• <tr id="yyy80"></tr>
  • <sup id="yyy80"></sup>
  • <tfoot id="yyy80"><noscript id="yyy80"></noscript></tfoot>
  • 99热精品在线国产_美女午夜性视频免费_国产精品国产高清国产av_av欧美777_自拍偷自拍亚洲精品老妇_亚洲熟女精品中文字幕_www日本黄色视频网_国产精品野战在线观看 ?

    GP prescribing in Northern Ireland by deprivation index: retrospective analysis

    2020-10-22 04:35:34JohnScottFrazerGlennRossFrazer
    Family Medicine and Community Health 2020年3期

    John Scott Frazer, Glenn Ross Frazer

    AbstrACt

    IntrODuCtIOn

    In 2010, the Marmot review outlined the startling reality that those living in greater deprivation are more likely to die prematurely.1Total life expectancy is reduced by 7 years for those living in the most income deprived areas compared with the least deprived areas, and an average of 17 more years are spent living with disability before death. This carries a significant economic burden in terms of increased NHS spending and more time lost from employment. The Scottish Burden of Disease Study2similarly reported that poorer areas in Scotland had twice the rate of illness or early death than richer areas and are also associated with poorer mental health, as well as higher rates of alcohol misuse, recreational drug use and tobacco use. It is not the case, however, that deprivation is associated with increased prevalence of all diseases equally. Interestingly, sensory organ disease, neck pain, lower back pain and migraine were more common causes of morbidity in wealthier areas. Heart disease and depression were prominent features in both groups. However, the relationship between socioeconomic deprivation and health is complex; although some lifestyle choices, such as smoking, become more common as deprivation increases, even non- lifestyle- related illnesses may themselves result in social stigma or loss of employment and subsequent social migration.

    Previous work has focused on the diagnoses of individuals within various socioeconomic groups. We present a nationwide analysis of differential rates of prescribing between areas of differing socioeconomic deprivation using a database of prescriptions signed nationally by general practitioners (GPs) in Northern Ireland. This approach has the distinct advantage of allowing us to quantify clinically significant illnesses which are difficult to characterise by other means, such as depression or symptomatic hypothyroidism. Furthermore, we present analysis of differences in cost of prescribing between areas of high and low deprivations. Our approach has importance not only for further characterising distribution of disease and identification of diseases not previously known to be associated with deprivation, but also for revealing unconscious social biases among prescribers, which may result in differences in care across the deprivation spectrum.

    MethODs

    We made use of three databases hosted by Open Data NI,3all of which are maintained under the UK Open Government Licence for public sector information4: the April 2019 GP Practice List Sizes dataset5; the 2017 Northern Ireland Multiple Deprivation Measures (NIMDM) dataset (grouped by 2014 wards and 2011 small areas (SAs))6; and the GP Prescribing Data datasets from May 2019 to October 2019 inclusive.7Postcodes were associated with wards and SAs using the Office for National Statistics Postcode Directory.8The 2017 NIMDM provides a measure of deprivation at the SA level and uses the seven ‘domains’ of deprivation with their associated weightings (income deprivation, 25%; employment deprivation, 25%; health deprivation and disability, 15%; education, skills and training, 15%; access to services, 10%; living environment, 5%; and crime and disorder, 5%) to provide an overall deprivation rank. Individual areas can then be ranked according to deprivation, although it should be noted that the ranking does not quantify the magnitude of differences in deprivation between areas.9There are four measures of multiple deprivation used in the UK, one for each country. The measures are unfortunately not directly comparable, as they use data from different time periods, different units of geographical area, and different deprivation domains and weights.

    Databases were combined by tagging each prescription with the postcode of the prescribing GP practice, and then the associated ward and deprivation data. Two GP practices closed during our 6- month analysis period and so were excluded. Among the 325 included GP practices, there were 238 unique postcodes. Twenty- three postcodes contained two GP practices; 10 contained three; 2 contained four; 4 contained five; 1 contained six; 2 contained seven; and 1 contained eight. These unique postcodes thus mapped to 174 wards of the total of 462 in Northern Ireland. We combined prescriptions from practices which shared a ward to list total prescriptions per ward, and using the NIMDM dataset ranked wards frommost to least deprived. Despite some practices sharing wards, wards were used as they were felt to capture the deprivation index most representative of the population living within a reasonable commute from the practice.

    Table 1 Prespecified drug classes and corresponding BNF chapter and section.

    Prescriptions were grouped by British National Formulary (BNF) chapter and section. Our primary analysis was of BNF sections, which group the drugs by most common indication. BNF sections were used as this was felt to provide the most favourable balance between a convenient clinical grouping of drugs by class and a reduction in the number of analysis and, therefore, risk of type I error. We prespecified 12 BNF sections of interest based on importance in terms of high burden of prescribing in general practice, as well as the public health importance of the conditions they aim to treat. Our prespecified sections of interest are listed in table 1. We calculated the number of prescriptions of all drugs and drug classes per 1000 practice- registered patients (PRP) within the outlined 6- month period for each ward. Prescriptions for pancreatin, sterile leg bags and non- sterile leg bags were excluded from our analysis due to non- standardised data entry. Prescriptions for dressings, appliances, incontinence appliances and stoma appliances were also excluded as their indications for prescription are difficult to associate with a particular illness. Kendall’s tau was used to assess the correlation between the number of prescriptions per 1000 PRPs of a drug or drug class and the associated deprivation rank. Kendall’s tau is calculated by dividing the difference between the number of concordant and discordant pairs by the sum of concordant and discordant pairs. This statistical measure was chosen due to the ordinal nature of our data.10We took a p value of <0.0005 to indicate statistical significance, calculated by application of the Bonferroni correction to the traditional α value of 0.05, corrected for 107 tests performed. Further exploratory analyses on sections of interest were carried out by analysing individual drugs within those classes. Cost was calculated using the gross cost per item provided in the prescribing database, which was taken directly from the BNF. Data analysis was performed in R Studio V.1.2.5033,11and plots were generated using Gnuplot V.5.2 patchlevel 7.12

