Publications by authors named "Ken Ho"

165 Publications

A Randomized, Double Blind, Placebo-Controlled, Phase 1 Safety and Pharmacokinetic Study of Dapivirine Gel (0.05%) Administered Rectally to HIV-1 Seronegative Adults (MTN-026).

AIDS Res Hum Retroviruses 2021 Sep 9. Epub 2021 Sep 9.

Johns Hopkins University, Medicine, Baltimore, Maryland, United States.

Introduction: Dapivirine (DPV), formulated as vaginal ring, demonstrated HIV risk reduction. MTN-026 explored DPV, formulated as rectal gel, for safety, pharmacokinetics, and acceptability.

Methods: HIV-uninfected men and women aged 18-45 years were enrolled at United States and Thailand sites and randomized 2:1 to receive DPV 0.05% or placebo gel via rectal applicator. A single dose phase was followed by 7 observed daily doses. Plasma, and fluid and tissue from both rectum and cervix were collected at baseline and after the final dose over 72 hours for pharmacokinetics, ex-vivo HIV-1 biopsy challenge, histology, and flow cytometry.

Results: 28 participants were randomized; 2 terminated early; 9 were female and 19 male; 12 were white, 11 Asian, 4 black and 1 other race/ethnicity. Mean age was 28.5 and 34.2 years in the DPV and placebo arms, respectively. Thirty adverse events occurred (all Grade 1 or 2, except one unrelated Grade 3) without study arm differences. DPV rectal tissue concentrations (median [interquartile range]) 0.5-1 and 2 hours after a single dose were 256 ng/gm (below limit of quantitation [BLQ], 666) and BLQ (BLQ, 600), respectively, then BLQ (BLQ, BLQ) from 24-72 hours; concentrations following multiple doses were similar. The largest median DPV plasma concentrations were 0.33 ng/mL (0.15, 0.48) after one dose and 0.40 (0.33, 0.49) after seven doses.

Conclusions: The DPV rectal gel was acceptable and without safety concerns. While DPV plasma concentrations were similar to the vaginal ring, rectal tissue concentrations were well below vaginal ring tissue concentrations, suggesting need for reformulation.
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http://dx.doi.org/10.1089/AID.2021.0071DOI Listing
September 2021

A Community Partnered Approach to Promoting COVID-19 Vaccine Equity.

Health Promot Pract 2021 Jul 26:15248399211029954. Epub 2021 Jul 26.

Neighborhood Resilience Project, Pittsburgh, PA, USA.

The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected communities of color. To dismantle these disparities, it is critical to promote COVID-19 vaccine equity, both through increasing vaccine access and addressing vaccine mistrust. This article describes a community-academic collaboration (the Community Vaccine Collaborative [CVC]), whose mission is to ensure COVID-19 vaccine equity among marginalized communities. Based in Pittsburgh, Pennsylvania, our group has focused on inclusion of marginalized groups into vaccine clinical trials, addressing vaccine mistrust, and building systems to ensuring equitable access to the COVID-19 vaccine. We review formation of the CVC, activities to-date, and recommendations for other communities interested in developing similar collaboratives.
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http://dx.doi.org/10.1177/15248399211029954DOI Listing
July 2021

A Novel Liver-targeted Testosterone Therapy for Sarcopenia in Androgen Deprived Men With Prostate Cancer.

J Endocr Soc 2021 Sep 19;5(9):bvab116. Epub 2021 Jun 19.

Department of Endocrinology, Princess Alexandra Hospital, Brisbane, Australia.

Objective: Androgen deprivation therapy (ADT) reduces muscle and bone mass, increasing frailty in men with prostate cancer. The liver mediates the whole body anabolic effects of testosterone. Based on first-pass metabolism, liver-targeted testosterone treatment (LTTT) entails oral delivery of a small dose of testosterone that does not raise peripheral blood testosterone levels. LTTT reduces blood urea and stimulates protein anabolism in hypogonadal men and postmenopausal women. We investigated whether LTTT prevents loss of lean and bone mass during ADT.

Method: A 6-month, double-blind, placebo-controlled study of testosterone 40 mg/day in 50 men. Primary outcome measures were lean mass and bone mineral content (BMC). Testosterone, urea and prostate-specific antigen (PSA) were monitored. Patients were withdrawn if PSA exceeded 4 ng/mL.

Results: 42 patients completed the study. Mean (95% CI) testosterone rose during LTTT but not placebo treatment [∆ 2.2 (1.3-3.0) -0.7 (-1.5 to 0.2) nmol/L;  < 0.01]. Mean PSA level did not change significantly during either treatment. Blood urea fell [∆ -0.4 (-0.9 to -0.1) mmol/L] during LTTT but not placebo [∆ 0.05 (-0.8 to 0.9) mmol/L]. BMC [∆ 49 (5 to 93) g;  < 0.02] and lean mass [∆ 0.8 (-0.1 to 1.7) kg;  = 0.04) increased compared to placebo. Five patients on LTTT withdrew from increased PSA levels, all returning to baseline levels.

Conclusion: LTTT shows promise as a simple therapy for preventing sarcopenia and bone loss during ADT. LTTT may induce reversible PSA rise in some patients. Further studies are required to optimize LTTT dose in ADT. LTTT has potential application in other catabolic states in men and women.
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http://dx.doi.org/10.1210/jendso/bvab116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294688PMC
September 2021

Co-living with migrant domestic workers is associated with a lower level of loneliness among community-dwelling older adults: A cross-sectional study.

