To study heterogeneoussurfaces in situ, the experimental technique mustboth have spatial resolution and be able to probe through gas or electrolyte.Traditional electron-based surface science techniques are difficultto use under high gas pressure conditions or in an electrolyte dueto the short mean free path of electrons. Since it uses visible light,SOR can easily be used under high gas pressure conditions and in thepresence of an electrolyte. In this work, we use SOR in combinationwith a light microscope to gain information about the surface underrealistic experimental conditions. We demonstrate this by studyingthe different grains of three polycrystalline samples: Pd during COoxidation, Au in electrocatalysis, and duplex stainless steel in corrosion.Optical light-based techniques such as SOR could prove to be a goodalternative or addition to more complicated techniques in improvingour understanding of complex polycrystalline surfaces with operando measurements.We have developeda microscope with a spatial resolution of 5 μm,which can be used to image the two-dimensional surface optical reflectance(2D-SOR) of polycrystalline samples in  For heterogeneous catalysis, this means the focus movesaway from ultrahigh vacuum (UHV) toward more realistic high-pressuresystems;1 in electrochemical studies, inthe fields of electrocatalysis or corrosion, it instead implies thatthe measurements are done while the sample is submerged in an electrolyteand a voltage is applied to the system.3 It is importantto correlate changes in catalytic activity or the onset of electrochemicalreaction to changes in the atomic structure and chemistry of the surfaceduring operando studies. Thus, it is essential tocombine surface-sensitive chemical or structural techniques with,for example, mass spectrometry (MS) in thermal catalysis or cyclicvoltammetry (CV), galvanostatic, and potentiostatic techniques inelectrochemistry.In the quest to understand complex industrial surface phenomena,there has been an increasing effort to perform operando studies of low-index surfaces,as these can serve as models for the individual facets of nanoparticle-basedcatalysts used in industries.5 Thus, it is now commonto look at larger single crystals with (100), (110), or (111) surfaceorientations, as well as some stepped surfaces, where the observedchemical activity can be attributed to structures or sites on thatspecific surface. However, this neglects the many other possible high-indexsurfaces with their different kinks and steps. Also, comparing largesingle crystals with a huge number of orientations is both dauntingand expensive.Both within gas catalysis and electrocatalysis,there has beena shift toward 6A proposed solution to these problems is theuse of samples thatexhibit many surface properties to be studied simultaneously. Forcatalytic studies, these could be polycrystalline samples, where thesurface exhibits grains of many orientations. Two-dimensional surfaceoptical reflectance (2D-SOR) and other 2D techniques with sufficientresolution let us probe surfaces with many possible surface orientations,while monitoring the response of the individual grains.8 However, most industrial materials, suchas duplex stainless steels, contain multiple phases with differentphysical and chemical properties. Industrial materials are almostalways polycrystalline and exhibit many different surface orientations,which may behave differently under corrosive conditions. Studies ofsimple single-phase model systems also neglect any interactions andsynergistic effects between the multiple phases, as well as the effectof grain boundaries.In corrosion surface science, single-phasesimple alloys or singlecrystals have been used as model systems to gain a fundamental understandingof the corrosion process and how it relates to surface structure andchemistry.in situ. This requires techniques that can provide 2D spatial informationon the surface state and activity with a spatial resolution high enoughto differentiate the different grains, as all grains need to be monitoredseparately and simultaneously. The technique must also be able toprobe the sample surface through the surrounding gas and electrolyte.Techniques such as surface X-ray diffraction (SXRD) can be used bothin gas phase9 and in electrochemistry10 but provide no spatial information about thesurface. Others, such as low-energy electron microscopy (LEEM) andphotoemission electron microscopy (PEEM), can provide 2D spatial informationabout the chemical state of the sample surface but are limited toUHV or high vacuum (HV) due to the low mean free path of electrons.13Thus, within the fields of thermal catalysis,electrocatalysis,and corrosion, there is a need to study heterogeneous surfaces suchas polycrystalline or multiphase materials 14 They have shownthat a simple setup measuring the optical reflectance from a metalsample can be used to gain information about the sample oxide or roughness.They further stipulate that even very thin oxides with a thicknessof only a few nanometers can be detected using this method.15 Since it works with visible light, 2D-SOR canbe used under high-pressure conditions and when the sample is submergedin an electrolyte. We have since developed this method further andhave also used it in combination with high-energy surface X-ray diffraction(HESXRD) where we correlate changes in the surface reflectance tochanges in the surface oxide thickness and roughness on a single-crystalPd(100) sample.17 We have shown that 2D-SOR signalis sensitive enough to detect the formation of a 2–3 Åthick surface oxide.18 We have also usedSOR in electrochemistry to study the anodization of Al and cyclicvoltammetry on single-crystal surfaces of Au(111) and Pt(100).19 Especially when combined with other operando techniques such as mass spectroscopy (MS) in gasphase or cyclic voltammetry (CV) in electrochemistry, 2D-SOR can aidin correlating changes in surface structure with changes in the chemicalactivity. Optical reflectance techniques have been used in the pastto study local electrochemical phenomena at surfaces, such as oxidationof nanoparticles, and corrosion.22Two-dimensional surface optical reflectance (2D-SOR) was introducedby Onderwaater et al.In this work,we have further developed the possibilities of 2D-SORby combining it with microscopy to study polycrystalline surfaceswhere we can resolve reflectance changes from individual grains. Webelieve this is a convenient and cost-effective setup to study thesurface of polycrystalline metals in three important fields of surfacescience: gas-phase catalysis, electrocatalysis, and corrosion. Todemonstrate the technique, we study CO oxidation on a polycrystallinePd sample, cyclic voltammetry on a Au polycrystal, and cyclic voltammetryon super duplex stainless steel. Using these three examples, we showhow the combination of 2D-SOR with additional techniques, can be usedto follow many grains on the micron level exhibiting different surfacestructures simultaneously under realistic experimental conditions.operando surface science,especially due to its ability to quickly investigate many surfaceorientations or surface structures at once, given its high spatialand temporal resolution. Two-dimensional SOR microscopy could be avaluable complementary technique when performing grazing incidentdiffraction or absorption experiments at synchrotrons.We believe that this technique makes a valuable addition to thearsenal of tools available for 218 as well as on electrochemistrycells.19 In this work, we will treat bothcases.The microscope setup1 was assAs a proof-of-concept, several samples which are of interesttothermal catalysis, electrocatalysis, and corrosion were investigatedusing the technique—a polycrystalline Pd sample used for COoxidation, a polycrystalline Au sample for electrocatalysis and asuper duplex stainless steel sample for corrosion study. These sampleshave surface features with sizes ranging from tens or hundreds ofmicrometers to several millimeters.ra < 0.03μm) Pd polycrystal of 99.994% purity,with a 6 mm hat diameter and an 8 mm base diameter purchased fromSurface Preparation Laboratory in Zaandam. Before the presented measurements,the sample surface was treated through three cycles of Ar+ sputtering and annealing to 1000 K and transferred in air to thethermal catalysis reactor. This sample was used in the gas catalysisreactor. To study the Pd sample during catalytic activity, the samplewas heated under gas conditions of 40% O2, 4% CO, and 56%Ar, at a pressure of 150 mbar and a total flow of 100 mLn/min. Prior to the experiment, the sample was heated to 240 °C,which is below the critical activation temperature of Pd. The experimentitself consisted of heating the sample beyond its activation temperatureat around 260 °C, and observing the resulting mass spectroscopyand SOR signals. The crystallographic orientations of the surfacegrains were characterized by electron backscatter diffraction (EBSD)using a scanning electron microscope (FEI Quanta 200 MKII) with anintegrated camera (Hikari XP) and a TSL-OIM system from energy-dispersiveX-ray analysis (EDAX).The Pd sample was a 2 mmthick hat-shaped polished (23 The gas supply into the reactor is regulatedwith a series of mass flow controllers (Bronkhorst EL-FLOW), and apressure controller (Bronkhorst EL-PRESS) is used to keep a constantpressure in the reactor. Using this system, we can reach flows between10 and 500 mLn/min at pressures between 10 mbar and 1 bar.Pressure gauges monitor the pressure before and after the reactor,which makes it possible to determine the reactor pressure througha calibration curve. A quadrupole mass spectrometer (Pfeiffer QMP220) into which a small amount of the exhaust gas was leaked througha leak valve was used to monitor the gas composition at the reactoroutlet. More details concerning the reactor, gas system, and its capabilitiescan be found in refs  was performed in 0.1 M HThe superduplex stainless steel sample from Sandvik (SAF SDSS2507) contained two phases: austenite grains in a matrix of ferritegrains. The sample was hat-shaped with a diameter of 6 mm and a basediameter of 13 mm. The sample was polished down to 0.25 μm diamondsuspension followed by oxide polishing suspension (OPS) polishing.Before the experiments, the sample was cleaned in acetone, ethanol,and ultrapure water. To study the behavior of the different phasesof the steel in a corrosive environment, CV in 1 M NaCl was performedwith a sweep rate of 50 mV/s, an upper vortex potential of 1.5 V,and a lower vortex potential of −0.9 V. To resolve the grainsof the super duplex stainless steel sample a 1.5× magnificationlens was used in combination with the Navitar microscopic lens system.25 A custom-made fused silica window provided optical access to thesample surface. The silica window was made in a top hat shape to letthe glass protrude into the cell leaving the bottom of the glass windowat the same height as the electrolyte outlet, as can be seen in 19 as there is nowno volume above the electrolyte outlet to trap gas in the form ofbubbles. These bubbles, which disturb the 2D-SOR image, often originatefrom electrochemical reactions on the surface such as the oxygen evolutionreaction (OER) or the hydrogen evolution reaction (HER). The lowerpositioning of the glass window also