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BACKGROUND Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia. Although serum clozapine levels can help guide treatment, they are underutilized owing to requirements for frequent venous blood draws and lack of immediate results. METHODS Clozapine levels measured with a novel immunoassay technology (which enables point-of-care development) were compared with those measured by standard liquid chromatography/tandem mass spectrometry (LC-MS/MS). Frozen serum aliquots of 117 samples (N = 48 patients with schizophrenia on clozapine; N = 24 patients with schizophrenia not on clozapine; N = 45 healthy controls) were sent to a national reference laboratory (NRL) for clozapine level determination by LC-MS/MS, and matching samples were subjected to novel immunoassay (3 runs). At a later date, another frozen aliquot from the same date was sent to the NRL for repeat testing. RESULTS The NRL obtained 18 false-positive clozapine results (mean 42.39 ± 32.06, range 21-159 ng/mL) in participants not on clozapine (N = 3) and healthy controls (N = 15). The immunoassay showed no false-positive clozapine results. The clozapine levels were correlated between both assays (r = 0.84, P < 0.0001), despite 16% higher clozapine levels with immunoassay (482.08 ± 270.88 ng/mL immunoassay, 414.98 ± 186.29 ng/mL LC-MS/MS [P = 0.03]). Agreement analysis using concordance correlation coefficient (CCC) for LC-MS/MS of the 2 aliquots yielded CCC = 0.869; 95% confidence interval = 0.690-0.970, whereas higher agreement results were observed for the 3 runs of immunoassay (CCC = 0.99; 95% confidence interval = 0.979-0.997). CONCLUSIONS The lack of false positives observed with immunoassay, higher repeat performance agreement, and good correlation with LC-MS/MS may indicate the more robust performance of immunoassay than that of LC-MS/MS clozapine-level determination.

Patients with severe mental illness are falsely characterized as aggressive by the media, perpetuating stigma. While exaggerated, some patients with severe mental illness are more aggressive without treatment. Clozapine may have a unique anti-aggressive effect in patients with schizophrenia-related disorders, independent of antipsychotic or sedative effects. Limited data in forensic and involuntary committed patients is currently available.This study evaluates clozapine's effects on hostility and aggression in court-ordered Black patients.This study analyzes a subgroup of Black patients from a larger prospective 24-week open-label clozapine study. All patients were involuntarily committed and enrolled from two participating state psychiatric hospitals. The primary outcome measured was total use of 'as needed' (PRN) or 'immediate need' (STAT) medications for aggression/hostility. Secondary outcomes included number and duration of seclusion and restraint (S/R) episodes, and changes in Brief Psychiatric Rating Scale (BPRS) hostility factor score.Sixty-nine patients were included in our analysis. Significant reductions were noted in PRN/STAT medication use over time (χTreatment with clozapine effectively reduced hostility and aggression within this cohort of involuntarily committed Black patients with mental illness compared to baseline. Specifically, it helped lower the total number of PRN/STAT medication administrations and improved clinician-rated hostility factor scores on the BPRS. Our findings are pertinent as data in forensic settings is lacking and Black patients have been infrequently included in large prospective clinical trials with clozapine.NCT02404155.

Clozapine is an effective antipsychotic for treatment-resistant schizophrenia. One limitation of clozapine use is required monitoring of absolute neutrophil count (ANC) because of the risk of clozapine-induced neutropenia. Standard monitoring requires venous blood draws, which is a significant barrier to clozapine use.This study assesses the feasibility of use and physician and patient satisfaction of a novel point-of-care (POC) measure of ANC using Athelas One, a device that calculates white blood cell count and ANC using a fingerstick blood sample. This is a subanalysis of a prospective, open-label clinical trial of clozapine treatment, during which patients received a venous blood draw and a capillary fingerstick at baseline and Week 2 of the study, and completed a 5-point Likert scale, comparing the 2 methods.Patients reported benefits from the fingerstick technology, including POC testing being important for their doctors and their health, improved treatment, avoiding sending blood away, and convenience. There was a trend for less concern about the effects of blood draws on health with a fingerstick, and greater physician satisfaction with POC sampling.This study suggests the feasibility, satisfaction, and ease by both clinicians and patients of using POC testing for ANC monitoring during clozapine treatment.

