Reversal of diabetic retinopathy in two patients following the use of physiologic insulin Resensitization.

We followed two patients with diabetic retinopathy over the course of their treatment with physiologic Insulin resensitization. Both patients showed improvement of their diabetic retinopathy, after treatment.

Cancer Patient Acceptance of HIV Screening at a Large Tertiary Cancer Center.

The U.S. Centers for Disease Control and Prevention (CDC), the U.S. Preventive Services Task Force (USPSTF) and the National Comprehensive Cancer Network (NCCN) recommend offering HIV testing for patients presenting for cancer care. Not recognizing and treating HIV infection adversely impacts both cancer treatment and HIV outcomes. Acceptance rates of oncology patients for HIV screening are not known. Our tertiary cancer center inserted language requesting permission to screen for HIV infection into the consent forms for initial presentation for cancer care. Willingness to undergo testing was examined in 29,549 consecutive new patients. These were analyzed by gender and age. Overall, 80.9% of patients agreed to HIV screening. Incorporation of language requesting permission for HIV screening into the consent form provided at presentation for cancer care, relieves clinicians from adding this task.

Physiologic Insulin Resensitization as a Treatment Modality for Insulin Resistance Pathophysiology.

Prevalence of type 2 diabetes increased from 2.5% of the US population in 1990 to 10.5% in 2018. This creates a major public health problem, due to increases in long-term complications of diabetes, including neuropathy, retinopathy, nephropathy, skin ulcers, amputations, and atherosclerotic cardiovascular disease. In this review, we evaluated the scientific basis that supports the use of physiologic insulin resensitization. Insulin resistance is the primary cause of type 2 diabetes. Insulin resistance leads to increasing insulin secretion, leading to beta-cell exhaustion or burnout. This triggers a cascade leading to islet cell destruction and the long-term complications of type 2 diabetes. Concurrent with insulin resistance, the regular bursts of insulin from the pancreas become irregular. This has been treated by the precise administration of insulin more physiologically. There is consistent evidence that this treatment modality can reverse the diabetes-associated complications of neuropathy, diabetic ulcers, nephropathy, and retinopathy, and that it lowers HbA1c. In conclusion, physiologic insulin resensitization has a persuasive scientific basis, significant treatment potential, and likely cost benefits.

Has Diarrhea Ceased to be a Concern in Persons Living With HIV? Results From a Cross-sectional Study.

ABSTRACT: Diarrhea has been associated with HIV throughout the epidemic. Few recent studies have addressed diarrhea in persons living with HIV (PLWH) despite evolving knowledge and ever-changing practice standards. The fact that patient care has become more complex, with comorbid conditions requiring additional attention without additional time allotment, potentiates the risk of common symptoms being overlooked. Patients (n = 190) 18 years and older, living with HIV, completed a questionnaire collecting information specific to attitudes, definitions, and beliefs regarding diarrhea. Of the 190 participants, only 5.3% said that they had diarrhea, but 11.1% described their bowel movements as being in the group associated with diarrhea. Approximately, 93.7% of the participants defined diarrhea as either soft or watery; 34.2% defined frequency as more than three times per day, but 64.2% said that it would have to be more than three times per day to mention it to a provider. PLWH continue to experience diarrhea warranting assessment and discussions between the PLWH and the provider.

GSK2818713, a Novel Biphenylene Scaffold-Based Hepatitis C NS5A Replication Complex Inhibitor with Broad Genotype Coverage.

Pan-genotype NS5A inhibitors underpin hugely successful hepatitis C virus (HCV) therapy. The discovery of GSK2818713 (13), a nonstructural protein 5A (NS5A) HCV inhibitor characterized by a significantly improved genotype coverage relative to first-generation NS5A inhibitor daclatasvir (DCV), is detailed herein. The SAR analysis revealed cooperative potency effects of the biphenylene, bicyclic pyrrolidine (Aoc), and methyl-threonine structural motifs. Relative to DCV, 13 improved activity against genotype 1a (gt1a) and gt1b NS5A variants as well as HCV chimeric replicons containing NS5A fragments from genotypes 2-6. Long-term treatment of subgenomic replicons with 13 potently and durably decreased HCV RNA levels for gt1a, gt2a, and gt3a. These properties, suitable pharmacokinetics, and the lack of cross-resistance resulted in the selection of 13 as a preclinical candidate.