    Figure 1 Choropleth map of Northern Ireland with each postcode plotted as a coloured point on the MAP, and associated multiple deprivation index (based on small areas) as dot colour (see key). Locations of GP practices are highlighted with a green dot. Zoomed views of Northern Ireland's two cities (Derry/Londonderry and Belfast) are also shown. GP, general practitioner.

    results

    Qualitative analysis of a choropleth map of SAs colour coded by deprivation rank revealed clear clustering of areas with similar rank (figure 1). Areas of deprivation surrounding GP practices were sufficiently homogeneous as to permit our assumption that practices tend to serve patients of a similar deprivation rank. Median deprivation rank among wards containing GP practices was 179.5 (IQR 84.3-292.3), compared with 264.5 (IQR 149.5-360.3) for those wards without practices. Indeed wards containing GP practices were skewed towards greater socioeconomic deprivation (skew=0.38, kurtosis=1.98, p=0.003),13as has been observed in a previous study.14

    We analysed a total of 2 764 303 prescriptions using Kendall’s tau to calculate the correlation with deprivation for each BNF section and individual prescription item. Since areas are ranked from most deprived to least deprived, those areas with a lower deprivation rank have a higher overall deprivation score, and thus a negative correlation coefficient indicates a greater degree of prescribing in areas with higher socioeconomic deprivation. Correlation coefficients for all BNF sections analysed are shown in online supplementary table 1, with selected results presented graphically in figure 2. Greater deprivation was correlated with higher rates of prescribing for the majority (82.2%) of BNF sections. Prescription of 8 of our 12 prespecified drug classes correlated significantly with higher deprivation according to our corrected p value (online supplementary table 1), with 11 of 12 reaching the traditional level of statistical significance. Correlation coefficients relating to a selection of individual drugs of interest are presented in figure 3.

    In the following paragraphs, r represents the Kendall’s tau correlation coefficient; n represents the number of prescriptions; D1and D10represent the mean prescriptions per 1000 patients per 6 months in the 1st decile (most deprived) and 10th decile (least deprived), respectively. Figure 4 presents our cost analysis across deprivation rank. Deprivation correlates weakly with greater overall cost per patient (r=?0.1232, p=0.016). However, when examining the mean prescription cost and the items per patient individually, it is clear that there are two competing trends. Higher mean medication cost correlates with reduced socioeconomic deprivation (r=0.3809, p<0.001). This trend is balanced by the correlation of number of items prescribed per patient with increasing deprivation (r=?0.3440, p<0.001). Overall, £13.79 more was spent per PRP over our 6- month period in the most compared with the least deprived decile (£112.96 vs £99.17), with 3.5 more items prescribed in the most deprived decile (12.4 vs 8.8). We also found that more expensive items tended to be prescribed in areas with lower socioeconomic deprivation (£11.27 per item vs £9.20 per item). When individual BNF sections were analysed, 62.1% of sections exhibited increasing drug cost in association with more positive individual drug correlation coefficients, suggesting that more expensive drugs were favoured in areas with lower deprivation even for similar indications.

    The University Healthcare Centre at Queen’s was a consistent outlier in terms of lower prescribing cost per patient (figure 4) and was found to have dramatically reduced prescribing of the majority of BNF sections and individual medications when compared with practices of similar deprivation rank. This is likely due to the very different population served by the University Healthcare Centre, including mostly students who are likely to be younger and have fewer comorbidities.

    Figure 2 Bubble plot to show the Kendall’s tau correlation coefficient of prescription rate of drug classes (grouped by British National Formulary section) with multiple deprivation index. More negative correlation coefficient indicates a greater degree of prescribing in areas with greater socioeconomic deprivation. Bubble area indicates the number of prescriptions of this class. Drug classes which differed significantly from zero (corrected p<0.0005) are highlighted in red. Key drug classes are labelled. ADHD, attention- deficit hyperactivity disorder; CNS, central nervous system.

    Figure 3 Trends of prescriptions per 1000 PRPs per 6 months plotted against deprivation rank, where each point represents a ward with pooled GP practices as described. Data are presented for selected individual drugs and British National Formulary sections of interest. Kendall’s tau correlation coefficient is presented in brackets next to the title. GP, general practitioner; PRP, practice- registered patient.

    DIsCussIOn

    summary

    We analysed open- source databases of all prescriptions signed by GP practices in Northern Ireland from May to October 2019 in order to calculate how prescription frequency and cost correlates with deprivation. We have uncovered two competing trends, resulting in cost per PRP correlating weakly with increased deprivation: a smaller amount of more expensive medications are prescribed in areas of lower deprivation. Possible explanations include an unconscious prescriber bias towards newer and more expensive medications in affluent areas, a more educated population likely to conduct independent research and specifically request newer medications, or possibly more affluent patients representing to their practice with an intolerance of side effects as an alternative to reduced compliance.15Indeed, there is some preceding evidence of unconscious prescriber bias among GPs in the UK, with a tendency for more expensive medication to be prescribed in practices with an attached dispensary.16Another argument sees treatments for issues faced in more deprived areas as more common, better researched or with a larger cohort of off- label drugs, thus reducing cost. Further study into the causes of these associations is needed.

    strengths and limitations

    Due to the large number of prescriptions analysed, we were able to observe several statistically significantly correlations with deprivation. This analysis across a varied national landscape of deprivation, between both urban and rural populations, lends itself well to eliciting overall patterns of prescribing. However, we do acknowledge the possibility of type I error due to the large number of analyses performed and attempted to mitigate this by prespecifying BNF sections of interest as outlined earlier.