allowed for the optics of theSOR microscope to be placed closer to the sample, enabling higheroptical magnification.The electrochemistry cell used for the Au and super duplex stainlesssteel experiments was a polyether ether ketone (PEEK) flow cell witha three-electrode system as shown in 3The resultsfrom the experiments involving the polycrystallinePd sample in the gas catalysis reactor are shown in A number of grains were selected and their relative reflectance change is shown in 18 and may be due to a thinner layer of oxide forming as the gas compositionchanges when the reactant gases are depleted by the chemical reaction.Other details of note are the spatial gradients visible on the edgesof some of the grains in panel (e), for example, the one at the tipof the red arrow. These could be attributed to gas diffusion as differentgrains may have different catalytic activity and thus the local gascomposition may differ between grains creating a diffusion gradientat grain boundaries. The effect may also be attributed to enhancedreactivity at the grain boundaries themselves, since atoms acrossseveral layers in their vicinity are displaced from their typicallow-energy lattice sites.From 2SO4 are summarized in 27 There is a rapid decrease inthe reflected intensity when the oxidation peaks are reached in theCV. A clear increase in the reflected intensity is seen, coincidingwith the position of the reduction peak in the CV.Results from CV on the Au polycrystalin 0.1 M HThe current in the CV is a flow of electrons that is proportionalto the change rate of the system and not the absolute state of thesystem. In contrast, the reflected light intensity is proportionalto the roughness and optical properties of the surface. Thus, theSOR intensity is proportional to the absolute state of the systemand not the change rate of the system. This means that the time derivativeof the SOR signal corresponds to the change in the state of the systemand can be compared to the current in the CV. Panel (b) shows theCV plotted together with the derivative of the SOR signal from threegrains on the polycrystalline gold surface. Taking the derivativeof the SOR signal results in peaks around a constant background, closelymatching the current of the CV. It can also be seen that the peaksof the SOR derivative overlap with the oxidation and reduction peaksof the CV. However, there is no drastic change in the SOR signal duringthe oxygen evolution reaction (OER) at around 2 V. There is also nopeak in the SOR derivative matching the peak of the OER at high potentials.This indicates that within the potential window of the experiment,there is no significant additional roughening or oxidation of thesample surface during the OER.2SO4 electrolyte.2727 An interpretation of this is that the (110)steps are primarily oxidized at the (210) surface. The orientationof grain 2 is very close to (111) and the reflectance voltammogramof grain 2 is very similar to the CV of Au(111) electrodes from theliterature.27 Grain 3 has a crystallographicorientation between the (111) and (110) direction, which correspondto a (221) surface in the stereographic triangle. This surface has(111) terraces and (111) steps. According to the SOR signal shownin 29 The surface stability determined from the combination of 2D-SOR,CV, and EBSD follows the trend where the most uncoordinated surfaceatoms are oxidized at the lowest potentials. The coordination numberof surface atoms for an face-centered cubic (FCC) crystal goes inthe order of 7 for (110), 8 for (100), and 9 for (111). At the (210)surface of grain 1, the (110) step atoms are the least coordinatedand seem to oxidize first. The (221) surface contains (111) terracesand (111) steps, where the step atoms are less coordinated than theterrace atoms, and hence oxidize at lower potentials than the (111)terrace atoms. The order of oxidation onset of the grains: 1, 3, and2 can be attributed and correlated to the coordination number of theleast stable surface atoms. Studies performed on electrooxidationof platinum, which is a similar system, showed that oxidation roughensthe surface and lift surface atoms from their equilibrium positions.30 This would result in a decrease in reflected intensity just as observedin this study. For platinum, it was also observed with HESXRD thatless coordinated surfaces oxidize at lower potentials.2From the EBSD datashown in With the SOR microscope, we can study different grains atthe surfaceexposed to the same experimental conditions. This makes the comparisonof different surface orientations and surface structures more reliablesince the external experimental conditions such as electrolyte concentrationand composition as well as temperature and potential can be kept thesame for all grains on the polycrystalline surface.In electrochemistry,polycrystalline surfaces are often used asworking electrodes. Here, we can clearly see that the current observedwith electrochemical techniques is composed of the sum of the contributionof each separate grain. This means that the crystallographic orientationspresent at the surface determine the electrochemical properties sincethey in turn depend on the atomic structure of the surface. A polycrystallinesurface may hence have very different electrochemical properties ifthere is any preferential orientation or texture of the grains atthe surface.33 grows in current density with each cycle. The current density ofthe cathodic peak at around 0.5 V, which corresponds to the reductionof Cr(VI) to Cr(III),33 does not increase as the cycles proceed. With everycycle, more Cr gets oxidized during the anodic sweep but is not reversiblyreduced during the cathodic sweep. This indicates that the dissolutionrate of Cr from the passive film increases with each sweep.Results from the super duplex stainless steel corrosionexperimentare summarized in 34 Due tothe differences in crystal structure and elemental composition betweenthe two phases, the passive film on the surface also differs betweenaustenite and ferrite.35 A change in thereflected intensity is caused either by a change in surface roughnessor by a change in the optical properties of the surface. Here, wecan observe a decrease in the SOR signal that corresponds to the oxidationof Cr(III) to Cr(VI), which seems to be the mechanism of degradationof the passive film and later the metal itself. According to our SORmeasurements, Cr(III) oxidation and dissolution is more prominentat the ferrite phase, which might be caused by a different oxide chemistryor structure. With our 2D SOR microscope, it is possible to monitorthe corrosion of real industrial materials in situ, submerged in the electrolyte, and under potential control. Measurementscan be performed in real time to catch the dynamics and behavior ofindividual grains down to tens of micrometers in size.4–5 s without sacrificing signal-to-noise ratio. Thus,the temporal resolution is primarily limited by the readout time ofthe CMOS sensor, and studies with much higher temporal resolutionthan demonstrated in this work are possible, given that a suitablecamera is used. As was mentioned in the operando techniques. Another advantage of 2D-SOR is thatthat the 2D spatial resolution enables operando studiesof heterogeneous surfaces. This is an important step that allows for operando studies to move away from single-crystal modelsystems. Well-controlled single-crystal studies have been vital fora fundamental understanding of surface science, both in the fieldsof catalysis and corrosion. Thus, with 2D-SOR, heterogeneous surfacesmore closely resembling those used in industrial applications canbe studied.We have presented three examples where 2D-SORwas used to gainvaluable insights into surface phenomena, demonstrating the strengthsof 2D-SOR as a surface science tool. We have shown that 2D-SOR canbe used to image both small areas of a polycrystalline sample, withspatial resolutions of 5 μm as was the case for the Pd and superduplex stainless steel measurements, as well as entire samples asdemonstrated in the Au measurement with a 7 mm field of view. We havefurther shown that 2D-SOR can resolve very small changes in reflectanceof less than 0.1%, as demonstrated in operando conditions, but provide no spatialinformation about the surface. Electron-based techniques, such asPEEM, provide spatially resolved information but are difficult tooperate at high gas pressures or in an electrolyte, necessary for operando measurements. Scanning probe techniques can beperformed in situ, such as electrochemical scanningtunneling microscopy (EC-STM), which can provide spatial structuralinformation at the atomic scale while electrochemical reactions takeplace at the surface.30 However, EC-STMis very cumbersome to perform and is limited to a small field of view.Further, electron and X-ray-based techniques can be intrusive andunwillingly alter the surface to be studied due to beam-induced damage.As demonstrated in this work, 2D-SOR provides spatially resolved informationabout the sample surface in a nonintrusive manner, and is compatiblewith both high gas pressures and the presence of an electrolyte. Another2D-capable technique which has been employed in electrochemistry issecond-harmonic generation imaging (SHGI) which has previously beenused to investigate a polycrystalline Au surface during CV.36 This technique is sensitive to the surface chargedensity which can be visualized as a function of the applied potential.Comparing 2D-SOR to SHGI, we can see that both techniques providespatially resolved surface-sensitive data. The main advantage of 2D-SORis the capability to use the technique in both electrochemistry andthermal catalysis, whereas SHGI can only be used in situations wherethere is a potential between the surface and the surrounding medium.Furthermore, the 2D-SOR setup is relatively inexpensive and simplecompared to SHGI. SHGI on the other hand provides information whichis easier to quantify and allows for distinguishing oxide formationfrom roughening. Thus, 2D-SOR microscopy helps to fill a gap in thetechniques available in the surface scientist’s toolbox.In the field of surface science, there are few toolscompatiblewith high gas pressures or a presence of an electrolyte that provide2D spatially resolved data. Techniques that use X-rays, such as HESXRDor surface-sensitive X-ray absorption spectroscopy (XAS), can probesurfaces in In the case of the electrochemistry application, the advantageof 2D-SOR is clear. We can determine the shape of the CV on a pergrain basis, and hence, we can learn what electrochemical reactionstake place at each grain. To verify this, we can compare the averagechange in reflectivity over the whole sample to the CV, which showswhich features in the CV can be detected by 2D-SOR. We can also followto what extent each grain is affected by the electrochemical reactionsas in the case of the steel, where irreversible changes occurred dueto oxidation of Cr(III) which was more prominent for the ferrite phase.For the case of the gold surface, we showed that we can image thesurface oxidation as a function of potential. The local CV for eachgrain can be correlated to the CV of the low-index gold surfaces fromthe literature. This information can be compared to the crystallographicorientation measured with EBSD. In summary, we