The use of benzodiazepine monotherapy for major depression before and after implementation of guidelines for benzodiazepine use.

WHAT IS KNOWN AND OBJECTIVE: The Department of Health (DOH) in Taiwan issued the 'Guidelines for Benzodiazepine Use in Sedation and Hypnosis' in March 2004, which clearly stated that benzodiazepines (BZDs) should not be used alone for the treatment of depression. However, the extent to which clinicians comply with the BZD guidelines was not known. This study aimed to evaluate whether sole prescribing of BZDs for major depression decreased after the implementation of the BZD guidelines. METHODS: This was a retrospective longitudinal trend analysis by analyzing the Longitudinal Health Insurance Database (LHID) from September 2002 to September 2005. The LHID contains all claims data from a random sample of 1,000,000 beneficiaries of the universal National Health Insurance programme in Taiwan. The 3-year study period was divided equally into six periods, before and after the implementation of the guidelines respectively. For each period, the proportion of patients with major depression (ICD-9-CM code 296.2x, 296.3x) treated with BZDs without any concomitant antidepressant was calculated in order to conduct a trend analysis. RESULTS AND DISCUSSION: A total of 5463 prescriptions of BZDs solely used for major depression were observed in the entire study period. In more than 80% of the BZD prescriptions in which BZDs were used alone for major depression, they were prescribed at doses higher than one prescribed daily dose/defined daily dose and were supplied for more than 7 days. The number of outpatients with major depression ranged from 2137 to 3326 during the 12 periods. The proportion of depressed patients treated with BZDs alone per 3 months (i.e., the non-compliance rate) fluctuated from 6·7% to 9·4% before implementation of the guidelines, and from 8·0% to 9·4% after implementation, in outpatient settings. In addition, the guideline non-adherence rates in inpatient settings varied from 7·0% to 11·8% and from 7·8% to 12·6% before and after the implementation of the BZD guidelines respectively. Further trend analyses indicated that the implementation of the guidelines was not associated with a reduced rate of sole prescribing of BZDs for major depression in either inpatient (P = 0·083) or outpatient settings (P = 0·925). WHAT IS NEW AND CONCLUSION: The formulation and implementation of the BZD guidelines appear not to be associated with a reduced rate of sole prescribing of BZDs for major depression, and more comprehensive efforts are required.

The coding-synonymous polymorphism rs1045280 (Ser280Ser) in beta-arrestin 2 (ARRB2) gene is associated with tardive dyskinesia in Chinese patients with schizophrenia.

BACKGROUND: Tardive dyskinesia (TD) is a severe and potentially irreversible adverse effect of long-term antipsychotic treatment. Typical antipsychotics are commonly binding to the dopamine receptor D2 (DRD2), but the occurrence of antipsychotic-induced TD is rather delayed; therefore, the development of TD may be associated with mediators or signalling complexes behind DRD2, such as beta-arrestin 2 (ARRB2), an important mediator between DRD2 and serine-threonine protein kinase (AKT) signal cascade. METHODS: A case-control study to evaluate the association between rs1045280 (Ser280Ser) and antipsychotic-induced TD was performed amongst 381 patients (TD/non-TD = 228/153). RESULTS: There was a significant difference in the genotype distribution between TD and non-TD groups (P = 0.025); furthermore, the allelic analysis indicated that patients with T allele had increased risk of TD occurrence (OR(T) = 1.58, 95% CI = 1.14-2.19, P = 0.007). CONCLUSIONS: To the best of our knowledge, this is the first study reporting a positive association between the SNP rs1045280 and TD in schizophrenic patients.

Allergic contact dermatitis caused by latanoprost ophthalmic solution.

PURPOSE: Latanoprost is a prostaglandin F2 alfa analog that lowers intraocular pressure by increasing uveoscleral outflow. Herein we describe two cases of allergic contact dermatitis (ACD) to latanoprost. METHODS: A 69-year-old man with open-angle glaucoma developed erythematous erosive swelling of bilateral eyelids after 4 months of latanoprost therapy. An 84-year-old man with open-angle glaucoma had pruritic erythematous plaques on the bilateral lower eyelids after latanoprost therapy for 4 months. RESULTS: In both cases, latanoprost was discontinued and the condition gradually resolved in 1 month. The eyelid lesions recurred in days upon latanoprost rechallenge, but subsided after cessation of rechallenge. CONCLUSIONS: ACD should be suspected if patients on latanoprost therapy have pruritus, erythema, swelling, or erosions on the eyelids even when the symptoms appear after several months of therapy, especially in the elderly.