Medication costs associated with early initiation of antiretroviral therapy.

The START Study randomly assigned 4685 persons with CD4+ counts >500 to either immediate treatment (2326 persons) or a group (2359) that had treatment delayed until the CD4+ count was <350 or clinical judgment dictated treatment. The average time in the study was three years. The immediate group (IG) had 42 serious clinical events and the delayed group (DG) had 96. Policy considerations for adopting these results should consider the cost of medications for early treatment, which is the purpose of this article. Cost of early treatment was estimated by assuming the delayed treatment group had been treated for the three-year average course of the study. However, 48% of the DG received ART before the study's end, so that portion of the group's time on ART was reduced to 1.5 years. Average wholesale prices in the United States of the five recommended ART regimens were discounted by 50% to reflect actual pricing. An average medication cost for the five regimens of $20,000 per person year was used. The three-year cost was $107,580,000 for the 52% who would have been treated for three years and for the 48% treated for an average of 1.5 years. The cost per clinical event avoided was $1,992,222. Formulae are provided that will allow the reader to adjust these results to reflect local prices and volumes. Additional factors to be considered should include the cost savings from avoiding serious clinical events, reduction in transmission of HIV for those being treated early in the infection and the issues associated with long-term adherence for those receiving ART at >500 CD4 counts.

The human papilloma vaccine: A time for NP leadership.

The human papilloma virus (HPV) causes approximately 30,700 annual cancer cases of the cervix, vulva, vagina, penis, oral cavity, and anus. Nurse practitioners can use their unique relationships with patients to advocate for the HPV vaccine. The purpose of this article is to update NPs on current knowledge regarding the HPV vaccine while providing appropriate information necessary for counseling patients and parents.

Physicians' and nurses' thoughts and concerns about introducing neonatal male circumcision in Thailand: a qualitative study.

BACKGROUND: Neonatal male circumcision (NMC) is an alternative approach to adult male circumcision for HIV prevention. Recent studies found that NMC was rarely performed in Thailand and that most Thai health professionals did not recognize that NMC could reduce the risk of HIV infection and would not want NMC services in their hospitals. This study explored the thoughts and concerns of Thai government health staff regarding the introduction of NMC in government health facilities as a public health measure. METHODS: In-depth interviews with physicians, nurses and physician administrators from four different levels of government hospitals in four provinces representing 4 regions of Thailand were conducted after provision of education regarding the benefits and risks of NMC. Interviews were audio recorded and analyzed using Atlas.ti software to develop themes. RESULTS: Six themes emerged from the data of 42 respondents: understanding of the benefits of NMC; risks of NMC; need for a pilot project; need for staff training and hospital readiness; need for parental/family education; and need for public awareness educational campaign. Major concerns included possible medical complications of NMC, infringement of child rights, and lack of understanding from staff and parents. The respondents emphasized the need for a clear policy, proper training of staff, financial and equipment support, and piloting NMC rollout before this measure could be fully implemented. CONCLUSIONS: Thai health professionals who took part in this study expressed several concerns if NMC had to be performed in their health care facilities. There is significant preparation that needs to be done before NMC can be introduced in the country.

Re-engagement in HIV Care: A Clinical and Public Health Priority.

As many as 40-50% of persons living with HIV (PLWH) who once were in HIV care are no longer in care. It is estimated that these individuals account for over 60% of HIV transmissions. So, preventing the leaving of care and re-engaging PLWH with care are crucial if the HIV epidemic is to be brought under control. Clinicians can improve retention by keeping in close contact with patients. Governmental public health agencies have great expertise in finding and engaging in care persons with sexually transmitted infections. This expertise can be used to re-engage PLWH with HIV care, but it can only be utilized if the agencies know that someone is out of care. Data on who has left care are in the hands of HIV providers. This requires a close working relationship between HIV providers and public health agencies.

