took them more frequently than once a week. Patients taking bush medicines mentioned 103 different plants used in remedies. Among the 12 most frequently mentioned, caraili, aloes, olive-bush, and seed-under-leaf were preferentially used for diabetes. Vervine, chandilay, soursop, fever grass, and orange peel were preferentially used for other indications. Patients who reported burning or numbness in the feet or feelings of tiredness, weakness, giddiness, or dizziness used bush medicines for diabetes more frequently than did patients who reported a range of other diabetes-related symptoms. Insulin-treated patients were less frequent users of bush medicines. It is concluded that bush medicines are taken regularly by many patients with diabetes in Trinidad. Plants most frequently used as remedies for diabetes have recognized hypoglycemic activity. Patients' culture, educational background, type of symptoms, and formal medical treatment may also influence the selection and use of bush medicines.     

Mutual influence between vesicourethral and anorectal function in spinal cord injury patients

Twenty two patients having mild to moderate hypertension were treated with a single daily dose of amlodipine for 4 weeks. Satisfactory response defined as final diastolic blood pressure < 90 mm of Hg and a reduction from baseline values > 10 mm of Hg could be achieved in 81.8% of patients in supine position and 70% of patients in standing position. Thirteen patients responded to 5 mg dose and 9 patients required 10 mg. Postural hypotension and reflex tachycardia were absent. Three patients has mild leg cramps and constipation. No deleterious effects were observed on liver, kidney and hemopoetic function, or on E.C.G. Changes. Amlodipine given once daily is effective and safe, and is a useful addition to the existing armamentarium of antihypertensive drugs.     

Reduced cognitive functions in a group of whiplash patients with demonstrated disturbances in the posture control system

Past studies examining whether or not cognitive changes actually have occurred as a result of a whiplash (WL) accident have produced varying results. The aim of this study was to identify possible cognitive dysfunctions in a group with persistent problems after whiplash due to injuries to the posture control system and related structures. The whiplash subjects (n = 23) were selected on the basis of their reduced gain in the Smooth Pursuit Neck Torsion test (SPNT). The WL group differed significantly from a closely matched control group on tests of learning and memory, and prolonged divided attention and concentration. After attempting to rule out other ways of interpreting these differences (such as pain, depression, medication, and premorbid health problems), these data were interpreted as lending support to the notion of a causal connection between the disturbed posture control system and some cognitive malfunctions.     

Composition and function of peripheral blood stem and progenitor cell harvests from patients with severe active rheumatoid arthritis

High-dose chemotherapy with autologous stem cell rescue has been proposed as an intensive therapy for severe rheumatoid arthritis (RA). In view of previous observations of abnormal haemopoiesis in RA patients, the composition and function of peripheral blood stem cell harvests (PBSCH) was investigated. Compared with PBSCH from healthy allogeneic donors mobilized with the same dose of G-CSF (filgrastim; 10 microg/kg/d, n = 14), RA PBSCH (n = 9) contained significantly fewer mononuclear cells (375 v 569 x 10(6)/kg, P = 0.03) and CD34+ cells (2.7 v 5.8 x 10(6)/kg, P = 0.003). However, there were increased proportions of CD14+ cells (P = 0.006) and CD14+ CD15+ cells (the phenotype of previously described 'abnormal' myeloid cells, P = 0.002) in the RA PBSCH which translated into 3.5- and 7-fold increases respectively on a per CD34+ cell basis. There were no differences in T-cell activation status as judged by proportions of CD4+ and CD8+ expressing CD45RA, CD45RO, HLA-DR and CD28 (RA PBSCH, n = 7, donor PBSCH, n = 5, P = 0.2-0.7). Phytohaemagglutinin responses determined fluorocytometrically with induction of CD69 expression were reduced in CD4+ and CD8+ cells following filgrastim administration in 3/3 RA patients tested. Compared with bone marrow as a potential source of CD34+ cells, PBSCH contained 11-fold more T cells (P < 0.0005), 8-fold more B cells (P < 0.0005) and 4-fold more monocytes (P = 0.02). In short-term methylcellulose culture there were no differences in colony counts (CFU-GM, CFU-GEMM, BFU-E) per CD34+ cell from PBSCH from RA patients (n = 11) and healthy donors (n = 10). Long-term culture initiator cells were cultured successfully from cryopreserved PBSCH from RA patients (n = 9). In conclusion, PBSCH from RA patients differed significantly in composition from normal individuals, but in vitro studies support normal stem and progenitor cell function. Changes in T-cell function occur during mobilization in RA patients. This work provides reassurance for the use of PBSCH as haematological rescue and baseline data for clinical trials of graft manipulation strategies in patients with RA.     

