Five-year outcomes after IVIG for mild cognitive impairment due to alzheimer disease.

BACKGROUND: The purpose of this study was to assess the five-year treatment effects of a short course of intravenous immunoglobulin (IVIG) in subjects with mild cognitive impairment (MCI) due to Alzheimer disease (AD). METHODS: Fifty subjects 50 to 84 years of age with MCI due to AD were administered 0.4 g/kg 10% IVIG or 0.9% saline every two weeks x five doses in a randomized double-blinded design as part of a two-year study. Twenty-seven subjects completed an additional three-year extension study. MRI brain imaging, cognitive testing, and conversion to dementia were assessed annually. Participants were stratified into early MCI (E-MCI) and late MCI (L-MCI). The primary endpoint was brain atrophy measured as annualized percent change in ventricular volume (APCV) annually for five years. ANOVA was used to compare annualized percent change in ventricular volume from baseline between the groups adjusting for MCI status (E-MCI, L-MCI). RESULTS: Differences in brain atrophy between the groups, which were statistically significant after one year, were no longer significant after five years. IVIG-treated L-MCI subjects did demonstrate a delay in conversion to dementia of 21.4 weeks. CONCLUSION: An eight-week course of IVIG totaling 2 g/kg in MCI is safe but is not sufficient to sustain an initial reduction in brain atrophy or a temporary delay in conversion to dementia at five years. Other dosing strategies of IVIG in the early stages of AD should be investigated to assess more sustainable disease-modifying effects. Trial registration ClinicalTrials.gov NCT01300728. Registered 23 February 2011.

Fourteen Year Follow-Up of Randomized Clinical Trials of Active Robotic-Assisted Total Hip Arthroplasty.

BACKGROUND: Active robotic total hip arthroplasty (THA) has been used clinically for over 20 years, but long-term results have never been studied. The aims of this study are to determine whether active robotic THA improves clinical outcomes and results in fewer revisions over a long-term follow-up. METHODS: Patients from 2 US Food and Drug Administration clinical trials (1994-1998 and 2001-2006) who had undergone THA using either an active robotic system or a traditional manual technique were examined to determine if any differences existed in radiographic analysis and patient pain and function using the University of California, Los Angeles; visual analog scale; Health Status Questionnaire (HSQ) pain; HSQ role physical; HSQ physical functioning; Harris pain scores; and the total Western Ontario and McMaster Universities Osteoarthritis Index scores at a mean follow-up of 14 years. RESULTS: The ROBODOC group had statistically significant higher HSQ pain and Harris pain scores and lower Western Ontario and McMaster Universities Osteoarthritis Index scores. There was no statistically significant difference in probability of a revision for wear between the groups (χ2 = 1.80; P = .179), and no revisions for loosening in either group. CONCLUSION: Prior studies have demonstrated improved implant fit and alignment with the use of this active robot system. This long-term study now shows no failures for stem loosening at a mean follow-up of 14 years and small but potentially important improvements in clinical outcomes in the robot group.

IVIG treatment of mild cognitive impairment due to Alzheimer's disease: a randomised double-blinded exploratory study of the effect on brain atrophy, cognition and conversion to dementia.