Potentially inappropriate prescribing for insomnia in elderly outpatients in Taiwan.

OBJECTIVE: This study was based on Taiwan's National Health Insurance (NHI) claim records with the aim of identifying specific types of potentially inappropriate sedative-hypnotic prescribing in elderly outpatients with insomnia. The potentially inappropriate prescribing included duplicate treatment, excessive dosage and duration or treatment and prescribing of hypnotics that are too long-acting. MATERIAL AND METHODS: This cross-sectional study was based on annual outpatient claim data for 2001 released by Taiwan's Bureau of National Health Insurance (BNHI). A subset was created for patients aged 65 years or older and coded as having insomnia. Physician consultation claim data were extracted and merged in 1 claim file consisting of ICD-9-CM codes, patient demographic data, specialty of physicians, medical institution code and pharmaceutical prescription content. RESULTS: Elderly patients with insomnia constituted 216,994 of the 1,000,193 files surveyed on outpatient claims in 2001. The mean age was 74.33 years and gender distribution was nearly equal. Of the prescribed sleep medications, 41.26% were hypnotic benzodiazepines, 29.36% were hypnotic non-benzodiazepines and 29.38% were sedative-anxiolytics. Approximately 1 in 25 patients (4.12%) of all the patients prescribed hypnotics received duplicate treatment, 1 in 8 an inappropriately (12.27%) high dosage (daily dose > 1.5 DDD, Defined Daily Dose), 1 in 3 (32.25%) more than 28 DDD per prescription and 1 in 6 (17.52%) a drug with an effect which was too prolonged. Physicians tended to consider patient gender but not age when prescribing. Clear trends were found between the specialty of the physician and the type of inappropriate prescribing. The type of medical institution was significantly related only to the excessive quantity of medication prescribed. CONCLUSIONS: Elderly people in Taiwan with insomnia receive potentially inappropriate prescriptions for sleep medications. Similar data could possibly be extracted from similar databases in other countries throughout the world. Some of these potentially inappropriate prescriptions are avoidable in terms of restricting the length of outpatient sedative-hypnotic treatment, introducing hypnotics in small dosage forms and continuously educating clinicians on the safety of geriatric medication.

Polymorphism of the adrenergic receptor alpha 2a -1291C>G genetic variation and clozapine-induced weight gain.

Weight gain, leading to further morbidity and poor treatment compliance, is a common consequence of treatment with clozapine. The substantial interindividual and interracial differences in drug-induced weight gain suggest that genetic factors may be important. Several studies showed that alpha-2, adrenoceptor may related to feeding behavior with rat or lipolytic activity of human adipocyte tissue, they are related to body weight change. In the study, we try to test the possible relation of clozapine-induced weight gain and adrenergic receptor alpha 2a -1291C>G genetic polymorphism in a long term follow up (14.0 +/- 6.2 months). Our results show the genotype GG (8.45 +/- 7.2 Kg) with higher mean body weight gain than genotype CC (2.79 +/- 6.1 Kg) (p = 0.023). The finding identify a genetic factor associated with clozapine-induced weight gain in schizophrenic patients.

Negative association between catechol-O-methyltransferase (COMT) gene Val158Met polymorphism and persistent tardive dyskinesia in schizophrenia.

Chronic administration of typical antipsychotic agents, which mainly act on the dopamine receptors, implicates a role of dopamine system on the susceptibility of tardive dyskinesia (TD). In the present study, the association between a functional Val158Met polymorphism of Catechol-O-methyltransferase (COMT) gene and TD occurrence and TD severity was investigated in 299 Chinese schizophrenic patients with long-term antipsychotic treatment (TD: 166, non-TD: 133). After adjusting the effects of confounding factors, there was no significant association between COMT genotype and TD occurrence (p=0.367). Among TD patients, we found no significant correlation between COMT genotypes and the total scores of abnormal involuntary movement scale (AIMS) (p=0.629). We concluded that this COMT polymorphism might not play a major role in the susceptibility of TD nor on the severity of TD.