Prolactin-related adverse effects contribute to nonadherence and adverse health consequences, particularly in women with severe mental illness. Treating these adverse effects may improve treatment acceptability, adherence, and long-term outcomes.Premenopausal women with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder were recruited for a randomized, double-blind, placebo-controlled 16-week trial of adjunct aripiprazole (5-15 mg/d). Participants had elevated prolactin (24 ng/mL) and were experiencing galactorrhea, amenorrhea, oligomenorrhea, or sexual dysfunction on a prolactin-elevating antipsychotic. Participants were evaluated biweekly for prolactin elevation and galactorrhea and completed a menstrual diary review. Psychiatric symptoms and adverse effects were closely monitored.Forty-six women were randomized (n = 25 aripiprazole, n = 21 placebo). Thirty-seven completed at least 8 weeks of the study (n = 20 [80%] aripiprazole and n = 17 [81%] placebo). Aripiprazole (mean dose, 11.7 ± 2.4 mg/d) was effective for lowering prolactin relative to placebo (P = 0.04). In addition, 45% (9/20) of the aripiprazole group had a normalized prolactin (24 mg/mL) compared with 12% (2/17) of the placebo group (P = 0.028). Galactorrhea resolved in 77% (10/13) of the aripiprazole-treated participants compared with 33% (4/12) in the placebo group (P = 0.028). Normalization of sexual function (16 on the Arizona Sexual Experience Scale) occurred in 50% on aripiprazole (7/14) versus 9% (1/11) on placebo (P = 0.030). No differences between groups in symptoms or adverse effects were noted. Overall, women rated a mean score of 4.6 ± 0.6 on a 5-point Likert scale for sexual function improvement, suggesting their particular satisfaction with improvement in this domain.Building upon prior studies, this rigorous evaluation confirms the utility of adjunctive aripiprazole as a strategy for improving prolactin and managing prolactin-related adverse effects in premenopausal women with psychosis.

While clozapine (CLZ) is the most effective antipsychotic drug for schizophrenia treatment, it remains underused. In order to understand the barriers of frequent blood draws for white blood cell counts (WBCs) and clozapine levels, we developed a psychiatrist survey and began an integrative approach of designing a point-of-care device that could eventually have real-time monitoring with immediate results.We ascertained barriers related to CLZ management and the acceptance of possible solutions by sending an anonymous survey to physicians in psychiatric practice (n=860). In parallel, we tested CLZ sensing using a prototype point-of-care monitoring device.255 responses were included in the survey results. The two barriers receiving mean scores with the highest agreement as being a significant barrier were patient nonadherence to blood work and blood work's burden on the patient (out of 28). Among nine solutions, the ability to obtain lab results in the physician's office or pharmacy was top ranked (mean±sd Likert scale [4.0±1.0]). Physicians responded that a point-of-care device to measure blood levels and WBCs would improve care and increase CLZ use. Residents ranked point-of-care devices higher than older physicians (4.07±0.87 vs. 3.47±1.08, p0.0001). Also, the prototype device was able to detect CLZ reliably in 1.6, 8.2, and 16.3 μg/mL buffered solutions.Survey results demonstrate physicians' desire for point-of-care monitoring technology, particularly among younger prescribers. Prototype sensor results identify that CLZ can be detected and integrated for future device development. Future development will also include integration of WBCs for a complete detection device.

Clozapine is the sole antipsychotic agent effective for the treatment of refractory schizophrenia. Sixty percent of clozapine-treated patients, however, fail to adequately respond. Minocycline, a tetracycline antibiotic, possesses antiinflammatory and neuroprotective properties that may play a role in schizophrenia. Clozapine is mainly metabolized by CYP1A2 enzymes, and minocycline may potentially inhibit CYP1A2 as hypothesized by case report data. To date, no pharmacokinetic interaction has been reported between minocycline and clozapine. This is a secondary analysis of a 10-week controlled study of adjunctive minocycline to clozapine in treatment refractory schizophrenia. Clozapine plasma levels were collected every two weeks during the study. 28 participants assigned to receive minocycline and 22 assigned to placebo were included. No differences existed in baseline demographics, clozapine dose or plasma levels. Average changes from baseline in clozapine plasma level (p = 0.033) were significantly higher in the minocycline group despite maintenance of stable doses. No statistically significant treatment differences were found in the norclozapine (p = 0.754) or total clozapine (p = 0.053) changes in plasma levels, although possible changes in total clozapine levels require further investigation. This analysis suggests that minocycline administration may lead to increased clozapine plasma levels. Further study is needed to examine possible explanations.