    Our model assumes that patients in each area visited their closest GP practice, and that GPs serve a homogeneously deprived community. In reality, patients are likely to commute a short distance to a familiar practice, and in fact, 24% of small output areas in Northern Ireland are known to be over 1.5 km from a GP practice.14However, this is likely to decrease the magnitude of correlation rather than appreciably skew results. We found a tendency for practices to be present in areas with greater socioeconomic deprivation, although controlled for any effect on our results by using relative deprivation rank of wards containing practices. This is, however, a potential source of bias; since analysis was conducted based on GP practice deprivation rank rather than that of the individual patient, individuals living in areas of low socioeconomic deprivation may not have had their ward deprivation rank captured in the analysis. We also assume that populations of wards are large enough so as to consider the demographics of the wards to be comparable, although the databases we used unfortunately do not provide this information to enable direct comparison. Thus, given that we analysed geographical areas, it is possible that our results suffer from the ecological fallacy; thus, further work would ideally include individual patient demographic data and the association of this with prescribing burden and deprivation, rather than aggregated data per GP practice. A further key assumption is that the prescriptions we analysed represent the entire burden of national prescribing. It is, of course, likely that hospital and private prescriptions make up a significant minority of prescriptions, although repeat prescriptions for long- term chronic health conditions are often supplied by the patients’ local GP practice. It should also be noted that the deprivation index simply provides a rank of deprivation between areas and does not quantify the difference in deprivation between them.

    Figure 4 Line graphs to demonstrate the association between items prescribed and costs of the items. The top graph demonstrates the cost per PRP over 6 months against deprivation, showing that cost per PRP increases with increasing deprivation. The middle graph demonstrates that the average item cost per PRP increases with decreasing deprivation. The bottom graph demonstrates that the number of items per PRP increases with increasing deprivation. The correlation coefficient calculated by Kendall’s tau is depicted on the bottom right of each graph. PRP, practice- registered patient.

    Comparison with existing literature

    Drugs correlated with increasing deprivation

    Bronchodilators, used in the treatment of chronic obstructive pulmonary disease (COPD) and asthma, diseases closely linked with cigarette smoking, exhibited the strongest correlation with deprivation (r=?0.4459, p<0.001, n=58 190, D1=457.4, D10=207.2), with salbutamol, tiotropium and theophylline demonstrating particularly strong trends. Respiratory corticosteroids were the third most correlated with deprivation (r=?0.3806, p<0.001, n=65 868, D1=269.9, D10=164.1); mucolytics exhibited a similar trend. Cromoglycates, leukotriene receptor antagonists and phosphodiesterase type 4 inhibitors are also associated with increasing deprivation, suggesting that the aforementioned trends also reflect the known increased prevalence of asthma with higher deprivation and are not due to smoking- related COPD alone.1718

    Drugs used in the treatment of mental health disorders also correlated with increased deprivation, including antipsychotics (r=?0.3858, p<0.001, n=76 420, D1=204.2, D10=101.7), antidepressants (r=?0.3785, p<0.001, n=88 480, D1=1153.6, D10=659.9), hypnotics and anxiolytics (r=?0.1733, p<0.001, n=35 272, D1=413.6, D10=296.2), and drugs used in substance dependence (r=?0.2373, p<0.001, n=17 101, D1=20.3, D10=28.8), reflecting the known correlation of increasing deprivation with poor mental health19and recreational drug and alcohol abuse, although the decile means in this case do not reflect the overall correlation. The unexpected correlation of prescription of vitamins with deprivation is dominated by thiamine (r=?0.4155, p<0.001, n=3025, D1=60.8, D10=20.7), a vitamin used specifically in those with alcohol dependence, further indicating the prevalence of this condition in more deprived areas (figure 3). Antiepileptic drugs are correlated with increasing deprivation (r=?0.3056, p<0.001, n=1 16 490, D1=317.2, D10=205.2), reflecting a previously observed but not yet fully understood trend.20Confounding this pattern is the fact that drugs in this class often have dual indications, with gabapentin (r=?0.3299, p<0.001, n=8863, D1=77.7, D10=34.3) also indicated for neuropathic pain and anxiety disorders, lamotrigine (r=?0.3264, p<0.001, n=16 034, D1=40.4, D10=24.0) also used as an adjunct in bipolar disorder among others and carbamazepine (r=?0.2327, p<0.001, n=13 301, D1=25.2, D10=14.7) indicated for trigeminal neuralgia and diabetic neuropathy. However, even drugs indicated solely for seizure control, such as levetiracetam (r=?0.2934, p<0.001, n=11 943, D1=23.1, D10=13.2), perampanel (r=?0.1633, p=0.002, n=1015, D1=1.43, D10=0) and Phenytoin sodium (r=?0.1523, p=0.003, n=3426,D1=4.8, D10=0.7) exhibited correlation with increasing deprivation.

