Risk of skin cancer in new users of thiazides and thiazide-like diuretics: a cohort study using an active comparator group.

BACKGROUND: Case-control studies report a dose-dependent increased risk of skin cancer in users of hydrochlorothiazide (HCTZ) vs. nonusers. The degree to which other thiazides and thiazide-like diuretics (TZs) are associated with skin cancer is less certain. OBJECTIVES: To assess the risk of skin cancer in new users of different TZs compared with new users of calcium channel blockers (CCBs). METHODS: We conducted a cohort study using a UK primary-care database (1998-2017), including 271 154 new TZ users [87·6% bendroflumethiazide (BFT), 5·8% indapamide and 3·6% HCTZ] and 275 263 CCB users. The outcomes were basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and cutaneous malignant melanoma (CMM). We estimated incidence rates (IRs) and IR ratios (IRRs) in short-term (< 20 prescriptions) and long-term (≥ 20 prescriptions) users of TZs and CCBs using negative binomial regression, and calculated rate differences (RDs) for selected results. We used fine stratification on the propensity score (PS) to control for 23 baseline covariates. RESULTS: Long-term use of HCTZ increased absolute and relative risks of SCC [PS-weighted IRR 1·95; 95% confidence interval (CI) 1·87-2·02; RD per 100 000 person-years 87.4], but not of BCC or CMM. Long-term use of indapamide was associated with an increased incidence of CMM (IRR 1·43; 95% CI 1·35-1·50). BFT was not meaningfully associated with the risk of any type of skin cancer. CONCLUSIONS: Our results corroborate the previously reported increased risk of SCC (but not of BCC or CMM) for long-term use of HCTZ. BFT may be a safer alternative for patients at increased risk of skin cancer.

Implementation of long-term non-participant reminders for flexible sigmoidoscopy screening.

The clinical effectiveness of screening is highly dependent on uptake. Previous randomised controlled trials suggest that non-participant reminders, which highlight the opportunity to re-book an appointment, can improve participation. The present analysis examines the impact of implementing these reminders within the English Flexible Sigmoidoscopy (FS) Screening Programme, which offers once-only FS screening to adults aged 55-59 years. We assessed the screening status of 26,339 individuals invited for once-only FS screening in England. A total of 10,952 (41.6%) had attended screening, and were subsequently ineligible. The remaining 15,387 had not attended screening, and were selected to receive a reminder, 1-2 years after their invitation. Descriptive statistics were used to assess the increase in uptake and the adenoma detection rate (ADR) of those who self-referred, six months after the delivery of the final reminder. Pearson's Chi-Square was used to compare the ADR between those who attended when invited and those who self-referred. Of the 15,387 adults eligible to receive a reminder, 13,626 (88.6%) were sent a reminder as intended (1,761 were not sent a reminder, due to endoscopy capacity). Of these, 8.0% (n = 1,086) booked and attended an appointment, which equated to a 4.1% increase in uptake from 41.6% at baseline, to 45.7% at follow-up. The ADR was significantly higher for those who self-referred, compared with those who attended when invited (13.3% and 9.5%, respectively; X 2 = 16.138, p = 0.000059). The implementation of non-participant reminders led to a moderate increase in uptake. Implementing non-participant reminders could help mitigate the negative effects of COVID-19 on uptake.

Offering male endoscopists as decoy option to nudge disinclined women to have colorectal cancer screening.