Background Clozapine is an effective antipsychotic for treatment-resistant schizophrenia that requires monitoring of the Absolute Neutrophil Count (ANC) due to the potential of clozapine induced neutropenia. Standard monitoring requires a routine venous draw which is considered one of the most significant barriers to patients starting or continuing the medication. This project assesses the feasibility, patient and clinician satisfaction with both venous blood drawing for ANC monitoring and a novel method for measuring ANC with a fingerstick using capillary blood. Methods During an open-label clinical trial of clozapine, participants with schizophrenia received both a venous blood draw and a capillary finger stick at baseline, week 2 and week 4. Capillary testing was done onsite using the newly FDA Class II cleared automated diagnostic device. This device performs tests on capillary finger stick samples collected directly into the provided test strip. This works by using a microfluidic test strip channel that creates a stained monolayer of white blood cells. Multiple images are taken of the monolayer and the cells are counted and classified by computer vision-based image analysis on a cloud server. This device offers technology that provides ANC results within 5 minutes using a small drop of blood drawn in the clinic and has been found to have a correlation to reference lab results of >0.94 in over 30, 000 testings. We measured patient satisfaction using a questionnaire with a 5-point Likert Scale rating domain of pain, worry, concern about blood volume, concern for where blood is sent and irritation with blood drawing and we anonymously measured clinical team members satisfaction with an anonymous survey. The study was conducted at two sites (one inpatient hospital and one research clinic) and approved by the Institutional Review Board at the University of Maryland and respective research committees. Results We enrolled 20 participants and 20 clinical team members for the surveys. Most patients believe the doctor is able to provide better care given immediate results. They also feel the elimination of unknown people touching the blood is a benefit of fingerstick monitoring. Patients indicated that they are more likely to remain on clozapine with fingerstick testing versus venous testing. There was a trend for higher agreement that using the venous blood draw negatively impacts their health (3.2 vs 2.8, p=0.068). In terms of pain, patients indicated that venous blood monitoring was slightly painful and more worrisome than fingerstick monitoring. Clinician ratings are high with mean scores >4 for satisfaction with device, satisfaction with immediate results, advancement in treatment, and improved patient care. Discussion The device is very user friendly and technology appears to be a significant advance for clinicians. Patients do not appear to worry about having venous blood draws or fingersticks but rate their most significant concern with venous blood draws is its negative effect on their health. However, patients strongly feel the fingerstick helps their doctors and their care. The use of POC devices may decrease or eliminate a significant barrier and may help improve the use of this underused evidence-based medication. Funding: This project was funded by NIMH R01MH102215 (Kelly PI). Athelas provided the Athelas One devices for two locations but provided no funding for the project.

Schizophrenia is a complex mental illness characterized by positive and negative symptoms. Antipsychotic medications are the main treatment for this condition; however, many patients have only a partial response. All currently available antipsychotics involve modulation of the dopamine system, although the underlying pathophysiology of this illness remains poorly understood. Increasing evidence suggests that inflammation plays a significant role in the development of schizophrenia. Thus, a medication that modulates both dopamine signaling and inflammation may be a promising treatment for schizophrenia. L-tetrahydropalmatine (l-THP) has modest affinity for dopamine receptors, acting as an antagonist at D1, D2, and D3 receptors. L-THP also has anti-inflammatory effects, decreasing levels of tumor necrosis factor-α and interleukin 6. We performed a 4-week, randomized, double-blind, placebo-controlled trial of oral l-THP (30 mg twice daily) as an adjunctive treatment in 63 adults with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) on stable antipsychotic medication. The primary psychiatric outcome measures were the presence of positive and negative symptoms. Plasma concentrations of 11 cytokines and C-reactive protein (CRP) were also measured. L-THP had no significant effect on any psychiatric measure but was well tolerated and associated with a significant decrease in extrapyramidal symptoms. L-THP significantly increased plasma concentrations, compared with placebo, of two inflammatory markers: soluble intracellular adhesion molecule 1 and CRP. These findings do not support the efficacy of L-THP as an add-on treatment for schizophrenia but suggest that L-THP may have previously unrecognized proinflammatory effects in people with this disease.

BACKGROUND: Cognitive behavior therapy for psychosis (CBTp) has been used with patients with schizophrenia for well over fifty years. Previous evaluations of CBTp have emphasized change in global scores of psychosis as the primary (if not the only) outcome, neglecting evaluation of change in patient distress and functioning. This method of practice is inconsistent with the theory and aims of the interventions used in CBTp, particularly from a recovery perspective. METHODS: Fifty-three patients with schizophrenia spectrum illnesses in an inpatient hospital were offered weekly, 60-minute group sessions of illness education using a CBTp framework. A retrospective review was completed, which examined participant attendance and average level of engagement across sessions. Primary outcomes were analyzed for subsets of patients and included change in distress secondary to symptoms (clinician derived rating scale and Clinical Global Impressions scale [CGI]), symptoms of depression (Calgary Depression Rating Scale [CDS]), global assessment of functioning (GAF), and severity of psychosis (Brief Psychiatric Rating Scale [BPRS]) from initiation of CBTp to discharge (or at time of data collection). Fourteen patients rated subjective distress and interference in functioning secondary to symptoms, satisfaction with CBTp group and utility of skills learned. RESULTS: On average, participants attended 32.0 (27.2) groups, or 70.6% of groups offered. Moderate to high engagement across sessions was observed in 84% of the sample. Analyses of change from initiation of CBTp to endpoint yielded significant reduction in distress secondary to symptoms on both clinician ratings (W=666, p

