UK Haemoglobin Disorders Peer Review: A Quality Standards-based review programme for sickle cell disease and thalassaemia.

We evaluated the impact of peer reviews in driving improvement in healthcare quality for people with haemoglobinopathy in the United Kingdom. We analysed compliance to four Quality Standards (QS)-based peer reviews from 2010 to 2020 to evaluate its impact in driving healthcare quality. Seventeen paediatric and 29 adult haemoglobinopathy centres were reviewed in 2010/11 and 2012/13 respectively; 33 paediatric and 33 adult centres were reviewed in 2014/16, and 32 paediatric and 32 adult centres were reviewed in 2018/2020. Compliance with QS and participant feedback were analysed to assess the impact of peer review programmes to drive improvement in quality of care. We noted that haemoglobinopathy centres significantly improved their compliance to QS between the first two review programmes, but not in the final review programme. In comparison to other disease-group reviews, the haemoglobinopathy departments were less able to address critical peer review recommendations in their own institutions. The peer review programme was unable to drive sustained improvement in healthcare quality, underscoring the need for sustained development and support for haemoglobinopathy services in the National Health Service. Further work is needed to understand why disparities exist among peer review-driven improvement initiatives within different disease groups.

Uttar Pradesh Association of Physicians of India Position Statement: Betel Quid (Paan) and Diabetes.

Betel quid (paan) chewing is common in India, especially in Uttar Pradesh. Betel quid has multifaceted relationship with health, including metabolic and psychosocial health. The current recommendations have been released keeping in view the public health and clinical importance of this addictive behavior. The objective of this document is to offer clinical guidance for screening, diagnosis and management of co-occurring betel quid chewing among persons with Diabetes Mellitus (DM). The document aims to provide education and guidance to clinicians engaged in care and management of persons with DM, and improve access to treatment for co-occurring betel quid chewing among persons with DM. The current recommendation grades are based on published evidence, and categorized as strong, intermediate, weak and no evidence. The strength of these recommendations is based on the level of evidence.

Uttar Pradesh Association of Physicians of India Position Statement: Tobacco Use and Metabolic Syndrome.

Tobacco use is one of the main preventable causes of mortality and morbidity worldwide. The global disease burden due to tobacco use is huge with projected mortality of eight million lives per year by 2030. Metabolic syndrome (MS) is defined as a constellation of cardiovascular and endocrine risk factors such as insulin resistance, obesity, raised blood pressure, and abnormal lipid profile. The relationship between tobacco use and MS has been well established. Also, the causal association between tobacco use and development of individual components of MS is well established. The Uttar Pradesh Association of Physicians of India (UP API) has drafted this position statement on managing tobacco use among persons with or at risk of developing Metabolic Syndrome (MS). This position statement presents evidence-based recommendations as described below. Scope and purpose The objective of this position statement is to offer clinical recommendations for screening, diagnosis and management of tobacco use among persons with or at risk of developing Metabolic Syndrome (MS). The purpose of this document is to aid in identification and treatment of maladaptive patterns of tobacco use i.e. tobacco use disorder (tobacco dependence, harmful use, abuse) in person with or at risk of developing MS. Intended Audience The position statement is targeted at the clinicians engaged in care and management of person with or at risk of developing Metabolic Syndrome (MS). This might also be of relevance to the policy makers considering the public health burden of both MS and tobacco use disorders.

[Identification of new conserved and variable regions in the 16S rRNA gene of acetic acid bacteria and acetobacteraceae family].

