Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis.

IMPORTANCE: Alcohol use disorders cause substantial morbidity and early mortality yet remain greatly undertreated. Medications are considerably underused. OBJECTIVE: To conduct a systematic review and meta-analysis of the benefits and harms of medications (US FDA-approved and others) for adults with alcohol use disorders. DATA SOURCES: PubMed, Cochrane Library, PsycINFO, CINAHL, EMBASE, FDA website, and clinical trials registries (January 1, 1970, to March 1, 2014). STUDY SELECTION: Two reviewers selected randomized clinical trials (RCTs) with at least 12 weeks' duration that reported eligible outcomes and head-to-head prospective cohort studies reporting health outcomes or harms. DATA EXTRACTION AND SYNTHESIS: We conducted meta-analyses using random-effects models and calculated numbers needed to treat for benefit (NNTs) or harm (NNHs). MAIN OUTCOMES AND MEASURES: Alcohol consumption, motor vehicle crashes, injuries, quality of life, function, mortality, and harms. RESULTS: We included 122 RCTs and 1 cohort study (total 22,803 participants). Most assessed acamprosate (27 studies, n = 7519), naltrexone (53 studies, n = 9140), or both. The NNT to prevent return to any drinking for acamprosate was 12 (95% CI, 8 to 26; risk difference [RD], -0.09; 95% CI, -0.14 to -0.04) and was 20 (95% CI, 11 to 500; RD, -0.05; 95% CI, -0.10 to -0.002) for oral naltrexone (50 mg/d). The NNT to prevent return to heavy drinking was 12 (95% CI, 8 to 26; RD -0.09; 95% CI, -0.13 to -0.04) for oral naltrexone (50 mg/d). Meta-analyses of trials comparing acamprosate to naltrexone found no statistically significant difference between them for return to any drinking (RD, 0.02; 95% CI, -0.03 to 0.08) or heavy drinking (RD, 0.01; 95% CI, -0.05 to 0.06). For injectable naltrexone, meta-analyses found no association with return to any drinking (RD, -0.04; 95% CI, -0.10 to 0.03) or heavy drinking (RD, -0.01; 95% CI, -0.14 to 0.13) but found an association with reduction in heavy drinking days (weighted mean difference [WMD], -4.6%; 95% CI, -8.5% to -0.56%). Among medications used off-label, moderate evidence supports an association with improvement in some consumption outcomes for nalmefene (heavy drinking days per month: WMD, -2.0; 95% CI, -3.0 to -1.0; drinks per drinking day: WMD, -1.02; 95% CI, -1.77 to -0.28) and topiramate (% heavy drinking days: WMD, -9.0%; 95% CI, -15.3% to -2.7%; drinks per drinking day: WMD, -1.0; 95% CI, -1.6 to -0.48). For naltrexone and nalmefene, NNHs for withdrawal from trials due to adverse events were 48 (95% CI, 30 to 112) and 12 (95% CI, 7 to 50), respectively; risk was not significantly increased for acamprosate or topiramate. CONCLUSIONS AND RELEVANCE: Both acamprosate and oral naltrexone were associated with reduction in return to drinking. When directly compared with one another, no significant differences were found between acamprosate and naltrexone for controlling alcohol consumption. Factors such as dosing frequency, potential adverse events, and availability of treatments may guide medication choice.

[Long-term functional results after macular hole surgery. Results of a prospective study]. / Funktionelle Langzeitergebnisse nach Makulaforamenchirurgie. Ergebnisse einer prospektiven Studie.

PURPOSE: This study reports on the long-term results of macular hole surgery with peeling of the ILM. METHODS: A total of 88 consecutive patients (71 female, 17 male, mean age 67 years) were prospectively evaluated. All patients underwent a standard pars plana vitrectomy with removal of the ILM and an intraocular gas tamponade. Preoperatively, as well as on each follow-up visit, a clinical examination including measurement of best corrected visual acuity, Goldman perimetry, and OCT was performed. RESULTS: The mean postoperative follow-up was 49 months; 83 (94%) patients were pseudophakic at the last examination. Anatomic closure was achieved in 84 (95%) patients. No late reopening of the macular hole was observed. Best corrected visual acuity improved in 82 patients (93%), remained unchanged in 2, and deteriorated in 4 patients. Best corrected visual acuity improved from a median of 0.2 preoperatively to a median of 0.6 postoperatively (p<0.001). Duration of symptoms as well as low preoperative visual acuity had no significant impact on anatomic and functional success. CONCLUSIONS: Macular hole surgery leads to good functional and anatomical results, even in the long term. A long history of visual impairment and low visual acuity before surgery are not contraindications to surgical intervention.