BACKGROUND: Women with serious mental illnesses like bipolar disorder and schizophrenia are more likely to be tobacco smokers as compared to women without mental illness. Antipsychotic medications may impact craving and nicotine’s rewarding effects via dopaminergic neurotransmitter activity. Differences in pharmacologic profiles and receptor affinity among antipsychotic agents may lead to variability in impact on craving and/or substance use. Aripiprazole, a partial dopamine agonist antipsychotic, may impact tobacco craving. To our knowledge, no one has specifically examined tobacco craving/usage patterns in women with psychotic disorders treated with adjunctive aripiprazole. METHODS: We report baseline and endpoint tobacco use/craving data for cigarette smokers completing a 16-week randomized double-blind placebo-controlled trial of adjunct aripiprazole vs placebo. Participants recruited were all women with high prolactin levels and not reporting any desire to change smoking behaviors, which provides the opportunity to look at a naturalistic population. Assessments included the Fagerstrom Test for Nicotine Dependence (FTND) Scale, the Tobacco Craving Questionnaire-Short Form (TCQ-SF), the Drug and Alcohol Use Summary, expired carbon monoxide (CO), and all answered questions about smoking habits at baseline, 8 weeks, and 16 weeks (endpoint). Between-group changes from baseline to endpoint were measured by Effect size (Cohen’s D) due to the underpowered pilot nature of the data. RESULTS: Of the 16 women smokers included, 9 were assigned to aripiprazole and 7 to placebo. The average age of participants was 38.5 years (SD=9.9) and mean age at onset of illness was 20.9 (SD=8). The average number of cigarettes smoked daily was 10.6 (SD=7.6) and the average years of smoking was 20.9 (SD=10.4). Of the 16 participants, 2 (12.5%) were diagnosed with bipolar disorder, 4 (25%) had schizoaffective disorder, and 10 (62.5%) had schizophrenia. There were no baseline differences in demographic or smoking measures between groups. During the 16-week study the FTND scores were moderately decreased with aripiprazole relative to placebo with an effect size (ES) of -0.49. The ES for expired CO favoring aripiprazole was -0.86, however there wasn’t a decrease in the aripiprazole group, only an increase noted in the study with placebo. Aripiprazole, compared to placebo, did not appear to affect the number of cigarettes smoked daily (ES= -0.22) or the TCQ-SF scores (ES= 0.20). DISCUSSION: This pilot study is the first to evaluate the effect of adjunct aripiprazole on measures of tobacco and use and craving in women smokers with psychotic disorders. In this small sample there were moderate effect size favoring adjunct aripiprazole on a decrease in dependency scores but not in craving and cigarette smoking. Future research should investigate the impact of aripiprazole on tobacco craving in a larger sample. Additionally, both men and women should be included for a representative sample and to examine potential sex differences. This study was funded by NIMH R01 (MH090071-04) (Kelly PI) and NIDA K23 (DA034034-01A1) (Wehring PI). Aripiprazole and matching placebo were supplied by Bristol-Myers Squibb/Otsuka.

BACKGROUND: Clozapine is an effective antipsychotic for treatment-resistant schizophrenia for which serum levels could guide therapy decisions. It is underutilized because it requires venous draws and several-day determination time with high performance liquid chromatography-tandem mass spectrometry (LC/MS-MS). This project evaluates if clozapine measured with a novel immunoassay technology, which could be developed into a fingerstick test, correlate with LC/MS-MS. This project also assesses the impact of demographic and clinical variables on assay results. METHODS: 117 serum samples (N=48 with schizophrenia on clozapine, N=24 with schizophrenia not on clozapine and N=45 healthy controls) were included. One aliquot was sent to a national reference laboratory (NRL) for determination by LC/MS-MS and another sent to Saladax for immunoassay (MyCare® Psychiatry Clozapine Assay Kit). The agreement was compared using Concordance Correlation Coefficient (CCC). Participants’ age, sex, race-ethnicity, smoking status, ascorbic acid, co-medications and complete metabolic panel were collected. Linear regression and mixed model were performed for both technologies correspondingly to examine the impact of these variables. RESULTS: Clozapine levels by the NRL had 19 false positive readings (mean 48.8 ± 14.3, range 21–138 ng/ml) in schizophrenia participants not on clozapine (N=3) and healthy controls (N=16). The immunoassay had no false positive results. A mixed effects model (with a time average of the NRL and 3 immunoassay runs), yielded a strong Pearson correlation (r=0.843, p

Background: Approximately one-third of people with schizophrenia have elevated levels of antigliadin antibodies of the immunoglobulin G type (AGA IgG) — a higher rate than seen in healthy controls. We performed the first double-blind clinical trial of gluten-free versus gluten-containing diets in a subset of patients with schizophrenia who were positive for AGA IgG. Methods: In this pilot feasibility study, 16 participants with schizophrenia or schizoaffective disorder who had elevated AGA IgG (≥ 20 U) but were negative for celiac disease were admitted to an inpatient unit for a 5-week trial. All participants received standardized gluten-free meals and were randomized in a double-blind fashion to receive a shake containing 10 g of gluten flour or 10 g of rice flour each day. Participants were rated for psychiatric, cognitive and gastrointestinal symptoms at baseline and end point. Results: Of the 16 participants, 14 completed the 5-week trial (2 discontinued early for administrative reasons). Compared with participants on the gluten-containing diet, participants on the gluten-free diet showed improvement on the Clinical Global Impressions scale (Cohen d = −0.75) and in negative symptoms (Cohen d = −0.53). We noted no improvement in positive or global cognitive symptoms, but did observe an improvement in attention favouring the gluten-free diet (Cohen d = 0.60). Robust improvements in gastrointestinal adverse effects occurred in the gluten-free group relative to the gluten-containing group. Adverse effects were similar between groups. Limitations: This study was limited by its small sample size; larger studies are needed. Conclusion: This feasibility study suggests that removal of gluten from the diet is associated with improvement in psychiatric and gastrointestinal symptoms in people with schizophrenia or schizoaffective disorder.