Association study of nicotinic-receptor variants and major depressive disorder.

BACKGROUND: Depressive patients are more likely to smoke than the general population and nicotine was found to reduce the incidence and severity of depressive symptoms in many studies. These findings suggest that nicotinic acetylcholine receptors (nAChRs) may be implicated in major depressive disorder. We tested the hypothesis that the allelic variant, 2 bp deletion, of the partially duplicated alpha7 nAChR gene confers susceptibility to major depressive disorder. METHODS: We genotyped alpha7 nAChR in 72 patients with major depressive disorder and 103 normal controls. RESULTS: The distribution of the partially duplicated alpha7 nAChR genotypes (P=0.027) and alleles (P=0.037) suggests a modest difference between depressive patients and controls. LIMITATIONS: The -2 bp allele is thought to be present only in the duplicated exon 6, and the impact of the partially duplicated alpha7 nAChR and its -2 bp variant remain to be determined. CONCLUSIONS: The -2 bp allele of partially duplicated alpha7 nAChR may have an influence on the risk for development of major depressive disorder. The levels of significance achieved are modest and the findings must be replicated in other studies.

Association analysis of the partially duplicated alpha7 nicotinic acetylcholine receptor genetic variant and Alzheimer's disease.

Changes in the nicotinic acetylcholine receptors (nAChRs) have been demonstrated for Alzheimer's disease (AD). Of these receptors, the alpha7 nAChRs, which are abundant on hippocampal interneurons, have been implicated in the cytotoxic role of the beta-amyloid. Increased mRNA levels of alpha7 nAChR in the peripheral lymphocytes and hippocampus of AD patients have been reported. We tested the hypothesis that the allelic variant, 2bp deletion, of the partially duplicated alpha7 nAChR gene confers susceptibility to Alzheimer's disease. The -2bp polymorphism was examined in 120 patients with AD and 98 normal controls. The distribution of the partially duplicated alpha7 nAChR genotypes (p = 0.372) and alleles (p = 0.465) did not differ significantly for AD patients and controls. This negative finding suggests that the partially duplicated alpha7 nAChR genetic polymorphism contributes no major effect to the development of AD. However, we suggest that the other genetic variation of the alpha7 nAChR gene, related to AD or the associated symptomatology, merits further investigation.

Measurement of the lambda(+)(c) lifetime.

The Lambda+c lifetime is measured using 9.0 fb(-1) of e+e- annihilation data collected on or just below the Upsilon(4S) resonance with the CLEO II.V detector at CESR. Using an unbinned maximum likelihood fit, the Lambda+c lifetime is measured to be 179.6+/-6.9(stat)+/-4.4(syst) fs. The precision of this colliding beam measurement is comparable to other measurements, which are based on fixed-target experiments, with different systematic uncertainties.

Association analysis of a functional catechol-o-methyltransferase gene polymorphism in schizophrenic patients in Taiwan.

The catechol-O-methyltransferase (COMT) gene was thought to be a candidate gene for schizophrenia because of its role in inactivating dopamine. This study examined the relationship between a functional polymorphism (val158met) of the COMT gene, schizophrenia and its associated behaviors. One hundred and ninety-eight Chinese schizophrenic patients and 188 controls were genotyped by polymerase chain reaction restriction fragment length polymorphism. Of the schizophrenic patients, 72 had a history of violence and 62 had a history of suicide attempts. The results failed to show significant association between val158met polymorphism and schizophrenia, violence or suicide. However, our results showed a significant difference in age at disease onset among different genotypes (F = 5.501, p = 0.005).

Association study of a nicotinic receptor variant with schizophrenic disorders.

Nicotine acetylcholine receptors (nAChRs) are implicated in the pathogenesis of schizophrenia because the prevalence of smoking among schizophrenic patients is extraordinarily high, and nicotine has been demonstrated to improve some psychophysiological dysfunction in schizophrenics. In addition, recent studies have suggested linkage of the alpha(7) nAChR gene region in families of schizophrenics. In a population-based association study, we tested the hypothesis that the allelic variant, with a 2-bp deletion, of the human alpha(7) nAChR gene confers susceptibility to schizophrenic disorders. We genotyped alpha(7) nAChR in 146 patients with schizophrenic disorders and 151 controls. The results showed no significant difference in genotype or allele frequencies between schizophrenic patients and control subjects. This suggests that alpha(7) nAChR 2-bp deletion plays no major role in the pathogenesis of schizophrenic disorders. Other nAChR variants in schizophrenic disorders may need further investigation.