The Acetobacteraceae family of the class Alpha Proteobacteria is comprised of high sugar and acid tolerant bacteria. The Acetic Acid Bacteria are the economically most significant group of this family because of its association with food products like vinegar, wine etc. Acetobacteraceae are often hard to culture in laboratory conditions and they also maintain very low abundances in their natural habitats. Thus identification of the organisms in such environments is greatly dependent on modern tools of molecular biology which require a thorough knowledge of specific conserved gene sequences that may act as primers and or probes. Moreover unconserved domains in genes also become markers for differentiating closely related genera. In bacteria, the 16S rRNA gene is an ideal candidate for such conserved and variable domains. In order to study the conserved and variable domains of the 16S rRNA gene of Acetic Acid Bacteria and the Acetobacteraceae family, sequences from publicly available databases were aligned and compared. Near complete sequences of the gene were also obtained from Kombucha tea biofilm, a known Acetobacteraceae family habitat, in order to corroborate the domains obtained from the alignment studies. The study indicated that the degree of conservation in the gene is significantly higher among the Acetic Acid Bacteria than the whole Acetobacteraceae family. Moreover it was also observed that the previously described hypervariable regions V1, V3, V5, V6 and V7 were more or less conserved in the family and the spans of the variable regions are quite distinct as well.

The role of baseline insomnia in moderating the hypnotic properties of quetiapine.

INTRODUCTION: The primary aim of this study was to investigate the effect of quetiapine on insomnia and alcohol craving (craving) in subjects with co-occurring insomnia and AUD. METHODS: Insomnia was assessed with the Insomnia Severity Index (ISI) and craving with the Penn Alcohol Craving Scale (PACS, primary) and Obsessive-Compulsive Drinking Scale (OCDS, secondary). A multivariable model adjusted for covariates (N = 123) evaluated the relationship between craving (PACS and OCDS total scores) and insomnia (ISI total score). To simultaneously assess the effects of treatment arm allocation and insomnia status, subjects (N = 115) were stratified into 4 groups, quetiapine-insomnia(N = 38), quetiapine-No insomnia(N = 19), placebo-insomnia(N = 38), and placebo-No insomnia(N = 20). Linear mixed-effects regression models adjusted for covariates compared the trajectories of ISI, PACS, and OCDS total scores across 12 weeks of treatment and at post-treatment follow-up at week 24, between the four groups. RESULTS: The ISI total score was positively associated with the PACS (p = 0.006) and OCDS (p = 0.001) total scores in the multivariable models. In the longitudinal analysis, when compared to the three other groups, subjects with insomnia treated with quetiapine showed a marked reduction in their insomnia scores with a return of insomnia after stopping treatment. There was no significant difference between the groups for the PACS and OCDS total score trajectories. DISCUSSION: Although craving is associated with insomnia, treatment with quetiapine may improve insomnia but not craving in patients with co-occurring AUD and insomnia.

Superficial angiomyxoma of the external ear not associated with Carney's complex: a case report.

Superficial angiomyxomas are rare tumours and multiple tumours occurring in the external ear are invariably associated with Carney's complex. In the present study, a solitary superficial angiomyxoma was found in a 20 year old lady; and there was no evidence of any of the components of Carney's complex at the time of presentation or at the end of 2 years of follow-up, after the surgical excision of the tumour.

The effect of Plasmodium falciparum infection on expression of monocyte surface molecules.

Plasmodium falciparum infection may result in severe malaria in susceptible individuals. The pathogenesis of severe disease is probably a combination of the sequestration of infected erythrocytes and overstimulation of the immune response. Monocytes are a key source of many of the pro-inflammatory agents implicated but also are found sequestered in blood vessels. However, little is known about the monocyte phenotype in malaria disease. Flow cytometry was performed on fresh whole blood to determine surface expression of four receptors during acute severe and non-severe malaria and again during convalescence when uninfected. Three hundred and fifty-six children with P. falciparum infection were studied and were found to show increased expression of intercellular adhesion molecule-1 (ICAM-1), urokinase plasminogen activator receptor (uPAR), CD23 and chemokine receptor 5 (CCR5) (P<0.001) during acute disease compared with convalescent levels. Using multivariate analysis, it was found that large increases in expression of ICAM-1 (odds ratio (OR) 2.44, 95% CI 1.80-3.32) and uPAR (OR 3.14, 95% CI 1.93-5.09) but small increases in expression of CD23 (OR 0.82, 95% CI 0.68-0.96) were independently associated with severe malaria. These results give an insight into the cellular processes occurring in severe malaria and suggest that pathology is based on a complex repertoire of pro- and anti-inflammatory processes.

Randomized, double-blind, placebo-controlled, short-term trial of ropinirole in restless legs syndrome.

BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) is a condition characterized by an urge to move the legs, usually accompanied by lower limb paresthesias. These symptoms worsen at rest, are relieved by activity, and are worse at night. Previous studies have suggested that dopaminergic drugs such as L-dopa and dopamine agonists, as well as benzodiazepines and opioids, can treat RLS successfully. The purpose of this study was to test the clinical efficacy of ropinirole, a D2/D3 agonist, in the treatment of RLS in a double-blind, short-term, placebo-controlled clinical trial. PATIENTS AND METHODS: After undergoing successful open-label titration and dose adjustments with ropinirole for RLS symptoms over a period of 4 weeks, 22 RLS patients (mean age=50.8; mean duration of symptoms=26.1 years) were randomized to receive either placebo (n=13) or ropinirole (n=9) for 2 additional weeks. Outcome measures included assessment of periodic leg movements in sleep (PLMS) recorded with nocturnal polysomnography and RLS symptoms as assessed with the International Restless Legs Syndrome Study Group (IRLSSG) Rating Scale. Secondary outcomes included sleep macroarchitecture. RESULTS: Results indicated that relative to placebo, ropinirole, at a mean dose of 1.4mg HS significantly decreased PLMS and RLS symptoms. Sleep macroarchitecture did not change. Side effects were typical of all dopamine agonists and were dose related. The majority of patients elected to continue treatment with ropinirole upon study completion. CONCLUSIONS: Ropinirole successfully treated long-standing RLS and can be considered a viable short-term treatment for this condition.

Impaired prepulse inhibition of acoustic startle in schizophrenia.

BACKGROUND: Schizophrenics show deficits in sensorimotor gating, as measured by prepulse inhibition of acoustic startle (PPI). The goal of this investigation is to further characterize PPI and habituation deficits in schizophrenia, and to examine whether differing subgroups of schizophrenics would show comparable PPI deficits. METHODS: PPI was measured in 24 male schizophrenic subjects (9 acutely decompensated inpatients and 15 stable outpatients) and in 20 age-matched normal control subjects. Schizophrenic subjects were rated for positive and negative symptoms at the time of testing. RESULTS: Schizophrenic subjects showed deficits in prepulse inhibition and habituation as compared to normal subjects. Similar latency facilitation was produced by the prepulse in both groups. Acutely decompensated inpatients and stable outpatients did not differ in percent PPI. PPI did not correlate with severity of positive or negative symptoms. CONCLUSIONS: These results suggest that schizophrenic subjects have impaired central inhibitory mechanisms as measured by PPI, and support the hypothesis that periods of relative clinical remission are not accompanied by normalization of sensorimotor gating.

Clinical and sensorimotor gating effects of ketamine in normals.

The clinical similarities between PCP psychosis and schizophrenia have contributed importantly to the development of the glutamate hypothesis of schizophrenia. Sensory gating, as measured by prepulse inhibition of the acoustic startle reflex (PPI), is impaired in patients with schizophrenia. In animals, the noncompetitive NMDA antagonists PCP and ketamine disrupt PPI in a way that resembles the defect seen in schizophrenia. The purpose of this work is to investigate the modulation of sensory gating in humans by subanaesthetic doses of ketamine. 16 healthy male subjects received a 60-min infusion of ketamine (0.5 mg/kg) or normal saline on two separate days in a randomized double-blind crossover design. Clinical ratings and PPI were done during the infusion on both days. Ketamine produced robust clinical effects. Dissociative symptoms as measured by the CADSS increased from 0 +/- 0.0 to 29.3 +/- 14.3; negative symptoms (Affect Rating Scale) increased from 17.2 +/- 0.8 to 24.8 +/- 3.1; and total BPRS scores increased from 18.3 +/- 0.8 to 26.4 +/- 5.1. ANOVAs for these ratings were all significant at the p <.000 level, although BPRS increases were not in the range seen in decompensated schizophrenic patients. The amplitudes of the startle responses to pulse-alone stimuli were not significantly different on ketamine and placebo days. Ketamine did not cause disruption in PPI as expected. On the contrary, in the first block of the PPI session ketamine significantly enhanced PPI (ANOVA; F=6.15, p =.026). These results indicate that the clinical effects of ketamine are not coupled with schizophrenic-like disruption of PPI in normal controls.