    Drugs used in the treatment of diabetes also correlate with deprivation (r=?0.3004, p<0.001, n=1 18 520, D1=456.8, D10=307.2), reflecting the literature.21Indeed metformin, one of the first- line treatments for type 2 diabetes, is the fourth most correlated with deprivation of all drugs analysed (figure 3). Lipid- regulating drugs (r=?0.3054, p<0.001, n=47 641, D1=657.5, D10=457.6), drugs for treating hypertension and heart failure (r=?0.2318, p<0.001, n=99 284, D1=541.4, D10=411.8), and beta- adrenoceptor blockers (r=?0.2587, p<0.001, n=45 728, D1=423.0, D10=315.4) also feature, as do diuretics, nitrates, calcium channel blockers, antianginal drugs, antiplatelet agents and drugs used in the treatment of obesity. This reflects high prevalence of the metabolic syndrome22and obesity2324in areas with increased deprivation. Drugs used in the treatment of gastro- oesophageal reflux disease (including proton pump inhibitors and antacids) correlate with increasing deprivation, along with urea [13- C], which is used in the diagnosis ofHelicobacter pyloriinfection.

    Antibacterial drugs were found to correlate with increased deprivation (r=?0.1177, p=0.021, n=8 86 666, D1=347.7, D10=290.6), as has been noted previously in an analysis of national prescribing data in Scotland.25

    Drugs with no correlation with deprivation

    Prescription contraceptives did not correlate with deprivation index (r=?0.0705, p=0.167, n=34 506, D1=90.3, D10=81.7), although unintended pregnancy has previously been associated with low socioeconomic status.2627This is in contrast to a study analysing contraceptive habits of women in the UK in the 1990s, which reported that women with a higher social class and level of education were more likely to use contraception.28It is likely that contraceptive practice has changed in the 30- year interval since that study, conceivably due to increasing education.29However, these results are difficult to interpret in the context of the Northern Irish population, as heavy segregation of areas based on religious affiliation is likely to confound trends of contraception usage.

    Zopiclone and zolpidem did not correlate with deprivation, despite their use in insomnia and high potential for addiction, in contrast to a previous study investigating the use of sedative medications by deprivation index in England.30Although drugs used in the treatment of attention- deficit hyperactivity disorder (ADHD) were not found to significantly correlate with deprivation when analysed as a cohort, some of the individual medications did correlate. Thus, we cannot state that we support the published association of ADHD with deprivation.31

    A host of medications used in the treatment of diseases not typically related to lifestyle were found to have no correlation with deprivation index, including treatments for hypothyroidism and hyperthyroidism, drugs for Parkinsonism and related disorders, drugs used in the treatment of dementia, anticoagulants, digoxin and antiarrhythmics.

    Drugs correlated with lower deprivation

    Only a small number of drug classes correlated with lower socioeconomic deprivation. Prescribing of vaccines and antisera correlated with lower deprivation (r=0.2176, p<0.001, n=8557, D1=8.5, D10=13.1). Two broad classes of vaccines are prescribed by GP practices: childhood immunisations and travel vaccines. The correlation was particularly clear for the typhoid vaccine, used almost exclusively before foreign travel. This trend may be attributed to a combination of a greater likelihood for foreign travel in the more affluent population and possibly a greater awareness of the need for vaccination among this group. Uptake of vaccines in general has been previously shown to correlate with lower socioeconomic deprivation.32Suggested explanations include a possible increased uptake of novel child health technologies in more educated and affluent areas, although conversely, these areas may in fact suffer from a greater susceptibility to vaccine scares.33It should be noted, however, that GP practices do not represent the entire burden of prescribing of vaccinations, as immunisations can also be administered through schools and employers.

    Glaucoma, which is often asymptomatic in the early phase, is primarily detected on screening. That the treatment for glaucoma is correlated with lower deprivation (r=0.1406, p=0.006, n=15 470, D1=42.7, D10=51.8) may suggest a greater engagement with eye check- ups and health screening in general in this group. Indeed, a study in London has described an association between glaucoma and greater socioeconomic deprivation,34although a systematic review and meta- analysis of studies comparing access to eye services concluded that more work is required in this area to fully identify and explain any access discrepancies.35

    Sex hormones, specifically estradiol (r=0.1795, p<0.001, n=21 033, D1=23.5, D10=36.7), a drug used in hormone replacement therapy, correlated with decreasing deprivation. Lawloret alhave previously reported this association in a retrospective analysis of over 4000 women, although it is unclear as to whether this represented a true effect or was influenced by confounders.36Further work in this area, ideally including well- controlled prospective studies, is required to further explore this relationship.

    Drugs related to allergy correlated with higher deprivation (r=?0.2278, p<0.001, n=38 871, D1=224.9, D10=155.5), but of interest is that epinephrine, the only emergency drug within this section, in fact correlated well with lower deprivation (r=0.2997, p<0.001, n=4650, D1=3.9, D10=6.5) (figure 3), which is consistent with emerging evidence of a higher prevalence of allergy among those with lower socioeconomic deprivation.37However, the result may be confounded by a greater awareness of the serious effects of anaphylaxis and the need to carry emergency injectors in more educated patients. These results may indicate a need for further targeting of more deprived populations for assessment and education regarding the use of these life- saving medications.

    Association of cost and number of prescriptions with deprivation

    Our observation that the number of prescriptions and overall cost of prescribing is associated with increased socioeconomic deprivation in Northern Ireland is in agreement with a previous retrospective study within the country, which found comparable numbers and cost of prescriptions over their study period among the subset of 55 GP practices analysed.38

    COnClusIOn

    The dichotomy between drugs used in the treatment of diseases predominantly associated with lifestyle factors, which correlate with high deprivation, and those used as treatments for the non- lifestyle- associated diseases, which generally do not correlate with deprivation, is impossible to ignore. Thus, the differing average prescription cost observed between different areas may represent development of newer and thus more expensive drugs for those diseases which are represented more equally across all areas, possibly due to increased investment or charitable donation. Our results provide a paradigm for further analysis and thought regarding differences in treatment between patients of differing socioeconomic class; we reveal discrepancies in cost of prescribing between areas of greater and lesser socioeconomic deprivation, highlighting a need for increased targeting of more deprived populations for education regarding not only healthy lifestyle choice but also contact with health professionals for appropriate assessment and screening.

