bluuebunny/crossref_metadata_2025 huggingface dataset:
Vasculopathy of the Antiphospholipid Syndromes Revisited: Thrombosis is the Culprit and Vasculitis the Consort
Authors: Lie JT
Published: January 2017

Whether the vasculopathy in APS is thrombosis or vasculitis is more than a mere academic interest; the distinction is important not only for unravelling the pathogenesis of vascular injuries in APS but also for selecting the appropriate choice of drug treatment. A diagnosis of vasculitis would call for treatment with corticosteroids and cytotoxic agents which are not without serious side effects and drug toxicity. The same powerful but potentially dangerous drugs are clearly quite ineffectual in treating or preventing thrombosis associated with APS which has been known to respond in the lowly and inexpensive aspirin.

The vasculopathy of APS remains almost exclusively thrombotic in nature according to our current state of knowledge, even if one were to accept capillaritis as a bona fide member in the family of vasculitides, the ‘microangiitis’. Vasculitis secondary to an independent underlying disease, such as SLE, may coexist with APS in a patient. In the management of APS patients, the distinction between a true vasculitis coincidental with and one that is causally related to APS affects clinical decision making, and not just a matter of semantics or an academic curiosity. In vasculopathy of APS, thrombosis is the culprit and vasculitis, when present, is the consort. This is still true until newer and more convincing evidence emerges and proves to be contrary.
Functional Effects of Anticardiolipin Antibodies
Authors: Harris EN , Pierangeli SS
Published: January 2017

The ‘lupus anticoagulant’ phenomenon is the best documented functional effect of antiphospholipid (aPL) antibodies, occurring either by inhibition of the prothrombinase and/or Factor X activation reactions. Understanding the mechanism by which aPL antibodies inhibit phospholipid dependent coagulation reactions may yield important clues about their ‘thrombogenic effects’ in vivo. We conducted a series of studies to determine the specificity, diversity, and mechanism by which aPL antibodies inhibit phospholipid dependent reactions. Results showed that purified immunoglobulins with lupus anticoagulant and anti-cardiolipin activities were absorbed by negatively charged phospholipids and both activities were recovered from the phospholipid-antibody precipitate. Purified aPL antibodies inhibited the prothrombinase reaction in a plasma free system in which β2-glycoprotein 1 (β2-GP1) was absent. Affinity purified aPL antibodies had 25–50 times the inhibitory activity of immunoglobulin preparations. The phospholipid binding proteins, β2-GP1 and placental anticoagulant protein I (PAP I), independently inhibited the prothrombinase reaction, and when these proteins were combined with aPL, inhibition of the prothrombinase reaction was additive. Antibodies of syphilis had no inhibitory effect, partially accounted for by lack of specificity for phosphotidylserine (PS). Although aPL antibodies inhibited the protein C activation reaction, there was no correlation of these activities with inhibition of the prothrombinase reaction. Together, these results show that aPL exert their effects by interaction with negatively charged phospholipids, in particular phosphotidylserine, but lack of correlation between inhibition of the prothrombinase and protein C activation reactions, suggests that the nature of the coagulation protein is also important.
Genetic Risk Factors for aPL Syndrome
Authors: Wilson WA , Gharavi AE
Published: January 2017

MHC class II alleles and C4 deficiency alleles have been variably associated with aPL syndrome, but the extensive linkage disequilibrium among many of these alleles has made it difficult to assign a causal role for any of them. Interethnic studies of these and other alleles in large cohorts of subjects would help to clarify the roles of these alleles in aPL syndrome.
Antiphospholipid Antibody Syndromes and the Internet
Authors: McCarty GA
Published: January 2017

Information regarding the antiphospholipid antibody syndrome is accessible on the Internet, and encompasses both physician specific and patient specific files. The quantity and quality of data available at these sites, however, varies greatly and both search-refining and data manipulating protocols and software need improvement.
Antiphospholipid Antibodies and Atherosclerosis
Authors: Vaarala O
Published: January 2017

The family of antiphospholipid antibodies includes antibodies binding to cardiolipin in serological test for syphilis, antibodies prolonging the clotting time in lupus anticoagulant test, antibodies reacting with plasma phospholipid-binding proteins, such as β2-glycoprotein I and prothrombin, and antibodies binding to oxidized low-density lipoprotein (LDL). Antiphospholipid antibodies are traditionally associated with arterial and venous thrombosis in patients with primary or secondary antiphospholipid syndrome. The recent studies, especially those on patients with myocardial infarction, extend the concept of antiphospholipid antibodies, and suggest that they play a role also in atherosclerosis.

