Monoclonal Antibody and Fusion Protein Biosimilars Across Therapeutic Areas: A Systematic Review of Published Evidence

Background

Despite regulatory efforts to formalize guidance policies on biosimilars, there remains a need to educate healthcare stakeholders on the acknowledged definition of biosimilarity and the data that underpin it.

Objectives

The objectives of the study were to systematically collate published data for monoclonal antibodies and fusion protein biosimilars indicated for cancer, chronic inflammatory diseases, and other indications, and to explore differences in the type and weight (quantity and quality) of available evidence.

Methods

MEDLINE, Embase, and ISI Web of Science were searched to September 2015. Conference proceedings (n = 17) were searched 2012 to July 2015. Included studies were categorized by originator, study type, and indication. To assess data strength and validity, risk of bias assessments were undertaken.

Results

Across therapeutic areas, 43 named (marketed or proposed) biosimilars were identified for adalimumab, abciximab, bevacizumab, etanercept, infliximab, omalizumab, ranibizumab, rituximab, and trastuzumab originators. Infliximab CT-P13, SB2, and etanercept SB4 biosimilars have the greatest amount of published evidence of similarity with their originators, based on results of clinical studies involving larger numbers of patients or healthy subjects (N = 1405, 743, and 734, respectively). Published data were also retrieved for marketed intended copies of etanercept and rituximab.

Conclusions

This unbiased synthesis of the literature exposed significant differences in the extent of published evidence between molecules at preclinical, clinical, and post-marketing stages of development, providing clinicians and payers with a consolidated view of the available data and remaining gaps.

     

The alpha-lipoic acid derivative DHLHZn: a new therapeutic agent for acute lung injury in vivo

Objective and design

An animal experiment was performed to demonstrate the anti-inflammatory effects of an alpha-lipoic acid (ALA) derivative, dihydrolipoyl histidinate zinc complex (DHLHZn) for acute lung injury (ALI) and to investigate the mechanism of action.

Material

Rats were randomly divided into three experimental groups: control group (n = 17), DHLHZn(?) group (n = 11, ALI model rats), and DHLHZn(+) group (n = 12, ALI model rats treated by DHLHZn).

Treatment

Lipopolysaccharides (LPS, 10 mg/kg) were administered intratracheally in the DHLHZn(?) group and the DHLHZn(+) group. For the DHLHZn(+) group, DHLHZn (100 mg/kg) was administered intraperitoneally 2 h prior to LPS administration.

Methods

Four hours after LPS administration, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The findings were analyzed using the Mann–Whitney U test.

Results

Total number of cells, number of neutrophils and lymphocytes, levels of various inflammatory cytokines, and NF-kB p65 concentration of BALF were significantly lower in the DHLHZn(+) group than in the DHLHZn(?) group (p < 0.05). ALI pathology scores were significantly lower in the DHLHZn(+) group than in the DHLHZn(?) group (p < 0.001).

Conclusions

Anti-inflammatory effects of DHLHZn for ALI were demonstrated by BALF and histopathological findings. The mechanism of action of DHLHZn was considered to be via inhibition of the NF-kB signaling pathway. DHLHZn is thus suggested to be a new prophylactic agent for ALI.

     

The Association Between Weight Status,Weight History,Physical Activity,and Cognitive Task Performance

Purpose

Physical activity has been shown to attenuate the association between overweight/obesity and deleterious cardiovascular health-related outcomes, with emerging work also taking the duration of overweight/obesity into consideration. No previous work, however, has explored the interrelationships between physical activity, obesity, and obesity duration in the context of cognitive task performance, which was the purpose of this study.

Method

Data from the 1999–2002 National Health and Nutrition Examination Survey were used (N = 2322 adults 60–85 yrs). Physical activity was assessed via self-report, with body mass index (BMI) directly measured. Participants were classified into one of eight mutually exclusive groups: (0) normal weight now and 10 years ago and active now (n = 195), (1) normal weight and 10 years ago and inactive now (n = 265), (2) normal weight now but not 10 years ago and active now (n = 46), (3) normal weight now but not 10 years ago and inactive now (n = 123), (4) overweight/obese now but not 10 years ago and active now (n = 117), (5) overweight/obese now but not 10 years ago and inactive now (n = 168), (6) overweight/obese now and 10 years ago and active now (n = 435), and (7) overweight/obese now and 10 years ago and inactive now (n = 973). The digit symbol substitution test (DSST) was employed to assess cognitive task performance.

