Table_2_Validation and comparison of the coding algorithms to identify people with migraine using Japanese claims data.DOCX

PurposeThe study aimed to validate and compare coding algorithms for identifying people with migraine within the Japanese claims database.MethodsThis study used the administrative claim database provided by DeSC Healthcare, Inc., that was linked to the results of an online survey administered to adult users of the health app “kencom®.” The ability of the 12 algorithms to detect migraines using diagnostic records alone or with prescription records was evaluated based on sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs). We used a migraine diagnosis judged based on respondents' self-reported symptoms according to the diagnostic criteria of the International Classification of Headache Disorders, version 3 (ICHD-3), as true.ResultsOf the 21,480 individuals, 691 had migraine according to the ICHD-3 criteria. The 12 algorithms had a sensitivity of 5.4–8.8%, specificity of 98.8–99.6%, PPVs of 19.2–32.5%, and NPVs of 96.9–97.0%. Algorithm 9 (migraine diagnostic records more than once AND at least one prescription record for migraine prophylaxis or triptans in the same month as diagnosis) produced the highest PPV, whereas Algorithm 2 (at least one diagnostic record of migraine or tension-type headache) had the highest sensitivity. Similar trends were observed when using the ID-Migraine or 4-item migraine screener, instead of the ICHD-3 criteria, for case ascertainment.ConclusionStrict algorithms, such as Algorithm 9, yielded a higher PPV but a lower sensitivity, and such algorithms may be suitable for studies estimating the relative risk. Conversely, algorithms based on a single diagnostic record, such as Algorithm 2, had a higher sensitivity and may be suitable for studies estimating the prevalence/incidence of disease. Our findings will help select a desirable algorithm for migraine studies using a Japanese claim database.</p

Table_3_Validation and comparison of the coding algorithms to identify people with migraine using Japanese claims data.DOCX

PurposeThe study aimed to validate and compare coding algorithms for identifying people with migraine within the Japanese claims database.MethodsThis study used the administrative claim database provided by DeSC Healthcare, Inc., that was linked to the results of an online survey administered to adult users of the health app “kencom®.” The ability of the 12 algorithms to detect migraines using diagnostic records alone or with prescription records was evaluated based on sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs). We used a migraine diagnosis judged based on respondents' self-reported symptoms according to the diagnostic criteria of the International Classification of Headache Disorders, version 3 (ICHD-3), as true.ResultsOf the 21,480 individuals, 691 had migraine according to the ICHD-3 criteria. The 12 algorithms had a sensitivity of 5.4–8.8%, specificity of 98.8–99.6%, PPVs of 19.2–32.5%, and NPVs of 96.9–97.0%. Algorithm 9 (migraine diagnostic records more than once AND at least one prescription record for migraine prophylaxis or triptans in the same month as diagnosis) produced the highest PPV, whereas Algorithm 2 (at least one diagnostic record of migraine or tension-type headache) had the highest sensitivity. Similar trends were observed when using the ID-Migraine or 4-item migraine screener, instead of the ICHD-3 criteria, for case ascertainment.ConclusionStrict algorithms, such as Algorithm 9, yielded a higher PPV but a lower sensitivity, and such algorithms may be suitable for studies estimating the relative risk. Conversely, algorithms based on a single diagnostic record, such as Algorithm 2, had a higher sensitivity and may be suitable for studies estimating the prevalence/incidence of disease. Our findings will help select a desirable algorithm for migraine studies using a Japanese claim database.</p

Table_1_Validation and comparison of the coding algorithms to identify people with migraine using Japanese claims data.DOCX