    ContributorsJSF and GRF conceived of the study design, analysed the data, drafted the manuscript and figures, and provided critical revision. JSF additionally provided details of clinical correlation of results for the discussion.

    FundingThe authors have not declared a specific grant for this research from any funding agency in the public, commercial or not- for- profit sectors.

    Competing interestsNone declared.

    Patient consent for publicationNot required.

    ethics approvalThere are no specific ethical declarations for this work, as non- identifiable, retrospective, open- source data were used.

    Provenance and peer reviewNot commissioned; externally peer reviewed.

    Data availability statementData are available upon reasonable request. Data regarding correlation coefficients for each drug can be made available upon reasonable request from the corresponding author.

    Open accessThis is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY- NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non- commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non- commercial. See: http:// creativecommons. org/ licenses/ by- nc/ 4. 0/.

    一本久久精品| 久久午夜福利片| 交换朋友夫妻互换小说| 丁香六月天网| 久久久久国产精品人妻一区二区| 免费大片18禁| 免费高清在线观看视频在线观看| 亚洲无线观看免费| 妹子高潮喷水视频| 国产av国产精品国产| 成人国语在线视频| 五月开心婷婷网| 十八禁网站网址无遮挡| 中文字幕久久专区| 国产精品熟女久久久久浪| 亚洲精品色激情综合| 美女大奶头黄色视频| 精品人妻熟女毛片av久久网站| 国产一级毛片在线| 久久久久网色| 卡戴珊不雅视频在线播放| 五月伊人婷婷丁香| kizo精华| 欧美日韩亚洲高清精品| 国产精品一二三区在线看| 欧美少妇被猛烈插入视频| 亚洲激情五月婷婷啪啪| 午夜福利,免费看| 国产欧美日韩一区二区三区在线 | 午夜91福利影院| 午夜激情久久久久久久| 一区在线观看完整版| 亚洲第一区二区三区不卡| 日日摸夜夜添夜夜添av毛片| 欧美精品亚洲一区二区| 99久久综合免费| 久久韩国三级中文字幕| 极品人妻少妇av视频| 最近中文字幕2019免费版| 人妻一区二区av| 精品人妻一区二区三区麻豆| 亚洲精品日本国产第一区| 丰满乱子伦码专区| 亚洲精品乱码久久久久久按摩| 两个人免费观看高清视频| 精品99又大又爽又粗少妇毛片| 精品一区二区三区视频在线| 久久久久久久精品精品| 五月玫瑰六月丁香| 欧美精品一区二区免费开放| 欧美三级亚洲精品| 亚洲,欧美,日韩| 免费少妇av软件| 女的被弄到高潮叫床怎么办| 高清欧美精品videossex| 国产成人免费无遮挡视频| 一区二区三区四区激情视频| 亚洲天堂av无毛| 人体艺术视频欧美日本| 欧美+日韩+精品| 91精品一卡2卡3卡4卡| 免费看不卡的av| 999精品在线视频| 99久久精品国产国产毛片| av天堂久久9| 久久久久久伊人网av| 大码成人一级视频| 爱豆传媒免费全集在线观看| 国产黄色免费在线视频| 免费看光身美女| 亚洲三级黄色毛片| 纯流量卡能插随身wifi吗| 九色亚洲精品在线播放| 欧美日韩国产mv在线观看视频| 9色porny在线观看| 中文精品一卡2卡3卡4更新| 99热国产这里只有精品6| 久久久亚洲精品成人影院| 国产熟女欧美一区二区| 久久精品国产亚洲av涩爱| 精品一品国产午夜福利视频| 久久久久精品性色| 丰满少妇做爰视频| 最近手机中文字幕大全| 一本一本综合久久| 