Based on the clinical studies and immunological findings, it seems that the differences in the specificity of antiphospholipid antibodies may reflect to their pathogenetic mechanisms and, finally, to their clinical consequences. The present review suggests that antibodies to oxidized LDL may not interfere directly with blood coagulation, but seem to have importance in the inflammation of the vessel wall in atherosclerosis and in vasculitis. Instead, antibodies to β2-glycoprotein I and to prothrombin show a closer association with thrombosis. It is possible that in the atherosclerotic plaque, the plasma proteins, such as β2-glycoprotein I or prothrombin, are bound to the endothelial surface and antibodies to cryptic epitopes revealed in these proteins are induced. These antibodies may contribute to the formation of atherosclerotic thrombosis by changing the balance of hacmostasis towards hypercoagulative state.
Modulation of Endothelial Cell Function by Antiphospholipid Antibodies
Authors: Meroni PL , Del Papa N , Beltrami B , Tincani A , Balestrieri G , Krilis SA
Published: January 2017

β2-glycoprotein I (β2-GP-I) the plasma cofactor for anti-phospholipid antibodies adheres on the endothelial surfaces and can be recognized by anti-β2-GP-I antibodies naturally occurring in patients with the anti-phospholipid syndrome. As for the cofactor binding to cardiolipin- or gamma irradiated-plates, the endothelial binding is mediated by the so-called phospholipid binding site, a cationic structure able to react with anionic molecules. Endothelial monolayers appear to represent a substrate able to bind β2-GP-I and to present it in a suitable manner in order to allow the binding of anti-β2-GP-I β2 antibodies. The complex between β2-GP-I and the respective antibodies induce an endothelial cell activation as demonstrated by the up-regulation of adhesion molecule expression, the secretion of proinflammatory cytokines and the modulation of arachidonic acid metabolism. Taken together these findings strongly sustain a pivotal role for β2-GP-I in allowing antibody deposition on the endothelium and in affecting endothelial cell functions potentially responsible for a procoagulant state.
Regulatory Mechanisms in Maintenance and Modulation of Transmembrane Lipid Asymmetry: Pathophysiological Implications
Authors: Bevers EM , Comfurius P , Zwaal RFA
Published: January 2017

The two leaflets of the plasma membrane of eukaryotic cells differ in lipid composition: the outer leaflet comprises mainly neutral choline containing phospholipids, whereas the aminophospholipids reside almost exclusively in the cytoplasmic leaflet. The importance of transmembrane lipid asymmetry may be judged from the fact that the cell invests energy to maintain this situation for which at least two regulatory mechanisms are held responsible. A translocase, selective for aminophospholipids, acts as an ATP-dependent pump for rapid inward movement of phosphatidylserine (PS) and phosphatidylethanolamine; in addition, a non-selective, but also ATP-dependent pump causes outward movement of phospholipids, be it at a much lower rate compared to the inward transport by the aminophospholipid translocase. These two systems, acting in concert, are thought to be the main players in the maintenance of a dynamic equilibrium of the phospholipids over both membrane leaflets.

Dissipation of membrane lipid asymmetry can be elicited in different cell types under a variety of conditions; in particular, platelets upon activation rapidly lose their normal plasma membrane lipid distribution, but also in other blood cells, lipid asymmetry can be lost, be it at a much lower rate and extent than in platelets. A putative protein, referred to as ‘scramblase’ has been described, which requires the continuous presence of elevated intracellular Ca2+-levels, to allow a rapid, nonselective and bidirectional transbilayer movement of phospholipids. Although scrambling of lipids does not require ATP as such, preliminary studies suggest the possible involvement of one or more phosphorylated proteins.

The most prominent consequence of the loss of phospholipid asymmetry is exposure of PS in the outer leaflet of the plasma membrane. Surface-exposed PS serves several important physiological functions: it promotes assembly of enzyme complexes of the coagulation cascade, it forms a signal for cell-cell recognition, which is important for cell scavenging processes. Surface-exposure of PS is an early phenomenon of apoptosis and appears to be involved in efficient removal of these cells. In addition, PS in the outer leaflet of cells is thought to play a role in cell fusion processes.

It may be clear from the foregoing, that the amount of PS present at the cell surface needs to be tightly controlled, and that an impairment of this process leads to either excessive- or diminished exposition of PS which may have several pathophysiological consequences.
The Diet at Christ's Hospital School in the 1920s and the Work of a Pioneer School Medical Officer, Dr G E Friend
Authors: Pemberton John
Published: January 2017

The diet at Christ's Hospital in the 1920s is described by the author, who was a pupil at the school from 1922 to 1930. The description was checked and confirmed by 14 of his surviving contemporaries. The deficiencies of the diet at that time are compared with the even worse diets recorded earlier. Great improvements in the diet were initiated by a remarkable doctor, G E Friend, when he was the school medical officer from 1913 to 1947.
Constant Lambert: His Illness at Christ's Hospital School and the Role of Dr G E Friend
Authors: Hoskins Trevor
Published: January 2017

The composer Constant Lambert suffered a near fatal attack of septicaemia while he was at school at Christ's Hospital in 1916. His survival owed no small part to the school medical officer, Gerald Friend, himself renowned for his work on nutrition and development.
Alfred Fröhlich and His Correspondence with Sir Ronald Ross
Authors: Gibson Mary E
Published: January 2017

An outline is given of the career of Alfred Fröhlich, and his correspondence with Sir Ronald Ross between 1901 and 1912 is described in detail.
Adolf Kussmaul (1822–1902): From Youth to Maturity under the Influence of Virchow
Authors: Breathnach C S , Westphal Wolfgang
Published: January 2017