PurposeThe study aimed to validate and compare coding algorithms for identifying people with migraine within the Japanese claims database.MethodsThis study used the administrative claim database provided by DeSC Healthcare, Inc., that was linked to the results of an online survey administered to adult users of the health app “kencom®.” The ability of the 12 algorithms to detect migraines using diagnostic records alone or with prescription records was evaluated based on sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs). We used a migraine diagnosis judged based on respondents' self-reported symptoms according to the diagnostic criteria of the International Classification of Headache Disorders, version 3 (ICHD-3), as true.ResultsOf the 21,480 individuals, 691 had migraine according to the ICHD-3 criteria. The 12 algorithms had a sensitivity of 5.4–8.8%, specificity of 98.8–99.6%, PPVs of 19.2–32.5%, and NPVs of 96.9–97.0%. Algorithm 9 (migraine diagnostic records more than once AND at least one prescription record for migraine prophylaxis or triptans in the same month as diagnosis) produced the highest PPV, whereas Algorithm 2 (at least one diagnostic record of migraine or tension-type headache) had the highest sensitivity. Similar trends were observed when using the ID-Migraine or 4-item migraine screener, instead of the ICHD-3 criteria, for case ascertainment.ConclusionStrict algorithms, such as Algorithm 9, yielded a higher PPV but a lower sensitivity, and such algorithms may be suitable for studies estimating the relative risk. Conversely, algorithms based on a single diagnostic record, such as Algorithm 2, had a higher sensitivity and may be suitable for studies estimating the prevalence/incidence of disease. Our findings will help select a desirable algorithm for migraine studies using a Japanese claim database.</p

Identification of Optogenetically Activated Striatal Medium Spiny Neurons by <em>Npas4</em> Expression

<div><p>Optogenetics is a powerful neuromodulatory tool with many unique advantages to explore functions of neuronal circuits in physiology and diseases. Yet, interpretation of cellular and behavioral responses following in vivo optogenetic manipulation of brain activities in experimental animals often necessitates identification of photoactivated neurons with high spatial resolution. Although tracing expression of immediate early genes (IEGs) provides a convenient approach, neuronal activation is not always followed by specific induction of widely used neuronal activity markers like <em>c-fos</em>, <em>Egr1</em> and <em>Arc</em>. In this study we performed unilateral optogenetic stimulation of the striatum in freely moving transgenic mice that expressed a channelrhodopsin-2 (ChR2) variant ChR2(C128S) in striatal medium spiny neurons (MSNs). We found that in vivo blue light stimulation significantly altered electrophysiological activity of striatal neurons and animal behaviors. To identify photoactivated neurons we then analyzed IEG expression patterns using in situ hybridization. Upon light illumination an induction of <em>c-fos</em> was not apparent whereas another neuronal IEG <em>Npas4</em> was robustly induced in MSNs ipsilaterally. Our results demonstrate that tracing <em>Npas4</em> mRNA expression following in vivo optogenetic modulation can be an effective tool for reliable and sensitive identification of activated MSNs in the mouse striatum.</p> </div

Identification of photoactivated neurons by IEG tracing.

<p>(A) Schematic used for in vivo photostimulation and histology in the mouse striatum. Blue light stimulation was given to the left striatum and the right striatum was used as the sham-treated control. Boxed areas indicate approximate striatal regions shown in B. (B) Representative images of coronal tissue sections from mice which received optogenetic stimulation in the left striatum showing ISH signals of <i>c-fos</i> (B1, B1'), <i>Npas4</i> (B2, B2'), <i>Arc</i> (B3, B3') and <i>Egr1</i> (B4, B4'). CPu, Caudate putamen. (C) Quantification of <i>c-fos</i>, <i>Npas4</i>, <i>Arc</i> and <i>Egr1</i> mRNA signals in the striatum after light stimulation. Induction of <i>c-fos</i> was not observed, whereas, a robust increase in <i>Npas4</i> mRNA signals appeared in the left striatum which received optogenetic stimulation. Although <i>Arc</i> was induced by photostimulation, the expression level was relatively high in the contralateral striatum. Any induction of <i>Egr1</i> was not apparent after illumination. Data represent mean ± SEM. ** Difference between groups was highly significant (p≤0.01), * Difference between groups was significant (p≤0.05). Scale bar: (B) 200 µm.</p

Expression of <i>c-fos</i> and <i>Npas4</i> in the striatum after 60 minutes of illumination.