夫妻午夜视频| 国产成人91sexporn| 3wmmmm亚洲av在线观看| 国产精品偷伦视频观看了| 国产白丝娇喘喷水9色精品| 亚洲丝袜综合中文字幕| 十八禁高潮呻吟视频| 国产精品蜜桃在线观看| 熟女人妻精品中文字幕| 午夜老司机福利剧场| 国产av国产精品国产| 成人18禁高潮啪啪吃奶动态图 | 哪个播放器可以免费观看大片| 岛国毛片在线播放| 国产精品一区二区三区四区免费观看| 高清黄色对白视频在线免费看| 久久精品人人爽人人爽视色| 亚洲人成网站在线观看播放| 久久久久久久亚洲中文字幕| 自线自在国产av| 妹子高潮喷水视频| 亚洲人与动物交配视频| av电影中文网址| 亚洲成人手机| 亚洲,一卡二卡三卡| 十分钟在线观看高清视频www| 最新中文字幕久久久久| 一本色道久久久久久精品综合| 2018国产大陆天天弄谢| 日韩不卡一区二区三区视频在线| 久久久午夜欧美精品| 成年美女黄网站色视频大全免费 | 18禁在线播放成人免费| 亚洲av福利一区| 国产一区二区在线观看av| 哪个播放器可以免费观看大片| 亚洲精品久久久久久婷婷小说| 亚洲国产精品一区二区三区在线| 国产精品一区二区在线观看99| 日韩,欧美,国产一区二区三区| 国产伦理片在线播放av一区| 日韩一区二区三区影片| 一区二区三区免费毛片| 最近最新中文字幕免费大全7| 搡女人真爽免费视频火全软件| 亚洲熟女精品中文字幕| 大香蕉久久成人网| 亚洲精品自拍成人| 亚洲精品aⅴ在线观看| 久久人妻熟女aⅴ| 欧美xxⅹ黑人| 一本一本久久a久久精品综合妖精 国产伦在线观看视频一区 | 女性生殖器流出的白浆| 不卡视频在线观看欧美| 久久久久久久久久成人| 尾随美女入室| 免费看光身美女| 国产精品一区二区三区四区免费观看| 日韩,欧美,国产一区二区三区| 少妇的逼水好多| 亚洲人成网站在线观看播放| 久久精品人人爽人人爽视色| 免费高清在线观看日韩| 99国产精品免费福利视频| 欧美激情 高清一区二区三区| 免费看不卡的av| 欧美老熟妇乱子伦牲交| 中国美白少妇内射xxxbb| 日日摸夜夜添夜夜添av毛片| 久久亚洲国产成人精品v| 亚洲精华国产精华液的使用体验| 久热这里只有精品99| 精品人妻在线不人妻| 热99久久久久精品小说推荐| 国产成人午夜福利电影在线观看| 久久久欧美国产精品| 尾随美女入室| 日韩欧美一区视频在线观看| 国产成人午夜福利电影在线观看| 女人久久www免费人成看片| 边亲边吃奶的免费视频| 老司机影院毛片| 久久女婷五月综合色啪小说| 免费看光身美女| 人体艺术视频欧美日本| 亚洲一区二区三区欧美精品| 草草在线视频免费看| 18禁裸乳无遮挡动漫免费视频| 色婷婷av一区二区三区视频| 2018国产大陆天天弄谢| 色哟哟·www| 伦理电影免费视频| videossex国产| 秋霞在线观看毛片| 国产日韩欧美在线精品| 欧美老熟妇乱子伦牲交| 亚洲三级黄色毛片| 欧美变态另类bdsm刘玥| 尾随美女入室| 黄色配什么色好看| 久久久久久久久久人人人人人人| 最近中文字幕2019免费版| 日本-黄色视频高清免费观看| 人妻夜夜爽99麻豆av| 日产精品乱码卡一卡2卡三| 国产精品 国内视频| 国产午夜精品久久久久久一区二区三区| 十分钟在线观看高清视频www| 青青草视频在线视频观看| 国产视频首页在线观看| 丝袜脚勾引网站| 性色av一级| 免费人成在线观看视频色| 日日摸夜夜添夜夜添av毛片| 免费观看av网站的网址| 人人妻人人澡人人爽人人夜夜| 成人亚洲精品一区在线观看| 99视频精品全部免费 在线| 永久网站在线| 91午夜精品亚洲一区二区三区| 亚洲一区二区三区欧美精品| 欧美日韩在线观看h| 国产精品秋霞免费鲁丝片| 女人精品久久久久毛片| 中文精品一卡2卡3卡4更新| 丰满乱子伦码专区| 国产黄片视频在线免费观看| 99九九在线精品视频| 女性被躁到高潮视频| 三级国产精品片| 18禁观看日本| 久久国产精品男人的天堂亚洲 | 久久久久国产精品人妻一区二区| 九九爱精品视频在线观看| 在线精品无人区一区二区三| 亚洲欧美一区二区三区黑人 | 黄片播放在线免费| videossex国产| 99热这里只有是精品在线观看| 国产 精品1| 97精品久久久久久久久久精品| 婷婷色av中文字幕| 高清在线视频一区二区三区| 日韩精品免费视频一区二区三区 | 精品一区二区三区视频在线| 国产乱来视频区| 亚洲精品乱码久久久v下载方式| 免费少妇av软件| 麻豆成人av视频| 亚洲成色77777| 男女免费视频国产| 亚洲色图 男人天堂 中文字幕 | 午夜福利,免费看| 99视频精品全部免费 在线| 亚洲一区二区三区欧美精品| 日日撸夜夜添| 成人漫画全彩无遮挡| 99九九在线精品视频| 99热全是精品| 99热这里只有精品一区| 国产精品人妻久久久久久| 欧美日韩一区二区视频在线观看视频在线| 在线天堂最新版资源| 欧美精品一区二区大全| 日本色播在线视频| 国产一区亚洲一区在线观看| 欧美性感艳星| 人妻人人澡人人爽人人| 国产日韩欧美视频二区| 乱码一卡2卡4卡精品| 免费大片黄手机在线观看| 