Inhibition of granulocyte-macrophage colony-stimulating factor (GM-CSF) activity by suramin and suramin analogues is correlated to interaction with the GM-CSF nucleotide-binding site.

Suramin and suramin analogues strongly inhibit both nucleotide interaction with the nucleotide-binding site of granulocyte-macrophage colony-stimulating factor (GM-CSF) and bioactivity of the molecule as assessed by competition photoaffinity labeling and cell proliferation assay, respectively. The half-maximal inhibition of cell proliferation by suramin occurs at 68 +/- 2.5 microM; three suramin analogues achieved comparable activity. The degree of competitive inhibition of nucleotide-binding by these compounds and the inhibition of GM-CSF bioactivity are correlated such that the compounds show similar rank-order by both of these methods. The strong interaction of suramin and related compounds with the nucleotide-binding site may mimic nucleotide-mediated inhibition of GM-CSF bioactivity and may be an important mechanism by which suramin acts as a pharmacological anti-growth factor agent.

Macular changes after peeling of the internal limiting membrane in macular hole surgery.

PURPOSE: To report the incidence of macular changes following pars plana vitrectomy with peeling of the internal limiting membrane (ILM) for idiopathic macular hole. DESIGN: Prospective consecutive series. METHODS: In a prospective study 105 eyes of 105 patients underwent vitrectomy for idiopathic macular holes. Surgery consisted of a standard three-port vitrectomy, induction of a posterior hyaloid detachment, removal of epiretinal membranes including the ILM, fluid-air exchange and intraocular gas tamponade (15% hexafluoroethane (C2F6) gas mixture) followed by head-down positioning for at least five days. No adjuvants were used during surgery. In addition to the clinical examination, static microperimetry using a Rodenstock scanning laser ophthalmoscope (SLO-105) was performed pre- and 6 or 12 weeks postoperatively. The stimulus size was 0.2 degrees (Goldmann II), intensities employed were 0 and 12 dB. For all tests, 20-degree fields were used. RESULTS: Anatomic closure of macular holes was achieved in 92 (87.6%) of 105 patients by one operation. Eight patients underwent a successful second procedure. The closure rate after two operations was 95.2%. Best corrected visual acuity increased from a median of 0.2 (range 0.05 to 0.5) preoperatively to a median of 0.5 (range 0.05 to 1.0) postoperatively. Anatomical macular changes were found in 8 (7.6%) patients: There were two cases of macular edema following secondary cataract extraction and six cases of retinal pigment epithelium changes. Formation of postoperative epiretinal membranes or late reopenings were not noted. Small, mostly asymptomatic paracentral scotomata were seen in 59 (56.2%) of 105 patients. CONCLUSION: Anatomical changes of the macula following vitrectomy with removal of the ILM are infrequent. However, paracentral scotomata observed in our series might be caused by a trauma to the nerve fibers during ILM peeling. To achieve reliable results a standardized procedure for microperimetry should be developed.

Indocyanine green-assisted peeling of the internal limiting membrane may cause retinal damage.

PURPOSE: To demonstrate possible retinal damage caused by indocyanine green dye for staining of the internal limiting membrane in surgery for idiopathic macular hole. METHODS: Consecutive interventional case series. We report on the ultrastructural findings of the internal limiting membrane in 10 eyes of 10 patients. RESULTS: All specimens revealed not only the internal limiting membrane, but also some small amounts of retinal elements, such as the plasma membrane of Müller cells and other undetermined structures. This indicates a cleavage plane not exactly at the inner undulating aspect of the internal limiting membrane but within the innermost retinal layers. CONCLUSION: Dilutions of indocyanine green as recommended in the literature may alter the structure of the retina to some degree. Possible factors responsible for this inadvertent action may include (1) concentration, (2) osmolarity pH, (3) time of tissue contact, and (4) mechanical factors from more forceful traction during peeling. Although functional consequences of these findings remain unclear as yet, factors that may induce damage to the innermost retina should be elucidated.