Effects of smoking on acoustic startle and prepulse inhibition in humans.

RATIONALE: Prepulse inhibition of the acoustic startle response (PPI) is a paradigm in which a startle response to an auditory stimulus is reduced when that stimulus is preceded by a lower intensity, non-startling stimulus (prepulse). PPI is used as an operational measure of sensorimotor gating in both humans and other mammals. Acute administration of nicotine enhances PPI in rats, an effect that has been recently demonstrated in humans. OBJECTIVES: We compared PPI in 12 male smokers and 14 male non-smokers tested in four repeat startle sessions across 2 test days in order to examine further the effects of smoking and smoking withdrawal on acoustic startle and PPI. METHODS: In a crossover design, the smokers smoked ad lib or abstained from smoking overnight prior to 9 a.m. testing. These 2 test days were in randomized order. On both days, smokers were immediately retested after smoking three cigarettes. Non-smokers were tested twice on each of 2 separate days. RESULTS: Across sessions, the smokers had reduced startle to pulse alone stimuli in the first block of each session when compared to the non-smokers. The non-smokers had no change in gating across their four test sessions. For the smokers, the abstinence condition produced a non-significant reduction in PPI compared to that of the ad lib smoking day. During the smoking abstinence session, smokers had comparable gating to non-smokers. Smoking immediately after washout produced a significant improvement in PPI such that gating in the smokers exceeded that of the non-smokers. CONCLUSION: Smoking after overnight washout from cigarettes enhanced sensorimotor gating compared to pre-smoking values and compared to gating in non-smokers.

Novel use of guanidinium isothiocyanate in the isolation of Mycobacterium tuberculosis DNA from clinical material.

Nucleic acid amplification technologies offer great promise for the rapid, sensitive and specific diagnosis of tuberculosis. However, the isolation of inhibitor-free DNA from biological specimens is a bottleneck of the PCR assay. Here we describe a simple method for the isolation of PCR-amplifiable DNA of Mycobacterium tuberculosis from all types of samples of pulmonary and extrapulmonary origin tested. Briefly, it involves concentration of the bacilli by high-speed centrifugation, removal of PCR inhibitors by a wash solution containing guanidinium isothiocyanate and the release of bacterial DNA by heating in the presence of detergents and Chelex-100 resin. The entire process is accomplished within approximately 3 h. The method has been validated on 780 samples of human, bovine and guinea pig origin including sputum, cerebrospinal fluid, pulmonary fluids, pus, fine needle aspirate, tissue, blood and milk.

Improved AMBER torsional parameters for the N-N rotational barrier in diacylhydrazines.

The structure and rotational barrier for substituted diacylhydrazines are of significant interest given the role this functionality plays in peptidomimetics and ecdysone agonists, the latter of which have application as extremely selective insecticides. Ab initio calculations show that the lowest energy conformations are typically nonplanar with essentially perpendicular nitrogen lone pairs. Molecular mechanics calculations using the AMBER force field in MacroModel yield minima and rotational barriers that are both quantitatively and qualitatively inconsistent with the ab initio results. In this work the AMBER N-N rotational barriers for all configurations of the parent, methyl and di-methyl substituted diformylhydrazines have been fitted to MP2/6-31 + G relative energies. The resulting AMBER torsional parameters have been validated by calculating the rotational barriers for N-t-butyl substituted diformylhydrazine, dibenzoylhydrazine and an azadipeptide. In each case the new AMBER rotational barriers compare favorably with the corresponding MP2 calculated rotational barriers.

Effect of endosulfan (thiodan) on vitellogenesis and its modulation by different hormones in the vitellogenic catfish Clarias batrachus.