Adolf Kussmaul (1822–1902) studied medicine at Heidelberg and Vienna, and practised in Kandern in the Black Forest until, in 1854, ill health forced him to quit country practice. Drawn by Rudolf Virchow to Würzburg, he took his MD there in 1855, after which he held academic posts in Heidelberg, Erlangen, Freiburg and Strasburg until 1888, when he retired to Heidelberg and in his closing years composed Jugenderinnerungen, memoirs of his youth. Periarteritis (polyarteritis) nodosa, pulsus paradoxus, the paradoxical rise in jugular venous pressure on inspiration in constrictive pericarditis and the “air hunger” of diabetic ketosis are all evidence of shrewd clinical observation and interpretation associated with his name.
William Harvey's Epitaph
Authors: Nutton Vivian
Published: January 2017

This paper gives the first published English translation of William Harvey's epitaph. The translation is based on a re-examination of the stone itself, and is accompanied by an explanatory commentary.
Paracelsus: the Hippocrates of the Renaissance
Authors: Siddiqui Mumtaz A , Mehta Nirav J , Khan Ijaz A
Published: January 2017

Paracelsus lived during the Renaissance. His sober spirit of scientific observation and critical reason were accompanied by emotional turbulence and a volcanic temperament. He remains both a mystery and an object of nostalgia. Paracelsus is today celebrated as the first modern medical scientist. Paracelsus' early life, achievements and latter years are described.
Henry Wade (1876–1955) and Cancer Research: Early Years in the Life of a Pioneer of Urological Surgery
Authors: Gardner D L
Published: January 2017

This paper describes the microscopic studies of human and experimental cancers made by Henry Wade during the years 1904–9. William Ford Robertson, his mentor, and Wade claimed to have discovered a microbial cause of human cancer. The claim was at once fiercely disputed. Wade turned to the investigation of a transmissible sarcoma of the dog, during which he demonstrated an early form of immune transplant rejection. He also undertook studies of Hodgkin's disease. Later in life, Wade established urological surgery at the Royal Infirmary of Edinburgh and became President of the Royal College of Surgeons of Edinburgh.
The Edwin Smith Surgical Papyrus: Description and Analysis of the Earliest Case of Aphasia
Authors: Minagar Alireza , Ragheb John , Kelley Roger E
Published: January 2017

The Edwin Smith surgical papyrus, which dates back nearly five millennia, is the oldest known medical text and contains the first written example of the word “brain”, as well as the earliest known descriptions of the meninges and the cerebrospinal fluid. The papyrus describes 48 cases and gives the first accounts of several forms of brain injury and their associated complications. The Egyptian author presents an analytical approach to the reported cases and classifies them as favourable, uncertain or intractable, depending on prognosis. The authors believe that case 20 of the papyrus presents the first possible case of aphasia, which occurred following head trauma. The patient, frustrated by his inability to speak, developed nuchal stiffness, which might have been due to meningeal irritation. The case concludes with the advice that a patient with such a grave condition should only be comforted, not treated.
The Prelude to Stethoscopy: Some French, British and Irish Contributions in the Early Nineteenth Century
Authors: Agnew Robin
Published: January 2017

In 1819, René Laënnec published his classical work on the newly invented stethoscope; this was translated into English by John Forbes in 1821. This article describes some of the early contributions by various authors in their attempts to link the new auscultatory signs to the underlying pathology in the thorax.
Duncan of Liverpool: Britain's First Medical Officer
Authors: Halliday Stephen
Published: January 2017

William Henry Duncan (1805–1863) was born in Liverpool, qualified in Edinburgh, then moved back to Liverpool to work in general practice. He became physician to the Liverpool Infirmary and began to campaign for improvements to the appalling living conditions of his patients. He was appointed Liverpool's Medical Officer of Health on 1 January 1847 — Britain's first.
‘Alas, Poor Yorick!’ The Death of Laurence Sterne
Authors: Hughes J T
Published: January 2017

The life and death of Laurence Sterne are examined. Sterne's body was taken from his grave and soon after appeared for dissection in Cambridge. The teaching of anatomy, the activities of body snatchers and the passage of the 1832 Anatomy Act are reviewed.
Leonard Ralph Braithwaite (1878–1942)
Authors: Storey Geoffrey O
Published: January 2017

Leonard Ralph Braithwaite lived and worked in Yorkshire all his life, with the exception of service overseas in World War I. He worked with Berkeley Moynihan early in his career, and went on to become a renowned surgeon and teacher in his own right.
Greek Professors of the Medical School of Constantinople during a Period of Reformation (1839–76)
Authors: Trompoukis Constantinos , Lascaratos John
Published: January 2017

A medical school was founded in Constantinople in 1827. Greek medics were involved with the new school right from its foundation, mainly because they had studied in Europe and knew other European and Asian languages. This paper reviews the lives of five of them: Stefanos Caratheodory; Constantinos Caratheodory; Sarantis Archigenis; Spyridon Mavrogenis; and Marco Pitsipio (Apostolidi Pasha), who was appointed a director of the Medical School. A few of the other Greek professors are also briefly discussed.
Hugh Cairns (1896–1952) and the Mobile Neurosurgical Units of World War II
Authors: Hughes J T
Published: January 2017

