bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Risk of Adverse Neurocognitive Outcomes With Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors
Authors: Khan Abdur Rahman , Bavishi Chirag , Riaz Haris , Farid Talha A. , Khan Sobia , Atlas Michel , Hirsch Glenn , Ikram Sohail , Bolli Roberto 
Published: January 2017

Background—
There is encouraging evidence of the efficacy of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors; however, their long-term safety remains unclear. We performed a meta-analysis of studies to evaluate the long-term safety of PCSK9 inhibitors.

Methods and Results—
Our search strategy yielded 11 studies (9 smaller early-phase and 2 larger outcome trials). The outcomes assessed were cumulative serious adverse events, musculoskeletal adverse events, neurocognitive adverse events, and stroke. Odds ratio (OR) was calculated using the Mantel–Haenszel method. Subgroup analysis was done to assess the difference in safety between the smaller early-phase studies and the larger outcome studies. Our meta-analysis suggested no difference in the incidence of serious adverse events (OR, 1.00; 95% confidence interval [CI], 0.88−1.15), musculoskeletal adverse events (OR, 1.01; 95% CI, 0.87−1.13), neurocognitive adverse events (OR, 1.29; 95% CI, 0.64−2.59), or stroke (OR, 1.44; 95% CI, 0.57−3.65) with the use of PCSK9 inhibitors. Subgroup analysis of the 2 large outcome studies did suggest an increased incidence of neurocognitive adverse events (OR, 2.85; 95% CI, 1.34−6.06) with the use of PCSK9 inhibitors. However, the overall incidence of neurocognitive adverse events and stroke was <1%, whereas the cumulative incidence of serious adverse events and musculoskeletal events was >10% in both the groups.

Conclusions—
Our analysis suggests that PCSK9 inhibitors are not associated with an increased risk of cumulative severe adverse effects, musculoskeletal effects, or stroke. There is a signal toward adverse neurocognitive effects, seen in the outcome studies with a larger sample size and longer follow-up. There should be close monitoring, for the increased risk of neurocognitive events in the ongoing outcome studies and post-marketing surveillance.
Sensitivity of Rain-Rate Estimates Related to Convective Organization: Observations from the Kwajalein, RMI, Radar
Authors: Henderson David S. , Kummerow Christian D. , Marks David A. 
Published: January 2017

AbstractGround radar rainfall, necessary for satellite rainfall product (e.g., TRMM and GPM) ground validation (GV) studies, is often retrieved using annual or climatological convective/stratiform Z–R relationships. Using the Kwajalein, Republic of the Marshall Islands (RMI), polarimetric S-band weather radar (KPOL) and gauge network during the 2009 and 2011 wet seasons, the robustness of such rain-rate relationships is assessed through comparisons with rainfall retrieved using relationships that vary as a function of precipitation regime, defined as shallow convection, isolated deep convection, and deep organized convection. It is found that the TRMM-GV 2A53 rainfall product underestimated rain gauges by −8.3% in 2009 and −13.1% in 2011, where biases are attributed to rainfall in organized precipitation regimes. To further examine these biases, 2A53 GV rain rates are compared with polarimetrically tuned rain rates, in which GV biases are found to be minimized when rain relationships are developed for each precipitation regime, where, for example, during the 2009 wet-season biases in isolated deep precipitation regimes were reduced from −16.3% to −4.7%. The regime-based improvements also exist when specific convective and stratiform Z–R relationships are developed as a function of precipitation regime, where negative biases in organized convective events (−8.7%) are reduced to −1.6% when a regime-based Z–R is implemented. Negative GV biases during the wet seasons lead to an underestimation in accumulated rainfall when compared with ground gauges, suggesting that satellite-related bias estimates could be underestimated more than originally described. Such results encourage the use of the large-scale precipitation regime along with their respective locally characterized convective or stratiform classes in precipitation validation endeavors and in development of Z–R rainfall relationships.
HSP70 Antibodies in 80 Patients with “Clinically Certain” Meniere's Disease
Authors: Hornibrook Jeremy , George Peter , Spellerberg Myfanwy , Gourley John 
Published: January 2017