OBJECTIVE: To determine the effect of intravenous immunoglobulin (IVIG) on brain atrophy and cognitive function in mild cognitive impairment (MCI) due to Alzheimer's disease (AD). METHODS: 50 participant 50-84 years of age with amnestic MCI were administered 0.4 g/kg 10% IVIG or 0.9% saline every 2 weeks for a total of 5 infusions (2 g/kg total dose) in a randomised double-blinded design. MRI brain was completed at baseline, 12  and 24 months. Cognitive testing was completed at baseline and every 4 months. Participants were stratified into early and late (LMCI) MCI stages. Average annualised per cent change in ventricular volume was computed as a measure of brain atrophy. RESULTS: There was significantly less brain atrophy (p=0.037, adjusted for MCI status) in the IVIG group (5.87%) when compared with placebo (8.14%) at 12 months; at 24 months, the reduction in brain atrophy no longer reached statistical significance. The LMCI participants who received IVIG performed better on Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog; p=0.011) and Mini-Mental State Examination (MMSE; p=0.004) at 1 year; these differences were not present after 2 years. There was no difference in conversion to AD dementia between the treatment and control groups after 2 years; however, at 1 year, there were fewer conversions from LMCI to AD dementia in the IVIG group (33.3%) when compared with control group (58.3%). CONCLUSIONS: This exploratory study provides limited evidence that a short course of IVIG administered in the MCI stage of AD reduces brain atrophy, prevents cognitive decline in LMCI and delays conversion to AD dementia for at least 1 year; however, this effect of IVIG appears to wane by 2 years. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT01300728.

Point-of-care lung ultrasound predicts hyperferritinemia and hospitalization, but not elevated troponin in SARS-CoV-2 viral pneumonitis in children.

SARS-CoV-2 often causes viral pneumonitis, hyperferritinemia, elevations in D-dimer, lactate dehydrogenase (LDH), transaminases, troponin, CRP, and other inflammatory markers. Lung ultrasound is increasingly used to diagnose and stratify viral pneumonitis severity. We retrospectively reviewed 427 visits in patients aged 14 days to 21 years who had had a point-of-care lung ultrasound in our pediatric emergency department from 30/November/2019 to 14/August/2021. Lung ultrasounds were categorized using a 6-point ordinal scale. Lung ultrasound abnormalities predicted increased hospitalization with a threshold effect. Increasingly abnormal laboratory values were associated with decreased discharge from the ED and increased admission to the ward and ICU. Among patients SARS-CoV-2 positive patients ferritin, LDH, and transaminases, but not CRP or troponin were significantly associated with abnormalities on lung ultrasound and also with threshold effects. This effect was not demonstrated in SARS-CoV-2 negative patients. D-Dimer, CRP, and troponin were sometimes elevated even when the lung ultrasound was normal.

Providing family planning counseling services for women with chronic medical conditions in an inpatient setting: A randomized feasibility trial.

OBJECTIVES: This study aimed to evaluate the feasibility and effectiveness of providing bedside family planning services to women with chronic medical conditions in the inpatient setting. STUDY DESIGN: We initiated a parallel randomized controlled trial of patients listed as female aged 18 to 44 years who were admitted to the hospital from February 2018 to May 2021 with at least one chronic medical condition associated with lower rates of contraception usage and no documentation of contraception. Patients who confirmed they were not using contraception were enrolled and randomized to one of the three arms. They received bedside family planning counseling and an offer of contraception prior to discharge (oral contraceptive pills, etonogestrel implant, or medroxyprogesterone injection), received a flyer recommending they talk with their outpatient physician about contraception, or received standard care. The primary outcomes were contraception use at 3 months and 12 months after discharge. RESULTS: Altogether 76 subjects were enrolled and randomized with 22 in the counseling arm and 27 each in the other arms. In the counseling arm, five (23%; 95% CI: 8.0%-45%) elected to receive contraception prior to discharge. Inferential statistics at follow-up were not able to be calculated due to high attrition. CONCLUSIONS: Providing counseling and offering immediate contraception initiation in the inpatient setting may be a feasible approach to improving contraception access for this population. Additional investigation into the acceptability, efficacy, and generalizability of this approach is warranted. IMPLICATIONS: Utilizing the inpatient setting may be a feasible approach for delivering contraception counseling to women with chronic medical conditions. This approach merits further study for effectiveness and acceptability. This study highlights the need for contraceptive counseling and initiation to become a standard part of hospital care for pregnancy-capable individuals.