In World War II, Hugh Cairns, Oxford Nuffield Professor of Surgery and brigadier in the Royal Army Medical Corps, designed and administered the mobile neurosurgical units that treated casualties with head injuries in the various campaigns fought by the British Army. Cairns also created the Combined Services Hospital for Head Injuries at St Hugh's College, Oxford, where the staff of the units were trained and where evacuated casualties were received. The excellent outcome of the head-injured in World War II and the impetus to the expansion of neurosurgery in the UK during and after that war were, in large measure, due to Cairns. Others had knowledge of neurosurgery but Cairns inspired surgeons, neurologists and nursing sisters to perform neurosurgery at the highest level on the battlefield.
Thomas Hodgkin's Journey through Spain in 1863 and 1864
Authors: Fernandez-Flores Angel , Yau Paula , Aguilera Beatriz , Oliva Horacio
Published: January 2017

In 1863 and 1864, Thomas Hodgkin travelled to Morocco, accompanying his close friend Sir Moses Montefiore, who stopped in Madrid on the way there and back to attend an audience with the Queen of Spain. Thomas Hodgkin's impressions of Spain were recounted in his book Narrative of a Journey to Morocco. The book reveals new aspects of Hodgkin's personality as well as his capacity for observation. It also describes Spain in the second half of the nineteenth century. Thus Thomas Hodgkin was a witness to one of the most vivid periods of the history of the country. The paper considers both aspects of Hodgkin's commentaries on Spain.
Sir David Monro, MD (1813–1877), of New Zealand: His Antecedents and His Descendants
Authors: Clair Rex E Wright-St
Published: January 2017

David Monro, MD, was a son of the third Professor Monro of Edinburgh. He went into practice in Edinburgh and then emigrated to the Nelson settlement in New Zealand. There he practised a little medicine, but was mostly a gentleman sheep-farmer. He was a member of the first parliament of New Zealand in 1854 and served as the second Speaker, when he did much to set up proper standing orders for the colonial legislature. He was knighted in 1866.
Some Presidents of the Medical Society of London
Authors: James D Geraint , Kinsella-Bevan R
Published: January 2017

John Coakley Lettsom (1744–1815) helped found the Medical Society of London in 1773. Its headquarters are in an elegant Regency building in central London, which contains a medical historical treasure trove. It celebrated its three hundredth session of lectures and social functions in 2003. Since 1850 the Presidency has been for one year only. In 1971 a group photograph of Presidents was arranged and a brief account of each of these distinguished men is given in the order of his seniority in the office.
The Life and Work of the Birmingham Radiologist Dr James Brailsford (1888–1961)
Authors: Kapadia H M , Banerjee A K , Arnott R G
Published: January 2017

James Brailsford went from humble beginnings to become an eminent radiologist through his ability, determination and immense diligence. He made a late start in medicine but became one of the world's leading authorities on skeletal diseases; he wrote the classic textbook The Radiology of Bones and Joints and described the eponymous Morquio-Brailsford syndrome. In 1934 he was elected first President of the British Association of Radiologists, of which he was founder. This later became the Faculty of Radiologists at the Royal College of Surgeons and is now the Royal College of Radiologists.
Andrew Halliday, Kt FRCPE (1781–1839): Service in the Napoleonic Wars and West Indies, and First Physician to the Seamen's Hospital Society
Authors: Cook G C
Published: January 2017

Sir Andrew Halliday (1781–1839) was domestic physician to HRH the Duke of Clarence (1765–1837) (who was later to become King William IV). He also served in the Napoleonic Wars — in Portugal, Spain and Waterloo — as well as in the West Indies, and became the first physician to the Seamen's Hospital Society. Unlike many of his contemporaries, Halliday was also a prolific author, many of his publications being on lunatic asylums in Great Britain and Ireland.
Sir William Burnett (1779–1861), Professional Head of the Royal Naval Medical Department and Entrepreneur
Authors: Penn Christopher
Published: January 2017

Sir William Burnett (1779–1861) had an active career as a Royal Navy surgeon in the French Revolutionary and Napoleonic Wars, including service at the battles of St Vincent, the Nile and Trafalgar. From 1822 to 1855 he was professional head of the Royal Naval Medical Department, when he provided effective leadership in a time of great change. Although his official work earned him the reputation of a “hardworking, unimaginative, somewhat harsh man”, his correspondence shows a very humane centre under the official carapace. His official performance and reputation were both eroded towards the end of his career by his determined promotion of zinc chloride, for which he held lucrative patents.
Sir Stuart Threipland (1716–1805), Physician-In-Chief to Prince Charles Edward Stuart during the Jacobite Uprising of 1745
Authors: Kaufman M H
Published: January 2017