Objectives: We tested the claim that a significant proportion of patients with Meniere's disease have antibodies to heat shock protein 70 (HSP70) antigen, which may lead to defective endolymphatic sac function and vertigo attacks. Methods: Serum samples were taken from 80 subjects with a “certain” diagnosis of Meniere's disease (American Academy criteria plus electrocochleographic confirmation of endolymphatic hydrops with tone burst stimuli) and were tested for HSP70 antibodies with the OTOblot (hsp70) Western blot assay. The response was recorded as negative, positive, or equivocal. Samples from 80 sex- and age-matched blood donors were used as controls. Results: Of 80 patients with “clinically certain” Meniere's disease, 14 were positive for HSP70 antibodies or equivocal; of 80 controls, 10 were positive or equivocal. There was no significant difference (p = 0.239). There was no correlation with bilateral disease, “activity” of Meniere's disease, or stage of Meniere's disease. Conclusions: Patients with an unequivocal diagnosis of Meniere's disease do not have a significantly raised incidence of HSP70 antibodies.
Status of Propranolol for Treatment of Infantile Hemangioma and Description of a Randomized Clinical Trial
Authors: Menezes Maithilee D. , McCarter Robert , Greene E. Anne , Bauman Nancy M. 
Published: January 2017

Objectives: Our primary objective was to review the current use of propranolol for treatment of infantile hemangioma (IH), specifically regarding 1) the age at initiation of therapy, 2) the method of initiation, 3) the use of other adjuvant therapy, 4) the duration of therapy and relapse rate, 5) the adverse events, and 6) the outcome. Our secondary objective was to describe a randomized, controlled, single-blinded trial comparing propranolol to prednisolone for treatment of IH. Methods: Ovid Medline and PubMed searches were completed for the MeSH keywords “propranolol” and “hemangioma.” Forty-nine English-language articles were published between June 2008 and September 2010, and 28 of these reported data from a total of 213 patients. Only 6 studies treated more than 10 patients, and these were selected for review in detail (154 patients). Results: The treatment was initiated during infancy in 92.9% of patients (mean, 4.5 months). Sixty-five percent of patients were treated with 2 mg/kg per day, and 25.3% with 3 mg/kg per day. Patients were monitored overnight at initiation of treatment in 3 series (59 patients), for 4 to 6 hours as outpatients in 2 series (62 patients), and initially as inpatients but later as outpatients in 1 series (32 patients). Propranolol was used as sole therapy in about two thirds of patients (103 patients). Treatment was ongoing in 46% of patients at the time of publication. The average treatment duration in the remaining patients was 5.1 months. Rebound growth occurred in 21% of patients after a mean of 4.3 months of therapy. Adverse events occurred in 18.1% of patients and included hypotension in 6, somnolence in 6, wheezing in 4, insomnia, agitation, and/or nightmares in 6, cool hands or night sweats in 2, gastroesophageal reflux in 3, and psoriasis-like rash in 1. All authors reported a favorable outcome with propranolol, but the definition of efficacy was not standardized. Conclusions: Propranolol is an attractive alternative to other treatments for IH. Despite apparent widespread use of this medication, the data are limited, and prospective studies are lacking for this indication. The relatively high rate of adverse effects supports the need for careful monitoring of patients on this therapy. Fastidious reporting of adverse events and objective evaluation of early and late outcomes are necessary to improve our understanding of the use of propranolol for this indication.
Infanticide in England and Wales
Authors: Marks M N , Kumar R 
Published: January 2017

In England and Wales children under one year of age are at four times greater risk of becoming victims of homicide than either older children or the general population. The annual rate of infant homicide (45 per million) has remained relatively constant since the Homicide Act (1957) in contrast with a progressive fall in the infant mortality rate. Details from Home Office records of all infants under a year who were the victims of homicide during 1982–1988 are presented. Infants were most at risk on the first day of life — neonates accounted for 21% of victims and 13% of the victims were between one day and one month old. Thereafter the proportion decreased steadily so that by the final quarter of the first year the risk of becoming a homicide victim equalled that of the general population. Excluding neonates, there were more male victims than female ones, especially in the first three months. A parent was the most likely perpetrator. For all neonaticides the mother was recorded as a suspect, 36% of these mothers were subsequently indicted, all but two were convicted of infanticide and all their convictions resulted in probation. For children over a day marginally more fathers than mothers were recorded as the prime suspect. Mother and father suspects were equally likely to be indicted and also equally likely to be convicted of a homicide offence. However, mothers received both less severe convictions and less severe sentences than fathers. Fathers were more likely than mothers to have killed their infants using violence which wounded. Nonetheless sentences were unrelated to the brutality of the offence: mothers who had killed with wounding violence received less severe penalties than fathers who had killed in a non-wounding way.
Coxsackie Virus Infections in Patients with Acute Cardiac Disease and Chest Pain
Authors: Bell Eleanor J. , Grist N. R. 
Published: January 2017