Health Soc Care Community 2021 Jul 20. Epub 2021 Jul 20.

School of Nursing, The Hong Kong Polytechnic University, Hung Hom, Hong Kong.

Loneliness (inclusive social loneliness and emotional loneliness) of older adults is a prominent public health issue internationally. Factors consistently associated with loneliness are age, gender, education, living arrangements, social network, and functional status. Intergenerational co-living with spouse and adult children is important for the exchange of social, emotional, practical, and financial support provided to older adults. Co-living with migrant domestic workers (MDWs) to care for older adults became an emergent phenomenon internationally, particularly in Asian countries. According to the convoy model of social relations, the effect of co-living with MDWs on older adults' loneliness is unknown. This study examined (1) the prevalence of loneliness among community-dwelling older adults; and (2) the association between co-living with MDWs and older adult loneliness. Using the Chinese version of the 6-item De Jong Gierveld Loneliness Scale on loneliness, 380 older adults were interviewed at busy points in Hong Kong, including subway stations. 35.3% of older adults experienced moderate-to-severe loneliness. Linear regression was performed to examine the association between co-living with MDWs and loneliness. The results showed that co-living with MDWs was significantly associated with lower levels of overall loneliness (β = -0.636; p = .022) and emotional loneliness (β = -0.298, p = .039), but not for social loneliness (β = -0.337, p = .084). While MDWs could be an attachment figure for older adults, they might not be effective in promoting the social integration of older adults. There is a need to investigate the barriers of social integration faced by older adults co-living with MDWs.
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http://dx.doi.org/10.1111/hsc.13520DOI Listing
July 2021

MECHANISMS IN ENDOCRINOLOGY: Paracrine and endocrine control of the growth hormone axis by estrogen.

Eur J Endocrinol 2021 May 6;184(6):R269-R278. Epub 2021 May 6.

Faculty of Medicine and Health, University of New South Wales,Sydney, New South Wales, Australia.

There is a strong biological link between the growth hormone (GH) and gonadal systems in growth, development and metabolism; however, regulatory interactions are poorly understood. Advances in estrogen biology and endocrine physiology have provided insights into mechanistic links between the two systems. Estrogens are synthesized from androgens by aromatase which is widely distributed in extragonadal tissues. Local generation of estrogens raise the possibility of paracrine control as an additional level to classical endocrine regulation of the GH system. To explore the mechanistic links, we review the pharmacology of estrogen, the effects of estrogen replacement, antagonism, and the impact of aromatase inhibition on the GH system as well as the metabolic sequelae. In men, estrogens derived from androgens drive the central secretion of GH, independent of the androgen receptor. In hypogonadal women, physiological replacement via a parenteral route evokes no effect while estrogen receptor antagonism and estrogen deprivation induce disparate effects, providing no consistent evidence that estrogens regulate the central secretion of GH via paracrine or endocrine mechanisms. However, delivery of estrogen by the oral route inhibits hepatic IGF-1 production, in turn increasing GH secretion via reduced feedback inhibition. This endocrine route-dependent effect of oral estrogen compounds on hepatic function induces detrimental metabolic effects on hypogonadal women. In conclusion, estrogens regulate the secretion and action of GH via complex paracrine and endocrine interactions and impart metabolic effects in a route- and gender-dependent manner. The metabolic sequelae of compounds mimicking, antagonizing, or depleting estrogens, should be considered in tailoring and optimizing their use.
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http://dx.doi.org/10.1530/EJE-21-0155DOI Listing
May 2021

Strategies to engage people with dementia and their informal caregivers in dyadic intervention: A scoping review.

Geriatr Nurs 2021 Mar-Apr;42(2):412-420. Epub 2021 Feb 24.

School of Nursing, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong. Electronic address:

Dyadic interventions simultaneously engage both people with dementia (PWD) and their informal caregivers (ICGs). This scoping review study identified the strategies for engaging dyads, described the perceptions of the dyads on these strategies, and reported the attrition rates of the dyadic interventions reported in the literature. Articles published up to July 2020, reporting a PWD-ICG-dyads intervention were searched in PubMed (Medline), PsycInfo, CINAHL, and the SSCI. Backwards citation chasing was conducted. A total of 37 studies were included. Seven engagement strategies were identified, which involved: ensuring a good-quality interventionist; offering take-home supporting materials; establishing peer support among the participants; tailoring the intervention content; conducting the intervention in a convenient location; conducting the intervention in a comfortable physical environment, and using a short and succinct programme. The dyads' subjective experiences of these strategies were reported. The attrition rates of the included studies were ranged 0% - 59.1%.
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http://dx.doi.org/10.1016/j.gerinurse.2021.02.002DOI Listing
February 2021

Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time?

J Endocr Soc 2021 Mar 9;5(3):bvaa205. Epub 2021 Feb 9.

Royal Veterinary College, University of London, London, UK.

The designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic. Experts in pituitary developmental biology, pathology, neurosurgery, endocrinology, and oncology, including representatives nominated by the Endocrine Society, European Society of Endocrinology, European Neuroendocrine Association, Growth Hormone Research Society, and International Society of Pituitary Surgeons. Clinical epidemiology, disease phenotype, management, and prognosis of pituitary adenomas differ from that of most NETs. The vast majority of pituitary adenomas are benign and do not adversely impact life expectancy. A nomenclature change to PitNET does not address the main challenge of prognostic prediction, assigns an uncertain malignancy designation to benign pituitary adenomas, and may adversely affect patients. Due to pandemic restrictions, the workshop was conducted virtually, with audiovisual lectures and written précis on each topic provided to all participants. Feedback was collated and summarized by Content Chairs and discussed during a virtual writing meeting moderated by Session Chairs, which yielded an evidence-based draft document sent to all participants for review and approval. There is not yet a case for adopting the PitNET nomenclature. The PANOMEN Workshop recommends that the term adenoma be retained and that the topic be revisited as new evidence on pituitary neoplasm biology emerges.
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http://dx.doi.org/10.1210/jendso/bvaa205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874572PMC
March 2021

Staying or moving: Results of a latent transition analysis examining intra-individual stability of recreational substance use among MSM in the Multicenter AIDS Cohort Study from 2004 to 2016.

Drug Alcohol Depend 2021 03 9;220:108516. Epub 2021 Jan 9.

Georgetown University Medical Center, Department of Medicine, 3800 Reservoir Road, NW PHC-5Washington, DC, 20007, USA.

Background: Studies have examined patterns of substance use among Men who have Sex with Men (MSM), but few have examined factors predicting transitioning from one substance use pattern to another. We investigated transitioning from one substance use pattern to another over a 12-year period (2004-2016) among the Multicenter AIDS Cohort Study participants.

Method: Alcohol, marijuana, heroin, cocaine, poppers, uppers (e.g., methamphetamines) and erectile dysfunction(ED) medications use in the last 6 months from 3568 US MSM was dichotomized (no/yes) to classify participants into substance use classes at each follow up visit. We fit latent transition models to calculate transition probabilities of moving from one substance use class to another over a 3, 4 and 6-year time period. Then fit regression models to identify factors associated with the probability of each participant staying in or moving from the same substance use class.

Results: Overall, cocaine and ED medication use declined but marijuana and heroin use increased over 2004-2016. We observed most participants (84.6 %-100 %) stayed in the same class. Increased age was associated with transition from the Minimal-use class to the Alcohol-only class (aOR = 1.06,95 %CI:1.01-1.13;p < 0.01) and non-White MSM reported lower odds of moving from the Alcohol-only class to the Alcohol-Popper class (aOR = 0.50,95 %CI:0.30-0.82;p <0.01). There were no difference in the transition probabilities by HIV-status.

Conclusion: Despite decline in substance use in general, participants are highly stable in their choice of substances. However, treating MSM as a homogeneous group can lead to an under-appreciation of the diversity of prevention needs and treatment of substance using MSM.
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http://dx.doi.org/10.1016/j.drugalcdep.2021.108516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901540PMC
March 2021

A discursive paper on the importance of health literacy among foreign domestic workers during outbreaks of communicable diseases.

J Clin Nurs 2020 Dec 2;29(23-24):4827-4833. Epub 2020 Oct 2.

Caritas Institute of Higher Education, Hong Kong, Hong Kong SAR, China.

Aim: Using an integrated model of health literacy, we discuss the importance of health literacy among foreign domestic workers in the provision of informal caregiving during outbreaks of communicable diseases. COVID-19 pandemic is used as an example.

Background: Adequate health literacy in the population is known to be important for the prevention of communicable diseases. Foreign domestic workers, a group of marginalised caregivers in private households, are generally presumed to have limited health literacy because of numerous socio-cultural disadvantages. To date, there is limited evidence that these informal healthcare providers receive support from community-based nurses.

Design: A discursive paper.

Conclusion: Foreign domestic workers, with varying levels of health literacy, may be viewed either as a resource to break the chain of infection or as a potential reservoir of communicable diseases in the community. Meanwhile, restrictions imposed in response to diseases transmissions (e.g. stay-at-home measures for COVID-19) may directly exacerbate the social support received by these foreign domestic works and their ability to access health-related information. There are also concerns about their ability to appraise and evaluate information related to communicable diseases at a time when fake news and misinformation are being disseminated through social media. Language and cultural barriers are important issues that need to be addressed to ensure that foreign domestic workers are in a position to follow public health recommendations.

Relevance To Clinical Practice: Nurses hold an important position in empowering foreign domestic workers with adequate health literacy, by engaging groups of foreign domestic workers in the community and their consulates in planning educational programmes and effectively disseminating information. At a time of global pandemic, an assessment of the health literacy levels of foreign domestic workers in places like Hong Kong is urgently required.
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http://dx.doi.org/10.1111/jocn.15495DOI Listing
December 2020

Multidisciplinary management of acromegaly: A consensus.

Rev Endocr Metab Disord 2020 12 10;21(4):667-678. Epub 2020 Sep 10.

Medical Research Unit in Endcrine Diseases, Hospital de Especialidades, Centro Médico Nacional, Siglo XXI, IMSS, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.

The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.
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http://dx.doi.org/10.1007/s11154-020-09588-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942783PMC
December 2020

Feasibility of Short-Term PrEP Uptake for Men Who Have Sex With Men With Episodic Periods of Increased HIV Risk.

J Acquir Immune Defic Syndr 2020 08;84(5):508-513

Fenway Health, Boston, MA.

Background: Pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate is efficacious in reducing HIV acquisition. For some gay, bisexual, and other men who have sex with men (MSM), daily ongoing PrEP may be unsuitable for use as a long-term prevention strategy because of episodic risk, cost issues, or concerns about the biological consequences of medication.

Setting: This study evaluated the feasibility of short-term, fixed-interval episodic PrEP (Epi-PrEP) for use among vacationing MSM. We describe the feasibility of implementing a clinic-based Epi-PrEP pilot program for 48 MSM who reported occasional condomless sex and anticipated a defined high-risk time.