国产有黄有色有爽视频| 久久99精品国语久久久| 久久久久久久久大av| 人人妻人人添人人爽欧美一区卜| 久久精品夜色国产| 考比视频在线观看| 交换朋友夫妻互换小说| 国产成人免费观看mmmm| 久久综合国产亚洲精品| a 毛片基地| 黄色欧美视频在线观看| 欧美+日韩+精品| 男女免费视频国产| 一本色道久久久久久精品综合| 精品久久久精品久久久| 午夜福利视频在线观看免费| 岛国毛片在线播放| 国产成人精品无人区| 免费观看a级毛片全部| 亚洲内射少妇av| 国产成人a∨麻豆精品| 久久久久国产精品人妻一区二区| 十八禁高潮呻吟视频| 国产成人一区二区在线| 亚洲av日韩在线播放| 又大又黄又爽视频免费| 精品久久久久久久久av| 亚洲婷婷狠狠爱综合网| 亚洲国产精品成人久久小说| 乱码一卡2卡4卡精品| 久久女婷五月综合色啪小说| 国产极品粉嫩免费观看在线 | 国产高清有码在线观看视频| 日韩亚洲欧美综合| 新久久久久国产一级毛片| 国产成人freesex在线| 美女主播在线视频| 男女高潮啪啪啪动态图| 中文字幕av电影在线播放| 午夜激情福利司机影院| 精品亚洲乱码少妇综合久久| 熟女av电影| 人成视频在线观看免费观看| 亚洲国产精品专区欧美| 黄色怎么调成土黄色| 亚洲av.av天堂| 免费大片18禁| 美女视频免费永久观看网站| 久久久久国产网址| 亚洲国产av新网站| 99九九线精品视频在线观看视频| 日韩亚洲欧美综合| 国产乱人偷精品视频| 国产探花极品一区二区| 久久热精品热| 爱豆传媒免费全集在线观看| 一二三四中文在线观看免费高清| 日韩一区二区三区影片| 大又大粗又爽又黄少妇毛片口| 成人亚洲欧美一区二区av| 一区在线观看完整版| 搡老乐熟女国产| a 毛片基地| 日本欧美视频一区| 高清午夜精品一区二区三区| 菩萨蛮人人尽说江南好唐韦庄| 欧美日韩视频高清一区二区三区二| 亚洲五月色婷婷综合| kizo精华| 街头女战士在线观看网站| 欧美日韩视频高清一区二区三区二| 精品一区二区三区视频在线| 午夜福利视频在线观看免费| 久久精品人人爽人人爽视色| 免费播放大片免费观看视频在线观看| 中文字幕av电影在线播放| 另类精品久久| 男女无遮挡免费网站观看| 99精国产麻豆久久婷婷| 视频区图区小说| 久久97久久精品| 成人二区视频| 色5月婷婷丁香| 国产极品天堂在线| √禁漫天堂资源中文www| 免费日韩欧美在线观看| 国产亚洲精品第一综合不卡 | 一本一本久久a久久精品综合妖精 国产伦在线观看视频一区 | av福利片在线| 观看美女的网站| 国产精品一二三区在线看| 考比视频在线观看| 亚洲精品aⅴ在线观看| 大码成人一级视频| 国产精品久久久久成人av| 丁香六月天网| 亚洲欧美一区二区三区黑人 | 欧美成人精品欧美一级黄| 日本黄色日本黄色录像| 极品人妻少妇av视频| 美女内射精品一级片tv| 国产欧美日韩一区二区三区在线 | 伦理电影免费视频| 日韩一区二区三区影片| 亚洲性久久影院| 69精品国产乱码久久久| 卡戴珊不雅视频在线播放| 纯流量卡能插随身wifi吗| 成人亚洲欧美一区二区av| 日韩大片免费观看网站| 一区二区三区免费毛片| 熟妇人妻不卡中文字幕| 久久精品人人爽人人爽视色| 亚洲av成人精品一二三区| 热re99久久国产66热| 黑人巨大精品欧美一区二区蜜桃 | 亚洲无线观看免费| av在线观看视频网站免费| 国产视频首页在线观看| 狂野欧美激情性bbbbbb| 久久毛片免费看一区二区三区| 日韩av不卡免费在线播放| 国产片内射在线| a级毛色黄片| 亚洲性久久影院| 亚洲熟女精品中文字幕| xxxhd国产人妻xxx| 三上悠亚av全集在线观看| 国产精品.久久久| 观看av在线不卡| 久久韩国三级中文字幕| 久久精品国产a三级三级三级| 欧美最新免费一区二区三区| 草草在线视频免费看| 亚洲国产最新在线播放| 久久久a久久爽久久v久久| 亚洲欧美精品自产自拍| 自拍欧美九色日韩亚洲蝌蚪91| 国产精品久久久久久精品电影小说| 亚洲精品久久成人aⅴ小说 | 美女国产视频在线观看| 亚洲四区av| 午夜免费观看性视频| 最新中文字幕久久久久| 免费日韩欧美在线观看| 人妻一区二区av| 美女主播在线视频| 精品少妇内射三级| 国产日韩欧美亚洲二区| 满18在线观看网站| 一级a做视频免费观看| 欧美 日韩 精品 国产| 国产免费一级a男人的天堂| 天美传媒精品一区二区| 老女人水多毛片| 日本免费在线观看一区| 日日撸夜夜添| 亚洲五月色婷婷综合| 免费av不卡在线播放| 国产精品人妻久久久影院| 精品一区二区三区视频在线| 亚洲国产精品999| 亚洲av男天堂| 亚洲精品第二区| 国产成人精品在线电影| 国产欧美另类精品又又久久亚洲欧美| 在现免费观看毛片| 精品视频人人做人人爽| 国产精品国产三级专区第一集| 亚洲美女黄色视频免费看| 免费观看性生交大片5| 亚洲精品乱码久久久v下载方式| 91午夜精品亚洲一区二区三区| 国国产精品蜜臀av免费| 水蜜桃什么品种好| 亚洲在久久综合| 亚洲av男天堂| 国产成人aa在线观看| 麻豆成人av视频| 