could disentangle thecontribution of the CV from the different grains on the surface. Inthe case of the super duplex stainless steel, we could observe thatthe changes to the surface structure corresponded to the oxidationof Cr(III) to Cr(VI) and that the ferrite phase corrodes faster thanthe austenite phase.operando capable techniques. By combining the 2D-SOR with MS in this work,we show how the surface orientation of the individual grains affectsthe oxidation behavior during catalytic CO oxidation, and correlatechanges in the grains to changes in overall catalytic activity. Furthermore,there are many other techniques that can determine the exact surfaceoxide properties. For example, high-energy X-ray diffraction (HESXRD)can determine the oxide structure. X-ray reflectivity (XRR) can beused in conjunction with that to determine the oxide thickness. Measurementswith 2D-SOR combined with HESXRD on single crystals have been performed,and it was observed that slow changes in the reflectivity correlateprimarily with oxide formation, whereas slow changes correlate primarilywith roughening.18 In this work, it wasalso shown that 2D-SOR is sensitive even to very thin surface oxidesand that a 30 Å oxide layer results in a 10% reduction of the2D-SOR intensity. The issue with the techniques mentioned above isthat they do not provide spatial resolution which is required to distinguishindividual grains. Therefore, the combination of 2D-SOR and any grazingincidence X-ray technique is a powerful way to study surfaces of complexmaterials systems under working conditions.In the case of gas-phase catalysis exemplifiedwith the Pd measurement,the learning outcome is more subtle. The primary limitation of 2D-SORis that the technique is not quantitative on its own, which makesit difficult to distinguish if a change in reflectivity is causedby roughening, oxidation or both. Instead, we can use 2D-SOR to observewhich grains exhibit a change in any of these properties, and whichdo not. We can further use 2D-SOR to learn about the magnitude andspeed of this change. The real strength of 2D-SOR, however, becomesapparent when combining 2D-SOR with other 37 In such a configuration, anyroughening should decrease the reflectivity similarly for all wavelengths,whereas the dielectric properties of the surface would change dueto oxide formation and change the reflectivity differently for differentwavelengths. Such a multispectral approach is a natural continuationof this work. It may also be possible to add polarizers to the setup,yielding a spatially resolved variant of ellipsometry.To obtain spatiallyresolved chemical and structural information,the 2D-SOR setup could be extended to use several LEDs of differentwavelengths, which would illuminate the sample consecutively. Thiswould allow the acquisition of spectrally resolved images, albeitwith a spectral resolution limited by the number of LEDs and theirrespective bandwidth. The result, however, would be a hybrid of 2D-SORand electroreflectance, which has been used to study oxides sincethe 1960s.17 It would then be possible to directly correlatea local change in the reflectivity with a local change in catalyticactivity.On topof these possible extensions of 2D-SOR itself, we plan toperform planar laser-induced fluorescence (PLIF) measurements on sampleswith slightly larger grains, where we hope be able to measure theactual catalytic activity on a per grain basis. This would build onprevious studies where PLIF has been combined with 2D-SOR on singlecrystals.18 Combining 2D-SOR with surface-sensitive XAScould enable the correlation of changes in reflectively to changesin the chemical state of the surface, for instance upon oxidationin gas phase or in electrochemistry. Two-dimensional SOR could alsobe used to study localized phenomena on surfaces. In corrosion, localcorrosion events, such as pitting corrosion and stress corrosion crackingcould be studied in situ for industrially relevantmaterials. Pitting corrosion is a problem both for structural materialssuch as steels39 and aluminum alloys but alsofor the stability of electrocatalysts40 and has previously been studied42 using opticalimaging. Another application of 2D-SOR could be to study the dynamicsof surface oxidation, which is of relevance in corrosion protectionand catalysis. Together with complementary techniques, 2D-SOR couldbe used to draw conclusions about how the crystallographic orientationsat the surface influence the orientation, crystal structure, and growthkinetics of surface oxides. Finally, 2D-SOR microscopy and other spatiallyresolved techniques could aid in the creation of surface structurelibraries, due to their ability to quickly study many different surfacestructures en masse. One measurement could provide data on severalhundred surface orientations. These libraries could, for example,be used as a training dataset for machine learning algorithms to increaseour fundamental understanding of processes at surfaces in operando conditions.As mentioned above, 2D-SOR can be used as anothersimple-to-usetechnique together with techniques such as HESXRD to correlate 2D-SORdata to changes in the atomic structure of the surface. It can alsobe combined with X-ray reflectivity (XRR) to correlate the 2D-SORsignal to changes in surface roughness or oxide film thickness.5operando conditions provide spatially resolved data. However,spatial resolution is essential to characterize and understand polycrystallineor heterogeneous surfaces with many different crystallographic surfaceorientations. In this work, we have shown that the 2D-SOR microscopytechnique, with high temporal resolution and with a spatial resolutionof 5 μm, can be used as an operando techniqueto monitor polycrystalline surfaces on a per grain basis during reactionsin gas-phase catalysis and electrochemistry. We can correlate eachgrain in the SOR image to a surface orientation as determined by EBSD.While this method cannot definitely determine if the change in reflectanceis due to roughness or oxidation, previous HESXRD measurements indicatethat slow changes in the surface reflectance correlate primarily toroughness while rapid changes correlate primarily to oxidation.18 This shows that the technique can be used todraw a qualitative conclusion when combined with other techniques.We believe that 2D-SOR microscopy can serve as a great complementto traditional surface science techniques, since it is nonintrusiveand can provide 2D spatial information on heterogeneous surfaces suchas polycrystalline surfaces. Since the technique uses light in thevisible range, SOR can penetrate gas and electrolyte, which is difficultwith traditional electron-based surface science techniques. Further,data from mass studies of surfaces made possible by 2D-SOR could beused as a training dataset for machine learning algorithms. This wouldallow us to draw conclusions from correlating data from many surfaceorientations measured with SOR and complementary techniques. Thisknowledge in turn could be used to tailor the chemistry and structureof industrially relevant surfaces in catalysis and corrosion for theneeds of tomorrow.Fewtraditional surface science techniques that work in


Patients in medium secure hospitals may be at particularly increased risk of coronavirus disease 2019 (COVID-19) infection and complications. We undertook a service evaluation involving all current in-patients within a single, English medium secure hospital to describe the uptake of the COVID-19 vaccine among this population. Data regarding capacity to consent to the vaccine, acceptance/refusal of this  and demographics was retrospectively collected from the patients’ clinical records and analysed. In total, 85 patients (92.4% of eligible patients) had capacity to decide if they wanted the COVID-19 vaccine. Of these 68 (80.0%) consented and 17 (20.0%) declined to consent. A similar proportion of patients aged under and over 40 years old consented to have the vaccine. Those from a Black Asian minority ethnic background were more likely to decline the vaccine than White British patients. The reasons for capacitous refusal appeared similar to those seen in the general population. In the UK (at the time of writing in April 2021), all adult mental health in-patients are being offered the COVID-19 vaccine as they can be considered to be in ‘Category 6’ as defined by the Joint Committee on Vaccination and Immunisation (JCVI) advice on priority groups for COVID-19 vaccination.4Compared with the general population, people with mental health disorders are at increased risk of negative physical and mental health outcomes  following SARS-CoV-2 infection.5 however, little is known about the vaccine uptake in people with mental disorders. We are not aware of any studies on COVID-19 vaccination uptake involving mental health patients detained in secure hospital settings.Factors that may promote or inhibit uptake of COVID-19 vaccine in the general population  are beginning to be elucidated,6 Most are admitted from prison and have a diagnosis of severe mental illness often complicated by histories of offending, substance misuse and trauma.7 Understanding COVID-19 vaccine uptake, and reasons for refusal, in patients in medium secure hospitals is especially important given the high prevalence of chronic physical health comorbidities such as obesity and diabetes seen in this population,8 as these conditions are also associated with poor clinical outcomes in severe COVID-19 disease.9Patients admitted to medium secure care have greatly increased mortality compared with the general population.We therefore undertook a rapid service evaluation within the medium secure hospital in which we work to examine the proportions of patients who accepted or declined to accept the COVID-19 vaccine, and explored the reasons for patients’ refusal of the vaccine. Given the findings in the general population, we were particularly keen to examine: if there was a difference in vaccine uptake between White and Black Asian minority ethnic (BAME) patients and if older patients were more likely to accept the vaccine than younger patients.The study took place at Arnold Lodge in Leicester, UK. This is a medium secure hospital that provides care for adult males and females. It was conducted as a service evaluation with local permission from the Nottinghamshire Healthcare NHS Foundation Trust Research and Evidence department. As per the JCVI guidance, all patients in the hospital were offered a COVID-19 vaccine. As part of this this they all had a capacity assessment and physical health evaluation completed by their consultant forensic psychiatrist.Data on the outcome of these assessments together with demographic data was collected from the patients’ electronic notes, anonymised and entered onto an electronic database for analysis. Descriptive statistics were reported for ‘eligibility to receive the vaccine’, age, gender, ethnicity (BAME or White British) and JCVI status.Of the 96 in-patients, 4 were ineligible for the vaccine because of recently having a COVID-19 infection. There was no statistically significant difference in the mean age of the 72 male and 20 female patients who comprised the group of 92 patients eligible to receive the vaccine . A quarter (23/92) of the eligible patients were BAME and three-quarters