Methods: This was a nonrandomized naturalistic study of an observational clinical intervention. The primary outcome assessed was adherence, as measured by self-report and plasma tenofovir levels.

Results: Of 54 MSM who enrolled in the study, 48 completed the 3-month visit. The majority (93.7%) had tenofovir concentrations consistent with daily use on returning from vacation. Almost 3/4 reported condomless sex during vacation, and about 1/3 reported recreational drug use. During the 3-month follow-up, 1 participant had become HIV-infected because of a lapse in continued access to the PrEP after study. Although adverse events were common, none were serious. More than 70% of participants indicated an interest in daily ongoing PrEP use.

Conclusions: Epi-PrEP was well tolerated by at risk MSM in this study, with high levels of medication adherence. Many participants felt the experience of initiating PrEP while on vacation could be a means for transition to long-term PrEP use.
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http://dx.doi.org/10.1097/QAI.0000000000002382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489298PMC
August 2020

Letter to the Editor: "Twice as High Diet-Induced Thermogenesis After Breakfast vs Dinner on High-Calorie as Well as Low-Calorie Meals".

Authors:
Ken K Y Ho

J Clin Endocrinol Metab 2020 07;105(7)

The Garvan Institute of Medical Research, St. Vincent's Hospital and the University of New South Wales, Sydney, NSW Australia.

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http://dx.doi.org/10.1210/clinem/dgaa244DOI Listing
July 2020

Growth Hormone Stops Excessive Inflammation After Partial Hepatectomy, Allowing Liver Regeneration and Survival Through Induction of H2-Bl/HLA-G.

Hepatology 2021 02 2;73(2):759-775. Epub 2020 Nov 2.

Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, Australia.

Background And Aims: Growth hormone (GH) is important for liver regeneration after partial hepatectomy (PHx). We investigated this process in C57BL/6 mice that express different forms of the GH receptor (GHR) with deletions in key signaling domains.

Approach And Results: PHx was performed on C57BL/6 mice lacking GHR (Ghr ), disabled for all GH-dependent Janus kinase 2 signaling (Box1 ), or lacking only GH-dependent signal transducer and activator of transcription 5 (STAT5) signaling (Ghr391 ), and wild-type littermates. C57BL/6 Ghr mice showed striking mortality within 48 hours after PHx, whereas Box1 or Ghr391 mice survived with normal liver regeneration. Ghr mortality was associated with increased apoptosis and elevated natural killer/natural killer T cell and macrophage cell markers. We identified H2-Bl, a key immunotolerance protein, which is up-regulated by PHx through a GH-mediated, Janus kinase 2-independent, SRC family kinase-dependent pathway. GH treatment was confirmed to up-regulate expression of the human homolog of H2-Bl (human leukocyte antigen G [HLA-G]) in primary human hepatocytes and in the serum of GH-deficient patients. We find that injury-associated innate immune attack by natural killer/natural killer T cell and macrophage cells are instrumental in the failure of liver regeneration, and this can be overcome in Ghr mice by adenoviral delivery of H2-Bl or by infusion of HLA-G protein. Further, H2-Bl knockdown in wild-type C57BL/6 mice showed elevated markers of inflammation after PHx, whereas Ghr backcrossed on a strain with high endogenous H2-Bl expression showed a high rate of survival following PHx.

Conclusions: GH induction of H2-Bl expression is crucial for reducing innate immune-mediated apoptosis and promoting survival after PHx in C57BL/6 mice. Treatment with HLA-G may lead to improved clinical outcomes following liver surgery or transplantation.
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http://dx.doi.org/10.1002/hep.31297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894545PMC
February 2021

Adaptation and psychometric testing of the hoarding rating scale (HRS): a self-administered screening scale for epidemiological study in Chinese population.

BMC Psychiatry 2020 04 14;20(1):159. Epub 2020 Apr 14.

School of Nursing, Tung Wah College, Ho Man Tin, Hong Kong SAR, China.

Background: Hoarding disorder is a chronic and debilitating illness associated with restrictions on activities of daily living, compromised social and occupational functioning, and adverse health outcomes. However, researchers lack a brief and self-administered screening measurement to assess compulsive hoarding in the Chinese speaking population. This study aimed to adapt and validate the Hoarding Rating Scale-Interview (HRS-I) to as a tool for screening compulsive hoarding behavior in Chinese population.

Methods: This study comprised two phases. During Phase 1, the English-language HRS-I was translated into Chinese (CHRS) (comprehensible for most Chinese speaking population, e.g., Cantonese & Mandarin) and subjected to an equivalence check. In Phase 2, the CHRS was validated by examining internal consistency, stability, and construct validity. Different samples were used appropriately to verify the items and reflect the psychometric properties.

Results: In Phase 1, the CHRS yielded satisfactory content (S-CVI = 0.93) and face validity ratings (comprehensibility = 100%, N = 20 participants of general public with age 18-72) and the English and Chinese versions were found to be equivalent (ICC = 0.887; N = 60 university staff and students). Phase 2 revealed satisfactory levels of internal consistency (Cronbach's α = 0.86; corrected item-total correlation = 0.60-0.74; N = 820 participants of general public), 2-week test-retest reliability (ICC = 0.78; N = 60 university students), and construct validity (one-factor CFA solution matched with the hypothesized model, χ/d.f. = 2.26, RMSEA = 0.049, CFI = 0.99, IFI = 0.99, NFI = 0.99; n = 520 participants of general public).