Introduction: In our study, we reviewed efficacy and complication rates of open subinguinal varicocelectomy (OSV) and loupe assisted subinguinal varicocelectomy (LASV) using seminal and hormonal parameters in a prospective randomized study. Materials and Methods: We prospectively studied 60 males with Grade 2 and Grade 3 varicocele. Thirty patients underwent OSV and the other 30 patients underwent LASV. Intra-operative and post-operative complications along with pre-operative and post-operative seminal, hormonal parameters and testicular volume were compared between the groups. Results: Sperm count, motility and morphology increased significantly in both groups, but the improvement was significantly better in LASV group. (Group A – improvement in sperm count, motility and morphology by 25%, 8.5%, 10.3%, respectively and in Group B – improvement in sperm count, motility and morphology by 110%, 68.59%, 71.1%, respectively. Decrease in serum follicular stimulating hormone (FSH), luteinizing hormone (LH) and increase in serum testosterone were significant in both groups, but the improvement was significantly better in LASV group. (Group A – serum FSH and LH decreased by 17.2%, 23%, respectively and serum testosterone increased by 13.7% and in Group B – serum FSH and LH decreased by 56.9%, 56.65%, respectively and serum testosterone increased by 95.9%). The recurrence (OSV = 13.2% and LASV = 0, P = 0.01) and complication rates were significantly lower in LASV group. Conclusion: Our study shows that LASV is significantly better than OSV regarding efficacy and complication rates.

Objective Clozapine is the most effective antipsychotic for treatment refractory people with schizophrenia, yet many patients only partially respond. Accumulating preclinical and clinical data suggest benefits with minocycline. We tested adjunct minocycline to clozapine in a 10-week, double-blind, placebo-controlled trial. Primary outcomes tested were positive, and cognitive symptoms, while avolition, anxiety/depression, and negative symptoms were secondary outcomes. Methods Schizophrenia and schizoaffective participants (n = 52) with persistent positive symptoms were randomized to receive adjunct minocycline (100 mg oral capsule twice daily; n = 29) or placebo (n = 23). Results Brief Psychiatric Rating Scale (BPRS) psychosis factor (P = 0.098; effect size [ES], 0.39) and BPRS total score (P = 0.075; ES, 0.55) were not significant. A change in total BPRS symptoms of more than or equal to 30% was observed in 7 (25%) of 28 among minocycline and 1 (4%) of 23 among placebo participants, respectively (P = 0.044). Global cognitive function (MATRICS Consensus Cognitive Battery) did not differ, although there was a significant variation in size of treatment effects among cognitive domains (P = 0.03), with significant improvement in working memory favoring minocycline (P = 0.023; ES, 0.41). The Scale for the Assessment of Negative Symptoms total score did not differ, but significant improvement in avolition with minocycline was noted (P = 0.012; ES, 0.34). Significant improvement in the BPRS anxiety/depression factor was observed with minocycline (P = 0.028; ES, 0.49). Minocycline was well tolerated with significantly fewer headaches and constipation compared with placebo. Conclusions Minocycline's effect on the MATRICS Consensus Cognitive Battery composite score and positive symptoms were not statistically significant. Significant improvements with minocycline were seen in working memory, avolition, and anxiety/depressive symptoms in a chronic population with persistent symptoms. Larger studies are needed to validate these findings.

Popular media often portray people with a mental illness as being aggressive, violent, and incarcerated as a result of their behavior. Despite exaggeration in the media, risks for some aggressive behaviors are in fact higher in individuals with schizophrenia. This is often the case with influence of comorbid substance use disorders. It is essential that mental health professionals are aware of treatments that may help with attenuating and treating behaviors that contribute to violence, aggression and incarceration. This paper reviews violence and incarceration in individuals with schizophrenia as well as recommendations, guidelines and benefits for the use of clozapine in this population. Clozapine remains one of the most underutilized evidence-based medications available in the psychiatric arena in the United States. It is a viable and recommended option in the forensic population and it may be helpful on the path to recovery as well as bring substantial savings to the criminal justice system.