were White British. Three patients were assessed as being in ‘Category 4’ of the JCVI system  and the remainder were in ‘Category 6’ by reason of their serious mental illness.Of the 92 patients who were eligible, 7 patients (7.6%) were considered by their consultant forensic psychiatrist to lack capacity to make the decision regarding the vaccine. For two of these patients it was judged by their clinical team to be in their best interests to be given the vaccine; for the other five patients, the clinical team judged it not to be in the patients’ best interests because they would require physical restraint which would cause disproportionate distress and have a negative impact upon therapeutic relationships.v. 28/34, 82.4.4%) consented to have the vaccine. Those from a BAME background were more likely to decline the vaccine than White British patients .In total, 85 patients (92.4% of eligible patients) had capacity to decide if they wanted the COVID-19 vaccine. Of these 68 (80.0%) consented and 17 (20.0%) declined to consent. A similar proportion of patients aged under and over 40 years old , the most commonly cited reasons were concerns about the safety profile/side-effects of the vaccine  and patients’ perception of having a low risk to their personal health from COVID-19 . Five patients were unwilling to explain their decision, two cited broader distrust of healthcare services and one had concerns about animal testing.Of those patients who gave capacitous refusal to have the vaccine  have also been identified as factors associated with hesitancy in vaccine uptake in the community.5This small-scale study in a single site shows that among a group of patients who are detained in a medium secure hospital setting, immunisation with the COVID vaccine was broadly acceptable and most patients gave consent to receive it. The latest overall NHS England statistics show that 76.9% of individuals identified as being in an at-risk group or who are an unpaid carer have had at least one dose of a vaccine,Although we were able to collect data from all in-patients at our medium secure hospital the relatively small number of participants and single site nature of this study limits the generalisability of our findings and prevented us from doing adequate powered statistical analysis of between-group differences.11 Further consideration needs to be given to how the uptake of COVID-19 vaccination can be improved in people with BAME ethnicity, especially as this group is also over-represented in secure hospital settings.12The indication that patients of BAME ethnicity were more likely than White patients to decline the vaccination echoes the findings of research conducted in the general hospital trust that serves our city (Leicester) which showed a reduced uptake of the vaccine in South Asian or Black staff compared with White staff .We acknowledge that the study has clear limitations as it describes the acceptability of a COVID-19 vaccine in a single secure hospital population in the UK. Nonetheless, the study demonstrates that similar services caring for people with severe mental disorders should be able to approach the vaccination process with confidence. As many people with severe mental disorder also have high levels of physical health conditions such as obesity, diabetes and cardiovascular problems that would increase the risk of a poor clinical outcome if they contract COVID-19, protecting this vulnerable population through vaccination must be a priority for all mental health services.


The prevalence of daily or occasional smoking among high school students in Sweden was approximately 20% in 2019, which is problematic since lifestyle behaviors are established in adolescence and track into adulthood. The Nicotine Exit (NEXit) Junior trial was conducted in response to a lack of evidence for the effects of text message smoking cessation interventions among high school students in Sweden.The aim of this study was to estimate the 3- and 6-month effects of a text messaging intervention among high school students in Sweden on smoking cessation outcomes.A 2-arm, single-blind randomized controlled trial was employed to estimate the effects of the intervention on smoking cessation in comparison to treatment as usual. Participants were recruited from high schools in Sweden using advertising and promotion by school staff from January 10, 2018, to January 10, 2019. Weekly or daily smokers who were willing to make a quit attempt were eligible for inclusion. Prolonged abstinence and point prevalence of smoking cessation were measured at 3 and 6 months after randomization.P=.39) or 4-week smoking cessation . Sensitivity analyses using imputation yielded similar findings. Unplanned Bayesian analyses showed that the effects of the intervention were in the anticipated direction. The findings were limited by the risk of bias induced by high attrition (42.1%). The trial recruited high school students in a pragmatic setting and included both weekly and daily smokers; thus, generalization to the target population is more direct compared with findings obtained under more strict study procedures.Complete case analysis was possible on 57.9% (310/535) of the participants at 6 months, with no observed statistically significant effect on 5-month prolonged abstinence (odds ratio [OR] 1.27, 95% CI 0.73-2.20; Higher than expected attrition rates to follow-up 6 months after randomization led to null hypothesis tests being underpowered; however, unplanned Bayesian analyses found that the effects of the intervention were in the anticipated direction. Future trials of smoking cessation interventions targeting high school students should aim to prepare strategies for increasing retention to mid- and long-term follow-up.IRCTN Registry ISRCTN15396225; https://www.isrctn.com/ISRCTN15396225RR2-10.1186/s13063-018-3028-2 A steady decline in smoking prevalence has been observed in Sweden over the past decade, with the most recent data indicating that 7% of the general population were daily smokers in 2018 -5. EffecMobile phone–based interventions could potentially have far reach among adolescents, as mobile phone ownership in this group is almost universal in Sweden. Of particular interest are text message interventions, as they rely on standard technology that is ubiquitous in all mobile phones, and they have shown promise in other populations. Three meta-analyses have concluded that text messaging interventions have a positive effect on smoking cessation: one reported a summary effect size of 0.25 (95% CI 0.13-0.38) , the secHowever, only three trials have investigated the effects of smoking cessation text messaging interventions in adolescent populations exclusively -11, and P=.02) [In 2018, we conducted the Nicotine Exit Junior (NEXit Junior) trial in response to the lack of evidence for the effects of text message smoking cessation interventions among high school students. We found that a 12-week text message smoking cessation intervention had a positive effect on the 4-week point prevalence of smoking cessation 3 months after randomization among weekly and daily smoking students  , as are A 2-arm, single-blind, parallel-groups randomized controlled trial was employed to estimate the effects of the NEXit Junior intervention on smoking cessation. The trial was prospectively registered (ISRCTN15396225) and a trial protocol was published in advance of trial recruitment . This reParticipants were simultaneously recruited from 630 high school units in Sweden. Students were recruited through paper advertising (poster and leaflets) and digital advertising , and by promotion by school staff . Recruitment began on January 10, 2018, and ended 1 year later .Students interested in participating in the trial sent a text message to a dedicated telephone number. An automatic response was sent back with a hyperlink to a webpage where information about the trial was presented and students were asked to leave informed consent by pressing a button. Students who consented to participate were taken to a web-based questionnaire including items for both eligibility screening and baseline assessment.High school students who reported being weekly or daily smokers, and were willing to make a quit attempt, were eligible for the trial. We included weekly smokers for two reasons: (1) this was the criterion for our previous trial of a text messaging smoking intervention among university students ,15, and The text message intervention was a 12-week automatic, and unguided, program consisting of a total of 121 messages. During the first 2 weeks of the program, participants received 2 to 4 messages per day, which reduced to 2 messages per day during week 3, 1 message per day during weeks 4 to 7, and on average 5 messages per week during weeks 8 to 12.The content of the messages was based on a similar intervention targeting university students in Sweden ,15, whicIndividuals allocated to the control group were advised that they would not obtain access to the novel intervention and that they instead could use the website of the national quit line  or contaAt 3 and 6 months after randomization, all participants were sent a text message with a hyperlink to a web-based follow-up questionnaire. Participants were sent two reminders 2 days apart, after which they were called by phone for follow-up (maximum of 10 attempts). The questionnaire contained items for the two primary outcomes: prolonged abstinence and point prevalence of smoking cessation.Prolonged abstinence, following the Russel standard , was defPoint prevalence of smoking cessation, a recommended outcome by the Society for Research on Nicotine and Tobacco , was defSample size was determined by assuming that differences in cessation rates between the two groups would be similar to what was observed in a previous study of a text messaging smoking cessation intervention targeting Swedish university students ,15. We tIt should be noted that the expected 10 percentage point difference is much higher than what has been synthesized in meta-analyses of text messaging smoking cessation support versus minimal smoking cessation advice. The meta-analyses suggested that the differences may be in the range of 3-4 percentage points , which mAfter baseline assessment, eligible students were randomly allocated to the intervention or control group with equal probability. This was done on the backend computer server using Java’s built-in random number generator; thus, the sequence generation was computerized and fully automatic. Allocation was thereby also fully concealed until interventions were assigned.Research personnel were blind to allocation at the time of randomization; however, participants were informed of which group they were allocated to. Follow-up assessments were completed using online questionnaires by participants on their phones; thus, group allocation was not revealed at the time of follow-up. However, there was a potential risk of group disclosure among those who did not respond to text message prompts and subsequently were called by research personnel to collect follow-up data (see Limitations).The analyses conformed with the prespecified analyses in the trial protocol . SpecifiAttrition analyses were planned to investigate potential differences between those who did