Conclusions: This study provides sufficient evidence of the reliability and validity of the CHRS for compulsive hoarding behavior screening in the Chinese population through self-administered method.
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http://dx.doi.org/10.1186/s12888-020-02539-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155259PMC
April 2020

MANAGEMENT OF ENDOCRINE DISEASE: Does gender matter in the management of acromegaly?

Eur J Endocrinol 2020 May;182(5):R67-R82

Garvan Institute of Medical Research; Department of Endocrinology, St Vincent's Hospital; and St Vincent's Clinical School, Faculty of Medicine, the University of New South Wales, Sydney, Australia.

Gonadal steroids modulate the effects of GH, with oestrogens attenuating and androgens augmenting GH action. Whether these divergent effects influence the clinical manifestation, management and prognosis of acromegaly have not been carefully reviewed. This review examines whether there is a gender difference in epidemiology, presentation, quality of life (QoL), morbidity, treatments and mortality of acromegaly. Acromegaly is more common in women who present at an older age with longer diagnostic delay. At presentation, women have a higher GH relative to IGF-1 level than men. QoL is more adversely affected in women both before and after treatment. Prevalence of hypertension and diabetes are greater in women than in men with acromegaly. Treatment outcomes with SSAs are comparable between sexes, but women may require a higher dose of pegvisomant for equivalent response. Mortality in untreated acromegaly is more profoundly affected in women; however, improved treatments in recent decades have resulted in normalisation of standard mortality ratios in both sexes. We conclude that gender does matter in the management of acromegaly, with women presenting later in life, with greater diagnostic delay, higher prevalence of comorbidities and experiencing worse QoL.
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http://dx.doi.org/10.1530/EJE-19-1023DOI Listing
May 2020

The promise of growth hormone in sport: doped or duped.

Authors:
Ken K Y Ho

Arch Endocrinol Metab 2019 Nov-Dec;63(6):576-581

The Garvan Institute of Medical Research, St Vincent's Hospital and the University of New South Wales, Sydney, Australia.

Skeletal muscle is a target tissue of GH. Based on its anabolic properties, it is widely accepted that GH enhances muscle performance in sports. Athletic performance depends on muscle strength and the energy required to power muscle function. The energy required to power muscle function is derived from a continuum of anaerobic and aerobic sources. Molecular and functional studies provide evidence that in muscle GH stimulates the anaerobic and suppresses the aerobic energy system, in turn affecting power-based functional measures in a time-dependent manner. In recreational athletes, GH improves anaerobic capacity but has not been proven to significantly enhance muscle strength, power, or maximum rate of oxygen consumption. GH appears likely to selectively benefit sprint events and not physical performance that depends on strength and endurance. Arch Endocrinol Metab. 2019;63(6):576-81.
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http://dx.doi.org/10.20945/2359-3997000000187DOI Listing
February 2020

A feminist phenomenology on the emotional labor and morality of live-in migrant care workers caring for older people in the community.

BMC Geriatr 2019 11 19;19(1):314. Epub 2019 Nov 19.

School of Nursing, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR.

Background: Global societal changes, such as increasing longevity and a shortage of family caregivers, have given rise to a popular worldwide trend of employing live-in migrant care workers (MCWs) to provide homecare for older people. However, the emotional labor and morality inherent in their interactions with older people are largely unknown. The aim of the present study is to understand the corporeal experiences of live-in migrant care workers in the delivery of emotional labor as seen in their interactions with older people by: (1) describing the ways by which they manage emotional displays with older people; and (2) exploring their morality as enacted through emotional labor.

Methods: We performed a secondary analysis drawing on feminist phenomenology to thematically analyze data from interviews with 11 female MCWs. Follow-up interviews were conducted with 10 participants. The participants had two to 15 years of experience in caring for older people in their homes in Hong Kong.

Results: Performing emotional labor by suppressing and inducing emotions is morally demanding for live-in MCWs, who experience socio-culturally oppressive relationships. However, developing genuine emotions in their relationships with older people prompted the MCWs to protect the interests of older people. Through demonstrating both fake and genuine emotions, emotional labor was a tactic that live-in MCWs demonstrated to interact morally with older people.

Conclusions: Emotional labor allowed live-in MCWs to avoid conflict with older people, and to further protect their own welfare and that of others. This study highlights the significance of empowering live-in MCWs by training them in ways that will help them to adapt to working conditions where they will encounter diverse customs and older people who will develop an increasing dependence on them. Thus, there is a need to develop culturally appropriate interventions to empower live-in MCWs to deliver emotional labor in a moral manner.
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http://dx.doi.org/10.1186/s12877-019-1352-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862863PMC
November 2019

Alterations in Oral Microbiota in HIV Are Related to Decreased Pulmonary Function.

Am J Respir Crit Care Med 2020 02;201(4):445-457

Division of Pulmonary, Allergy and Critical Care Medicine and.