Stuart Threipland (1716–1805), the son of Sir David Threipland, second baronet of Fingask Castle, was an ardent Jacobite. He obtained the Edinburgh MD degree in 1742, was admitted a fellow of the Edinburgh College of Physicians in 1744 and was elected its President in 1766. He accompanied “Bonnie” Prince Charles Edward Stuart during the Jacobite uprising of 1745 and went into exile shortly after the battle of Culloden in April 1746. He returned to Edinburgh under an Act of Indemnity in 1747. While he succeeded to the baronetcy after the death of his father in 1746, he was not technically allowed to use this title during his lifetime because his father's title and ancestral estates had been confiscated after the Battle of Sheriffmuir in 1715. He practised in Edinburgh for the rest of his life and outlived all of the other great Jacobite figures involved in the 1745 uprising.
Sir William Kynsey and the Development of Health Care in Sri Lanka
Authors: Uragoda C G
Published: January 2017

The Portuguese (1505–1656), the Dutch (1656–17%) and the British (1796–1948) successively occupied Ceylon (now Sri Lanka). Only the British succeeded in governing the entire country, while the jurisdiction of the other two western powers was limited to the maritime provinces only. The Portuguese and the Dutch were not concerned with the provision of medical care to the local population. It was really the British who created a new health care system in the country and popularized western medicine. The infrastructure that the British set up has endured to the present day. Sir William Kynsey (Figure 1) was the longest-serving head of the Civil Medical Department or its successors in Ceylon. He assumed office at a time when the health service was in its formative years, and the manner in which he shaped its direction has had a lasting impression on the health care system in the country. It is therefore rather strange that Kynsey's death should have gone unnoticed in the columns of both the British Medical Journal and the Lancet at the time. Even the now century-old Ceylon Medical Journal, which accorded him pride of place by carrying an article by him as the opening paper of its very first issue, made only passing reference to his death1.
Mozart's Last Months and Controversial Death
Authors: Davies Peter J
Published: January 2017

The controversies about the cause of Mozart's death are related to the unusual nature of his symptoms as recounted by lay people, the absence of a medical record, the inordinate amount of publicity given over to the sensational poisoning allegations, and the substantial difficulty in the evaluation of the diverse original sources1–20. The controversies are especially concerned with the question of preexisting chronic illness and the interpretation of the swellings. A chronology of major events in the last few months of Mozart's life is given in Table 1.
Influence of Abnormal Screens on Delays and Prognostic Indicators of Screen-Detected Breast Carcinoma
Authors: Ganry O , Peng J , Dubreuil A
Published: January 2017

Background:

Delay to diagnosis following an abnormal screening result is associated with morbidity such as anxiety, but its effect on prognosis is unknown.

Methods:

Using data from the Somme area breast cancer screening programme (France), we identified 29,511 women aged 50–69 years who underwent screening between 1996 and 2000. We prospectively followed women with an abnormal screening result until completion of the assessment process and evaluated the effect of delay to notification, diagnosis and treatment on prognostic indicators.

Results:

Women with high-suspicion screens (n=976) compared with those with intermediate-suspicion screens (n=1008) were investigated more promptly, presented larger tumours (62% vs 42%, p=0.03), and were more likely to be lymph node positive (36% vs 17%, p=0.02). Compared with a delay to diagnosis ≤1 month, the odds ratio for tumour size greater than 10 mm was 1.4 (95% confidence interval[CI], 0.90–1.90) for a delay of 1 to ≤6 months, and 1.8 (95% CI, 1.02–2.85) for a delay >6 months. Similarly, a 1.4-fold and 2-fold increased risk of lymph node involvement was observed for delays of >3 to ≤6 months and >6 months, respectively, compared with the reference interval.

Conclusion:

The authors' findings suggest that women with high-suspicion mammograms were investigated more promptly, and that delays to diagnosis of asymptomatic breast carcinoma >6 months were associated with progression of the cancer measured by tumour size >10 mm and lymph node metastasis.
Psychological Consequences of Screening Mammography
Authors: Cockburn Jill , Staples Margaret , Hurley Susan F , De Luise Trudy
Published: January 2017

To examine the psychological consequences at a number of stages in the screening process for women attending a screening mammography programme. Setting- A pilot mammographic screening programme in Melbourne, Australia. Method — The psychological consequences questionnaire (PCQ; a reliable and valid measure of the psychological consequences of screening mammography) was used to measure the emotional, social, and physical functioning of women in a mammographic screening programme and a control community sample. A screening group (in whom no abnormality was detected at initial screen; n=142) had four measurements: at screening clinic; before results were received; one week after all-clear results were received; and eight months after initial visit. The recall group (who were recalled for further investigation which showed the detected abnormality to be benign; n = 58) had measurements at the same points as the screening group and an additional measurement while waiting at the recall assessment clinic. A randomly selected community control group (n = 52) had measurements one week, two weeks, three weeks; and eight months after consenting to participate.

Emotional, social, and physical functioning of women in the screening group did not change over time and at no point differed significantly from that of community controls. The profiles of emotional and physical dysfunction of women in the recall group differed significantly from those of the screening and control groups. The level of emotional and physical dysfunction in the recall group was highest while waiting at recall assessment clinic, and scores were still significantly higher than scores obtained at comparable times from screening and control groups one week after obtaining notification that there was no sign of cancer (emotional P< 0·001; physical P < 0·05). This difference had disappeared eight months after the screening visit, when the level of emotional and physical functioning was similar to that of the screening and control groups. Social dysfunction scores did not change significantly over time and were similar for all three groups.

