Medullary Thyroid Cancer: An Experience from a Tertiary Care Hospital of a Developing Country.

Background: Medullary thyroid carcinoma (MTC) is a rare type of thyroid cancer that occasionally occurs as part of MEN2A. The universal treatment of MTC is total thyroidectomy with central lymph node dissection. For disease progression, carcinoembryonic antigen (CEA) and calcitonin (CTN) need to be followed. Our aim was to study the presence and patterns of the above-mentioned characteristics of MTC in our population. Methodology: This retrospective study was conducted in a tertiary care hospital of Pakistan in which data of thirty-two medullary thyroid cancer patients over the past 20 years were reviewed and analysed after fulfilment of inclusion criteria. Their clinical, pathological, biochemical and treatment modalities were recorded through a retrospective review of their medical record files. Results: The mean age of patients was 42.88 ± 2.67 years in our study, with a male-to-female ratio of 2:1. Patients with sporadic MTC were 68.8%, while 31.2% were familial. The rates of metastasis were highest in bones followed by lungs and liver. Total thyroidectomy was performed in 26 (81.2%) patients and among those chemotherapy and XRT were performed in one and two patients, respectively. Histologically, the mean tumour size was 7.62 ± 3.64 cm. Median pre-surgery calcitonin was 5756 pg/ml that decreased to 29.3 pg/ml post-surgery. Median pre-surgery CEA level was 246.5 ng/ml that decreased to 6.39 ng/ml post-surgery. Two patients were RET positive. Conclusion: MTC usually presents in the fourth decade of life with male predominance and mostly sporadic occurrence. Total thyroidectomy with subsequent serial calcitonin and CEA levels thereafter are the mainstay of treatment and follow-up.

Inter-agency collaboration and disaster management: A case study of the 2005 earthquake disaster in Pakistan.

In post disastrous situations, coordinated and integrated interventions aimed at relief and rehabilitation not only help facilitate reaching out to the affected communities in a timely fashion but also pave the way to channel scarce and valued resources towards end users in an efficient and effective manner. This article attempts to trace the origins and gradual development of 'inter-agency collaboration' and the implications thereof for disaster management strategies in Pakistan through an analysis of relief and rehabilitation interventions undertaken by the Government of Pakistan in collaboration with local and international Non-governmental Organisations (NGOs) and relief agencies in the ex post of the 2005 earthquake. Data for this study were collected through structured and semi-structured interviews from government officials, representatives of NGOs and relief agencies and ordinary women and men in the earthquake stricken localities of Balakot and Mansehra districts of Pakistan. On the heels of the 2005 earthquake, both local NGOs and faith-based organisations in concert with international NGOs and relief agencies from around the world rushed to assist Pakistan in it's rescue and relief operations at a time when the country was faced with the twin dilemma of both the non-existence of peculiar institutional arrangements for disaster management and a lack of the necessary technical and financial resources. The aftermath of the 2005 earthquake offered opportunity to the Government of Pakistan and the NGOs and relief agencies alike to transform their individual interventions into a robust and organised 'inter-agency collaboration', which was later on realised in the form of establishment of a national disaster management organisation called the 'Earthquake Reconstruction and Rehabilitation Authority (ERRA)'. The establishment of ERRA not only paved the way for avoiding duplication and wastage of resources but also ensued in reaching out to the affected communities in a timely fashion. The Pakistani case offers implications in terms of highlighting the salience of establishing 'inter-agency collaboration' in other settings.

Meta-Analysis of Inclisiran for the Treatment of Hypercholesterolemia.