Mechanisms of HIV-associated chronic obstructive pulmonary disease (COPD) are poorly understood. The oral microbiome shapes the lung microbiome, and gut dysbiosis can affect lung diseases; however, relationships of the oral and gut microbiome to COPD in HIV have not been explored. To examine alterations in the oral and gut microbiome associated with pulmonary disease in persons with HIV (PWH). Seventy-five PWH and 93 HIV-uninfected men from the MACS (Multicenter AIDS Cohort Study) performed pulmonary function testing. Sequencing of bacterial 16S ribosomal RNA in saliva and stool was performed. We used nonmetric multidimensional scaling, permutational multivariate ANOVA, and linear discriminant analysis to analyze communities by HIV and lung function. Oral microbiome composition differed by HIV and smoking status. Alterations of oral microbial communities were observed in PWH with abnormal lung function with increases in relative abundance of , , and . There were no significant associations between the oral microbiome and lung function in HIV-uninfected individuals. No associations with HIV status or lung function were seen with the gut microbiome. Alterations of oral microbiota in PWH were related to impaired pulmonary function and to systemic inflammation. These results suggest that the oral microbiome may serve as a biomarker of lung function in HIV and that its disruption may contribute to COPD pathogenesis.
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http://dx.doi.org/10.1164/rccm.201905-1016OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049920PMC
February 2020

A Consensus on the Diagnosis and Treatment of Acromegaly Comorbidities: An Update.

J Clin Endocrinol Metab 2020 04;105(4)

Department of Medicine, CIBERER, Universidad Autónoma de Madrid, Madrid, Spain.

Objective: The aim of the Acromegaly Consensus Group was to revise and update the consensus on diagnosis and treatment of acromegaly comorbidities last published in 2013.

Participants: The Consensus Group, convened by 11 Steering Committee members, consisted of 45 experts in the medical and surgical management of acromegaly. The authors received no corporate funding or remuneration.

Evidence: This evidence-based consensus was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence following critical discussion of the current literature on the diagnosis and treatment of acromegaly comorbidities.

Consensus Process: Acromegaly Consensus Group participants conducted comprehensive literature searches for English-language papers on selected topics, reviewed brief presentations on each topic, and discussed current practice and recommendations in breakout groups. Consensus recommendations were developed based on all presentations and discussions. Members of the Scientific Committee graded the quality of the supporting evidence and the consensus recommendations using the GRADE system.

Conclusions: Evidence-based approach consensus recommendations address important clinical issues regarding multidisciplinary management of acromegaly-related cardiovascular, endocrine, metabolic, and oncologic comorbidities, sleep apnea, and bone and joint disorders and their sequelae, as well as their effects on quality of life and mortality.
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http://dx.doi.org/10.1210/clinem/dgz096DOI Listing
April 2020

Associations of Urine Biomarkers with Kidney Function Decline in HIV-Infected and Uninfected Men.

Am J Nephrol 2019 25;50(5):401-410. Epub 2019 Sep 25.

Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, California, USA,

Background: HIV-infected (HIV+) persons are at increased risk of chronic kidney disease, but serum creatinine does not detect early losses in kidney function. We hypothesized that urine biomarkers of kidney damage would be associated with subsequent changes in kidney function in a contemporary cohort of HIV+ and HIV-uninfected (HIV-) men.

Methods: In the Multicenter AIDS Cohort Study, we measured baseline urine concentrations of 5 biomarkers from 2009 to 2011 in 860 HIV+ and 337 HIV- men: albumin, alpha-1-microglobulin (α1m), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and procollagen type III N-terminal propeptide (PIIINP). We evaluated associations of urine biomarker concentrations with annual changes in estimated glomerular filtration rate (eGFR) using multivariable linear mixed models adjusted for demographics, traditional kidney disease risk factors, HIV-related risk factors, and baseline eGFR.

Results: Over a median follow-up of 4.8 years, the average annual eGFR decline was 1.42 mL/min/1.73 m2/year in HIV+ men and 1.22 mL/min/1.73 m2/year in HIV- men. Among HIV+ men, the highest vs. lowest tertiles of albumin (-1.78 mL/min/1.73 m2/year, 95% CI -3.47 to -0.09) and α1m (-2.43 mL/min/1.73 m2/year, 95% CI -4.14 to -0.73) were each associated with faster annual eGFR declines after multivariable adjustment. Among HIV- men, the highest vs. lowest tertile of α1m (-2.49 mL/min/1.73 m2/year, 95% CI -4.48 to -0.50) was independently associated with faster annual eGFR decline. Urine IL-18, KIM-1, and PIIINP showed no independent associations with eGFR decline, regardless of HIV serostatus.

Conclusions: Among HIV+ men, higher urine albumin and α1m are associated with subsequent declines in kidney function, independent of eGFR.
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http://dx.doi.org/10.1159/000502898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856405PMC
September 2020

Examination of Polypharmacy Trajectories Among HIV-Positive and HIV-Negative Men in an Ongoing Longitudinal Cohort from 2004 to 2016.

AIDS Patient Care STDS 2019 08;33(8):354-365

1Department of Infectious Diseases, Georgetown University Medical Center, Washington, District of Columbia.

Polypharmacy is the concurrent use of five or more medications. We used group-based trajectory analysis to identify groups of non-HIV medication polypharmacy and investigate associated risk factors among HIV-positive and HIV-negative men in the Multicenter AIDS Cohort Study (MACS) from 2004 to 2016. Each participant was assigned to mutually exclusive groups based on their observed patterns of polypharmacy over time. Risk factors associated with membership with resulting groups were investigated using a multinomial generalized logit model with repeated measures. There were 3160 participants (54.3% HIV positive) included in the study. The overall prevalence of polypharmacy was 33.1% and was higher in HIV-positive than HIV-negative participants (36.2% vs. 30.0%;  < 0.001). Four distinct groups of polypharmacy emerged over time among all participants and among HIV-positive participants only: (1) nonpolypharmacy, (2) slow increasing polypharmacy, (3) rapid increasing polypharmacy, and (4) sustained polypharmacy. Being HIV positive, being 50 years of age or older, having medication insurance coverage, and having increased health care use were positively associated with membership in groups with sustained or increasing polypharmacy. Half of participants in each analysis had membership in one of the three high polypharmacy groups. This study revealed that access to care, through medication insurance coverage and health care use, was a key driver of polypharmacy in this cohort. Further exploration of medically appropriate and inappropriate prescribing practices in the context of polypharmacy and its impact on health outcomes in this and other populations is warranted.
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http://dx.doi.org/10.1089/apc.2019.0057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661916PMC
August 2019

The Use and Abuse of Growth Hormone in Sports.