Lens subluxation: 10-years' experience at Chang Gung Memorial Hospital, Kaohsiung.

BACKGROUND: This study aimed to describe the clinical manifestations and surgical outcomes of subluxated lens. METHODS: Reviewing charts from January 1991 to June 2000, we studied 110 patients (123 eyes) who had lens subluxation at Chang Gung Memorial Hospital, Kaohsiung. For 21 eyes, patients accepted conservative treatment, and 102 eyes underwent surgery (8 eyes had Marfan syndrome; 18 eyes had idiopathic dislocation; and 76 eyes had experienced trauma). Indications of surgery included reduction in visual acuity, uncorrectable refractive error, and secondary glaucoma. RESULTS: There were 81 male and 29 female patients. Their mean age was 47.6 years (range, 2-76 years). The mean post-operative follow-up period was 22.24 months (range, 2-118 months). In spite of the different lens statuses, similar visual results were found between the surgical treatment group and the nonsurgery group. In the surgery group, 47 eyes (46.1%) achieved best corrected visual acuity (BCVA) of 20/40 or better. A total of 80 eyes (78.4%) achieved an improvement (log MAR change >0.3) in BCVA. The major postoperative complications included glaucoma (11 eyes), retinal detachment (9 eyes) and intraocular lens dislocation into the vitreous cavity (3 eyes). CONCLUSIONS: Results indicate that the presence of a subluxated lens alone is not an absolute indication for surgical removal. The lens status had no significant influence on surgical outcome. Most cases can achieve an improvement in BCVA after appropriate management.

Study of charmless hadronic B meson decays to pseudoscalar-vector final states.

We report results of searches for charmless hadronic B meson decays to pseudoscalar( pi(+/-), K+/-, pi(0), or K(0)(S))-vector( rho, K(*), or omega) final states. By using 9.7x10(6) BB pairs collected with the CLEO detector, we report the first observation of B(-)--->pi(-)rho(0), B(0)-->pi(+/-)rho(-/+), and B(-)-->pi(-)omega, which are expected to be dominated by hadronic b-->u transitions. The measured branching fractions are (10.4(+3.3)(-3.4)+/-2.1)x10(-6), (27.6(+8.4)(-7.4)+/-4.2)x10(-6), and (11.3(+3.3)(-2.9)+/-1. 4)x10(-6), respectively. Branching fraction upper limits are set for all of the other decay modes investigated.

Observation of B --> K(+/-) pi(0) and B --> (K)0 pi(0), and evidence for B --> pi(+)pi(-).

We have studied charmless hadronic decays of B mesons into two-body final states with kaons and pions and observe three new processes with the following branching fractions: beta(B-->pi(+)pi(-)) = (4.3(+1. 6)(-1.4)+/-0.5)x10(-6), beta(B-->K(0)pi(0)) = (14.6(+5.9+2.4)(-5.1-3. 3))x10(-6), and beta(B-->K(+)/-pi(0)) = (11.6(+3.0+1.4)(-2.7-1.3))x10(-6). We also update our previous measurements for the decays B-->K(+)/-pi(-/+) and B+/--->K(0)pi(+/-).

The treatment of Pseudomonas keratoscleritis after pterygium excision.

PURPOSE: To assess the effect of intensive topical and intravenous antibiotics plus oral prednisolone and surgical debridement in Pseudomonas keratoscleritis after pterygium excision. METHODS: We describe three cases of P. aeruginosa-induced keratoscleritis occurring 10 days to 18 months after uncomplicated pterygium excision. Treatment included early conjunctival debridement, topical and intravenous antibiotics, and low-dosage oral prednisolone. RESULTS: All three patients responded to the combined therapy. Microorganisms were eliminated, and ulcers were healed within 8 weeks. Treatment was not extended beyond that, and infection did not recur. No evisceration was required. The patients' best corrected visual acuities are 20/200, 20/400, and 20/120, respectively. CONCLUSION: Early diagnosis and prompt, intensive medical and surgical treatment may save a patient's vision and forestall evisceration.