Women have been largely underrepresented in clinical trials in schizophrenia yet have a different presentation of symptoms, such as higher affective symptoms compared to men. Thus, adjunctive antipsychotic treatment, particularly low-dose aripiprazole, in women may be an effective strategy, particularly for its effects on anxious or depressive symptoms. Premenopausal women with schizophrenia or bipolar disorder were recruited for a randomized double-blind, 16-week trial of adjunct aripriprazole (5 to 15 mg day). The primary study population was those with symptomatic hyperprolactinemia (these results reported elsewhere). Stable participants were evaluated biweekly for psychiatric symptoms using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Calgary Depression Rating Scale (CDS), and the Clinical Global Improvement (CGI). The Psychological General Well Being Index (PGWB) and the Repeatable Battery for Assessment of Neurological Symptoms (RBANS) were performed monthly and end of study, respectively. Forty-four women were randomized and received medication (N = 24 aripiprazole and N = 20 placebo). Four aripiprazole participants discontinued (2 clinical worsening, 1 patient choice, and 1 nonadherence) and 3 discontinued in the placebo group (patient choice, medication nonadherence and administrative pharmacy error). There were no significant treatment differences in BPRS, SANS, CDS, or CGI scores between the aripiprazole and placebo groups ( > .05). Robust response on the total BPRS (>30% response) was noted in (12%) in the aripiprazole group vs. none in the placebo group ( = .12). There were no differences in RBANS or PGWB index scores and no differences in side effects noted. This clinical trial suggests that adjunct treatment aripiprazole to treat symptomatic hyperprolactinemia in clinically stable women does not significantly improve psychiatric symptoms in most patients. However, 12% of women had robust symptom improvements (>30%) in BPRS scores, and 10% had worsening of BPRS scores leading to discontinuation. No significant improvements were noted in any other clinical ratings such as anxiety, depression or cognition. Nonetheless, adjunct aripriprazole is a safe strategy for stable patients when added for symptomatic hyperprolatinemia, and future work should help distinguish which factors may predict robust symptoms improvements and which women may have clinical worsening that occur in about 10%–12% of patients using this strategy.

OBJECTIVE: To evaluate the darning method of inguinal hernia repair with polypropylene. MATERIAL AND METHODS: 125 Patient of unilateral or bilaterally inguinal hernia were admitted. After thorough investigations, all patients were operated for hernia repair by standard procedure using no-1 polypropylene. Patients were operated under spinal, general anesthesia or local anesthesia. Patients were followed up at one week, four weeks and six months after operation for wound healing and complications. RESULTS: Out of 125 patients, ranging in age from 18 to 85 Years, 90 patients (72%) were given spinal anesthesia, 28 Patients, (22.4%) were operated under general anesthesia, 7 patients under local anesthesia. Patients were discharged from the hospital after 4 days. 20 Patients were above 50 yr. who were operated under spinal anesthesia were catheterized to prevent urinary retentions. Recurrence rate was 1.6% CONCLUSION: Darning methods of inguinal hernia repair with polypropylene is a safe and cheaper method of hernia repair.

BACKGROUND: Morbidity and premature mortality is high in schizophrenia. Poor diets, low rates of physical activity, substance use, and lack of preventative care predispose patients to poor physical health and comorbid medical diseases. Women with schizophrenia have distinct preventative and physical health needs which poses and even greater burden on disease risk. We evaluated laboratory measures and health indices in women with schizophrenia having antipsychotic-induced hyperprolactinemia. METHODS: This study includes data from a one-time fasting laboratory screening visit in women treated with prolactin elevating antipsychotics (N=43). Laboratories were drawn in the follicular phase of the menstrual cycle if possible. Women were between the ages of 18–50 years and had a known high prolactin level (

SUMMARY: Twelve patients with empyema of the gall bladder were diagnosed among 325 cases of gall-bladder disease presenting to our department of surgery in three years period (March 2010 to March 2013). Abdominal pain was present for average of eight days in four cases andin four cases, for between one and four months. In some cases, the disease was painless and was found unexpectedly at operation for chromic cholecystitis disease. The severity of the problem was subdued by the often scanty physical signs. Less than 50% the patients had pyrexia of more than 38.5C and the presence of sepsis was rarely suspected clinically. None of the patients died. This considerable morbidity could be reduced by the wider use of blood culture in cases of cholecystitis and by greater awareness that empyema of the gallbladder is sometimes chronic, painless, and afebrile. INTRODUCTION: Empyema of the gall bladder was described extensively in surgical texts of the early years of this century1-3 but now rarely mentioned4. In addition, it appears to have been largely forgotten that its course can be chronic2, 3. It could be due to the wider use of antibiotics, along with the increasingly followed policy of early cholecystectomy for acute gall-bladder disease4-6. We have recently treated several elderly patients in whom the disease was markedly milder event. As the number of old people in the population is rising, it seemed important to determine whether this neglected disease is still an important problem and to redefine its natural history. We decided, therefore, to review all cases of empyema of the gall bladder which had presented to our hospital over a period of three years. METHODS: Empyema was defined as an inflamed gall bladder which contained pus (figure 1, 2, 3).The presence of inflammation and pus were established from the operation record, the gallbladder swab report, and the histology report on the resected gall bladder, cases of generalized infection of the biliary tree were designated as cholangitis and excluded from the study. From the 325 sets of case notes, 12 patients (3.69%) were identified who fulfilled these criteria and, on stringent review by all the authors, were agreed to be true examples of this disease. These cases were analyzed to determine their age and sex distribution, and their clinical and pathological features. RESULTS: The 12 patients were mostly elderly, their average age being 60 years (range 40-80 years). There were nine women and three men, giving a female preponderance of three to one. Six patients had no abdominal pain and the empyema were found unexpectedly, two at ultrasonography and in a further four patients, empyema was found at routine cholecystectomy, after a long history of apparently mild pain. The remaining six patients (50%) presented with abdominal pain of sufficient