Endocr Rev 2019 08;40(4):1163-1185

Garvan Institute of Medical Research, St. Vincent's Hospital, University of New South Wales, Sydney, New South Wales, Australia.

GH is banned by the World Anti-Doping Agency as a performance-enhancing anabolic agent. Doping with GH likely began in the early 1980s and became more prevalent with the advent of recombinant technology well before any scientific evidence of benefit. The expectation that GH improves physical function stems from its anabolic and lipolytic properties. Athletic performance depends on muscle strength and the energy required to power muscle function. In recreational athletes, GH selectively improves anaerobic sprint capacity but has not been proven to significantly enhance muscle strength, power, or maximum rate of oxygen consumption. GH is secreted as a family of isoform peptides in a pulsatile manner reflecting intermittent secretion and rapid clearance. Its anabolic actions are largely mediated by IGF-I, which stimulates whole-body protein synthesis, including skeletal muscle and collagen proteins. Two methods have been validated for detecting GH abuse in athletes. The first (the isoform method) is based on distinguishing pure recombinant 22-kDa GH from the heterogeneous isoforms secreted from the pituitary. The second (the marker method) is based on measuring blood levels of GH-responsive proteins, specifically IGF-I and the N-terminal propeptide of type III collagen (P-III-NP). Only a handful of athletes have been caught since the implementation of GH doping tests in 2004. The low rate likely reflects the limitation of in-competition testing using current methods. Improved detection rates may be achieved by more out-of-competition testing, introducing athletes' biological passports, and the development of novel methods. Governance, operational, technical, and political factors influence the effectiveness of an anti-doping program.
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http://dx.doi.org/10.1210/er.2018-00265DOI Listing
August 2019

The technology implications of master's level education in the professionalization of nursing: A narrative inquiry.

J Adv Nurs 2019 Sep 6;75(9):1966-1975. Epub 2019 Jun 6.

School of Nursing, Tung Wah College, Hong Kong, Hong Kong.

Aims: (a) To explore the meanings of master's education in the professionalization of nursing; and (b) to describe the core attributes that nurses gained through master's study.

Design: Narrative inquiry.

Methods: From June 2017 to June 2018, unstructured interviews were conducted with 12 master-prepared nurses at advanced nursing position with minimum 5 years of postregistration experience. Collaborative thematic narrative analysis was conducted on verbatim transcripts. Members checking, peer validation and audience validation assured verisimilitude and utility.

Results: There was a need to fit one's own assertion for professional growth in nursing career structure. Master's study equipped nurses with specialty skills and knowledge with enhanced reflexivity, which nurtured morality, problem-solving ability and capacity to collaborate inter-professionally. Master-prepared nurses demonstrated effective clinical leadership through acting as change agents.

Conclusions: Master's level education and master-prepared nurses are instrumental to the professionalization of nursing by expanding the roles of nurses. Nursing career mentoring will maximize nurses' agency in healthcare system. Developing innovative inter-professional pedagogy will nurture the reflexivity of master-prepared nurses.
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http://dx.doi.org/10.1111/jan.14044DOI Listing
September 2019

Neuropsychological changes in efavirenz switch regimens.

AIDS 2019 07;33(8):1307-1314

University of Pittsburgh School of Medicine.

Background: Efavirenz is associated with side effects involving the central nervous system. However, it remains largely unknown whether switching off EFV improves neuropsychological performance.

Methods: We utilized data from the Multicenter AIDS Cohort Study (MACS). Participants were categorized by their use of EFV: never on EFV (No EFV), continuously on EFV (No Switch-OFF) and on EFV and then switched off (Switch-OFF). Baseline time points were defined as visits when first neuropsychological data were available. In Analysis 1, we compared neuropsychological and Center for Epidemiological Studies-Depression Scale (CES-D) scores before and after EFV switch in Switch-OFF group, aligning participants at the time of switch. Analysis 2 evaluated trajectory of neuropsychological/CES-D score among the three groups.

Results: This analysis included 1989 HIV-seropositive participants with neuropsychological data (1675 in No EFV, 44 in No Switch-OFF, and 270 in Switch-OFF group). At baseline, participants had a median age of 37 years, median CD4 cell count 442 cells/μl, and 22.9% viral suppression rate. In Analysis 1, neuropsychological and CES-D scores did not show clinically significant changes over 2 years prior to and 4 years after switch in Switch-OFF group. In Analysis 2, trends in neuropsychological and CES-D scores in the three different groups did not show significant differences during a median of 3.2 years of follow-up.

Conclusion: Discontinuation of EFV is not associated with changes in neuropsychological performance or severity of depression in men. Furthermore, we did not observe differences among participants who were never on EFV, continuously on EFV, and on EFV and then switched off.
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http://dx.doi.org/10.1097/QAD.0000000000002206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588288PMC
July 2019

Disparate Effect of Aromatization on the Central Regulation of GH Secretion by Estrogens in Men and Postmenopausal Women.