When to consider acute HIV infection in the differential diagnosis.

Patients presenting with fever, pharyngitis, and lymphadenopathy are likely to have mononucleosis; however, patients with acute HIV infection may present with similar symptoms. Acute HIV infection should be considered as a differential diagnosis if test results for mononucleosis are negative. This article describes when to order HIV testing and discusses the importance of early intervention for acute HIV infection.

The Influence of Trust in Physicians and Trust in the Healthcare System on Linkage, Retention, and Adherence to HIV Care.

Lack of trust by the patient in the physicians or the healthcare system has been associated with poorer health outcomes. The present study was designed to determine if trust in physicians and the healthcare system among persons newly diagnosed with HIV infection was predictive of patients' subsequent linkage, retention, and adherence to HIV care. 178 newly diagnosed HIV infected patients were administered the trust-in-physicians and trust-in-healthcare system scales. Median trust-in-physicians and trust-in-healthcare system scores were compared for all the mentioned subsequent linkage, retention, and adherence to HIV care. Univariate logistic regression using the trust-in-physician scale confirmed significant association with retention in care (p = 0.04), which persisted in multivariate analyses (p = 0.04). No significant association was found between trust-in-physicians and linkage to care or adherence to antiretroviral therapy. Trust in the healthcare system was not associated with any of the outcomes. Patients with higher trust in physicians were more likely to be retained in HIV care. Trust at diagnosis may not be a barrier to better clinical outcomes, either because trust changes based on subsequent interactions, or because trust is not a determining feature. Interventions to improve retention in care could include improving trust in physicians or target persons with low trust in physicians.

Thai health care provider knowledge of neonatal male circumcision in reducing transmission of HIV and other STIs.

BACKGROUND: Male circumcision (MC) reduces the risk of female-to-male transmission of HIV and other sexually transmitted infections (STIs). MC has not been practiced as a disease prevention measure in Thailand probably because of low recognition of its benefits among stakeholders. Neonatal male circumcision (NMC) is simpler, safer and cheaper than adult MC. This study aimed to assess Thai health care provider knowledge of benefits implementing NMC in Thailand. METHODS: Multi-stage sampling identified 16 government hospitals to represent various hospital sizes and regions of the country. Researchers administered a fixed choice questionnaire, developed by the research team based on a previous study, to physician administrators, practicing physicians, and nurses whose jobs involved NMC clinical procedures or oversight. The participants reviewed printed educational materials on the benefits of NMC during questionnaire completion. Data were analyzed using descriptive statistics, chi square tests, odds ratios, and logistic regression. RESULTS: One hundred thirty-three individuals participated in this quantitative study. Only 38% of the participants agreed that NMC reduced the risk of sexual transmission of HIV while 65% indicated that they knew that NMC prevented STIs. Most participants recognized the benefits of NMC on hygiene (96%) as well as cancer prevention (74%). Major concerns raised were potential trauma to the child, child rights and safety of NMC. After reviewing written information about the benefits of NMC, 59% of the participants agreed that NMC should be offered in their hospital. Physicians and nurses who had previous experience with circumcising patients of all ages were more reluctant to have NMC performed in their hospital. CONCLUSIONS: A clear policy advocating NMC, thorough preparation of health facilities, and staff training are needed before NMC could be used in Thailand as prevention strategy for HIV and other STIs.

Effect of an Empowerment Intervention on Antiretroviral Drug Adherence in Thai Youth.