and did not respond to follow-up. A penalized logistic regression model (lasso) was used to identify the baseline characteristics that were potentially predictive of nonresponse. This allowed us to explore departures from the missing completely at random (MCAR) assumption underlying the primary complete case analyses. Sensitivity analyses using multiple imputation with chained equations  were perIn addition to the prespecified analyses, unplanned Bayesian analyses were performed. The higher than anticipated attrition rate underpowered the planned null hypothesis tests, and the Bayesian analyses were included to calculate the probability that the intervention had an effect on smoking outcomes. Using a Bayesian approach also removes the emphasis on null hypothesis testing and prespecified significance thresholds, which can be sensitive to single data points and can create counterintuitive results -38. NormAll analyses were performed in R (version 3.6.1); Bayesian inference was performed using the probabilistic programming language Stan (RStan version 2.19.1).The CONSORT flow diagram in P values, are presented in Complete case analysis was possible on 57.9% (310/535) of participants at 6 months and on 77.2% (413/535) of participants at 3 months. Sample estimates of prolonged abstinence and smoking cessation (primary outcomes), along with ORs, 95% CIs, and P<.05 threshold; thus, a null finding could not be ruled out. None of the other ORs was statistically significant.The OR for 4-week point prevalence of smoking cessation, which was statistically significant at the 3-month follow-up, was no longer distinguishable from 1 at the 6-month follow-up at the conventional We explored potential deviations from the MCAR assumption underlying the primary analyses in P=.25) and 4-week point prevalence of smoking cessation . This suggests that the findings in The analyses of 6-month primary outcomes with imputed data found similar effect estimates of the intervention as the complete case analysis for 5-month prolonged abstinence . There was no additional contact with participants throughout the trial period; thus, the trial closely resembles how the intervention would be used in routine care. In addition, inclusion criteria were broad, excluding only those who smoked on a monthly basis or less. The trial may therefore be seen as measuring effectiveness rather than efficacy, which strengthens the external validity of the findings. However, the limitations of this trial should be taken into account when interpreting the findings and the generalizability of the results, especially the high attrition rates.The most severe limitation of the 6-month findings from the NEXit Junior trial was the risk of bias induced by the high attrition rate (42.1%). Although we found no evidence of systematic missingness, and the findings were robust under imputation, high attrition increases the probability that unobserved factors may predict nonresponse, and thereby bias both the primary and sensitivity analyses. This issue has previously been raised as a concern when studying young adults , and futA second limitation was the lack of blinding of trial participants, which may induce performance bias, an issue prevalent in trials of health interventions as participants are often aware that they signed up for a trial of a particular intervention. Performance bias may be the source of the measured effects rather than the interventions themselves; thus, future trials should prioritize making study information to participants consonant with allocation to intervention and control groups. Additionally, caution should be taken when assessing the present findings since the outcomes were self-reported. This does not necessarily warrant a concern of bias in and of itself; however, in combination with the nonblinding of participants, the risk of performance bias is exacerbated.Finally, although all processes were automated and participants were treated equally within trial groups, there was a risk of detection bias due to calling nonresponders to collect follow-up data. Despite the fact that the research personnel responsible for the telephone interviews were experienced and instructed not to prompt participants to disclose allocation, some participants are expected to reveal the group to which they were randomized to, and thereby create a risk of bias. However, we judged this risk to be inferior to the increased risk of attrition bias, which would have been induced by not collecting outcome data from those not responding to initial attempts. Furthermore, the analyses revealed no differences in baseline or outcome data between early and late responders, suggesting that the risk of disclosure bias did not lead to any actual bias .These limitations may all influence effect estimates by introducing bias. One way to address these sources of bias post hoc is to consider accounting for them in analyses using causal models . Toward Higher than expected attrition rates to follow-up 6 months after randomization led to null hypothesis tests being underpowered. Although null findings could not be ruled out, unplanned Bayesian analyses suggested that the effects of the intervention were in the anticipated direction both at the 3- and 6-month follow-ups. Future trials of smoking cessation interventions targeting high school students should aim to blind participants to avoid risk of performance bias, and also prepare strategies for increasing retention to mid- and long-term follow-up.When making policy decisions to implement text messaging interventions for smoking cessation in high schools, consideration should be taken to other alternatives with stronger evidence for long-term effects. However, such decisions should also consider that text messaging interventions are relatively cheap to implement and potentially have great reach among those who may benefit. Moreover, although the effects past the 3-month follow-up period have been difficult to establish due to study limitations, the evidence put forth herein suggests that the intervention was more likely than not to have a positive effect, even in the long run. Considering the health benefits that could come from quitting smoking at such an early age, text messaging interventions could be an important part of a public health campaign in this population.


Is legislation requiring insurers to cover 12 months of short-acting hormonal contraception associated with an increase in 12-month contraceptive prescriptions?This cohort study found that more than 80% of prescriptions for contraceptives cover 3 months or fewer. Legislation mandating insurance coverage of annual prescriptions was not associated with an increase in 12-month prescriptions, although it was associated with a shift from 1-month prescriptions to prescriptions for 2 to 3 months.Eliminating the need to return to a pharmacy every 30 or 90 days to refill prescriptions will likely require changes beyond insurance coverage and may necessitate outreach and education to clinicians and insurers. This retrospective cohort study of hormonal contraceptive users examines the quantity of contraceptive supply dispensed 3 years before and 3 years after the 2016 policy change requiring insurers to cover dispensation of a 12-month supply of short-acting, hormonal contraception. Eighteen states, including Oregon, have passed legislation requiring insurers to cover dispensation of a 12-month supply of short-acting, hormonal contraception.To determine whether Oregon’s 2016 12-month supply law was associated with an increase in contraceptive supply received.This retrospective cohort study of hormonal contraceptive users using Oregon’s All Payer All Claims database examined the quantity of contraceptive supply dispensed 3 years before and 3 years after the 2016 policy change. We also assessed changes among patients attributed to Title X clinics.Legislation requiring insurers in Oregon to cover a 12-month supply of contraception to continuing users.Receipt of a 12-month supply of hormonal contraceptionThis cohort study of insured users  of short-acting hormonal contraception included 639 053 contraceptive prescriptions. Results indicated that more than 80% of prescriptions for contraceptives cover 3 months or fewer. Most women in the study population used the oral contraceptive pill, lived in a metropolitan area, and were privately insured. We did not observe a significant association between the passage of the 12-month supply policy and receipt of a 12-month supply . Receipt of a 12-month supply was more common for Medicaid recipients than the privately insured . We did find a shift from 1 month to 2 to 3 months supply being dispensed. The policy change was associated with a small, overall increase in quantity dispensed . Title X clinics prescribed 3 months more of contraceptive supply than non–Title X clinics . However, the policy change was not associated with increased contraceptive supply dispensed at Title X clinics.In this cohort study of insured users of short-acting hormonal contraception, the passage of a 12-month contraceptive supply policy was not associated with an increase in contraceptive supply dispensed. In the US, many women rely on the oral contraceptive pill to prevent pregnancy. With perfect use, it has 99% efficacy in preventing pregnancy.2 However, breaks in use are common, reducing the effectiveness of oral contraceptives.2The ability to decide if or when to become pregnant is fundamental to individual rights, health, and people’s role in society.3 Contraceptive 12-month supply policies require insurers to cover the cost of dispensing a full 12 months of coverage per prescription.4 In the absence of such policies, clinicians can prescribe a 12-month supply, but insurance coverage typically dictates the amount a person receives.5 These policies thus focus on changing insurance company behavior to improve access.The Affordable Care Act eliminated cost-sharing for contraceptives. Twelve-month prescription policies are an essential next step to reduce barriers to contraceptive access.7 Despite this evidence, a national survey in 2017 found that most women in the US (70%) receive a contraceptive supply of 3 months or less.8 Currently, 18 states have adopted legislation requiring insurers to cover the provision of 6 to 12 months of contraceptive supply at a time.4 For these policies to be effective, insurance companies would need to comply and be held accountable for following the revised coverage guidelines. Similarly, clinicians would need to change their standard prescribing patterns to write for an extended supply of contraception, and pharmacists would need to dispense the full supply. However, there have been little data to demonstrate whether these policies have been fully implemented and led to changes in prescribing practices.The justification for 12-month supply policies is based on studies demonstrating that women are more likely to continue contraceptive use when dispensed at least a 6-month supply.5 Individuals who had not used the prescribed contraceptive method previously were to be dispensed a 3-month supply; after this 3-month trial, insurers would be required to cover a full year’s supply.5 The law covered all short-acting methods of contraception: the pill, patch, and ring.On