Paracentral scotomata: a new finding after vitrectomy for idiopathic macular hole.

AIMS: To report the occurrence of paracentral scotomata after pars plana vitrectomy for idiopathic macular holes. METHODS: In 15 patients static microperimetry using a Rodenstock scanning laser ophthalmoscope (SLO-105) was performed preoperatively and 6 or 12 weeks postoperatively (stimulus size 0.2 degrees (Goldmann II), employed intensity 0 and 12 dB, 20 degrees fields in all tests). Surgery consisted of standard three port vitrectomy including removal of epiretinal membranes and the inner limiting membrane. RESULTS: Postoperative paracentral scotomata were detected in areas that were tested normally before surgery. They were mostly located temporally and/or inferiorly and often appeared like nerve fibre bundle defects. The greatest dimension varied from 1.2 degrees to 4.0 degrees (360-1200 microm), smallest dimension from 0.25 degrees to 2.0 degrees (75-600 microm). In three patients more than one scotoma was observed. CONCLUSION: Small, mostly asymptomatic, paracentral scotomata as a complication after vitrectomy for idiopathic macular hole have not been reported in the literature so far. Whether they are caused by trauma to the nerve fibres during surgery or other factors remains unknown.

Peripheral visual field defects after macular hole surgery: a complication with decreasing incidence.

AIM: To prospectively evaluate peripheral visual fields after vitrectomy for idiopathic macular holes. METHODS: Goldmann perimetry was performed in 105 patients before, as well as 6 weeks and 12 months after macular hole surgery. RESULTS: Only one patient (< 1%) with a stage III macular hole developed an asymptomatic postoperative visual field defect. The scotoma was wedge-shaped, peripherally located in the temporal quadrant, and remained unchanged during the following 12 months. CONCLUSION: Peripheral visual field defects after macular hole surgery can be a complication of very low incidence. A rather low pressure set during air-fluid exchange as well as special aspects of the surgical technique may be responsible for this low incidence of peripheral visual field defects.

Macular hole size as a prognostic factor in macular hole surgery.

BACKGROUND/AIM: In 1991 there was a series of successful closures of a macular hole after vitrectomy and membrane peeling. Today this technique has become a standard procedure. The aim of this study was to evaluate the role of optical coherence tomography in diagnosing and staging, as well as in predicting, the functional and anatomical outcome after macular hole surgery. METHOD: In a prospective study 94 consecutive patients (20 male, 74 female) with a mean age of 67.6 (SD 6.0) years and a macular hole stage II (n = 8), III (n = 72), and IV (n = 14) according to the classification by Gass were examined with optical coherence tomography (OCT) before pars plana vitrectomy. Macular hole diameters were determined at the level of the retinal pigment epithelium (base diameter) and at the minimal extent of the hole (minimum diameter). Calculated hole form factor (HFF) was correlated with the postoperative anatomical success rate and best corrected visual acuity. The duration of symptoms was correlated with base and minimum diameter of the macular hole. RESULTS: In eyes without anatomical closure of the macular hole after one surgical approach (13/94) the base diameter (p1) and the minimum diameter (p2) were significantly larger than in cases with immediate postsurgical closure (p1 = 0.003; p2 = 0.028). There was a significant negative correlation between both the base and the minimum diameter of the hole and the postoperative visual function (p1 = 0.016; p2 = 0.002). In all patients with HFF >0.9 the macular hole was closed following one surgical procedure, whereas in eyes with HFF <0.5 anatomical success rate was 67%. Better postoperative visual outcome correlated with higher HFF (p = 0.050). There was no significant correlation between the duration of symptoms and base or minimum diameters (p1 = 0.053; p2 = 0.164), respectively. CONCLUSION: Preoperative measurement of macular hole size with OCT can provide a prognostic factor for postoperative visual outcome and anatomical success rate of macular hole surgery. The duration of symptoms did not correlate with the diameters measured. Base and minimum diameters especially seem to be of predictive value in macular hole surgery.