A pilot study was conducted to determine effects of an empowerment intervention on antiretroviral therapy (ART) adherence among Thai youth living with HIV/AIDS. It compared two groups of 23 young persons (15-24 years) who receive ART from AIDS clinics at two community hospitals. One hospital's patients served as the experimental group, and the other as a control group. The experimental groups attended five sessions that empowered them to take control of their own health. The control group received the standard of care. The data were analyzed using descriptive statistics and Chi-square statistics. Before the empowerment, no one from the experimental group or the control group had ART adherence ≥ 95%. After the intervention, the 82.6% of the experimental group had ≥ 95% adherence compared to the control group, which had 21.7% adherence (p < .0001). The empowerment intervention resulted in a significant increase in ART adherence among Thai youth.

Factors Related to Sexual Self-Efficacy among Thai Youth Living with HIV/AIDS.

Studies of sexual behavior among HIV-infected Thai youth show conflicting results due to the different ages of the respondents. This study examined the relationships between sexual self-efficacy and risk behaviors among 92 HIV-positive Thai youth aged 14 to 21 years. A questionnaire previously validated in Thailand measured sexual self-efficacy. There were low levels of sexual activity with 13 respondents having sex in the last 6 months. The sexual self-efficacy scales were inversely related to the risk behaviors of having sex, having multiple partners, and drinking alcohol in the last 6 months. The scores of the sexual self-efficacy scale and its subscales were significantly lower in those aged 17 to 21 than in 14 to 16. Sexual risk behaviors were significantly higher in those aged 17 to 21 than in 14 to 16. These findings suggest that interventions to increase sexual self-efficacy should be emphasized as HIV-infected Thai youth reach late adolescence.

Effects of Internet-based instruction on HIV-prevention knowledge and practices among men who have sex with men.

HIV infection is increasing among men who have sex with men. In this study, the effects of Internet-based instruction on HIV-prevention knowledge were evaluated. The sample consisted of 162 men-who-have-sex-with-men volunteers in Thailand. The research instruments included a demographic data questionnaire, a knowledge test, and an HIV preventive practice questionnaire. The participants completed these instruments upon entry to the study and four months later. After entry to the study, the participants were given access to a previously-developed Internet-based instruction on HIV risk behaviors. Data were analyzed using descriptive statistics and paired t-test. After accessing the Internet-based instruction, the average score of HIV-prevention knowledge among the sample increased significantly, from 11.17 to 15.09 (maximum score of 20 points). The average score of practicing HIV prevention among the sample increased significantly, from 62.94 to 76.51 (maximum score of 99 points). This study demonstrated that Internet-based instruction was effective in improving HIV-prevention knowledge and practices among men who have sex with men. This suggests that Internet-based instruction could be developed for use in other countries and evaluated in a similar way.

ATTITUDES AND BEHAVIOR AMONG RURAL THAI ADOLESCENTS REGARDING SEXUAL INTERCOURSE.

Early initiation of sexual intercourse has been associated with negative consequences, such as higher rates of unwanted pregnancy and HIV infection. This study examined the attitudes and behavior of rural Thai adolescent students aged 16 to 20 years from northern Thailand regarding sexual intercourse. Differences between participants who previously had sexual intercourse and those who had not were explored. Those who had not previously had sexual intercourse were asked about the reasons why they had not had sex, their future plans for having sex and their dating experiences. More than 70% of participants stated they had not previously had sexual intercourse but one third of this group reported engaging in other sexual behavior. There were significant differences by gender, religion, ethnicity, and household income between those who had previously had sex and those who had not. Among those who had not previously had sexual intercourse, concern for their parents' feelings was the most common reason for delaying intercourse. About two-thirds of this group had plans not to have sexual intercourse until after marriage; nearly half of them reported currently having a boyfriend/girlfriend. Interventions aimed at delaying sexual intercourse should involve adolescents in their design and include their attitudes for delaying intercourse. Because of many gender differences seen in our study, interventions should be designed differently for males and females in rural northern Thailand.

Capability of Thailand to implement newborn male circumcision: a nation-wide survey.