This programme was planned in order to study the reproductive dysfunction caused by endosulfan in the fish Clarias batrachus with special reference to vitellogenesis. Vitellogenin was measured by radioimmunoassay. Endosulfan caused a drastic reduction in the plasma vitellogenin which was partially reversed by estradiol-17 beta (E2) in intact and ovariectomized fish. Hormones in combination were more effective than any single hormone in overcoming the impact of endosulfan. Triiodothyronine (T3), ovine luteinizing hormone releasing hormone (oLHRH) were effective in minimizing the effect of endosulfan whereas cortisol (F) and ovine somatotropic hormone (oStH) did not reduce the effect of endosulfan. Amongst the combined hormone treatments, E2 + oLHRH and E2 + T3 were the most potent in overcoming the effect of endosulfan on vitellogenesis.

The association of suicide attempts and comorbid depression and substance abuse in psychiatric consultation patients.

Substance abuse has been associated with attempted suicide and suicide. Few studies have examined the prevalence and associations of combined depression and substance abuse in suicide attempters. A chart review study of 1136 adult general hospital patients referred for psychiatric consultation between 1995 and 1998 was conducted to assess this further. Among 371 cases with self-harm, 311 (84%) attempted suicide. Suicide attempters were younger and diagnosed more often with comorbid substance abuse than patients without self-harm. Depressive disorders were found in 59% and substance abuse disorders in 46%. Comorbid depression and substance abuse was the most frequent category in suicide attempters, i.e., in 37%. Self-reported suicide intent was associated with increasing age, male gender, and comorbid depression and substance abuse. The suicide rate in suicide attempters was 322 per 100,000 patient-years, and 131 per 100,000 in consultation patients without self-harm. It is concluded that comorbid depression and substance abuse is associated with attempted suicide in psychiatric consultation patients. Suicide attempters should be thoroughly assessed for substance abuse. The increased suicide rate in psychiatric consultation patients with and without suicide attempts warrants further research.

Value of a single Widal test in the diagnosis of typhoid fever.

Results of a single Widal test in patients with bacteriologically confirmed typhoid fever (116), clinically suggestive but culture negative fever (170) and non-typhoidal febrile illness (98) and in normal control children (54) were analysed. Positive Widal test (antibody titre against S. typhi O antigen of 1:160) was recorded in 61.2 per cent of patients with bacteriologically confirmed typhoid fever and in 58.8 per cent with culture negative but clinically suggestive typhoid fever. In contrast, the same titre was observed in 10.2 per cent patients with other febrile illnesses of known etiology and in 1.8 per cent of normal children. Differences in the positivity of Widal test in patients with bacteriologically confirmed typhoid fever and clinically suggestive but culture negative fever were highly significant (P < 0.000001) when compared to that of patients with non-typhoidal febrile illnesses and normal controls. High specificity and positive predictive value in 1:160 dilution makes the Widal test acceptable as a diagnostic tool.

Cessation related perceptions and behavior of former and current smokeless tobacco users.

Four hundred fourteen former and 73 current users of smokeless tobacco were questioned about their experiences in giving up smokeless tobacco. Their responses were compared with those of 463 ex-smokers to determine whether former smokeless tobacco users differed from former smokers in using specific cessation techniques. Of the smokeless tobacco users, 77% were interested in quitting, but only 7% wanted to quit "now." Seven percent of the daily users reported that a college-based health or fitness professional had advised them to quit. Former smokeless tobacco users were significantly more likely than former smokers to report that smoking cigarettes was related to their efforts to give up smokeless tobacco than former smokers were to report using smokeless tobacco as a strategy to stop smoking, Former smokeless tobacco users were also significantly more likely than former smokers to report current tobacco use. Smokeless tobacco cessation programs based on the transtheoretical approach to behavior change are recommended.

Fatal atypical mycobacterial infection in a cardiac transplant recipient.

A 37-year-old female underwent heart transplantation for giant cell myocarditis. The patient died within three-and-a-half months of cardiac transplantation. Postmortem specimens from the heart and lung showed multiple necrotizing granulomas with numerous acid-fast bacilli. Polymerase chain reaction done on both the postmortem samples confirmed the presence of atypical mycobacterial infection. This fatal case of atypical mycobacteriosis in a cardiac transplant patient is reported for its rarity.