Point-of-care Lung Ultrasound Is Useful to Evaluate Emergency Department Patients for COVID-19.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) can be a life-threatening lung disease or a trivial upper respiratory infection depending on whether the alveoli are involved. Emergency department (ED) evaluation of symptomatic patients with normal vital signs is frequently limited to chest auscultation and oro-nasopharyngeal swabs. We tested the null hypothesis that patients being screened for COVID-19 in the ED with normal vital signs and without hypoxia would have a point-of-care lung ultrasound (LUS) consistent with COVID-19 less than 2% of the time. METHODS: We performed a retrospective, structured, blinded ultrasound review and chart review in patients 14 years or older with symptoms prompting ED evaluation for COVID-19. We excluded those with known congestive heart failure or other chronic lung conditions likely to cause excessive B-lines on LUS. We used a two-sided exact hypothesis test for binomial random variables. We measured LUS diagnostic performance using computed tomography as the gold standard. RESULTS: We reviewed 77 charts; 49 met inclusion criteria. Vital signs were normal in 30/49 patients; 10 (33%) of these patients had LUS consistent with viral pneumonitis. We rejected the null hypothesis (p-value <0.001). The treating physicians' interpretations of their own point-of-care LUS had a sensitivity of 100% (95% confidence interval (CI), 74%, 100%), specificity 88% (95% CI, 47%, 100%), likelihood ratio (LR) positive of 5.8 (95% CI, 1.3, 25), and LR negative of 0.05 (95% CI, 0.03, 0.71) when compared to CT findings. CONCLUSION: LUS had a meaningful detection rate for pneumonitis in symptomatic ED patients with normal vital signs who were being evaluated for COVID-19. We recommend at least LUS be used in addition to polymerase chain reaction testing when evaluating symptomatic ED patients for COVID-19.

Point of care lung ultrasound is useful when screening for CoVid-19 in Emergency Department patients.

Background CoVid-19 can be a life-threatening lung disease or a trivial upper respiratory infection depending on whether the alveoli are involved. Emergency department (ED) screening in symptomatic patients with normal vital signs is frequently limited to oro-nasopharyngeal swabs. We tested the null hypothesis that patients being screened for CoVid-19 in the ED with normal vital signs and without hypoxia would have a point-of-care lung ultrasound (LUS) consistent with CoVid-19 less than 2% of the time. Methods Subjects Subjects were identified from ED ultrasound logs. Inclusion criteria Age 14 years or older with symptoms prompting ED screening for CoVid-19. Exclusion criteria Known congestive heart failure or other chronic lung condition likely to cause excessive B lines on LUS. Intervention Structured blinded ultrasound review and chart review Analysis We used an exact hypothesis tests for binomial random variables. We also measured LUS diagnostic performance using computed tomography as the gold standard. Results We reviewed 77 charts; 62 met inclusion criteria. Vital signs were normal in 31 patients; 10 (32%) of these patients had LUS consistent with CoVid-19. We rejected the null hypothesis (p-value for bitest <0.001). The treating physicians' interpretation of their own point of care lung ultrasounds had a sensitivity of 100% (95% CI 75%, 100%) and specificity of 80% (95% CI 68%, 89%). Conclusion LUS has a meaningful detection rate for CoVid-19 in symptomatic emergency department patients with normal vital signs. We recommend at least LUS be used in addition to PCR testing when screening symptomatic ED patients for CoVid-19.

A Randomized, Placebo-Controlled, Blinded, Crossover, Pilot Study of the Effects of Dextromethorphan/Quinidine for the Treatment of Neurobehavioral Symptoms in Adults with Autism.

Prior studies have demonstrated successful irritability treatment using dopaminergic antagonists in autistic patients. The purpose of this pilot study was to assess the effect of dextromethorphan/quinidine (DM/Q) in autistic adults (18-60 years of age). This was a randomized, blinded, crossover, study of 14 patients randomized to DM/Q or a placebo for 8 weeks, washed out for 4 weeks, then crossed over to the opposite treatment. There were no serious adverse events. Subjects were significantly lower on the Aberrant Behavioral Checklist for Irritability (ABC-IR) (F1,10 = 7.42; p = 0.021). Improvements in aggression and Clinical Global Impression were also seen. The findings suggest that DM/Q is well-tolerated and associated with improvements in irritability and aggression in adults with autism.