January 1, 2016, Oregon implemented legislation requiring all public and private insurers to cover the provision of 12 months of contraceptive coverage at once for all individuals renewing a prescription.9Following the policy change, the state of Oregon’s Reproductive Health Program disseminated information on the policy and its evidence base to clinicians enrolled in the state’s network of 150 publicly funded contraceptive clinics. This network of publicly funded clinics consisted of sites receiving Medicaid and Title X funding. Title X clinics are community health centers that receive funds from the federal government specifically designated to provide comprehensive contraceptive counseling and services. Title X clinics provide care for people with no insurance, Medicaid, and private insurance. Title X clinics receive grant funds that allow them to cover the costs of services for uninsured people. It is possible that Title X funds were used to cover a 12-month supply prior to the policy change. Oregon’s Reproductive Health Program reimbursed for contraceptive claims from private clinicians and those in the Title X network. Oregon Medicaid covered the cost of a 12-month supply from the beginning of the policy change. It is not known how, or if, private insurance plans complied with the law. There were no incentives or penalties tied to the policy and we were unaware of any regulatory oversight performed to ensure implementation of the policy or accountability for adhering to the law. Some private insurance plans—including large national plans with a presence in Oregon—may not have been aware of the Oregon policy change. Furthermore, self-insured commercial plans were not subject to state law.We used Oregon’s All Payer All Claims database to analyze the effect of this policy change on the quantity of contraceptives prescribed and dispensed for publicly and privately insured women in Oregon. We hypothesized that the policy change would be associated with an increase in the supply of short-acting methods of contraception  dispensed. We also assessed the policy’s effect for women who received contraceptives from Title X clinics. Given Title X clinics' emphasis on evidence-based reproductive health guidelines, we hypothesized that Title X clinics would be more likely to dispense prescriptions with a 12-month supply than non–Title X clinics.5 The institutional review board at Oregon Health & Science University approved the study, which waived written informed consent because all data were deidentified. We analyzed data spanning May 1, 2021, to September 10, 2021. We followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.We conducted a retrospective cohort study of insured women in Oregon (ages 12 through 51 years) using short-acting forms of hormonal contraception between January 1, 2013, and December 31, 2018, allowing for 3 years of data before and after the January 1, 2016, policy change.10 We combined medical and pharmaceutical claims data for all beneficiaries who received between 21 (>1 pack) and 420 days (<15 packs) worth of short-acting contraceptives. We included individuals who had complete demographic data and were between 12 and 51 years of age when the prescription was dispensed  data for privately insured enrollees. The APAC database contains claims from the largest 25 commercial insurers in Oregon, excluding information from small carriers with fewer than 5000 enrollees and from certain federal programs such as the Federal Employee Health Benefits Program.ispensed . We cond5 We defined new prescriptions as prescriptions for whom the person would have run out of their last prescription more than 30 days before their next prescription was filled, as well as the first prescription for each beneficiary in our data set.11We excluded claims for prescriptions dispensed in quantities fewer than 21 days and more than 420 days (15 packs); claims of fewer than 21 days may be for noncontraceptive use, and claims of more than 420 days were rare (<1%). We also excluded claims for short-acting contraceptives if they occurred at the same time as a hormonal contraceptive injection or implant . We excl12 We used organizational and health care professional NPIs to determine clinic Title X status and confirmed it was a Title X clinic by linking billing zip code with the Office of Population Affairs Title X Directory of clinics.13We matched the National Provider Identifier (NPI) of the prescriber with data from the National Plan & Provider Enumeration System (NPPES) to determine whether the prescribing clinician was part of a Title X clinic.Our primary outcome was a binary variable indicating the receipt of a 12-month supply of contraceptives. To determine whether a prescription was dispensed as a 12-month supply, we calculated the number of months  that each dispensing quantity would have covered if taken at the recommended dose. To account for people who may be taking active oral contraceptives pills continuously , we defined 12-month supply as any prescription dispensed in quantities between 12 to 15 packs. We then aggregated the data to the beneficiary-year level by including only the claim for the largest quantity dispensed in each given calendar year. We prioritized the claim with the largest quantity dispensed in each calendar year to try and identify whether the policy change was associated with an increase in the maximum amount dispensed. In a secondary analysis, we repeated our models using month supply as a continuous variable, truncating the continuous variable at 12 months.14We included the following claim-level characteristics: payer (Medicaid or private insurance), age, rural residence , and whether the prescriber was at a Title X clinic.We estimated 3 models. We conducted a logistic regression examining the association between the policy and our primary outcome: receipt of 12 months or more of contraception, controlling for payer type, age category, geographic area, and contraceptive type. Our second model used linear regression to estimate the association between the policy and the continuous measure of months of contraceptives prescribed, controlling for payer type, age category, geographic area, and contraceptive type. Finally, given Title X’s specialized funding and emphasis on reproductive health care, we conducted a subanalysis examining whether the policy had a differential effect on Title X clinics vs other prescribers. We ran a linear regression model that included an interaction term between the policy and whether the prescriber was a Title X clinic, controlling for payer type, age category, and geographic area. In all 3 models, we clustered standard errors at the prescriber level (by NPI).We also conducted a sensitivity analysis where we examined the sensitivity of our findings to our definition of new prescription. We ran our models with 2 different definitions of new prescription to assess whether our findings would change with variations in the definition of new prescription. Our baseline definition of new prescription was that an individual had not used the method in at least 30 days. We reran the models changing the definition to 90 days (n = 558 293) and 180 days (n = 513 465); our results remained robust  for all analyses.Our final sample consisted of 639 053 prescriptions, among a population that was largely privately insured (71.8%) and in a metropolitan area (78.6%) . Most prP < .001). The trend was similar for privately insured women. The share of women with private insurance receiving 1 month of coverage decreased from 41% to 28% (P < .001), while the share receiving 2 to 3 months of coverage increased from 46% to 56% (P < .001).Overall, only 3.5% of short-acting contraceptive users in Oregon received a 12-month supply prior to the policy change .Prior to the policy change, women in Title X clinics were significantly less likely to receive a 1- to 3-month supply than women attending a non–Title X clinic  and are exempt from state law.9 Additional research is needed to better understand the degree to which these factors played in the minimal policy effect we observed.Although Medicaid guaranteed coverage for a 12-month supply in Oregon, coverage by private plans for dispensing a 12-month supply may vary. The prevalence of self-insured private plans in Oregon may also partially explain our findings. Among Oregon’s privately insured population, 43% are covered by self-insured plans.22 As of 2020, 12-month supply laws have been enacted in 18 states (including Oregon),23 but limited evidence exists on whether they have been fully implemented. Additional research is needed to understand the effect of these policy changes on contraceptive supply and identify barriers to policy implementation.Ongoing, low rates of 12-month supplies of oral contraception represent missed opportunities to promote reproductive autonomy. Previous research has documented that women who received a greater supply of oral contraception had increased continuous use and decreased rates of unintended pregnancy.20 Our use of claims data allowed us to see what was reimbursed by the insurer. We were unable to see the quantity that was initially prescribed and compare this to what was dispensed by the pharmacist or reimbursed by the insurer. However, in Oregon, Medicaid has fully reimbursed for a 12-month supply since the policy change. This indicates that for the 90.1% of Medicaid recipients who did not receive a 12-month supply following the policy change, that factors other than insurance coverage were responsible for the smaller supply.This study has several limitations. Our study relied on administrative data; we did not have information on individual values or fertility preferences. We also lacked information on additional demographic and clinical variables that may have affected contraceptive use, such as pregnancy history. Some individuals might not want a 12-month supply—for example, if they want to become pregnant within the next year. However, the small share of individuals who received a 12-month supply, particularly for the privately insured (1%), suggests some unmet need for long-term contraceptive supply.24 To address this limitation, we examined enrollment in private and self-insured plans across our study period. We did not observe a decrease in enrollment following the Supreme Court decision suggesting that the self-insured population in Oregon’s APAC data remained stable  use in Oregon increased over the study period, rising from 10% to 15% of all contraceptive users in Medicaid. This study focused on individuals choosing to use short-acting forms of contraception. However, increases in LARC use at the population level would be unlikely to affect the number of pill packs prescribed by a clinician.This cohort study found that a law mandating a 12-month contraceptive supply coverage was not associated with an increase in prescriptions covering 12 months, and only a modest increase in total supply dispensed. Increasing prescriptions to encompass a 12-month supply will likely require broad outreach to patients, health care professionals, and payers, as well as enforcement from state governments. Federal policy mandating coverage of a 12-month supply is another strategy to support access for individuals using short-acting contraception.