Statin therapy is the gold standard for hypercholesterolemia. However, a significant number of patients cannot achieve their target low-density lipoprotein (LDL) levels despite a maximal dose of statin therapy, and some cannot tolerate statins at all. Approval of proprotein convertase subtilisin/kexin type 9 inhibitors has been revolutionary for those patients. However, the need for frequent injections limits patient compliance with their use. Recently, a twice-yearly injection of inclisiran, a small interfering RNA, has been shown to inhibit hepatic synthesis of proprotein convertase subtilisin/kexin type 9. However, patient randomized clinical trial has been underpowered for clinical end points, necessitating a meta-analysis of those trials. The weighted mean difference was used to describe continuous variables, and pooled risk ratios, calculated using a random effects model, were used to describe discrete variables. Data from 3 randomized clinical trials comprising 3,660 patients showed that inclisiran decreased LDL cholesterol levels by 51% (95% Confidence Interval, 48 to 53%; p < 0.001) compared with placebo. It was associated with a 24% lower major adverse cardiovascular events rate (risk ratios = 0.76; 95% Confidence Interval, 0.61 to 0.92). It also significantly decreased total cholesterol by 37%, apolipoprotein B by 41%, and non high-density lipoprotein (HDL) cholesterol by 45% (all p < 0.001). No differences were found in adverse events, abnormalities in liver function tests, or creatine kinase levels between the treatment strategies. However, a mild injection site reaction occurred more frequently in the inclisiran group. In conclusions, in patients with hypercholesterolemia, inclisiran decreased LDL level by 51% without significant adverse effects. Additionally, it was associated with a lower major adverse cardiovascular event rate.

Short-term versus long-term triple antithrombotic therapy for patients with coronary stents and requiring oral anticoagulation: a meta-analysis of randomized clinical trials.

BACKGROUND: The cornerstone therapy for patients with coronary stents is dual antiplatelet therapy (DAPT). In 5-10% of these patients, oral anticoagulation (OAC) is clearly indicated in addition to DAPT. However, the optimal duration of this triple antithrombotic therapy (TAT) remains uncertain. PATIENTS AND METHODS: Scientific databases and websites were searched for randomized clinical trials (RCTs). RCTs were included if patients undergoing coronary stent placements with additional indications of chronic OAC were randomly assigned to either short-term TAT or long-term TAT. Short-term TAT was defined as no more than 6 weeks of TAT, and long-term TAT was defined as 6-12 months of TAT RESULTS: Using data from three RCTs and 1883 patients, short-term TAT was associated with decreased rates of major adverse cardiovascular events, cardiac mortality, all-cause mortality, and any-bleeding events compared to long-term TAT, but similar rates of myocardial infarction, stroke, stent thrombosis, and thrombolysis in myocardial infarction major bleeding. Furthermore, in subgroup analysis, short-term TAT was associated with decreased rates of major adverse cardiovascular events, cardiac mortality, all-cause mortality, and any-bleeding compared to 12-month TAT, but similar rates compared to 6-month TAT. CONCLUSION: In patients who require chronic OAC therapy and undergo coronary stent placement, short-term TAT was associated with better efficacy and safety outcomes compared to long-term TAT.

A Meta-Analysis of Aspirin for the Primary Prevention of Cardiovascular Diseases in the Context of Contemporary Preventive Strategies.

BACKGROUND: The role of aspirin for primary prevention of cardiovascular diseases remains controversial, particularly in the context of contemporary aggressive preventive strategies. METHODS: Relevant randomized clinical trials were included, and risk ratios (RRs) were calculated using random-effects models. Additional moderator analyses were performed to compare the pooled treatment effects from recent trials (those reported after the guidelines of the National Cholesterol Education Program Third Adult Treatment Panel were published in 2001; thus, conducted on the background of contemporary preventive strategies) to the results of older trials. RESULTS: Data from 14 randomized controlled trials involving 164,751 patients were included. Aspirin use decreased myocardial infarction risk by 16% compared with placebo (RR 0.84; 95% confidence interval [CI], 0.75-0.94); however, in the moderator analyses, aspirin was not associated with a decreased risk of myocardial infarction in recent trials, but was in older trials (P-interaction = .02). Overall, aspirin use significantly increased the occurrence of major bleeding (RR 1.49; 95% CI, 1.32-1.69) and hemorrhagic stroke (RR 1.25; 95% CI, 1.01-1.54). In moderator analyses, the risk of major bleeding (P-interaction = .12) or hemorrhagic stroke (P-interaction = .44) with aspirin was not significantly different between the older and new trials. Differences between aspirin and placebo in the risks for all-cause stroke, cardiac death, and all-cause mortality were not found. CONCLUSIONS: In the context of contemporary primary prevention guidelines, the effect of aspirin on myocardial infarction risk was significantly attenuated, whereas its major bleeding and hemorrhagic stroke complications were retained. Therefore, in contemporary practice, routine use of aspirin for the primary prevention of cardiovascular events may have a net harmful effect.