This study was designed to gain baseline information on the capability of the hospitals of Thailand to provide newborn male circumcision (NC) and on the opinions of health-care personnel towards NC. Two questionnaires were sent to every hospital in Thailand that might have obstetrical services. One questionnaire requested information about the degree to which NC was provided by the hospital. The second questionnaire targeted health-care providers' opinions about NC. The response rate was 55.1% (747/1355). Of the 562 hospitals that had deliveries in 2010, 8.2% (46) provided at least one NC. Thirty-eight percent (35/92) of private hospitals and 2.3% (11/470) of government hospitals provided the service. The primary reason for performing NC was parental request (82.6%). Some providers (31.3%) said that NC was easy to perform and 39.1% thought NC was safe. Most respondents (91.8%) stated that physicians should perform the procedure instead of nurses, and choices about undergoing NC should be left to parents (55.0%). NC was rarely performed in government hospitals, and its staffs seemed to not recognize the health benefits of NC. A massive education program for health-care providers would be necessary before implementing a national program for NC. More information on the opinions of health authorities, health-care personnel and parents as well as cost-effectiveness studies are needed before a proper policy can be implemented.

Verifying quantitative stigma and medication adherence scales using qualitative methods among Thai youth living with HIV/AIDS.

HIV/AIDS-related stigma has been linked to poor adherence resulting in drug resistance and the failure to control HIV. This study used both quantitative and qualitative methods to examine stigma and its relationship to adherence in 30 HIV-infected Thai youth aged 14 to 21 years. Stigma was measured using the HIV stigma scale and its 4 subscales, and adherence was measured using a visual analog scale. Stigma and adherence were also examined by in-depth interviews. The interviews were to determine whether verbal responses would match the scale's results. The mean score of stigma perception from the overall scale and its 4 subscales ranged from 2.14 to 2.45 on a scale of 1 to 4, indicating moderate levels of stigma. The mean adherence score was .74. The stigma scale and its subscales did not correlate with the adherence. Totally, 17 of the respondents were interviewed. Contrary to the quantitative results, the interviewees reported that the stigma led to poor adherence because the fear of disclosure often caused them to miss medication doses. The differences between the quantitative and the qualitative results highlight the importance of validating psychometric scales when they are translated and used in other cultures.

Counseling about the HPV vaccine: desexualize, educate, and advocate.

Information is provided for clinicians who treat adolescents and adult women to use when counseling patients about human papillomavirus (HPV) vaccine. A literature search was done to determine: (1) reasons for refusal of the vaccine, including cost and concerns that immunization against HPV will lead to promiscuity; (2) potential for non-sexual transmission of HPV; (3) non-genital locations of HPV; (4) non-genital cancers associated with HPV. Vaccines for Children Program and the Affordable Care Act eliminate many costs.Neither biological nor behavioral evidence supports the idea that sexual behavior changes after immunization. HPV is transmitted from person to person by non-sexual routes including mother to child at birth and apparently by touch after birth. HPV is persistent in the environment, including medical environments. It has been found on apparently sterilized instruments used in vaginal exams. Pathogenic HPV has been recovered from breast tissue, sinonasal areas, and nipples as well as from hair follicles on arms, legs, scalps, eyebrows, and pubic hair. Pathogenic HPV was found in 6.5% of the oral cavities of a random sample of Americans. HPV is known to cause anal and oral cancers. It has also been associated with skin cancers, breast tumors, and prostate cancers. It is not known if the vaccine is protective against these cancers, but it is useful to educate about these other routes of transmission and non-genital HPV linked cancers so that patients/parents do not just focus on the sexual nature of the human papillomavirus.

Discovery of epigenetic regulator I-BET762: lead optimization to afford a clinical candidate inhibitor of the BET bromodomains.

The bromo and extra C-terminal domain (BET) family of bromodomains are involved in binding epigenetic marks on histone proteins, more specifically acetylated lysine residues. This paper describes the discovery and structure-activity relationships (SAR) of potent benzodiazepine inhibitors that disrupt the function of the BET family of bromodomains (BRD2, BRD3, and BRD4). This work has yielded a potent, selective compound I-BET762 that is now under evaluation in a phase I/II clinical trial for nuclear protein in testis (NUT) midline carcinoma and other cancers.