Energy limitation of hummingbird populations in tropical and temperate communities.

Regular censuses were conducted at both a temperate alpine and a tropical lowland site to determine seasonal changes in the composition of hummingbird communities and the availability of their food. From these data we calculated the total daily energy demand by the hummingbirds (Daily Energy Expenditure; DEE) and the daily energy supply available from floral nectar (Daily Energy Production; DEP) for each community census. Despite differences in habitat type and hummingbird community structure between these two sites, the hummingbird populations were often at or near carrying capacity. On average, all of the daily nectar production was cropped by the birds. We suggest that the supply/demand economics of coevolved mutualisms favour the evolution of complete resource use.

MMPI-2 interpretation of patients with cerebrovascular disease: a correction factor.

The validity of the conventional Minnesota Multiphasic Personality Inventory (MMPI) interpretation as applied to neurologic patients has been increasingly questioned on the grounds of the test's psychiatric normative base and inclusion of items that may be sensitive to bona fide neurologic symptoms. This study used 110 patients with cerebrovascular disease (CVD) to (i) determine whether the 370-item pool of the MMPI-2 (abbreviated form) contains a unitary neurologic symptom factor, and (ii) devise a systematic approach to correct for patient endorsement of such items. Commonly endorsed items that differentiated the CVD sample from a group of normal adults were factor analyzed. Bona fide neurologic complaints (21 items) emerged as the major discriminative source of variance in the 370 MMPI-2 item pool that tends to inflate estimates of psychopathology (Scales 1, 2, 3, and 8), alter profile codes types, and potentially affect decision-making related to the diagnosis and treatment of CVD patients. Recommendations regarding a greater reliance upon content scales and the use of a corrective scoring key are discussed.

A procedure for assessing storage and retrieval on the Wechsler Memory Scale-Revised.

A methodology to assist in distinguishing deficient memory storage from compromised retrieval operations is presented for use with the Logical Memory (LM) and Visual Reproduction (VR) subtests of the Wechsler Memory Scale-Revised (WMS-R; Wechsler, 1987). A 21-item five-option multiple choice recognition test for LM and a cuing technique for VR are presented, followed by descriptive data based on a sample of 94 psychiatric inpatients (mixed diagnoses) and a sample of 99 brain-injured (BI) patients. The BI sample performed worse than the psychiatric sample on all of the LM and VR measures, with VR-CUED showing the highest degree of discrimination. In both groups, many subjects initially acquired much more information than they reported during the standard free recall format. The supplemental scoring format and reference data reported herein provide clinically useful information regarding a person's ability to store and access new information.

MMPI-2 interpretation and closed-head trauma: cross-validation of a correction factor.

A substantial body of research suggests that the MMPI-2 contains a number of items that are sensitive to closed-head trauma (CHT) and other neurologic conditions. A correction procedure was recommended by Gass (1991) using an index consisting of 14 neurologically sensitive items that were extracted from a predominantly male veteran sample of CHT patients. The generalizability of these correction items was assessed in the present study by investigating the MMPI-2 scoring characteristics of an outpatient referral sample of 54 CHT patients (28 male, 26 female) who had sustained recent and mild head trauma. Their frequency of endorsement of MMPI-2 was contrasted with that of the MMPI-2 normative sample (N = 2,600). Chi-square analyses identified the 15 MMPI-2 items that best differentiated this CHT sample from normal subjects. The results indicate that: (a) unlike those in an inpatient psychiatric sample (n = 524), the MMPI-2 items that best distinguished the CHT Ss from normals consisted of neurologic symptom content; (b) of these 15 items, 10 were included in the 14-item correction (Gass, 1991); and (c) 13 of the 14 correction items effectively discriminated the cross-validation sample of CHT Ss from normals. These findings offer empirical support for the application of the MMPI-2 correction with patients who have mild and recent head trauma.

MMPI correlates of poststroke neurobehavioral deficits.