A comprehensive meta-analysis of stem cell therapy for chronic angina.

BACKGROUND: A substantial proportion of patients with coronary artery disease do not achieve complete revascularization and continue to experience refractory angina despite optimal medical therapy. Recently, stem cell therapy has emerged as a potential therapeutic option for these patients. However, findings of individual trials have been scrutinized because of their small sample sizes and lack of statistical power. Therefore, we conducted an updated comprehensive meta-analysis of available randomized controlled trials (RCTs) with the largest sample size ever reported on this subject. HYPOTHESIS: In patients with chronic angina stem cell therapy improves clinical outcomes. METHODS: Scientific databases and websites were searched for RCTs. Data were independently collected by 2 investigators, and disagreements were resolved by consensus. Data from 10 trials including 658 patients were analyzed. RESULTS: Stem cell therapy improved Canadian Cardiovascular Society angina class (risk ratio: 1.53, 95% CI: 1.09 to 2.15, P = 0.013), exercise capacity (standardized mean difference [SMD]: 0.56, 95% CI: 0.23 to 0.88, P = 0.001), and left ventricular ejection fraction (SMD: 0.63, 95% CI: 0.27 to 1.00, P = 0.001) compared with placebo. It also decreased anginal episodes (SMD: -1.21, 95% CI: -2.40 to -0.02, P = 0.045) and myocardial perfusion defects (SMD: -0.70, 95% CI: -1.11 to -0.29, P = 0.001). However, no improvements in all-cause mortality were observed after a relatively short follow-up. CONCLUSIONS: In patients with chronic angina on optimal medical therapy, stem cell therapy improves symptoms, exercise capacity, and left ventricular ejection fraction. These findings warrant confirmation using larger trials.

High-volume forced diuresis with matched hydration using the RenalGuard System to prevent contrast-induced nephropathy: A meta-analysis of randomized trials.

BACKGROUND: Contrast-induced nephropathy (CIN) is a well-recognized complication of coronary angiography that is associated with poor outcomes. Several small randomized controlled trials (RCTs) have recently shown that in patients with chronic kidney disease (CKD), furosemide-induced forced diuresis with matched hydration using the RenalGuard system can prevent its occurrence. However, individual studies have been underpowered and thus cannot show significant differences in major clinical endpoints. HYPOTHESIS: Forced diuresis with matched hydration using the RenalGuard system improves clinical outcomes in patients undergoing coronary angiography. METHODS: Scientific databases and websites were searched for relevant RCTs. The pooled risk ratios were calculated using random-effects models. The primary endpoint was CIN, and the secondary endpoints were major adverse clinical events (MACEs) and the need for renal replacement therapy. RESULTS: Data from 3 trials including 586 patients were analyzed. High-volume forced diuresis with matched hydration using the RenalGuard system decreased risk of CIN by 60% (risk ratio: 0.40, 95% confidence interval: 0.25 to 0.65, P < 0.001), MACE rate by 59%, and the need for renal replacement therapy by 78%, compared with the standard of care. CONCLUSIONS: In patients with CKD undergoing coronary angiography, high-volume forced diuresis with matched hydration using the RenalGuard system significantly reduces the risk of CIN, MACE rate, and the need for renal replacement therapy. Larger RCTs with sufficient power are needed to confirm these findings.

Candidate gene studies of attention-deficit/hyperactivity disorder.