Preservation of tubal function in patients with nasopharyngeal carcinoma, post-irradiation

Nineteen nasopharyngeal carcinoma (NPC) patients were subjected to eustachian tube function testing before and 5 years after irradiation. Tubal patency and clearance function of the eustachian tube showed deterioration if maximum irradiation dosage was more than 70 Gy, whereas dynamic function of the eustachian tube was preserved. Development of middle ear complications in NPC patients post-irradiation was caused by both tubal and inflammatory factors. To preserve tubal function, maximum irradiation dosage to NPC should be limited to 70 Gy. To decrease the inflammatory reaction, firstly, middle ear effusion should be drained by repeated myringotomies instead of grommet insertion, and secondly, sinusitis should be evaluated and treated, because sinusitis can aggravate otitis media with effusion.     

Metrifonate benefits cognitive, behavioral, and global function in patients with Alzheimer's disease

OBJECTIVE: To evaluate the efficacy and safety of metrifonate, an acetylcholinesterase inhibitor, in patients clinically diagnosed with probable Alzheimer's disease (AD) of mild to moderate severity. METHODS: A prospective, 36-week, multicenter, double-blind, randomized, parallel group study of metrifonate in probable AD patients, including a 2-week screening period, a 26-week double-blind treatment period, and a follow-up visit at 8 weeks post-treatment. A total of 24 ambulatory clinics in the United States in a variety of settings, including contract research organizations, public health facilities, and universities. Patients met diagnostic criteria for probable AD as defined by the work group of the National Institute for Neurological and Communicative Diseases and Stroke and the Alzheimer's Disease and Related Disorders Association. Patients had Mini-Mental State Examination (MMSE) scores of 10 to 26 and Ischemic Scores (Rosen Modification) of <4. A total of 408 patients were enrolled. Percentages of patients completing double-blind treatment were 88% and 79% in the placebo and metrifonate groups, respectively. Rates of discontinuation due to adverse events were 4% in the placebo group and 12% in the metrifonate group. Placebo or metrifonate was administered once daily. Metrifonate-treated patients received a loading dose of 100 to 180 mg based on weight (2.0 mg/kg) for 2 weeks, followed by a maintenance dose of 30 to 60 mg based on weight (0.65 mg/kg) for 24 weeks. Primary efficacy variables were the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the Clinician's Interview-Based Impression of Change with Caregiver Input (CIBIC-plus). Secondary efficacy variables included the Neuropsychiatric Inventory (NPI), the Disability Assessment in Dementia, the Global Deterioration Scale (GDS), the ADAS-Noncognitive subscale (ADAS-Noncog), the MMSE, and the Clinician's Interview-Based Impression of Severity with Caregiver Input (CIBIS-plus). Outcome measures reflected changes from baseline at week 26 for all variables. Safety was assessed with incidences of premature termination, treatment-emergent events and mortality, and routine safety evaluations. RESULTS: After 26 weeks of metrifonate therapy, a 2.86-point treatment difference (p = 0.0001) was observed in the ADAS-Cog scores of the intent-to-treat AD patients. The treatment difference in the mean CIBIC-plus score at this time was 0.28 points (p = 0.0071). At week 26, treatment differences also were observed in the mean NPI total score (p = 0.0161). Analysis of the remaining secondary efficacy variables showed treatment differences that favored metrifonate but did not reach statistical significance. Metrifonate adverse events were predominantly mild in intensity. No hepatotoxicity was observed. CONCLUSIONS: Metrifonate was safe and well-tolerated. It enhanced not only the cognitive and global function, but also the behavioral function of patients diagnosed with mild to moderate AD. Therefore, metrifonate appears to be useful in the symptomatic treatment of AD.