BackgroundChronic obstructive pulmonary disease (COPD) and heart failure (HF) are chronic conditions with high acute care utilization. Disease-specific order sets were developed for patients with COPD or HF in Calgary to reduce total days in hospital for this population of patients. However, many patients have comorbidities which may contribute to hospital utilization; thus, disease-specific order sets may not be an optimal solution to reduce overall acute care utilization.MethodsInpatient data on Calgary hospitalizations for COPD or HF between April 1, 2017 - March 31, 2019 and associated diagnoses were identified. Outcomes included total days in hospital and length of stay for COPD and HF patients stratified by number of comorbidities.ResultsTotal days in hospital increased with the number of comorbidities for both conditions. During the study period, 131 patients with COPD and no comorbidities had a median length of stay of three days (IQR: 3) compared to 3,911 COPD patients with one to five comorbidities with a median length of stay of seven days (IQR: 9). There were 47 patients with HF and no comorbidities with a median length of stay of four days (IQR: 5) compared to 6,273 HF patients with one to five comorbidities with a median length of stay of nine days (IQR: 12). Common comorbidities included hypertension, type 2 diabetes, and acute renal failure. COPD and HF are frequently comorbid. ConclusionsTotal days in hospital for patients with COPD or HF is positively correlated with the number of comorbidities. COPD or HF patients with between one to five comorbidities  represent the majority of total days in hospital, and the majority of patients. This highlights the importance of focusing on patients with comorbidities in efforts to reduce hospital utilization, and suggests that concurrent management of commonly occurring comorbidities for HF and COPD patients may be necessary to achieve this goal. Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are chronic conditions with high morbidity and acute care utilization. They are among the top four diagnoses for inpatient hospitalizations in Alberta . Many guAt least one comorbidity  has been observed in >95% of patients with COPD . ManagemThe prevalence of comorbidities in HF is also high, with up to 40% of patients having five or more non-cardiac comorbidities . The proOur objective was to evaluate the frequency of comorbidities among patients with COPD or HF admitted to Calgary hospitals and their influence on length of stay and total patient-days in hospital. A secondary objective was to identify the most commonly occurring co-morbidities with COPD and HF.Data sourcesThe province of Alberta in Canada publicly administers healthcare to all residents and tracks access to healthcare using a unique personalized healthcare number (PHN). All hospital discharges for individuals with a valid PHN are recorded and compiled in the Inpatient Discharge Abstract Database. This dataset includes up to 25 diagnostic codes using the International Classification of Disease 10th version (ICD-10) and provides information on hospital location as well as admission and discharge date which, allows for calculation of length of hospital stay.Study populationThe Discharge Abstract Database was used to identify all patients over the age of 18 with a valid PHN admitted to a Calgary hospital from April 1, 2017 to March 31, 2019 who had an ICD-10 diagnostic code for either COPD or HF recorded in any position in their discharge abstract. COPD was defined with ICD-10 codes J41, J42, J43, and J44 which have been validated in population-based health administrative databases and compared to chart reviews for sensitivity . HF was Case ascertainmentFor our analysis, we created a ‘patient profile’ by assigning all diagnosis codes associated with a patient for any admission during the study period to that patient for all admissions during the study period, even if it was not coded as a diagnosis on a particular hospital admission. The rationale for a ‘patient profile’ is that any recently documented diagnosis is likely to have contributed to overall patient morbidity, complexity of management, and total days in hospital or readmission during the study period . The priAge at initial admission over the study period, sex, and comorbidities were explored as covariates. Comorbidities were defined using the Elixhauser Comorbidity Index and analyzed both as a continuous variable, and stratified as: 1) 0 comorbidities (a single diagnosis of either COPD or HF); 2) between one and five comorbidities inclusive; and 3) greater than five comorbidities. Coding algorithms to define the 31 Elixhauser comorbidity groupings using ICD-10 codes have been previously reported by Quan et al. . Five coStatistical analysisAnalyses were performed separately for COPD and HF. Baseline characteristics were explored descriptively. Proportions were described as percentages, and continuous variables were described as means with standard deviations (SD), and medians with first and third quartiles . Wilcoxon rank-sum tests and Kruskal-Wallis non-parametric tests were used to compare continuous variables, and chi-squared tests were used to compare proportions. Crude and adjusted (for age and sex) multilevel linear regression was performed with person as the hierarchy to explore how number of Elixhauser comorbidities as a continuous variable over the study period correlated with length of stay with results reported as coefficients and 95% confidence intervals (CI). STATA/SE 14.2  and Oracle SQL were used for all statistical analyses with an alpha of 0.05. Graphics were performed using Tableau and Microsoft Excel. Ethics approval was granted through the Conjoint Health Research Ethics Board at the University of Calgary (Reference number: REB19-1520).Between April 1, 2017 and March 31, 2019, the total number of distinct adult patients with COPD or HF was 5,032 and 7,197 respectively; 131 patients with COPD had no comorbidities, 3,911 had one to five comorbidities, and 990 had more than five comorbidities. 47 patients with HF had no comorbidities, 6,273 had one to five comorbidities, and 877 had more than five comorbidities. Baseline characteristics of the study cohort are presented in Table COPDThe mean (SD) number of comorbidities was 2.7 1.3) and 6.8 (1.1) for patients with one to five and greater than five comorbidities, respectively. The most common comorbidities for COPD patients were uncomplicated hypertension (34.6%), congestive HF (28.4%), arrhythmias (23.3%), fluid and electrolyte disorders (21.5%), and complicated diabetes (20.2%)  was 525 for those with no comorbidities, 88,855 for those with 1-5 comorbidities, and 26,167 for those with more than five comorbidities  number of 3.2 1.2) and 6.6 (1.0) comorbidities in patients with one to five and greater than five comorbidities, respectively. HF patients’ most common comorbidities were uncomplicated hypertension (45.9%), arrhythmias (45.3%), complicated diabetes (37.2%), fluid and electrolyte disorders (26.6%) and chronic pulmonary disease (20.3%) (Table .2 and 6.There was a significant difference in median length of stay for patients based on number of Elixhauser comorbidities. Patients with no comorbidities (a single diagnoses of HF) had a significantly shorter length of stay  compared to those with one to five comorbidities ; and those with more than five comorbidities   Figure .The cumulative number of days in hospital during the study period  was 262 for those with no comorbidities, 135,555 for those with one to five comorbidities, and 47,247 for those with more than five comorbidities . This suggests that efforts to reduce patient-days in hospital could focus on patients with one to five comorbidities, who represent ‘average’ patients, compared to ‘outliers’ who have either a single diagnosis (for whom a disease-specific order set is most appropriate) or more than five comorbidities (for whom a disease-specific order set is least appropriate). The most common co-morbidities associated with COPD and HF, including uncomplicated hypertension, arrhythmias, complicated diabetes and fluid, and electrolyte imbalances.In the first Canadian national study to identify comorbidities with HF, hypertension, diabetes, and acute renal failure were commonly diagnosed . InternaOrder sets for COPD exacerbations have been associated with reductions in length of stay . HoweverDespite order sets being based on clinical practice guidelines resistance to implementation can be present due to practice inertia and lack of generalizability across practices . OptimizOur results define a population of patients to prioritize in efforts to reduce total hospital utilization for all patients with HF or COPD based on the number of comorbidities. We have shown that patients admitted to Calgary hospitals with COPD or HF have a similar comorbidity profile to those in other studies. Our results suggest that co-management of the commonly occurring comorbidities in this population may be beneficial in reducing overall hospital utilization, compared with disease-specific order sets.LimitationsInherent in the use of administrative data is the risk for misclassification bias. We used validated codes for HF  and COPDAlthough our analysis shows that comorbidities contribute to total days in hospital, we did not investigate the impact of single-disease order sets on reducing total days in hospital for patients with HF  or COPD Total days in hospital for patients with COPD or HF is highly correlated with the number of comorbidities. Patients with COPD or HF and between one to five comorbidities (compared to those with no comorbidities and those with more than five comorbidities) represent the majority of total days in hospital, and the majority of patients. Patients with COPD and HF admitted to Calgary hospitals commonly present with a ‘syndrome’ of related diagnoses that is similar to comorbidities identified in prior research including hypertension, arrhythmias, diabetes, and fluid and electrolyte imbalances. This highlights the importance of focusing on patients with comorbidities in efforts to reduce hospital utilization, and suggests that concurrent management of commonly occurring comorbidities for HF and COPD patients may be necessary to achieve this goal.