亚洲国产av新网站| 日韩亚洲欧美综合| 亚洲精品一二三| 人人妻人人澡人人看| 国产老妇伦熟女老妇高清| 色5月婷婷丁香| 日韩制服骚丝袜av| 国产精品久久久久久精品电影小说| 一个人看视频在线观看www免费| 免费不卡的大黄色大毛片视频在线观看| 国产精品国产三级国产专区5o| 女人久久www免费人成看片| 日日啪夜夜爽| 欧美激情国产日韩精品一区| 亚洲伊人久久精品综合| 国产精品一区www在线观看| 91精品三级在线观看| 色婷婷av一区二区三区视频| 国产片特级美女逼逼视频| 在线播放无遮挡| 国产一区二区在线观看av| 女性被躁到高潮视频| 欧美+日韩+精品| 一级毛片 在线播放| 免费黄色在线免费观看| 女人久久www免费人成看片| 日韩av免费高清视频| 晚上一个人看的免费电影| 欧美xxⅹ黑人| 色视频在线一区二区三区| 日本91视频免费播放| 国产极品天堂在线| 好男人视频免费观看在线| 国产成人午夜福利电影在线观看| 亚洲av.av天堂| 国产视频内射| 免费观看av网站的网址| 啦啦啦视频在线资源免费观看| 两个人免费观看高清视频| 亚洲av男天堂| 午夜精品国产一区二区电影| 亚洲精品视频女| 99九九在线精品视频| a级片在线免费高清观看视频| 色婷婷av一区二区三区视频| 性色av一级| 美女大奶头黄色视频| 日韩欧美精品免费久久| 国产成人一区二区在线| 亚洲av.av天堂| 在线观看www视频免费| 精品熟女少妇av免费看| 国产精品女同一区二区软件| tube8黄色片| 一区在线观看完整版| 久久久久网色| 亚洲中文av在线| 国产视频首页在线观看| 乱码一卡2卡4卡精品| 街头女战士在线观看网站| 在现免费观看毛片| 岛国毛片在线播放| 欧美另类一区| videos熟女内射| 男人操女人黄网站| av女优亚洲男人天堂| 亚洲经典国产精华液单| 久久影院123| 久久久久久久亚洲中文字幕| 五月伊人婷婷丁香| 亚洲人与动物交配视频| 亚洲成人av在线免费| 青青草视频在线视频观看| 男人添女人高潮全过程视频| 看非洲黑人一级黄片| 少妇人妻精品综合一区二区| 插逼视频在线观看| 午夜免费鲁丝| 亚洲精品久久成人aⅴ小说 | 国产男女内射视频| 亚洲国产精品国产精品| 欧美精品一区二区免费开放| 美女国产高潮福利片在线看| 夫妻性生交免费视频一级片| 亚洲av电影在线观看一区二区三区| 极品少妇高潮喷水抽搐| 哪个播放器可以免费观看大片| 九色亚洲精品在线播放| 久久99一区二区三区| 婷婷色综合www| 国产成人精品在线电影| 国产成人免费无遮挡视频| 亚洲性久久影院| 97在线视频观看| 久久久久久久亚洲中文字幕| 一区二区av电影网| 如何舔出高潮| av播播在线观看一区| 免费黄色在线免费观看| 午夜福利网站1000一区二区三区| 国模一区二区三区四区视频| 日本黄色日本黄色录像| 亚洲情色 制服丝袜| 成人午夜精彩视频在线观看| 又粗又硬又长又爽又黄的视频| 欧美精品高潮呻吟av久久| 精品一区二区免费观看| 国产精品久久久久久久久免| 这个男人来自地球电影免费观看 | 亚洲国产最新在线播放| 国产在线免费精品| 亚洲情色 制服丝袜| 热99久久久久精品小说推荐| 亚洲综合色网址| tube8黄色片| 色婷婷av一区二区三区视频| 中文字幕免费在线视频6| 欧美精品一区二区免费开放| 少妇人妻精品综合一区二区| 大话2 男鬼变身卡| 丰满少妇做爰视频| 久久精品人人爽人人爽视色| 最近中文字幕高清免费大全6| 尾随美女入室| 91久久精品国产一区二区三区| 精品视频人人做人人爽| 日韩三级伦理在线观看| 亚洲少妇的诱惑av| 日韩不卡一区二区三区视频在线| 蜜桃国产av成人99| 中文欧美无线码| 麻豆精品久久久久久蜜桃| 亚洲激情五月婷婷啪啪| 一级毛片电影观看| 精品人妻一区二区三区麻豆| 亚洲美女视频黄频| 国产欧美日韩一区二区三区在线 | 国产精品一二三区在线看| 国产极品天堂在线| 久久精品夜色国产| 亚洲精品日韩在线中文字幕| 少妇熟女欧美另类| 日产精品乱码卡一卡2卡三| a级毛色黄片| 久久99蜜桃精品久久| 另类精品久久| 最黄视频免费看| 中文字幕亚洲精品专区| 一区在线观看完整版| 晚上一个人看的免费电影| av福利片在线| 午夜精品国产一区二区电影| 久久久久精品久久久久真实原创| 亚洲美女搞黄在线观看| 美女国产视频在线观看| 国产色爽女视频免费观看| 亚洲av福利一区| 一区二区日韩欧美中文字幕 | 满18在线观看网站| 成年人午夜在线观看视频| 男的添女的下面高潮视频| 99热6这里只有精品| 亚洲精品,欧美精品| 天堂俺去俺来也www色官网| 成人手机av| 欧美 日韩 精品 国产| 日韩不卡一区二区三区视频在线| 国产在线一区二区三区精| av免费在线看不卡| 国产免费又黄又爽又色| 九色成人免费人妻av| 热99久久久久精品小说推荐| 久久人人爽av亚洲精品天堂| 一个人看视频在线观看www免费| 久久青草综合色| 免费看光身美女| 91精品国产国语对白视频| 国产成人精品在线电影| 一本久久精品| 我的老师免费观看完整版|