Reduction of Amyloid in the Brain and Retina After Treatment With IVIG for Mild Cognitive Impairment.

OBJECTIVE: To assess whether intravenous immunoglobulin (IVIG) in subjects with mild cognitive impairment (MCI) results in a reduction in amyloid in the central nervous system (CNS). METHODS: Five subjects with MCI underwent baseline Florbetapir positron emission tomography and retinal autofluorescent imaging. All were administered IVIG (Octagam 10%) at 0.4 g/kg every 14 days for a total of 5 infusions. After 3 months, standard uptake value ratio (SUVR) and amyloid retinal deposits were reassessed. RESULTS: Three subjects had a reduction in amyloid SUVR and all 5 subjects had a reduction in amyloid retinal deposits in at least 1 eye. CONCLUSIONS: A short course of IVIG over 2 months removes a measurable amount of amyloid from the CNS in persons with MCI.

Safety and Observations from a Placebo-Controlled, Crossover Study to Assess Use of Autologous Umbilical Cord Blood Stem Cells to Improve Symptoms in Children with Autism.

The aim of this exploratory study was to assess the safety and clinical effects of autologous umbilical cord blood (AUCB) infusion in children with idiopathic autism spectrum disorder (ASD). Twenty-nine children 2 to 6 years of age with a confirmed diagnosis of ASD participated in this randomized, blinded, placebo-controlled, crossover trial. Participants were randomized to receive AUCB or placebo, evaluated at baseline, 12, and 24 weeks, received the opposite infusion, then re-evaluated at the same time points. Evaluations included assessments of safety, Expressive One Word Picture Vocabulary Test, 4th edition, Receptive One Word Picture Vocabulary Test, 4th edition, Clinical Global Impression, Stanford-Binet Fluid Reasoning and Knowledge, and the Vineland Adaptive Behavior and Socialization Subscales. Generalized linear models were used to assess the effects of the response variables at the 12- and 24-week time periods under each condition (AUCB, placebo). There were no serious adverse events. There were trends toward improvement, particularly in socialization, but there were no statistically significant differences for any endpoints. The results of this study suggest that autologous umbilical cord infusions are safe for children with ASD. Tightly controlled trials are necessary to further progress the study of AUCB for autism. Stem Cells Translational Medicine 2018;7:333-341.

Isolated radial scar diagnosis by core-needle biopsy: Is surgical excision necessary?

PURPOSE: Radial scar and radial sclerosis (RS) are considered benign breast lesions with proliferative features. There is sparse literature on frequency of cancer upgrade in these patients without atypical features found on image-guided needle biopsy. This study retrospectively reviews cases of isolated RS diagnosed on needle biopsy and evaluates the cancer upgrade after subsequent surgical excision. METHODS: We conducted a retrospective cross-sectional study of cases with an isolated RS diagnosis based on needle biopsy and subsequent surgical pathology among all patients between January 1, 2009 and December 31, 2013. Patients with concomitant atypia, lobular carcinoma in situ on core biopsy, complete excision of very small RS with needle biopsy, and radiology-pathology discordance were excluded. An upgrade from the needle biopsy of RS was defined as surgical excision pathology that revealed ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), and/or invasive lobular carcinoma (ILC). RESULTS: 10,921 image-guided needle biopsy pathology reports were collected and 88 patients (0.81 %) were identified as having isolated RS. Of these 88 patients, 63 (72 %) underwent excision. The upgrade rate to cancer on subsequent surgical excision was 1.59 % (1/63) for DCIS; 0 % (0/63) for IDC; and 0 % (0/63) ILC. Twenty-five patients who did not undergo surgical excision had stable imaging studies with mean (±SD) 26 (±20) months follow up. CONCLUSIONS: Isolated radial scar on needle biopsy may not warrant routine surgical excision given relatively low cancer upgrade rates. Advancement in breast imaging, pathology and multidisciplinary approaches to care may effectively guide non-surgical management of RS.