Given that up to 10% of women are recalled for further investigations on first round screening, significant numbers of women may have psychological consequences. This speaks for the necessity for accurate reading of mammograms to minimise the false positive recall rate, and for counselling services to be available at recall assessment centres.
Preventing Manifestations of Hereditary Haemochromatosis through Population Based Screening
Authors: Haddow James E , Ledue Thomas B
Published: January 2017

To evaluate the efficacy of identifying presymptomatic hereditary haemochromatosis through population based screening.

Review the hereditary pattern, prevalence, and clinical manifestations of haemochromatosis. Estimate the detection and false positive rates associated with available screening and diagnostic tests. Develop examples of screening protocols and other components that would be necessary for proper implementation. Identify potential barriers and objections.

Hereditary haemochromatosis, an autosomal recessive disorder with a prevalence of three to five per thousand in the general population, is associated with a wide variety of clinical manifestations, usually beginning in mid to late adult years. Identifying and treating this disorder after symptoms appear can arrest its progress but usually cannot reverse existing damage to joints, liver, pancreas, pituitary gland, and other organs. Measuring transferrin saturation in serum is now known to be a reliable screening test for haemochromatosis when applied to a general population of healthy adults, detecting about 80% of cases, with a 0·3% false positive rate. Liver biopsy with iron staining and total iron concentration is the recommended diagnostic test for subjects with positive screening tests. Treatment with phlebotomy can then prevent manifestations. Effective systematic identification and management of presymptomatic haemochromatosis in the general population is best accomplished within the framework of an organised screening programme. Potential barriers include accessibility of young adult populations and attitudes in the health community that severe clinical manifestations are relatively uncommon. It is recommended that pilot programmes be undertaken to determine the feasibility of introducing screening for haemochromatosis as part of routine health care.
Screening for Melanoma and Options For-Its Evaluation
Authors: Elwood J M
Published: January 2017

A review of the published evidence presented here argues that screening for melanoma is recommended and practised at present, but with wide diversity of opinions about its value; there is evidence that screening has considerable potential for benefit, but the evidence of actual benefit is limited; and there are substantial costs and potential hazards from screening.

On this basis the evaluation of screening procedures for melanoma is important, and options for this are discussed. The ideal study design to assess the efficacy of melanoma screening in reducing mortality is a large scale randomised trial. This may need a well coordinated proposal involving several centres in one or more countries, and the cost would be substantial. Without such a trial, however, it is most likely that increasing resources will be put into poorly designed screening programmes of unknown value.

The simplest and strongest designs use individual randomisation, but group randomisation designs may have practical advantages, though they require a greater sample size. Designs based on general population screening, and on screening only high risk groups, are both considered. They answer different questions. In countries with high incidence the value of general population screening is probably the more critical. Not enough is known to specify the type and frequency of screening precisely; both screening by doctors and self screening require evaluation, and annual screening should probably be tested. The age range at risk will depend on the local incidence, but is likely to be quite wide — for example, 45–69, and both sexes need inclusion. Thus a suggested design for a moderate to high incidence area would be a trial, randomised by individual or group, assessing at least two annual rounds of both screening by doctor and self screening (ideally by a factorial design), for adults aged 45–69, with mortality over several years' follow up as the critical outcome. In an area with good data systems such a study could compare screening offered to some 260.000 subjects with 10 times that number of controls passively followed up, with 90% power to detect a one third reduction in mortality. A general assessment of costs over five years gave estimates of $8.3 million for the screening programme and $2.4 million for the evaluation.

The much weaker designs, area based cohort studies using individual data or a simpler ecological comparison, and case-control studies, are also considered. If well designed with attention to their methodological limitations they may be valuable but are unlikely to be as definitive as a randomised trial.
Tumour Markers and Screening for Gastrointestinal Cancer: A Follow up Study in Finland
Authors: Hakama Matti , Stenman Ulf-Hakan , Knekt Paul , Järvisalo Jorma , Leino Aila , Hakulinen Timo , Maatela Jouni , Aromaa Arpo
Published: January 2017

Screening for gastrointestinal cancer is based mainly on a barium contrast x ray method and on identification of occult blood in stools. The methods are relatively expensive, not always acceptable to the participants, and there is only limited evidence of their effectiveness in reducing the mortality from gastrointestinal cancer. Objective - To investigate the validity of several tumour markers as a screening test for stomach cancer and for colorectal cancer.

A registry of 36 265 serum samples drawn during 1968–72 was linked to the cancer registry. Follow up was during 1968–80 when 94 stomach cancers and 95 colorectal cancers were identified. One to two matched case-control design was applied, and the concentrations of CEA, CA 19–9, CA 50, and TATI were assessed.