<p>(A1–B2) No significant expression of either <i>c-fos</i> (A1, A2) or <i>Npas4</i> (B1, B2) was observed in the striatum after 60 minutes of ChR2(C128S)-mediated activation of MSNs. Scale bar: 100 µm.</p

In vivo optical and physiological system for control of striatal MSNs in mice.

<p>(A) A sagittal section of the mouse brain showing selective expression of ChR2(C128S) in striatal MSNs as visualized by enhanced yellow fluorescent protein (EYFP) signals. Strong fluorescence was observed in the caudate putamen (CPu) as well as the targets of striatal MSNs such as the external segment of the globus pallidus (GP), the entopeduncular nucleus (EP) and the substantia nigra pars reticulata (SNR). (B) Schematic of the electrophysiological set-up used for in vivo photostimulation and electrophysiological recordings in awake mice. (C) A representative electrophysiological recording from the striatum. Photostimulation (a single 100-ms pulse, represented by a blue rectangle) in the striatum evoked neuronal excitation. The excitation lasted more than 1 minute (data not shown). Scale bar: (A) 1 mm.</p

Distribution of <i>Npas4</i> ISH signals in the striatum after unilateral blue light illumination.

<p>Schematic diagrams of the striatum were constructed by superimposing images of stained coronal tissue sections on figures from a standard mouse brain atlas <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052783#pone.0052783-Franklin1" target="_blank">[27]</a>. <i>Npas4</i> ISH signals in the illuminated striatum (CPu) are represented by blue dots. Signals outside the striatum are not shown. (A–I) Photoactivation-induced expression of <i>Npas4</i> in the mouse striatum is shown from bregma +0.50 mm to bregma −1.46 mm. The location of the optical fiber is depicted in F. The areas adjacent to the optical fiber appear in gray shade (F, G). (D–H) Strong <i>Npas4</i> induction took place in almost the entire extent of the striatal region close to the optical fiber. (A–B) <i>Npas4</i> expression level was relatively weaker along the ventral part of the rostral striatum. ac, Anterior commissure; cc, Corpus callosum; CPu, Caudate putamen; fi, Fimbria of the hippocampus; GP, Globus pallidus; ic, Internal capsule.</p

Optical stimulation-induced <i>Npas4</i> expression was mostly limited to the ChR2(C128S) expressing MSNs.

<p>(A1) A representative fluorescent image of coronal tissue sections indicates strong expression of the transgene (<i>ChR2(C128S)-EYFP</i>) in the striatum. (A2) After unilateral light stimulation <i>Npas4</i> mRNA expression was induced in the ipsilateral striatum (CPu, Caudate putamen). Note that <i>Npas4</i> induction was also observed in the cerebral cortex in some cases (asterisks, A2). Boxed areas in A2 are shown in higher magnification in A3 and A4. Induction of <i>Npas4</i> was observed from the dorsal (A3) to the ventral (A4) striatum. (B1–B3) Most of the striatal MSNs expressed the transgene <i>ChR2(C128S)-EYFP</i> (B1, red). After illumination <i>Npas4</i> (green) was expressed in the ipsilateral striatum (B2). Almost all <i>Npas4</i>-expressing cells were co-labeled with <i>ChR2(C128S)-EYFP</i> (B3). (C1–C3) Cholinergic interneurons were identified by <i>Chat</i> expression (C1, red). There was almost no co-labeling for <i>Npas4</i> (green) and <i>Chat</i> (red) (C2, C3). (D1–D3) <i>Npas4</i> (green) mRNA expression was not induced in <i>Pvalb</i> (red)-positive GABAergic interneurons. (E1–E3) Strong expression of <i>ChR2(C128S)-EYFP</i> (red) was observed in the contralateral sham-treated striatum (E1, E3) where <i>Npas4 (green)</i> expression was almost absent (E2, E3). CPu, Caudate putamen; GP, Globus pallidus. Scale bars: (A1, A2) 500 µm, (A3, A4) 100 µm, (B1–E3) 50 µm.</p

Recovery and blastocyst rates of embryos frozen and thawed in ETC using a cryotube or V-tube.

Recovery and blastocyst rates of embryos frozen and thawed in ETC using a cryotube or V-tube.</p