Previous studies have shown that a large proportion of women invited for bowel cancer screening prefer endoscopists of the same gender. We tested whether women who are initially disinclined to undergo flexible sigmoidoscopy screening would be more willing to have the test with a female practitioner if they were also offered a decoy appointment with a male practitioner. We conducted two online experiments with women aged 35-54, living in England, who did not intend to undergo flexible sigmoidoscopy screening. In both experiments, women were randomised to two conditions: (1) control (appointment with a female endoscopist) and (2) decoy (two appointments to choose from, one with a male endoscopist and one with a female endoscopist). Experiment 1 (N = 302) verified the conditions for the decoy using a conventional intention scale, while experiment 2 (N = 300) tested how the presence of the decoy influences the likelihood of women choosing the appointment with the female practitioner in a discrete choice task. While experiment 1 showed that the presence of the decoy increased intentions to attend the appointment with the female practitioner (p = 0.02), experiment 2 confirmed that women were more likely to choose the appointment with the female endoscopist if they were also offered the decoy (p < 0.001). In both experiments, the presence of the decoy decreased perceived difficulty of the screening decision and cognitive effort required to make the decision. Offering disinclined women a male practitioner increased intention to have the test with an endoscopist of the same gender. This suggests that male screening practitioners can be used as decoy options to increase the likelihood that women choose female practitioners and facilitate the screening decision.

Testing behavioral interventions to optimize participation in a population-based colorectal cancer screening program in Catalonia, Spain.

The aim of the study was to measure the effect of three cost-neutral behavioral interventions on participation compared to the standard invitation letter in a population-based colorectal cancer screening program in 2014. For that purpose, a four-arm randomized field trial was conducted among 5077 individuals aged 50 to 69 years. Over an 8-week period, each week was randomly allocated to the intervention or the control conditions. Individuals assigned to the intervention conditions additionally received a prompt to write down the date to pick up the screening test in a pharmacy. Two of the three intervention groups also included an additional paragraph in the invitation letter on either: 1) the high proportion of individuals participating regularly (social norms condition) or 2) the importance of regular participation (benefit condition). We measured screening participation before and after receiving a reminder letter six weeks after the screening invitation. An overall 8.0 percentage point increase in CRC screening was achieved as a direct result of receiving a reminder letter; however none of the intervention strategies influenced participation. The only significant difference was found for newly invited individuals. There, participation rates decreased from 34.9% to 24.2% when the invitation mailing mentioned the importance of regular participation (OR: 0.60; 95% CI: 0.38-0.95). While none of the intervention strategies improved participation rates we found that praising the benefit of regular screening may discourage individuals who have never been invited before as the continuous behavior may be perceived as a large request. Nevertheless, the reminder letter boosted participation rates independently of the intervention assigned.

Exercise prescription for the overweight and the obese: how to quantify and yet keep it simple.

An activity point system (APS) is presented that assists healthcare providers and health professionals with a way to prescribe exercise in a semiquantitative manner and to motivate their patients to begin an exercise programme. Activity points are specific to one's body weight, body mass index and activity intensity for 10-minute bouts of activity performed. With a goal of accumulating 100-300 activity points per week, the APS provides a simple yet quantitatively accurate way to prescribe exercise for overweight and obese adults.

A particulate isotopic standard of uranium and plutonium in an aluminosilicate matrix.

Mixed-actinide microstandard particles have been produced for calibration and performance testing of isotope-ratio mass spectrometers and ion and electron microprobe instruments. The spherical micrometer-size particles consist of an aluminosilicate matrix loaded with 2.2% by weight of isotopically certified uranium and 0.11% by weight of isotopically certified plutonium. The uranium and plutonium isotopic compositions have been verified by both thermal ionization mass spectrometry and secondary ionization mass spectrometry (SIMS). The elemental composition of the microspheres has been determined by both electron microprobe and SIMS analysis.

High-level expression, purification, and enzymatic characterization of full-length Thermus aquaticus DNA polymerase and a truncated form deficient in 5' to 3' exonuclease activity.