The mean values of the markers between the cases and the controls were almost the same for the total material. Case-control differences were found between the 11 sets with an interval of less than one year between drawing the sample and diagnosis of the cancer. The highest validity was found in CEA for colorectal cancer (specificity 91%; sensitivity 64%) and in CA 19–9 for stomach cancer (specificity 74%; sensitivity 73%). Conclusion — CEA, CA 19–9, CA 50, or TATI are not valid screening tests. Case-control differences were found with a potential one year screening interval, but they were not large enough for sufficient validity.
Encouraging Attendance at a Screening Mammography Programme: Determinants of Response to Different Recruitment Strategies
Authors: Schofield P E , Cockburn J , Hill D J , Reading D
Published: January 2017

To predict attendance at a mammographic screening programme after a community health promotion campaign and attendance after a personal invitation in addition to that campaign. Setting – A pilot mammographic screening programme in Melbourne, Australia. Methods — Attendance was encouraged by a community health promotion campaign and one year later, a personal invitation was sent to all women who had not yet attended. Drawn from two regions of a defined area (close to and distant from the screening centre), 618 women were interviewed before the programme started, and subsequent attendance at the programme was recorded.

Over half of the women (58%) in the sample residing close to the screening centre and 44% of women in the more distant sample attended. The personal invitation boosted attendance, particularly in the distal sample where attendance was more than doubled. Overall, attendance was predicted by ease of access to the programme; positive intention to attend; moderate experience of, perceived susceptibility to, concern about, and knowledge of breast cancer; adoption of other preventive health behaviours; having a job; and older age. Proximity to the programme, positive initial intentions, having heard of a mammogram, no concern about radiation from a mammogram, high personal control over health, and belonging to a club were associated with attendance after exposure to only the health promotion campaign. A personal invitation encouraged attendance among women without these characteristics.

A personal invitation in addition to a community promotion campaign seems to overcome many barriers to attendance. Attendance may be further increased by informing women of the benefits of early detection and improving access to the screening centre.
Use of Anonymous Newborn Serosurveys to Evaluate Antenatal HIV Screening Programmes
Authors: Holland F J , Ades A E , Davison C F , Parker S , Berry T , Hjelm M , Wilcox A H , Cubitt D , Hudson C N , Peckham C S
Published: January 2017

To evaluate the extent to which antenatal HIV screening programmes identify HIV infected women who go to term.

Comparison of results of two surveillance systems. An anonymous neonatal HIV serosurvey was used to estimate the numbers of HIV infected women giving birth; reporting by obstetricians was used to assess the proportion who had been identified.

Three Thames regions.

729 105 neonatal blood samples were tested, of which 484 were HIV seropositive. Newborn HIV seroprevalence is increasing, at different rates, in inner London, suburban London, and in non-metropolitan districts. During the past four years the proportion of infected women who have been identified before delivery is 16.9%, but less than half of these were diagnosed during pregnancy. In 1993 only five of the 128 (4%) previously undiagnosed infected women delivering babies were identified by antenatal screening.

Despite increased emphasis on antenatal testing for HIV in areas of higher prevalence the number of undiagnosed women delivering babies continues to increase. Consideration should be given to alternative strategies for offering antenatal HIV testing. Antenatal screening programmes should be monitored continuously by comparing anonymous neonatal seroprevalence with clinical reports from obstetricians.
Improving Breast Screening Uptake: Persuading Initial Non-Attenders to Attend
Authors: Turner Katrina M , Wilson Brenda J , Gilbert Fiona J
Published: January 2017

Firstly, to determine whether the acceptance rate of the second invitation for breast screening (sent to women who have failed to attend after the first invitation) might be increased by an accompanying letter from a general practitioner (GP letter). Secondly, to identify the additional costs of sending such a letter.

465 women registered with four practices in a single health centre were recruited into a randomised controlled trial in which the intervention was the inclusion of a standard, photocopied letter signed by the non-attender's doctor with the second invitation to attend for breast screening. The control group received only the standard invitation from the breast screening centre. The costs associated with the intervention were assessed from data supplied by the breast screening centre, supplemented by direct observation of the preparation of second invitations and semistructured interviews with the staff taking part.

The attendance rate of the test group one month after the second invitation for screening was significantly higher than that of the control group (21% v 10%, P<0.01). The average cost of a GP letter included with the invitation was 1.1 pence and the marginal cost for each extra attender was 9.6 pence. No non-monetary costs were identified.

The inclusion of a GP letter appeared to be effective and feasible in increasing the attendance rate to the second invitation. This intervention should be tested in other screening groups to confirm the effectiveness of a GP letter and its cost effectiveness.
Is Screening Once at Age 65 an Effective Method for Detection of Abdominal Aortic Aneurysms?
Authors: Khoo D E , Ashton H , Scott R A P
Published: January 2017

To evaluate whether a single screening at 65 or screening at 65 and 70 are the methods of choice to detect the majority of abdominal aortic aneurysms (AAA) suitable for treatment.

District general hospital, district general practice and community.

Data were collated from four studies (a pilot, a control trial, and two cohorts) of abdominal ultrasound screening of an invited group of 11 666 men and women aged 65–80 to derive age related prevalence, invitation acceptance rates, and operative mortality. Deaths from AAA rupture were obtained from district registrars' returns.