A Comparison of In-person, Telephone, and Secure Messaging for Type 2 Diabetes Self-Management Support.

Ongoing interaction between diabetes educators and patients is necessary for making and sustaining behavior changes essential for glycemic control and subsequently reducing the complications of diabetes. PURPOSE: The purpose of this study was to determine the feasibility of diabetes self-management support (DSMS) delivered via telephone or secure message and to compare clinical outcomes (A1C, LDL), behavioral goal achievement, and health maintenance task completion. METHODS: In sum, 150 persons with type 2 diabetes who completed diabetes self-management education self-selected DSMS methods: 1 in-person visit (n = 47), 3 brief visits by phone (n = 44), or 3 by secure message (n = 59) through electronic health record. DSMS included evaluation of goal achievement, barriers and facilitators, problem solving, and review of health maintenance exams. Self-reported data were collected at 9 months. RESULTS: There were no significant differences among groups in main outcomes between baseline and 9-month follow-up. Behavioral goals were achieved by 59% of in-person participants, 73% phone, and 77% secure message. Sixty-two completed the intervention per protocol: fewer online than in-person or phone groups. Mean attempts to contact participants was significantly greater in the secure message group. Phone contact was significantly longer than secure message. CONCLUSIONS: Telephone and secure message was feasible for providing DSMS. Three brief contacts by phone or secure message resulted in similar outcomes when compared to an in-person visit. Secure messaging required less staff time, but increased patient engagement is needed.

Adapting the Group Lifestyle Balance™ Program for Weight Management Within a Large Health Care System Diabetes Education Program.

PURPOSE: The purpose of this translation study was to evaluate the feasibility and effectiveness of an adapted Group Lifestyle Balance (GLB) intervention for weight management implemented through an existing diabetes education program within a large health care delivery system for overweight/obese individuals with diabetes, prediabetes, or neither condition. METHODS: Adults with BMI ≥ 25 kg/m2 participated in an adapted GLB intervention designed to be appropriate regardless of diabetes status. Effectiveness was based on changes in weight and minutes of physical activity between baseline and completion of the 12-week core. Differences between subjects based on diabetes status were also examined. RESULTS: A total of 111 subjects with diabetes, prediabetes, and no diabetes completed baseline survey data and attended at least 9 of the 12 core sessions from April 2010 through December 2011. All achieved significant weight loss, and the proportion of subjects who reported exercising at least 150 minutes/week increased. CONCLUSIONS: The adapted GLB intervention for weight management implemented through an existing diabetes education program in a large health care system was feasible and effective in the population, regardless of participants' diabetes status.

Utilizing clinical support staff and electronic health records to increase tobacco use documentation and referrals to a state quitline.

The purpose of this study was to determine if incorporation of a workflow in the electronic health record (EHR) that empowered medical assistants (MA) to become tobacco-cessation promoters, would increase tobacco documentation and referral for cessation counseling. MAs in three primary care centers were trained to ask every patient, at every visit, about tobacco use then document this status in the EHR. Patients ready to quit were electronically referred to the quitline for tobacco cessation counseling. Documentation of tobacco status, ongoing verification of tobacco use, and chief complaint recording was compared before and after the intervention. Logistic regression analysis indicated that after adjusting for differences between care centers, there were increased odds in initial documentation (OR = 1.52; 95% CI = 1.42 - 1.62) and ongoing verification (OR = 2.86; 95% CI = 1.42 - 1.62) in 2010 in comparison with 2009. Recording of tobacco cessation as the chief complaint in current smokers increased 91% (OR = 1.91; 95% CI = 1.56 - 2.34). Documentation and referrals for smoking cessation can be increased in organizations using EHR by empowering MAs to promote tobacco cessation and providing electronic referral options.