The Thermus aquaticus DNA polymerase I (Taq Pol I) gene was cloned into a plasmid expression vector that utilizes the strong bacteriophage lambda PL promoter. A truncated form of Taq Pol I was also constructed. The two constructs made it possible to compare the full-length 832-amino-acid Taq Pol I and a deletion derivative encoding a 544-amino-acid translation product, the Stoffel fragment. Upon heat induction, the 832-amino-acid construct produced 1-2% of total protein as Taq Pol I. The induced 544-amino-acid construct produced 3% of total protein as Stoffel fragment. Enzyme purification included cell lysis, heat treatment followed by Polymin P precipitation of nucleic acids, phenyl sepharose column chromatography, and heparin-Sepharose column chromatography. For full-length 94-kD Taq Pol I, yield was 3.26 x 10(7) units of activity from 165 grams wet weight cell paste. For the 61-kD Taq Pol I Stoffel fragment, the yield was 1.03 x 10(6) units of activity from 15.6 grams wet weight cell paste. The two enzymes have maximal activity at 75 degrees C to 80 degrees C, 2-4 mM MgCl2 and 10-55 mM KCl. The nature of the substrate determines the precise conditions for maximal enzyme activity. For both proteins, MgCl2 is the preferred cofactor compared to MnCl2, CoCl2, and NiCl2. The full-length Taq Pol I has an activity half-life of 9 min at 97.5 degrees C. The Stoffel fragment has a half-life of 21 min at 97.5 degrees C. Taq Pol I contains a polymerization-dependent 5' to 3' exonuclease activity whereas the Stoffel fragment, deleted for the 5' to 3' exonuclease domain, does not possess that activity. A comparison is made among thermostable DNA polymerases that have been characterized; specific activities of 292,000 units/mg for Taq Pol I and 369,000 units/mg for the Stoffel fragment are the highest reported.

A particulate isotopic standard of plutonium in an aluminosilicate matrix.

Plutonium isotopic microstandard particles have been produced for mass spectrometer calibration. The particles may also be useful as an elemental standard for calibration of electron and ion microprobe instruments. The standard consists of spherical, micrometer-size aluminosilicate particles loaded with plutonium of known isotopic distribution. The morphology, elemental composition, and plutonium isotopic composition of the particles have been characterized.

Isolation, characterization, and expression in Escherichia coli of the DNA polymerase gene from Thermus aquaticus.

The thermostable properties of the DNA polymerase activity from Thermus aquaticus (Taq) have contributed greatly to the yield, specificity, automation, and utility of the polymerase chain reaction method for amplifying DNA. We report the cloning and expression of Taq DNA polymerase in Escherichia coli. From a lambda gt11:Taq library we identified a Taq DNA fragment encoding an epitope of Taq DNA polymerase via antibody probing. The fusion protein from the lambda gt11:Taq candidate selected an antibody from an anti-Taq polymerase polyclonal antiserum which reacted with Taq polymerase on Western blots. We used the lambda gt11 clone to identify Taq polymerase clones from a lambda Ch35:Taq library. The complete Taq DNA polymerase gene has 2499 base pairs. From the predicted 832-amino acid sequence of the Taq DNA polymerase gene, Taq DNA polymerase has significant similarity to E. coli DNA polymerase I. We subcloned and expressed appropriate portions of the insert from a lambda Ch35 library candidate to yield thermostable, active, truncated, or full-length forms of the protein in E. coli under control of the lac promoter.

Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase.

A thermostable DNA polymerase was used in an in vitro DNA amplification procedure, the polymerase chain reaction. The enzyme, isolated from Thermus aquaticus, greatly simplifies the procedure and, by enabling the amplification reaction to be performed at higher temperatures, significantly improves the specificity, yield, sensitivity, and length of products that can be amplified. Single-copy genomic sequences were amplified by a factor of more than 10 million with very high specificity, and DNA segments up to 2000 base pairs were readily amplified. In addition, the method was used to amplify and detect a target DNA molecule present only once in a sample of 10(5) cells.

HindIII and Sst I restriction sites mapped on rabbit poxvirus and vaccinia virus DNA.

The DNAs of two closely related orthopoxviruses, rabbit poxvirus (RPV) and vaccinia virus (VV), were mapped by overlapping-fragment analysis using restriction endonucleases HindIII and Sst I. The exact arrangement of these fragments was accomplished by total digestion of isolated partial restriction products and by end-fragment determination. RPV and VV DNAs showed identical restriction patterns in an internal region comprising approximately 60% of the genome. The size, by electrophoretical analysis of the RPV DNA, was 118 X 10(6) daltons, some 6 X 10(6) daltons less than VV DNA. The two opposite terminal restriction fragments of RPV DNA cross-hybridized to each other.