J Clin Endocrinol Metab 2019 07;104(7):2978-2984

Garvan Institute of Medical Research, Sydney, New South Wales, Australia.

Context: Estrogen receptor antagonism by tamoxifen inhibits GH secretion in both men and postmenopausal women, suggesting that estrogen, albeit at low concentration, stimulates GH secretion. However, systemic estrogen replacement in postmenopausal women does not enhance GH secretion. To clarify the role of estrogen in mediating GH secretion, we investigated the effect of estrogen deprivation by using aromatase inhibitors.

Aim: To determine whether estrogens mediate GH secretion in men and postmenopausal women.

Design: The effects of letrozole, an aromatase inhibitor, and tamoxifen were compared in an open-label crossover study. Eight men and 14 women received tamoxifen (20 mg/d) and letrozole (2.5 mg/d) for 2 weeks each. The primary endpoints were GH response to arginine stimulation and gonadal steroid levels.

Results: In men, letrozole significantly (P < 0.05) reduced the peak GH response to arginine (mean ± SEM; Δ -49.4% ± 18.1%). Tamoxifen also reduced the mean peak GH, but this did not reach statistical significance. In postmenopausal women, letrozole did not affect peak GH, whereas tamoxifen significantly (P < 0.05) reduced peak GH (Δ -47.3% ± 10%). In men, letrozole reduced circulating estradiol (from 43.1 ± 2.8 to 12.7 ± 1.3 pmol/L; P < 0.001), whereas in women estradiol was undetectable (<11 pmol/L) at baseline and throughout letrozole therapy.

Conclusion: Because estrogen deprivation reduced circulating GH, we conclude that estrogens regulate GH secretion in men. In postmenopausal women, the neutral effect of aromatase inhibition is likely explained by pre-existing estrogen deficiency. The inhibition of GH secretion by tamoxifen in menopause suggests a non-estrogen receptor-mediated mechanism of action. In contrast to men, estrogen is unlikely to mediate GH secretion in postmenopausal women.
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http://dx.doi.org/10.1210/jc.2019-00265DOI Listing
July 2019

Tenofovir disoproxil fumarate initiation and changes in urinary biomarker concentrations among HIV-infected men and women.

AIDS 2019 03;33(4):723-733

Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Healthcare System.

Objectives: Urinary biomarkers of kidney injury may have potential to identify subclinical injury attributable to tenofovir disoproxil fumarate (TDF) toxicity.

Design: This observational study included 198 HIV-infected participants from the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study, who initiated TDF between 2009 and 2015 and had urine samples collected at baseline before and after TDF initiation.

Methods: We used linear mixed-effects models controlling for urine creatinine and time on TDF to evaluate the effects of TDF initiation on changes in 14 urinary biomarkers.

Results: Within 1 year after TDF initiation, concentrations of trefoil factor 3 [+78%; 95% confidence interval (CI) +38%, +129%), alpha-1 microglobulin (α1m) (+32%; 95% CI +13%, +55%), clusterin (+21%; 95% CI +6%, +38%), uromodulin (+19%; 95% CI +4%, +36%), and kidney injury molecule-1 (KIM-1) (+13%; 95% CI +1%, +26%) significantly increased, whereas interleukin-18 (IL-18) significantly decreased (-13%, 95% CI -7%, -25%). Subsequent to the first year of TDF use, biomarker concentrations stabilized, and these changes were not statistically significant. When stratifying by baseline viremia (HIV-1 RNA < vs. ≥80 copies/ml), concentration changes for most biomarkers during the first year of TDF use were greater among aviremic vs. viremic participants, with significant differences in α1m (+80 vs. +22%), KIM-1 (+43 vs. +10%), beta-2 microglobulin (+83 vs. -10%), YKL-40 (+33 vs. -5%), and IL-18 (+20 vs. -27%).

Conclusions: TDF initiation was associated with substantial changes in urinary biomarkers of kidney injury within the first year of use, particularly among aviremic participants. A urinary biomarker panel may be a clinically useful tool to detect and monitor the heterogeneous effects of TDF on the kidney.
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http://dx.doi.org/10.1097/QAD.0000000000002114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400312PMC
March 2019

Prevalence and Correlates of PrEP Awareness and Use Among Black Men Who Have Sex with Men and Women (MSMW) in the United States.

AIDS Behav 2019 Oct;23(10):2694-2705

Center for LGBT Health Research, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.

Men who have sex with men and women (MSMW), including those who are Black, experience HIV-related disparities compared to men who have sex with men only (MSMO). Few studies have assessed the prevalence and correlates of pre-exposure prophylaxis (PrEP) awareness and use among Black MSMW. We recruited MSM ≥ 18 attending Black Gay Pride events between 2014-2017. We conducted multivariable logistic regressions to assess differences in PrEP awareness and use among HIV-negative Black MSM (n = 2398) and within Black MSMW (n = 419). MSMW were less likely than MSMO to report PrEP awareness (p < 0.001). Among PrEP-aware MSM, MSMW were more likely than MSMO to report PrEP use (p < 0.05). MSMW receiving gay community support were more likely to be PrEP-aware (p < 0.01). MSMW reporting any past-year STI diagnoses were more likely to report PrEP use (p < 0.01). Findings suggest that PrEP awareness campaigns tailored for Black MSMW, concomitant with STI-to-PrEP interventions, will facilitate greater PrEP uptake in this population.
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http://dx.doi.org/10.1007/s10461-019-02446-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713621PMC
October 2019
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