During 1964 and 1965 infections with Coxsackie virus types A4, B1, B2, B4 or B5 were diagnosed in 9 cases of acute pericarditis ( 2 with myocarditis), 1 of acute myocarditis, 8 of Bornholm disease and 1 of acute chest pain attributed to myocardial ischaemia. Echovirus 6 was isolated from a case of Bornholm disease with antibody response to Coxsackie B 1 virus. Echovirus type 25 was isolated from an additional case of acute myocarditis. During epidemics Coxsackie viruses probably contribute significantly to acute cardiac disease. The virological diagnosis is often difficult to achieve, and it is important to attempt virus isolation from early specimens in addition to testing paired sera.
The Place of Relief Colostomy in Resection for Carcinoma of the Left Colon and Upper Rectum
Authors: Samuels M. J. 
Published: January 2017

A review of 167 consecutive cases of resection and anastomosis for carcinoma of the left colon and upper rectum over a 5-year period is described. An attempt was made to determine whether relief colostomy was associated with a lower incidence of anastomotic dehiscence. The overall figures of this survey show a 5-fold increase in anastomotic leaks where proximal decompression had not been used. In all regions relief colostomy was shown to have a protective effect, but this was especially true in the patients submitted to anterior resection for growths in the upper third of the rectum. The subsequent operation for closure of the colostomy did not add to the overall operative mortality in this series.
The Role of Thyroxine Binding in the Establishment of Thyroid Status
Authors: Harland W. A. , Orr J. S. 
Published: January 2017

This paper reviews previously published evidence concerning the view of thyroxine metabolism which holds that thyroxine exchanges rapidly and freely throughout its distribution space. This view is essential for the well known concept of ‘free thyroxine’, that small fraction of the plasma hormone not bound to protein but in equilibrium with the specific binding proteins. ‘Free thyroxine’ is held to be the biologically active fraction of the plasma hormone. A considerable body of evidence inconsistent with the ‘free thyroxine’ hypothesis is examined and details of experiments indicating the essentially permanent nature of thyroxine binding are reviewed. It is concluded that the ‘free thyroxine’ concept as currently defined, is no longer acceptable. A new model of thyroxine metabolism is presented.
Extended Therapy in Patients with Established Urinary Tract Infection
Authors: Lawson D. H. , Gleadle R. I. , Linton A. L. 
Published: January 2017

Sixty-six patients with established urinary tract infection were given a 3-month course of antibacterial therapy and the effect of this upon the recurrence rate of urine infections investigated. Even in patients with no radiological evidence of renal damage the recurrence rate was 40 per cent at 2 years and this rose to 75 per cent in the group with impaired renal function and abnormalities present on intravenous pyelography. It is concluded that an initial 10 day course of therapy is indicated in females suffering from their first or second attack of acute urinary tract infection. If this becomes established, a 3-month course of therapy is suggested and following this, further recurrences demand careful renal investigation. In the male, all cases of urinary tract infection should be investigated after the initial therapy. Finally, the management of those patients with no anatomical lesion who suffer from recurrent attacks of infection after a 3-month course of therapy has not yet been clearly defined. There is no evidence that either ampicillin, nitrofurantoin or nalidixic acid is superior to sulphadimidine in the treatment of patients with established urinary tract infection.
An Assessment of Digoxin Radio-Immunoassay
Authors: Whiting B. , Sumner D. J. , Goldberg A. 
Published: January 2017