A growing body of behavioral and molecular genetics literature has indicated that the development of attention-deficit/hyperactivity disorder (ADHD) may be attributed to both genetic and environmental factors. Family, twin, and adoption studies provide compelling evidence that genes play a strong role in mediating susceptibility to ADHD. Molecular genetic studies suggest that the genetic architecture of ADHD is complex, while the handful of genome-wide scans conducted thus far is not conclusive. In contrast, the many candidate gene studies of ADHD have produced substantial evidence implicating several genes in the etiology of the disorder. For the 8 genes for which the same variant has been studied in 3 or more case-control or family-based studies, 7 show statistically significant evidence of association with ADHD based on pooled odds ratios across studies: the dopamine D4 receptor gene (DRD4), the dopamine D5 receptor gene (DRD5), the dopamine transporter gene (DAT), the dopamine beta-hydroxylase gene (DBH), the serotonin transporter gene (5-HTT), the serotonin receptor 1B gene (HTR1B), and the synaptosomal-associated protein 25 gene (SNAP25). Recent pharmacogenetic studies have correlated treatment nonresponse with particular gene markers, while preclinical studies have increased our understanding of gene expression paradigms and potential analogs for human trials. This literature review discusses the relevance and implications of genetic associations with ADHD for clinical practice and future research.

Assessing the Reliability and Validity of the Sheehan Irritability Scale in Patients With Major Depressive Disorder.

OBJECTIVE: Irritability is a significant component in the clinical manifestation of major depressive disorder (MDD). The Sheehan Irritability Scale (SIS) was developed to assess irritability-related symptoms in patients with psychiatric disorders. Data from a phase 2 clinical trial (June 2008-July 2009) was utilized to evaluate the psychometric properties of the SIS. The trial population included patients diagnosed with MDD, according to DSM-IV and confirmed via the MINI diagnostic scale, who had inadequate response to citalopram. METHOD: The secondary analyses included 586 patients from the United States and India. Data from the SIS, depression severity measures (17-item Hamilton Depression Rating Scale [HDRS-17], Montgomery-Asberg Depression Rating Scale [MADRS], Quick Inventory of Depressive Symptomatology-Self-Report [QIDS-SR]), and other measures (Sheehan Disability Scale [SDS], Clinical Global Impressions-Severity of Illness scale [CGI-S]) were used in the psychometric evaluation. All statistical tests used a significance level of .05 unless otherwise noted. RESULTS: Internal consistency (0.92-0.99) and test-retest reliability (0.83 to 0.98) were excellent. Concurrent validity was demonstrated through strong correlations between the SIS total score and HDRS-17, QIDS-SR, SDS, CGI-S, and MADRS scores. SIS total scores were significantly different by clinical severity level (P < .001). Minimally important difference estimates suggest that a 7- to 8-point change in the SIS total score may be clinically meaningful. CONCLUSIONS: The SIS has excellent reliability, acceptable validity, and good responsiveness, making the SIS appropriate for use in clinical research and practice. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00692445.

Validation and agreement across four versions of the asthma control questionnaire in patients with persistent asthma.

OBJECTIVE: The objectives of this study were to: 1) examine the psychometric properties of three shortened versions of the Asthma Control Questionnaire (ACQ) and their comparative performance with the original 7-item ACQ in persistent asthma patients; and 2) explore the concordance of asthma control outcomes from the four versions of the ACQ when compared with international guidelines for asthma control. METHOD: Post-hoc analyses of two large (n=737 and n=772) Phase III, randomized, double-blind, parallel-group, multi-center placebo-controlled studies of mometasone furoate/formoterol fumarate combination formulation compared with monotherapies in subjects with persistent asthma previously treated with low-dose or medium-dose inhaled glucocorticoids. This study examined the psychometric performance of the four ACQ versions and the concordance between these four versions with each other and international guidelines. RESULTS: The psychometric results for all four versions of the ACQ were robust, with Cronbach alphas ≥0.82 and test-retest ICCs ≥0.75. All versions of the ACQ were strongly correlated with each other (r≥0.97), as well the overall score from the AQLQ12+ for both baseline and change scores (|r|≥0.74). When the four ACQ versions were compared to each other, both cross sectional and longitudinal change concordances were mostly substantial, but agreements were lower when compared to international guidelines classifications. CONCLUSION: All ACQ versions have similar and strong psychometric properties. Classifications of change over time using the original ACQ and a six-item version without SABA use provided generally fair to moderate agreement with the international guidelines criteria for asthma control.