MMPI profiles of 130 male veterans with cerebrovascular accidents were examined in relation to type and degree of neuropsychological deficit, hemispheric location of lesion, and time poststroke. Three neurobehavioral factors (Verbal, Visuospatial, Sensorimotor) were extracted from the Halstead-Reitan Battery and Wechsler Memory Scale. Canonical analyses revealed verbal impairment to be associated with greater openness in reporting emotional difficulties (Scale F) and limited social facility (Scale Hy). Sensorimotor deficits were associated with anxiety and distress (Pt) in patients with left hemisphere (LHD) but not right hemisphere damage (RHD). Although RHD and LHD patients had similar composite MMPI profiles, neuropsychological deficits in RHD were unrelated to MMPI scores. Time poststroke was independent of MMPI findings in both LHD and RHD samples.

Familial Creutzfeldt-Jakob disease: a neuropsychological case study.

The spectrum of neuropsychological features of familial Creutzfeldt-Jakob disease (CJD) have seldom been reported, possibly because of (a) the rarity of this hereditary form of prion disease; (b) frequent delays in diagnosis, and; (c) the typically rapid demise of the patient, which affords little opportunity for comprehensive testing or serial analysis. Here we describe the neurobehavioral characteristics of a 48-year-old right-handed male (JD) who presented with complaints of poor depth perception, unsteady gait, and unusual sensory experiences in his face and neck. JD was followed serially over the final 4 months of his 5-month illness. Immediately following hospital admission, he underwent a neuropsychological evaluation that revealed moderate to severe impairment of delayed (30-minute) verbal memory, tactual performance in his right hand, and word-finding ability. In contrast, other abilities that are commonly classified within the verbal, visuospatial, and memory domains showed minimal or no compromise. Parallel studies of electroencephalographic activity revealed diffuse slowing and, later, 1-Hz rhythmical discharges over the left hemisphere, and mild prominence of the lateral ventricles and cerebral sulci on magnetic resonance imaging. Autopsy revealed spongiform changes and reactive astrocytosis, and genetic testing demonstrated a codon 200 mutation in the prion protein gene. These findings indicate that CJD can result in clinical manifestations compatible with multifocal asymmetric cerebral involvement before more diffuse neurodegeneration ensues, providing a strong impetus for the study of additional cases. This long-term understanding can help to determine whether the multiple loci of clinical involvement are specified by genetic or epigenetic factors, or both.

[Preoperative scanning laser ophthalmoscopy: findings in idiopathic macular foramen]. / Präoperative Scanning-Laser-Ophthalmoskopie. Befunde bei idiopathischem Makulaforamen.

BACKGROUND: The aim of our study was a detailed morphological and functional assessment of macular foramen stages II-IV by scanning laser ophthalmoscopy (SLO) and fundus perimetry including a correlation with clinical findings. METHODS AND MATERIALS: Included in this prospective study were 78 patients where SLO imaging and fundus perimetry were performed with the SLO-105 (Rodenstock) prior to pars plana vitrectomy for macular foramen on one eye. Both the size and shape the of macular foramen were assessed. Deep (0 dB) and relative (12 dB) scotomata were tested using the Goldmann II stimulus in the 20 degrees field of the SLO. Imaging was performed with the infrared laser and confocal aperture C2. RESULTS: The size of macular foramen ranged from 140 microns to 800 microns (median: 420 microns) and 20 (26%) had irregular, polycyclic borders. In 21 patients (27%) a bright sector could be seen just outside the hole. Deep scotomata were notably smaller than the visible macular hole in 4 patients (6%) and 18 deep scotomata (25%) extended beyond the hole. There was a weak inverse correlation between the size of deep, relative scotomata and the diameter of the macular holes with the visual acuity (r = -0.46; r = -0.39 or r = -0.53), but no correlation with the duration of symptoms could be demonstrated. CONCLUSION: Polycyclic borders were seen as a new feature of some idiopathic macular foramen. This may be due to asymmetric traction or adhesions on the macular area. Also, deep scotomata either smaller or larger than the visible macular hole were found.

[Imaging of vitreoretinal adhesions in the partner eye of patients with penetrating macular foramina in optical coherence tomography]. / Darstellung vitreoretinaler Adhärenzen in Partneraugen von Patienten mit durchgreifenden Makulaforamina in der optischen Kohärenztomographie.

