Background-Most ulcers are caused, one can deduce, by Helicobcter pylori or by use of non-steroidal anti-inflammatory drugs (NSAIDs). Whether both together are worse than one alone is something that is quite unknown. Aim-To study both factors in order to see whether they interact together positively. Method-A case control study of ulcer bleeding in elderly patients chosen without weeding. Results-NSAID usage increased risk substantially. So did H pylori infection (but relative risk less than three). Neither seemed to interact. Their actions were discretely intact. Conclusion-H pylori eVects ulcer bleeding in an adverse manner but does not make the risk of NSAIDs worse. (Gut 1997; 41: 459-462) Keywords: peptic ulcer; gastric ulcer; duodenal ulcer; haematemesis; melaena; NSAIDs; Helicobacter pylori It is now established that most peptic ulcers are caused by Helicobacter pylori or non-steroidal anti-inflammatory drugs (NSAIDs). 1-7The prevalence of H pylori infection rises with age. For example, in one study, it was 29.7% in those less than 30 years old and was 63% at age 55-65. 8 However, it is less clear whether H pylori or NSAIDs act independently or synergistically in the development of dyspepsia, ulcers and ulcer complications. Such information would be important in understanding pathogenesis and identifying patients at particularly high risk of ulcer complications. We therefore investigated whether H pylori and NSAID usage interacted to increase the risk of developing peptic ulcer bleeding in the elderly. Methods SUBJECTS AND DRUG USAGEOur subjects were derived from 487 patients over the age of 60 who were consecutively admitted to the two acute Nottingham hospitals (University and City Hospitals) with peptic ulcer bleeding between April 1986 and January 1991, and 480 age and sex matched controls identified at the time of admission. Drug usage by cases and controls was established prospectively by using a structured questionnaire in the context of studies reported elsewhere. H PYLORI STATUSIn 1993, 166 cases and 205 controls were identified as still alive and residing locally. Their general practitioners were asked to identify those whom it was appropriate to approach for a blood sample. These patients were visited at home and a serum sample obtained for H pylori serology status using the Porton Cambridge Helico G ELISA test. 9 The manufacturer's recommended cut-oV value of 10 units per ml, validated in our laboratories, was used to define patient serology as positive or negative. STATISTICAL METHODSLogistic regression analysis was used to quantify the influence of risk factors. Variables entered into the model were age, NSAID usage, H pylori status, and H pylori/NSAID interaction. We hoped to study 100 cases and 100 controls in order to have 90% power to detect anticipated diVerences in NSAID usage of 35% v 15% and 95% power to detect anticipated diVerences for H pylori prevalence of 75% v 50% in cases v controls. Although only 175 subjects could be studied, the study still had 85% power to detec...

Malaria has had an enormous impact on human history, not least in times of war. The disease has been treatable by a natural remedy, quinine, since the 17th century, but the production of synthetic antimalarial agents was first achieved in Germany in the wake of the Great War of 1914-1918, in which malaria had caused immense problems. In the 1920s research workers in the Bayer laboratories of the IG Farbenindustrie consortium developed the 8-aminoquinoline plasmoquine (the forerunner of primaquine). They went on to develop the acridine dye, atebrin (mepacrine) and the 4-aminoquinolines, Resochin (developed at the end of the Second World War in America as chloroquine) and Sontochin. British attempts to match the advances achieved by the Germans were at first unproductive, partly because collaboration between academic and industrial organizations in the UK was beset by concerns over patent rights. However, with the outbreak of World War II, when supplies of antimalarials were scarce, ICI succeeded in the large-scale production of mepacrine (essential to prosecution of the war, particularly in the Far East) and also initiated a programme of collaborative research that eventually led to the discovery of proguanil (Paludrine); this, in its turn led to the diaminopyrimidine, pyrimethamine. A massive cooperative screening programme in the USA during World War II eventually bore fruit in the realization of the therapeutic potential of chloroquine, and in the later development of amodiaquine and primaquine. Some of this work also influenced the subsequent discovery of mefloquine and halofantrine at the Walter Reed Army Institute of Research.