Using a commercially available digoxin radio-immunoassay kit, an accuracy of the order of ±10 per cent has been achieved. Precision could be improved by increasing the ratio (volume of plasma/volume of radioactive digoxin). The assay permitted separation of clinically toxic and non-toxic patients with plasma digoxin values of 3.5±0.6 (S.D.) ng. per ml. and 1.4±0.6 ng. per ml. respectively (p <0.001). A correlation between blood urea and plasma digoxin concentration was demonstrated (r=0.57, p <0.001). The assay was particularly useful in the confirmation and follow-up of suspected digoxin poisoning in attempted suicide, and in renal failure to arrive at a modified digoxin dosage schedule.
Urinary Zinc in Hepatic Cirrhosis
Authors: Allan J. G. , Fell G. S. , Russell R. I. 
Published: January 2017

Plasma Zinc and renal clearance of Zinc have been studied in patients with various chronic hepatic disorders. Plasma Zinc levels were reduced in patients with all forms of chronic hepatic disease and were of no value in differentiating these conditions. The renal clearance of Zinc was found to be significantly higher in patients with chronic hepatic disease of alcoholic aetiology (1.25 ml./min.) compared with those of non-alcoholic aetiology ( 0.52 ml./min.) and normal subjects ( 0.33 ml./min.). The renal clearance of Zinc may be of value in identifying chronic hepatic disease in which alcohol is aetiologically involved.
Erythromycin and Anaerobes: in Vitro Aspects
Authors: Watt B. 
Published: January 2017

Anaerobic organisms are being increasingly recognised as important causes of serious infection in man. Sampling procedures, transport of specimens and laboratory techniques need to be constantly monitored and improved if the causative organisms are to be consistently recovered from clinical specimens. Once the organisms have been isolated, their susceptibility to antibiotics should be determined so that the clinician can base his antibiotic therapy on reliable laboratory results. There are many variables in the sensitivity testing of anaerobes – these may account for the difficulty reported by some workers in obtaining consistently reliable results with some antibiotics, including erythromycin. These problems can be largely overcome if a standardised procedure is adopted. It is clear from the published data that erythromycin has considerable in vitro activity against many strains of anaerobic bacteria, both spring and non-sporing. There is a broad spectrum of activity with some strains being very sensitive and a few strains being resistant. M.I.C. values range from 0.04 μg./ml. to 20 μg./ml. or more. Further studies are now needed to assess the role of erythromycin in the treatment of anaerobic infections in vivo.
Elemental Diet Therapy in the Management of Complicated Crohn's Disease
Authors: Russell R. I. , Hall M. J. 
Published: January 2017

The purpose of this report was to study the types of complications of Crohn's disease which may benefit from the use of elemental diets. The elemental diet Vivonex was used in the management of patients with Crohn's disease with local complications but without nutritional deficiency. Sole treatment of this kind was found to be of value in promoting healing of perianal or anal ulceration and anal fissures; it was also of value in allowing subacute ileal obstruction to settle, thus postponing surgery and allowing better bowel and nutritional preparation for surgery. Patients with bile acid-induced diarrhoea associated with severe ileal Crohn's disease noted improvement in the diarrhoea on the elemental diet, and the treatment was also useful in reducing ileostomy output and helping ileostomy skin lesions to heal in a patient with severe skin excoriation related to leakage of excessive ileostomy fluid output.
Fibrinolysis and Thrombosis: Pathways and Inhibitors
Authors: Samama M. 
Published: January 2017

The mechanism of fibrinolysis has been reviewed taking into account its two pathways extrinsic and intrinsic and the important role of α 2plasmin inhibitor. A clear distinction is now well documented on the mechanism of fibrinolysis in a liquid phase and in a solid phase. The role of fibrin as an important trigger of fibrinolysis in vivo is demonstrated. Finally a relationship between hypofibrinolysis and thrombosis is highly probable.
Δ4-Ethyloestrenol in Recurrent Deep Venous Thrombosis
Authors: Nilsson B. , Nilsson I. M. , Hedner U. 
Published: January 2017

Twenty-one patients with recurrent deep venous thrombosis were treated with an anabolic steroid (Δ4-ethyloestrenol) for up to 56 months. All had been shown to have a deficient fibrinolytic response to vascular occlusion and/or low vessel wall plasminogen activator content. Therapy resulted in improvement in clinical and fibrinolytic parameters and no significant side effects were seen.
Necrotising Enterocolitis Experience with 54 Neonates
Authors: Dolan P. , Azmy A. F. , Young D. G. , Ziervogel M. 
Published: January 2017