Occurrence of Spigelian Hernia is rare accounting for 0.12% of all ventral hernias 1 . It is most commonly reported in adults while pediatric cases are rare. Though the association of Spigelian-Cryptorchidism syndrome has been comprehensively reported in pediatric patients, the same has not been detailed so far for the adult patient population. We herein discuss two cases of Spigelian hernia, both adults in whom intra-operative exploration revealed associated ipsilateral undescended testis. Not only is the pre-operative diagnosis seldom if ever, the imaging studies may not be successful in differentiating the type of hernia2,3. Even in the present cases radiological studies were inconclusive and definitive diagnosis was only attained intra-operatively.

INTRODUCTION: Laparoscopic Cholecystectomy has evolved as the standard of care for the treatment of Gall Stone disease over the past decade. Several patient and procedure related factors have been implicated in setting of failure to complete the procedure by minimal invasive method and various scores have been developed to precisely predict a Difficult Laparoscopic Cholecystectomy. AIMS: The present study was conducted to ascertain various patient related preoperative risk factors for conversion of laparoscopic Cholecystectomy to open method and to validate the Risk Score for conversion. SETTINGS & DESIGN: A total of 100 patients with diagnosis of Gall Stone Disease admitted to our surgical Unit between October 2011 and April 2013 were assessed for various pre-determined risk factors and were accordingly categorized into three levels of anticipated difficulty according to RSCLO and our new scoring system. The patients were then subjected to Laparoscopic Cholecystectomy by the same surgical team and the procedure was then graded as difficult or not according to the pre-defined criteria. The findings were analysed by appropriate statistical analysis. RESULTS: Presence of factors like Male sex, history of attacks of acute cholecystitis, increased GB wall thickness, presence of supra-umbilical abdominal scar, obesity and a contracted GB were associated with a significantly higher rate of conversion to open method. RSCLO was found to correlate better with the outcome in this setting than our New Scoring System. CONCLUSION: Several patient related factors may be helpful in predicting a Difficult Laparoscopic Cholecystectomy pre-operatively. RSCLO Scoring system may be useful as a pre-operative tool to predict intra-operative difficulty during LC.

Introduction: Fournier's gangrene is an aggressive disease with high morbidity and mortality. The aim of this study was to assess risk factors associated with mortality among patients of Fournier's gangrene. Materials and Methods: Between May 2011 and September 2012, all patients of Fournier's gangrene treated at our center were included in the study. All patients underwent emergency surgical debridement and received broad spectrum intravenous antibiotics. Their baseline characteristics, treatment, and follow-up data were recorded and analyzed. Results: A total of 30 patients were included in the study. Of these, six patients (20%) died during the treatment. Age >55 years, total leukocyte count >15000 cumm, extent of the area involved, septic shock at admission, visual analog scale (VAS) >7 at admission, and Fournier gangrene severity index (FGSI) score >8 at admission were significantly associated with increased mortality. Conclusion : In patients of Fournier's gangrene, increased age, total leukocyte count, extent of the area involved, septic shock at admission, VAS score, and FGSI score at admission have a significant association with mortality.

Background: Accumulating evidence suggests minocycline (MINO) is effective as an adjunct treatment in schizophrenia. We previously reported significant improvement in avolition, anxiety/depression and working memory and a trend for positive symptoms and total Brief Psychiatric Rating Scale (BPRS) scores with MINO in a double-blind, placebo-controlled trial. We also found a >30% reduction in total BPRS scores in 25% of the MINO group compared to 4% in placebo (P = .04). Here we examine variables associated with symptom improvements.

Background: Benign ethnic neutropenia (BEN) is the occurrence of absolute neutrophil counts (ANC) of less than 1500 cells/mm3 observed in 10% to 30% of African and Middle Eastern ancestry individuals with no increased susceptibility to pyogenic infections. Recent evidence implicates polymorphism in the Duffy Antigen Receptor for Chemokines gene (DARC) in BEN persons of African descent. Until mid-2015 in the United States, the FDA clozapine treatment guidelines for ANC monitoring were based on normative ANC values in European ancestry populations without considerations for BEN. Compared with Caucasians, African Americans are less likely to be initiated on clozapine and their treatment twice as likely to be discontinued for neutropenia. Gathering data indicate no increased agranulocytosis risk in clozapine-treated BEN individuals. Advancing knowledge of BEN pathophysiology could reduce a substantial barrier to clozapine treatment in African-American patients.

Background: Hyperprolactinemia, a side effect of antipsychotic treatment, causes amenorrhea, oligomenorrhea, galactorrhea, gynecomastia, and sexual dysfunction. These side effects increase risk of antipsychotic nonadherence and pose significant problems in the long-term management, particularly in women with severe mental illness.