Direct and indirect costs of employees with treatment-resistant and non-treatment-resistant major depressive disorder.

OBJECTIVE: Treatment-resistant depression (TRD) imposes substantial cost from the perspective of employers. The objective of this study was to assess direct healthcare costs and indirect (disability and medical-related absenteeism) costs associated with TRD compared with non-treatment-resistant major depressive disorder (MDD). METHODS: Employees with one or more inpatient, or two or more outpatient/other MDD diagnoses (ICD-9-CM: 296.2x, 296.3x) from 2004 through 2007, ages 18-63 years, were selected from a claims database. Employees who initiated a third antidepressant following two antidepressant treatments of adequate dose and duration or who met published TRD criteria were classified as TRD likely (N = 2312). The index date was the date of the first antidepressant, starting 1/1/2004. The control group was an age- and sex-matched cohort of employees with MDD but without TRD. All had continuous eligibility during the 6-month pre-index (baseline) and 24-month post-index (study) period. McNemar tests were used to compare baseline comorbidities. Wilcoxon signed-rank tests were used to compare costs from employer perspective. RESULTS: TRD-likely employees were on average 48 years old, and 64.8% were women. Compared with MDD controls, TRD-likely employees had significantly higher rates of mental-health disorders, chronic pain, fibromyalgia, and higher Charlson Comorbidity Index. Average direct 2-year costs were significantly higher for TRD-likely employees ($22,784) compared with MDD controls ($11,733), p < 0.0001. Average indirect costs were also higher among TRD-likely employees ($12,765) compared with MDD controls ($6885), p < 0.0001. LIMITATIONS: Limitations of claims data related to accuracy of diagnosis coding and lack of clinical information apply to this study. CONCLUSIONS: Based on comorbidities and healthcare resources used, patients with TRD appeared to represent a clinically complex subgroup of individuals with MDD. TRD was associated with significant cost burden.

The genetics of ADHD: a literature review of 2005.

Investigations into the genetic basis of attention-deficit/hyperactivity disorder (ADHD) continue to yield compelling results as candidate gene studies reveal more information about this elusive disorder. Family, twin, and adoption studies further the notion that ADHD is a highly heritable disorder with direct genetic and environmental influence. The year 2005 saw many ADHD candidate gene studies, with most focused on the catecholaminergic candidates. Although many genes were studied in 2005, a large portion of findings has been supportive of the roles of dopaminergic genes' relationship to clinical phenotypes and drug response. These studies often require replication. Clinical implications continue to be speculative, as larger sample sizes are needed to validate findings to the general population. Further understanding of endophenotypes and the impact of comorbidities also is necessary for proper clinical intervention. Forthwith, we provide a summary of ADHD genetic studies published in 2005.

Programmable high-speed polarization multiplexed optical scanner.

A fast digital-analog control polarization-based optical scanner with complete three-dimensional beam-forming programmability is described. Its features include low power consumption and large-aperture liquid-crystal-based optics, digital repeatability, and time-multiplexed accurate analog beam forming. Analog frequency and amplitude control of the nematic liquid-crystal beam-former cells permits continuous fine-scan programmability over a 0.66-mrad horizontal deflection, a 0.75 mrad vertical deflection, and an infinity-to-1.84-m focal-length longitudinal scan. First demonstrations included an 8-point volumetric scan and a 2-bit digital lens scan, both at 1310 nm, with a 35-micros random-access time.

Liquid-crystal-deflector based variable fiber-optic attenuator.

A compact, low-component-count, no-moving-parts variable optical attenuator (VOA) is demonstrated for the first time by means of beam spoiling that is implemented via an electrically reconfigurable nonpixelated nematic liquid-crystal deflector. The VOA design features an in-line alignment polarization-insensitive design that does not use bulky polarization splitting and combining optics. The proof-of-concept VOA at 1550 nm demonstrates a 30-dB attenuation range, a 2.5-dB insertion loss, a < or = 0.8-dB polarization-dependent loss, and a 1-s maximum attenuation reset time. The VOA design can counter performance-reducing environmental effects such as excess-loss increases due to temperature variations.