BACKGROUND: Vitreoretinal adhesions play a crucial role in the development of a macular hole. To visualize vitreoretinal adhesion we used optical coherence tomography to investigate fellow eyes of patients with macular holes. METHODS: In a prospective study we scanned the retina in 188 patients with a macular hole stage III or IV (Gass classification). The foveal shape and vitreous were classified into grades. RESULTS: Of the 188 patients 45% showed no vitreous reflex, 45% a partial vitreous detachment with foveolar adhesions, and 10% a vitreous detachment with complete separation from the fovea. While eyes with normal foveolar shape displayed partial vitreous detachment in 33%, this figure rose to 66% in eyes with a macular hole stage I. CONCLUSION: Diffuse thickening of the fovea is followed by an intraretinal split and formation of a cyst. The shape of the foveolar adhesion suggests that continuing anteroposterior vitreal traction leads to a retinal break and formation of a full-thickness macular hole.

MMPI-2 scale F(p) and symptom feigning: scale refinement.

The F(p) scale of the MMPI-2 is widely used to help identify exaggeration of psychological problems in psychiatric, forensic, and neuropsychological settings. The scale was constructed by selecting all MMPI-2 items (N = 27) that were endorsed by less than 20% of a sample of VA psychiatric inpatients and 20% of the normative sample used in restandardizing the MMPI-2. Although F(p) is used to measure symptom exaggeration and malingering, 4 of its 27 items load on the Lie (L) scale, which is known to be a measure of defensiveness and symptom underreporting. These four items, which express a denial of occasional anger, irritability, and procrastination, could conceivably measure an uncommon expression of defensiveness. This study used 150 neuropsychological referrals to test the hypotheses that (a) the four L scale items measure defensiveness, not exaggeration, and (b) the elimination of these items improves the utility of F(p) in assessing symptom exaggeration. The results indicate that the four L scale items are associated with defensiveness, not with symptom exaggeration. One third of the patients had an average T-score artifact of 9.5 points on F(p) as a result of endorsing these L scale items, with a range of 0T to 21T. Using the K scale as a criterion for level of problem disclosure, a shortened version of F(p) (omitting the four L scale items) was superior to F(p) as a measure of symptom exaggeration (r = -.46 vs. -.36, r2 = 21% vs. 13% of the variance). The implications for clinical practice are discussed.

MMPI-2 short form: psychometric characteristics in a neuropsychological setting.

A 180-item short form of the MMPI-2 (MMPI-2-180) was recently developed by Dahlstrom and Archer and has been proposed for clinical use under special circumstances. This study investigated the psychometric characteristics of the MMPI-2-180 in order to delineate its strengths, limitations, and appropriate scope of clinical application. Using a neuropsychological referral sample (N = 205), we examined accuracy of the short-form as it pertains to the following (a) the prediction of basic scale scores and profile code types, (b) the identification of high-point scales, and (c) the classification of scores as pathological (T > or = 65) or normal range. The results indicate that the MMPI-2-180 provides an unreliable basis for predicting clinical code types, identifying the high-point scale, or predicting the scores on most of the basic scales. In contrast, scores on the MMPI-2-180 are accurate predictors of whether the full-scale scores fall within the pathological range (T > or = 65). These findings suggest that (a) standard interpretive procedures involving profile configuration should not be used, in most cases, with the 180-item short-form results, (b) properly interpreted, this shortened version provides potentially useful information regarding the probable presence of various problem areas, and (c) this information is very limited when contrasted with that obtained using the complete or abbreviated (i.e., 370 item) version of the MMPI-2.

Interpretation of VIQ-PIQ and intersubtest differences on the Spanish version of the WAIS.

Although the Spanish version of the Wechsler Adult Intelligence Scale (WAIS; Escala de Inteligencia Wechsler para Adultos [EIWA]) is the most frequently used intellectual assessment for Spanish speaking clients in the United States, there is little information available on score differences necessary to establish reliable and abnormal differences between Performance IQ (PIQ) and Verbal IQ (VIQ), and between the various subtests of the EIWA. The present study, based on EIWA standardization data (N = 616 Puerto Ricans), reports reliability data and base rates to assist in evaluating the clinical significance of PIQ-VIQ differences. The results demonstrated substantial similarity between the EIWA and the English versions of the Wechsler tests. The interpretation of these differences is discussed, and tables are presented of statistically and clinically significant differences.