The prevalence of AAA increased with age being greater overall in men (6·8%) than in women (1·2%). From ages 65 to 80 the prevalence in men increased from 5·4% to 10·4%, and in women from 0·6% to 2·1%. In men and women 4% of patients dying from AAA rupture were aged 65 or under and 85% of deaths occurred over the age of 70. Acceptance rates for screening decreased between 65 and 80 from 80·5% to 66·2% in men and from 72·7% to 58·3% in women. In elective or symptomatic patients operative mortality was zero up to the age of 70, increasing to 7·1% in older patients.

Men should be screened at age 65 to obtain a high acceptance rate and to identify those with AAA most likely to benefit from treatment. The prevalence is relatively low at this age so an additional screen at age 70 is recommended, which would pick up a further 3·7% of patients with AAA, at which age intervention is likely to be of benefit.
Tailored Written Invitations for Second round Breast Cancer Screening: A Randomised Controlled Trial
Authors: Meldrum Patricia , Turnbull Deborah , Dobson Hilary M , Colquhoun Carol , Gilmour W Harper , McIlwaine Gillian M
Published: January 2017

Firstly, to determine if attendance for second round mammography screening in those sent a tailored letter (that is, making reference to their screening history) is increased compared with those sent a standard letter; secondly, to investigate the acceptability of tailored letters.

North West Glasgow Breast Screening Centre.

A randomised controlled trial.

Overall attendance was unrelated to whether the women were sent a tailored or standard letter; 60% of those sent the standard letter attended (922/1531) compared with 62% of those sent the tailored letter (956/1552) (χ2 = 0·61, P = 0·4) (difference 2%; 95% confidence interval − 2% to 5%). There were no significant differences in percentage attendance within each of the study subgroups: women who attended previously and received an all clear result, women who attended previously and received a false positive result, women who were invited previously and failed to attend, and women who were previously too young to be invited for screening. However, there was a statistically significant difference in percentage attendance between these four groups, independent of letter type (χ2 = 510, P<0·00001). Although women found the letters acceptable and understandable, they did not seem to pay close attention to the content.

Tailoring invitation letters does not have a significant effect on uptake rates for breast screening and does not justify the additional workload required.
UK Cervical Cancer Screening Programme: Setting a Research Agenda
Authors: Davies Christina , Brown Jackie
Published: January 2017

The UK national cervical cancer screening programme aims at reducing the incidence of and mortality from carcinoma of the cervix. It is generally agreed that high grade cervical intraepithelial neoplasia should be treated aggressively, but the appropriate management strategies for women with lesser degrees of abnormality are uncertain because of the inability to distinguish lesions that are likely to progress to invasive disease from those that will regress spontaneously. The role of human papillomavirus (HPV) and the possible usefulness of HPV testing as a secondary screening tool in women with borderline or mild dyskaryosis is also unknown.

This paper proposes an agenda for research into the uncertainties within the UK screening programme, suggesting that priority should be given to determining the most appropriate referral and management policies and the use of HPV DNA assay for women with borderline and mild dyskaryosis, so that those women at highest risk of developing invasive disease are treated. A randomised controlled trial is needed. The practical and methodological difficulties which would need to be considered and the need to convene a multidisciplinary research team to develop and implement the trial are highlighted.
Breast Screening: Adverse Psychological Consequences One Month after Placing Women on Early Recall Because of a Diagnostic Uncertainty. A Multicentre Study
Authors: Ong Giok , Austoker Joan , Brett Jo
Published: January 2017

Background—

It was the original intention of the UK National Health Service Breast Screening Programme (NHSBSP) to place women who were not diagnosed with cancer on three yearly routine recall (RR). In 1994–5 approximately 16 500 women, aged SO to 64, were placed on early recall (ER) at a shorter time interval, of which about 98% will have a normal result. This large number exceeds the expectations of the NHSBSP.

Objective—

To establish the adverse psychological consequences (PCs) for women one month after placement on ER because of a diagnostic uncertainty, and if detected, to suggest practical solutions to reduce them.

Methods—

Thirteen breast screening centres throughout the UK participated in the study. From March to October 199S all women who were placed on ER because of a diagnostic uncertainty were identified and compared with groups of women placed on RR (after mammography, assessment, fine needle aspiration, and a benign biopsy). These women were invited to complete a postal questionnaire one month after they were placed on ER or RR. One reminder was sent.

Results—

Overall 75% of women completed the questionnaire. The adverse PCs of placing women on ER because of a diagnostic uncertainty were higher (63%; n=81 of 130) than those of women placed on RR after mammography (29%; n=38 of 130) (P<0.00001) or assessment (50%; n=64 of 128)(Plt;0.05), but lower than the adverse PCs of women who underwent a benign biopsy (87%; n=26 of 30)(P<0.05). Factors that were significantly associated with subsequent adverse PCs were identified.

Conclusions—

The adverse PCs of being placed on ER because of a diagnostic uncertainty were significantly higher than those of women who turned out to have a false-positive mammographic result after assessment. Possible practical solutions are discussed.