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2 vs 17.8 months, P less then .0001) and OS (unreached vs 60.8 months, P less then .0001) in the former group. We then examined the additive value of PET/CT on the hematologic response achieved at 6 months and found that PET/CT (-) is associated with significantly increased median TTNT and OS for the very good partial response (VGPR) group and the less than VGPR group. Importantly, PET/CT retained prognostic significance after adjusting for multiple other predictive variables. We conclude that a PET/CT (-) at 6 months confers a significant prognostic advantage for patients with newly diagnosed MM and adds significant value to the hematologic response assessment.

Although pharmacist-provided diabetes services have been shown to be effective, the effectiveness of telepharmacy (TP) in diabetes management has not been clearly established. This systematic review and meta-analysis aims to evaluate the effectiveness of diabetes TP services.

PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched (from inception through September 2021) to identify published studies that evaluated the effect of TP services in patients with diabetes mellitus and reported either glycosylated hemoglobin (HbA1c) or fasting blood glucose (FBG) outcomes. Mean difference (MD), weighted mean difference (WMD), relative risk (RR), and 95% confidence intervals were calculated using the DerSimonian and Laird random-effects model.

36 studies involving 13,773 patients were included in the systematic review, and 23 studies were included in the meta-analysis. TP was associated with a statistically significant decrease in HbA1c (MD, -1.26%; 95% CI, -1.69 to -0.84) from baseline. FBG was not significantly affected (MD, -25.32 mg/dL; 95% CI, -57.62 to 6.98). Compared to non-TP service, TP was associated with a lower risk of hypoglycemia (RR, 0.48; 95% CI, 0.30-0.76). In a subset of studies that compared TP to face-to-face (FTF) pharmacy services, no significant difference in HbA1c lowering was seen between the 2 groups (WMD, -0.09%; 95% CI, -1.07 to 0.90).

Use of TP was associated with reduction of HbA1c and the risk of hypoglycemia in patients with diabetes mellitus. High-quality randomized controlled trials are needed to validate the effectiveness of diabetes TP services relative to FTF services.

Use of TP was associated with reduction of HbA1c and the risk of hypoglycemia in patients with diabetes mellitus. High-quality randomized controlled trials are needed to validate the effectiveness of diabetes TP services relative to FTF services.

Social distancing measures aimed at controlling the spread of coronavirus disease 2019 (COVID-19) are likely to have increased social isolation among those older than 70 instructed to shield at home. This study examines the incidence of loneliness by gender over the first 10 months of the COVID-19 pandemic among persons aged 70 and older in the United Kingdom, and the impact of changing social networks and perceived social support on the new occurrence of loneliness.

Participants (N = 1,235) aged 70 and older with no reports of loneliness before the pandemic who participated in 7 rounds of the Understanding Society COVID-19 Study (April 2020-January 2021) and the main Understanding Society Study conducted during 2019. Cox regression analyzed the time to a new occurrence of loneliness.

Among older people who hardly ever/never felt lonely before the pandemic, 33.7% reported some degree of loneliness between April 2020 and January 2021. Living in a single-person household, having received more social support before the pandemic, changes in support receipt during the pandemic, and a deteriorating relationship with one's partner during the pandemic increased the risk of experiencing loneliness. Older women were more likely than older men to report loneliness, even when living with a partner.

During the 3 COVID-19-related lockdowns in the United Kingdom, changes in older people's social networks and support resulted in a significant onset of loneliness. Findings highlight the risks of shielding older persons from COVID-19 in terms of their mental well-being and the importance of strengthening intergenerational support.

During the 3 COVID-19-related lockdowns in the United Kingdom, changes in older people's social networks and support resulted in a significant onset of loneliness. Findings highlight the risks of shielding older persons from COVID-19 in terms of their mental well-being and the importance of strengthening intergenerational support.Acute graft-versus-host disease (GVHD) requiring second-line treatment represents a highly morbid complication of allogenic hematopoietic cell transplantation (HCT). Recent studies have defined short-term outcomes after second-line treatment for acute GVHD, but longer-term outcomes have not been well defined. We examined overall survival (OS) and failure-free-survival (FFS) of 216 patient who had HCT who received second-line treatment for acute GVHD. Failure time for FFS was defined as the earliest of death, relapse, or implementation of third-line treatment. Multivariable Cox regression was used to identify risk factors for mortality and failure, and predictive models were derived for 6- and 12-month mortality. Point estimates of OS at 6 and 12 months were 59% (95% confidence interval [CI], 52-65) and 52% (95% CI, 45-68), respectively. Point estimates of FFS at 6 and 12 months were 42% (95% CI, 35-48) and 37% (95% CI, 31-43), respectively. Predictive models for both end points included serum albumin and total bilirubin concentrations at the onset of second-line treatment, patient age at onset of second-line therapy, and a combination of abdominal pain/stage 4 gut involvement. Optimism-corrected areas under the receiver-operator characteristic curve and Brier scores were 77.4 and 0.169 for 6-month mortality, respectively, and 80.0 and 0.169 for 12-month mortality. We identify risk factors associated with mortality and failure after second-line treatment of acute GVHD, provide historical benchmarks for assessment of FFS and OS in other studies, and propose predictive models for 6- and 12-month mortality that could be used to generate population-specific benchmarks.