We thank the authors of this Response Letter for their comment on our previous article . In our Based on our suggestion, the manufacturer proposed a new cut-off of 0.7 U/mL (Response Letter). We thus recalculated the sensitivity using exactly the same cohort and we obtained a sensitivity of 97.3% , which is in line with other immunoassays [As proposed by the authors of this Response Letter, we also measured the neutralizing antibodies using a surrogate virus neutralization test (sVNT), an ACE2 receptor binding inhibition assay . For that purpose, 150 remaining samples from our previous study were tested. Among them, 144 samples were collected >15 days since diagnosis [The EliA SARS-CoV-2-Sp1 IgG test has a highly significant correlation with the sVNT assay  and at the IFU cut-off of 10 U/mL, the agreement with the sVNT was 74.7%. With the adapted cut-off of 0.7 U/mL proposed in this Response Letter, the agreement increases to 87.3% with 17 samples being negative with the sVNT but positive with the IgG assay, and 2 samples being positive with the sVNT and negative with the IgG assay.We agree that measurement of neutralizing antibodies is of importance because they represent the real protective immunity of antibodies . DiffereInterestingly, a significant and continuous decrease of neutralizing antibodies was observed over time  using the sVNT assay which is in line with the serological assays. Nevertheless, if the residual antibody response drives the strategy and/or the administration for a boost dose of the vaccine, the use of sVNT (or pVNT) assays should be preferred, especially since they are now implementable on several automated platforms. In addition, they could be adapted to assess specifically the neutralizing capacity towards mutated spike proteins observed in variant strains.


Considering dolomite microbial experiments, one can imply the involvement of microbes in the formation of ancient dolomite, as microbes have shown the ability to overcome the dolomite kinetic barrier. Despite that fact, the ability of microbes in mediating dolomite diagenesis has not been investigated. In this study, microbes were applied to mediate replacement of Ca by Mg in different CaCO3 precursors. The microbial replacement experiments were based on the enrichment of aerobic halophilic heterotrophic microbial consortia sampled from sediments collected from Al-Subiya sabkha in Kuwait. Two experiments were performed in saturated media at 35°C for 14 and 30 days simulating the conditions of microbial dolomite experiments. The change in mineralogy was examined via powder X-ray diffraction (XRD), and the change in texture and compositional microstructures was examined using scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS). The effect of microbes on the alteration of CaCO3 precursors was studied by comparing biotic experimentations with abiotic controls. The biotic samples were shown to result in the favorable conditions for dolomite formation including an increase in pH and alkalinity, but no changes were observed in mineralogy or compositional microstructure of CaCO3 precursors. Our results suggest the inability of aerobic halophilic heterotrophic microbial consortia to introduce Mg replacement on CaCO3 precursors in a timely manner that is comparable to primary precipitation in microbial dolomite experiments. The inability of the enriched microbial consortia to mediate replacement can be ascribed to different factors controlling the diagenetic process compared to primary precipitation in microbial dolomite experiments.Recent laboratory experiments have exhibited microbes as promising agents in solving the perplexing origin of ancient dolomite by demonstrating microbial capability to mediate dolomite nucleation and growth. However, dolomite crystals from laboratory experiments have shown irrelevant characteristics to ancient dolomite from mineralogical and petrological perspectives. A major irrelevant characteristic is that ancient dolomite was assumed to be formed after the replacement of Ca by Mg in precursor CaCO Several laboratory studies have proposed the organogenic dolomite formation model after the successful precipitation of dolomite-like microscopic crystals by different microbial groups . The mecAlthough microbial experiments have shown potential contributions toward solving the origin of dolomite in ancient sediments, different characteristics among laboratory dolomite and dolomite in nature require further explanation to conclude a unifying microbial mechanism for their involvement. First, precipitates of microbial experiments exhibit different morphologies of spheroids and dumbbell-shaped crystals  in contr3 + Mg2+ ⇔ CaMg(CO3)2 + Ca2+ [H2O]62+ . The hal[H2O]62+ . Two expin situ using a laboratory thermometer. Details on seawater analysis and results are in Al-Subiya area is located at the northeastern part of Kuwait between latitudes 29°22′ and 29° 40′ N and longitudes 47° 46′ and 48° 05′ E. This area is characterized by gravel plain, shallow depressions, sand plains, slopes, and coastal sabkha . The coa3 precursors of bivalve shell, crab skeletons, and single-phase calcite were used in this experiment to examine microbial ability to mediate replacement  was used to detect change in texture and compositional structure. Details of sample preparation and machines settings are in Microbes from the sediment were enriched in nutritious media to support their growth and activity. The composition of the media was prepared to selectively grow halophilic heterotrophic microbial consortia. Details about the process of microbial enrichment are in lacement . Furtherlacement . The pH lacement . Minerallacement . The expThe pH considerably increased in all enriched samples with an average increase in 1.52 (σ = 0.09), but insignificant changes were observed in the control samples .0.845Mg0.155CO3 to Ca0.94Mg0.006CO3 based on ICDD matches and compared to the standard RRUFF calcite . After day 10, the control media COA1 was turbid and accidentally contaminated due to multiple handling, which resulted in changing pH and alkalinity. The pH, alkalinity, and conductivity of the other control media COA2, COC1, and COC2 remained almost constant. The pH of the saline control SA1, SA2, SC1, and SC2 dropped from 9 to an average pH of 8.17, the conductivity remained almost constant, and the alkalinity showed an increase after day 20 in all samples where alkalinity was higher in aragonite samples SA1 and SA2 compared to calcite samples SC1 and SC2. The results of pH, alkalinity, and conductivity throughout the incubation period are shown in 3 matrix  and was related to NaCl integration  where the formation of low-temperature and pre-metamorphic dolomite demonstrates non-metasomatic features that are associated with diagenetic replacement . The suctal belt .3, creating an alkaline environment  due to kinetic factors (3 starting materials where the reactive surfaces are important for the permeation of the dolomitizing fluids. A hydrothermal dolomitization experiment demonstrated that the reaction rate of Ca replacement by Mg in carbonate is proportional to the development of porosity, cavities, and trench within the rims of reactive surfaces (2+–H2O complexes (2+ ions for dolomitization was restricted. Fifth, it is important to note that the high-resolution chemical and morphological characteristics of starting materials is a crucial factor in dolomitization. For example, the finer is the grain size, the more susceptible is calcium carbonate to dolomitization (3 replacement by dolomite is a coupled dissolution-recrystallization process (Many reasons can stand behind this failure, individually and collectively. First, the replacement reactions require a pumping system of fluids with a high Mg content in order to be able to dolomitize calcium carbonates . In our  factors . The sca factors . Third, surfaces . Fourth,omplexes ; therefotization . In our  process , the ini3 starting materials such as karst, limestone, and coral skeleton. Furthermore, other microbial groups, such as cyanobacteria, can be used for future replacement experiments, as cyanobacteria can concentrate the level of magnesium preferentially on their sheath (3 precursors is governed by different factors in comparison to the primary precipitation process. The importance of Mg abundance, longer reaction time, formation of reactive surfaces, high microbial biomass, fine-grain CaCO3 precursors, and episodic periods of dissolution and recrystallization reactions and their synergy toward low-temperature microbial replacement reactions require further investigations.This work can be considered as a cornerstone for future microbial dolomitization studies that can investigate microbial ability to overcome dolomitization kinetics. Future experiments for microbial dolomitization at ambient Earth’s surface conditions can examine different CaCOr sheath . Moreover sheath . We belivia XRD nor SEM-EDS. The inability of the enriched microbial consortia to replace Ca by Mg in CaCO3 precursors can be related to the short timeline of our experiments. Indeed, secondary replacement is a lengthy process compared to dolomite primary precipitation experiments. The precursor CaCO3 materials were neither porous or permeable nor microbes were able to introduce porosity/permeability that would increase reactive surfaces for dolomitizing fluids to flow and conduct replacement. Finally, the controlling factors of microbial dolomite primary precipitation are likely dissimilar to the controlling factors of replacive microbial dolomite.Here, we performed experiments aimed to study the role of aerobic halophilic microbial consortia in replacement of Ca by Mg in calcium carbonate precursors at low temperature. The samples with microbial enrichment showed increased pH and alkalinity in a supersaturated media, and no replacement was observed neither The original contributions presented in the study are included in the article/AA and MD contributed to the conception of the research and study design, involved in data interpretation, preparation of the final draft of the manuscript to be published, agreed to be accountable for all aspects of the work, and ensuring that questions related to the accuracy or integrity of any part of the work are investigated and resolved appropriately. AA was responsible for conducting all laboratory experiments, collecting data, data analysis, and writing the first draft of the manuscript. Both authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor is currently organizing a research topic with one of the author MD.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.