Biliary obstructions are rarely caused by a foreign body and have received sparse attention. We present an unusual case with pruritis and abdominal pain caused by impacted full length surgical gauze within the common bile duct. The patient had previously undergone an open cholecystectomy. Radiological investigations were inconclusive and suggestive of either a calculus or a cholangiocarcinoma. Surgical exploration revealed full length surgical gauze within the common bile duct. Because imaging modalities are often non-determinant, the possibility of biliary tract obstruction from a foreign body should be borne in mind for patients with unusual presentations, especially those who have previously undergone surgery.

Background: Several methods for detection of single nucleotide polymorphisms (SNPs; e.g., denaturing gradient gel electrophoresis and denaturing HPLC) are indirectly based on the principle of differential melting of heteroduplex DNA. We present a method for detecting SNPs that is directly based on this principle. Methods: We used a double-stranded DNA-specific fluorescent dye, SYBR Green I (SYBR) in an efficient system (PE 7700 Sequence Detector) in which DNA melting was controlled and monitored in a 96-well plate format. We measured the decrease in fluorescence intensity that accompanied DNA duplex denaturation, evaluating the effects of fragment length, dye concentration, DNA concentration, and sequence context using four naturally occurring polymorphisms (three SNPs and a single-base deletion/insertion). Results: DNA melting analysis (DM) was used successfully for variant detection, and we also discovered two previously unknown SNPs by this approach. Concentrations of DNA amplicons were readily monitored by SYBR fluorescence, and DNA amplicon concentrations were highly reproducible, with a CV of 2.6%. We readily detected differences in the melting temperature between homoduplex and heteroduplex fragments 15‐167 bp in length and differing by only a single nucleotide substitution. Conclusions: The efficiency and sensitivity of DMA make it highly suitable for the large-scale detection of sequence variants. © 2001 American Association for Clinical Chemistry Detection of variations in the canonical sequence of the human genome is a cornerstone for the analysis of genetic diseases, genetically influenced traits, and the origin and structure of populations. Single nucleotide polymorphisms (SNPs) 1 comprise the most abundant category of DNA sequence variation, occurring at a rate of ;1 per 500 nucleotides in coding sequences and at a higher rate in noncoding sequences (1 ). Genome wide there are several million common SNPs. SNPs are highly amenable for high-throughput genotyping using efficient methodologies, including DNA arrays (2‐ 4) , mass spectrometry (5 ), and PCR end-plate read methods such as TaqMan (PE 7700 Sequence Detector) (6 ). For this reason, detection of SNPs of moderate or high abundance (i.e., with rare allele frequencies of .10%) has been made a high priority and may be successfully accomplished by analyzing a relatively small complement of chromosomes. Sequencing of 10 chromosomes (five persons) detects approximately two-thirds of all sequence variants with a frequency of 10%. However, SNPs that alter gene expression or affect structure of the gene product often are rare. Sequencing of 10 chromosomes detects ,10% of sequence variants with a frequency of 1%, a frequently used definition for polymorphism. The continuing requirement for detection of rare SNPs will maintain the need for high-throughput, inexpensive methods for sequence variant detection. Sequence variant detection methods access physical properties of DNA. Several of the most powerful methods for SNP detection [e.g., denaturing gradient gel electrophoresis (DGGE) and denaturing HPLC (dHPLC)] are ultimately based on the thermodynamic properties of DNA duplexes or singlestranded DNA [i.e., single strand conformational polymorphism (SSCP) analysis]. For many years it has been understood that the relative thermostability of a DNA duplex increases with increas

Introduction: Acute scrotum is a common reason for emergency consultation. Early scrotal exploration is mandatory if torsion of the testis suspected clinically. Objectives: To study management and clinical outcome of patients admitted with acute scrotal condition. Methods: This was a prospective observational study involving 60 patients hospitalized for Acute scrotum at tertiary rural centre, from September 2014 to September 2016. Patients admitted with complaints of acute pain and swelling of scrotum irrespective of age and gender were included in the study. Patient with painless scrotal swelling and those with chronic scrotal pain were excluded from the study. Patients were monitored post-operatively till discharge and followed for 1 month for any complications. Results: Of the 60 patients in our study, acute epididymo-orchitis (36.6%) was the dominant cause of acute scrotal swelling followed by scrotal abscess (23.3%). 51.6% of the patients were managed conservatively, which were diagnosed as epididymoorchitis and haematocele. 14 patients underwent incision and drainage who diagnosed as scrotal abscess; 7 patients diagnosed as fournier's underwent debridement; 5 underwent orchidectomy or orchidopexy while 3 underwent B/L orchidopexy. Out of 8 cases of torsion of testis, bilateral orchidopexy was done in 3 cases (37.5%) in which we were able to salvage the affected testis. Out of the 60 patients, maximum patients (41 patients) required a hospital stay of 1-10 days. All patients were followed up for a period of 1month after discharge. None of the patients had any serious complications. Conclusion: Acute scrotum can be successfully managed by consevative methods after exclusion of Torsion of testis. Early exploration can salvage the testis in cases of torsion of testis. Key words: Acute orchiepididymitis; Acute scrotal swelling; Fournier's gangrene; Orchidectomy; Orchidopexy; Torsion of testis.