Fifty-four neonates transferred to the neonatal surgical unit because of acute necrotising enterocolitis (N.E.C.) are presented. Eleven died (20.4%), of whom seven were treated conservatively and four by operation. Ten patients required surgical exploration because of intestinal perforation, obstruction or suspected perforation. Another five neonates presented with intestinal perforation and were treated by percutaneous catheter drainage of the peritoneal cavity because of their extreme prematurity. Nine patients developed a colonic stricture diagnosed between six weeks and a year after the onset of the disease. Another six patients showed a segment of colonic narrowing detected on barium enema radiography without clinical evidence of bowel obstruction. They were treated conservatively and showed complete resolution at follow up studies.
Acute Renal Failure: The Tip of the Iceberg?
Authors: Power D. A. , Haughney J. , Nicholls A. J. , Asfar S. K. , Engeset J. , Catto G. R. D. , Edward N. 
Published: January 2017

This study reports the experience, during a six-year period, of the Aberdeen Renal Unit in the treatment of patients with acute renal failure. The combination of a relatively stable population base and a single regional dialysis centre has allowed the incidence of acute renal failure to be assessed. Approximately 30 patients per million population were dialysed annually for acute renal failure; 69 per cent of these patients (20.5 per million population per year) were dialysed for acute reversible intrinsic renal failure (ARIRF) and mortality in this group was 44 per cent. Patients with more severe disease at the time of presentation to the renal unit, as defined by a clinical severity score, had significantly reduced survival rates. However, it was not possible to predict the outcome in individual cases; ten of 24 patients with clinical severity scores which indicated a poor prognosis survived the period of oliguria and were discharged from hospital. The fact that other renal units dialyse fewer patients per million population per year for ARIRF probably reflects a reluctance to refer patients whose general condition appears poor. As the overall mortality rate reported in this study does not differ significantly from rates reported previously from centres treating a smaller proportion of patients, such decisions may not be correct. It is well known that facilities in Britain for treating patients with end-stage renal disease are inadequate; it now appears likely that some patients who might benefit from acute dialysis are being denied treatment for a potentially reversible disease process.
A Recurring Question — How Many Beds for Dementia?
Authors: Christie A.B. , Whitfield E.M. , Wood E.R.M. 
Published: January 2017

Experience at Crichton Royal in dealing with dementia over a thirty year period has been used to develop two models of bed requirements for dementia sufferers. The first based on results from the periods 1957 to 1959 and 1974 to 1976 and the second on experience in the years 1974–75 and 1984–85. The variables considered were demographic change, admission of a constant proportion of the at risk group and changes in individual patient survival between groups of patients admitted. Projections based on the earlier model suggested that the SHAPE provision of 10 beds per 1000 of the over 64 population would be insufficient to maintain established standards of care. The later model, however, finds SHAPE numbers appropriate. The reasons for the change of view — Inaccuracy in estimate of increasing male survival and significant under-estimates of population growth — Nullify each other. The conclusion is that SHAPE is a useful model provided the demographic changes and patient survival change are carefully monitored.
The Health Status and Health Needs of Chinese Population in Glasgow
Authors: Liao Xiao-Hui , McIlwaine G. 
Published: January 2017

This cross sectional study explored the health problems and health needs in the local Chinese community in Glasgow. Several data collection methods have been used in this study, including face-to-face and telephone structured interviews, postal and hand delivered questionnaires. A total of 800 questionnaires were processed, and 493 were completed, giving an overall response rate 61.6%. The results from the present survey indicated that the health status of Chinese residents in Glasgow is poorer than that of the local population. The most important findings of the study is that the Chinese community in Glasgow underuse health services, and unmet health needs exist in the community. The main barrier to effective use of present health services and benefit from the health promotion and health education programmes is language difficulties. Following discussion with the local community, options for improving the health services for the Chinese community in Glasgow were obtained. The findings of the study have implications for health service purchaser/providers of health care to the Chinese population generally in Scotland.