Prolonged duration of intravenous (IV) vasopressor dependence in critically ill adult patients with vasodilatory shock results in increased length of stay in both the intensive care unit (ICU) and hospital, translating to higher risk of infection, delirium, immobility, and cost. Acceleration of vasopressor liberation can aid in reducing these risks. Midodrine is an oral α 1-adrenergic receptor agonist that offers a potential means of liberating patients from IV vasopressor therapy. This clinical review summarizes primary literature and proposes a clinical application for midodrine in the recovery phase of vasodilatory shock.

Five studies with a total of over 1,000 patients conducted between 2011 and 2021 were identified. In observational studies, midodrine administration was demonstrated to lead to faster time to liberation from IV vasopressor therapy and shorter ICU length of stay in patients recovering from vasodilatory shock. These findings were not replicated in a prospective, multicenter, randomized controlled trial. In this review, literature evaluating midodrine use for IV vasopressor liberation is summarized and study limitations are discussed.

On the basis of this review of current literature, recommendations are provided on selecting appropriate candidates for adjunctive midodrine in the recovery phase of vasodilatory shock and considerations are discussed for safely and effectively initiating, titrating, and discontinuing therapy.

On the basis of this review of current literature, recommendations are provided on selecting appropriate candidates for adjunctive midodrine in the recovery phase of vasodilatory shock and considerations are discussed for safely and effectively initiating, titrating, and discontinuing therapy.Due to the large amounts of calcium transferred to milk from mammary glands, periparturient dairy goats face challenges with calcium metabolism disorder and hypocalcemia. MALT1 inhibitor in vivo Serotonin (5-hydroxytryptamine, 5-HT), the product of 5-hydroxy-l-tryptophan (5-HTP) catalyzed by tryptophan hydroxylase 1, is a multifunctional monoamine thought to be a homeostatic regulator of the animal. The objective of the current study was to investigate the effects and underlying mechanisms of intramuscular 5-HTP injections on calcium homeostasis in the goat mammary glands. In the in vivo experiment, 30 multiparous Guanzhong dairy goats were randomly assigned to 2 groups, one group was injected with 5-HTP intramuscularly and the other group was injected with normal saline. From the first 10 d of the expected date for delivery, 5-HTP or saline was injected into goats through the shoulder muscle every morning before feeding, with a dose of 1 mg/kg per body weight. In the in vitro experiment, goat mammary epithelial cells (GMEC) were treated with 100 μM 5-HT for the evaluation of 5-HT in calcium transportation. The results demonstrated that 5-HTP treatment had no effect on the basic composition of colostrum (P > 0.05) but increased the serum 5-HT concentrations on days -5, -4, -3, and 5 relative to parturition (P less then 0.05). The 5-HTP injection group had greater serum calcium concentration on day 4 and greater serum parathyroid hormone-related protein (PTHrP) on days -5, -4, -1, 3, 4, and 5 compared with the saline injection group (P less then 0.05). It was further confirmed that 5-HT could increase intracellular calcium levels by increasing PTHrP and decreasing plasma membrane Ca2+-ATPases1 (PMCA1) in GMEC (P less then 0.05). In conclusion, 5-HTP treatment in multiparous goats during the transition period from pregnancy to lactation is a feasible way to protect goats from calcium metabolism disorder.Despite the rapid and broad implementation of CRISPR-Cas9-based technologies, convenient tools to modulate dose, timing, and precision remain limited. Building on methods using synthetic peptide nucleic acids (PNAs) to bind RNA with unusually high affinity, we describe guide RNA (gRNA) spacer-targeted, or 'antispacer', PNAs as a tool to modulate Cas9 binding and activity in cells in a sequence-specific manner. We demonstrate that PNAs rapidly and efficiently target complexed gRNA spacer sequences at low doses and without design restriction for sequence-selective Cas9 inhibition. We further show that short PAM-proximal antispacer PNAs achieve potent cleavage inhibition (over 2000-fold reduction) and that PAM-distal PNAs modify gRNA affinity to promote on-target specificity. Finally, we apply antispacer PNAs for temporal regulation of two dCas9-fusion systems. These results present a novel rational approach to nucleoprotein engineering and describe a rapidly implementable antisense platform for CRISPR-Cas9 modulation to improve spatiotemporal versatility and safety across applications.Social connection is an understudied target of intervention for the health of individuals providing care for a family member with Alzheimer's disease and related dementias (ADRD). To guide future research, we discuss considerations for interventions to promote social connection, with a particular focus on reducing loneliness (a) include caregiver perspectives in designing and delivering interventions; (b) adapt to stages of dementia; (c) consider caregiving demands, including the use of brief interventions; (d) specify and measure mechanisms of action and principles of interventions; (e) consider dissemination and implementation at all stages of research. With support from the National Institute on Aging for a Roybal Center for Translational Research in the Behavioral and Social Sciences of Aging, we are developing a portfolio of mechanism-informed and principle-driven behavioral interventions to promote social connection in ADRD caregivers that can be flexibly applied to meet a diverse set of needs while maximizing resources and reducing demands on caregivers.