Background In several countries, extended interval COVID-19 vaccination regimens are now used to accelerate population coverage, but the relative immunogenicity of different vaccines in older people remains uncertain. In this study we aimed to assess the antibody and cellular responses of older people after a single dose of either the BNT162b2 vaccine (tozinameran; Pfizer–BioNTech) or ChAdOx1 nCoV-19 vaccine (Oxford University–AstraZeneca). Methods Participants aged 80 years or older, who did not live in a residential or care home or require assisted living, and had received a single dose of either the BNT162b2 vaccine or ChAdOx1 nCoV-19 vaccine were eligible to participate. Participants were recruited through local primary care networks in the West Midlands, UK. Blood samples and dried blood spots were taken 5–6 weeks after vaccination to assess adaptive immune responses using Elecsys electrochemiluminescence immunoassay and cellular responses by ELISpot. Primary endpoints were percentage response and quantification of adaptive immunity. Findings Between Dec 29, 2020, and Feb 28, 2021, 165 participants were recruited and included in the analysis. 76 participants had received BNT162b2 (median age 84 years, IQR 82–89; range 80–98) and 89 had received ChAdOx1 nCoV-19 (median age 84 years, 81–87; 80–99). Antibody responses against the spike protein were detectable in 69 (93%) of 74 BNT162b2 vaccine recipients and 77 (87%) of 89 ChAdOx1 nCoV-19 vaccine recipients. Median antibody titres were of 19·3 U/mL (7·4–79·4) in the BNT162b2 vaccine recipients and 19·6 U/mL (6·1–60·0) in the ChAdOx1 nCoV-19 vaccine recipients (p=0·41). Spike protein-specific T-cell responses were observed in nine (12%) of 73 BNT162b2 vaccine recipients and 27 (31%) of 88 ChAdOx1 nCoV-19 vaccine recipients, and median responses were three-times higher in ChAdOx1 nCoV-19 vaccine recipients (24 spots per 1 × 10 6 peripheral blood mononuclear cells) than BNT162b2 vaccine recipients (eight spots per 1 × 10 6 peripheral blood mononuclear cells; p<0·0001). Humoral and cellular immune responses against spike protein were correlated in both cohorts. Evidence of previous SARS-CoV-2 infection was seen in eight participants (n=5 BNT162b2 recipients and n=3 ChAdOx1 nCoV-19 recipients), and was associated with 691-times and four-times increase in humoral and cellular immune responses across the whole cohort. Interpretation Single doses of either BNT162b2 or ChAdOx1 nCoV-19 in older people induces humoral immunity in most participants, and is markedly enhanced by previous infection. Cellular responses were weaker, but showed enhancement after the ChAdOx1 nCoV-19 vaccine at the 5–6 week timepoint. Funding Medical Research Council, National Institute for Health Research, and National Core Studies.

Aim: To use Prescribing Analysis and Costs data to investigate factors associated with differences in rates of nonsteroidal anti‐inflammatory drug prescribing in Nottingham general practices. Results: Poisson regression analysis revealed that the Age, Sex and Temporary Resident Prescribing Unit Index was the largest identifiable influence; larger practice size and a higher index of deprivation were also significantly associated with lower prescribing, whilst the number of partners was associated with higher levels of prescribing. However, even after correcting for the influence of age, sex and temporary residents, there was an 5.9‐fold variation in rates of prescribing. A similar Poisson regression analysis to identify factors associated with admission to hospital with ulcer bleeding in the elderly over the preceding 57 months identified the rate of nonsteroidal anti‐inflammatory drug (NSAID) prescribing as the only significant influence. Conclusion: The data are compatible with 1 hospital admission per 2823 NSAID prescriptions (95% confidence intervals 2098–8110) and they emphasize the need for strategies to reduce levels of NSAID prescribing.

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