Results

After adjustments, only individuals who were inactive (groups 1, 3, 5, and 7) had significantly lower cognitive task performance.

Conclusion

Being inactive, regardless of weight classification and duration of overweight/obesity, was inversely associated with cognitive task performance in this national sample of older adults.

     

Minocycline affects human neutrophil respiratory burst and transendothelial migration

Objective

This study aimed at investigating the in vitro activity of minocycline and doxycycline on human polymorphonuclear (h-PMN) cell function.

Methods

h-PMNs were isolated from whole venous blood of healthy subjects; PMN oxidative burst was measured by monitoring ROS-induced oxidation of luminol and transendothelial migration was studied by measuring PMN migration through a monolayer of human umbilical vein endothelial cells. Differences between multiple groups were determined by ANOVA followed by Tukey’s multiple comparison test; Student’s t test for unpaired data for two groups.

Results

Minocycline (1–300 µM) concentration dependently and significantly inhibited oxidative burst of h-PMNs stimulated with 100 nM fMLP. Ten micromolar concentrations, which are superimposable to C _max following a standard oral dose of minocycline, promoted a 29.8 ± 4 % inhibition of respiratory burst (P < 0.001; n = 6). Doxycycline inhibited ROS production with a lesser extent and at higher concentrations. 10–100 µM minocycline impaired PMN transendothelial migration, with maximal effect at 100 µM (42.5 ± 7 %, inhibition, n = 5, P < 0.001).

Conclusions

These results added new insight into anti-inflammatory effects of minocycline exerted on innate immune h-PMN cell function.

     

Fasting Glucose and the Risk of Depressive Symptoms: Instrumental-Variable Regression in the Cardiovascular Risk in Young Finns Study

Purpose

Type 2 diabetes (T2D) has been associated with depressive symptoms, but the causal direction of this association and the underlying mechanisms, such as increased glucose levels, remain unclear. We used instrumental-variable regression with a genetic instrument (Mendelian randomization) to examine a causal role of increased glucose concentrations in the development of depressive symptoms.

Method

Data were from the population-based Cardiovascular Risk in Young Finns Study (n = 1217). Depressive symptoms were assessed in 2012 using a modified Beck Depression Inventory (BDI-I). Fasting glucose was measured concurrently with depressive symptoms. A genetic risk score for fasting glucose (with 35 single nucleotide polymorphisms) was used as an instrumental variable for glucose.

Results

Glucose was not associated with depressive symptoms in the standard linear regression (B = ?0.04, 95% CI [?0.12, 0.04], p = .34), but the instrumental-variable regression showed an inverse association between glucose and depressive symptoms (B = ?0.43, 95% CI [?0.79, ?0.07], p = .020). The difference between the estimates of standard linear regression and instrumental-variable regression was significant (p = .026)

Conclusion

Our results suggest that the association between T2D and depressive symptoms is unlikely to be caused by increased glucose concentrations. It seems possible that T2D might be linked to depressive symptoms due to low glucose levels.

     

Polymorphism rs547984 on human chromosome 1q43 is not associated with primary open angle glaucoma in a Saudi cohort

Background

To investigate the association between polymorphism rs547984, located in close proximity to the Zona Pellucida Glycoprotein 4 (ZP4) gene on human chromosome 1q43 and primary open angle glaucoma (POAG).

Method

Polymorphism rs547984 was genotyped using Taq-Man® assay in 185 subjects comprising of 90 unrelated POAG cases and 95 controls of Saudi origin.

Results

Association analysis between cases and controls revealed no significant genotype distribution under additive (p = 0.356), dominant (p = 0.517) and recessive (p = 0.309) models. Besides, the allele frequency distribution was also found to be non-significant (p = 0.70). The minor “A” allele frequency was found to be 0.49 and 0.50 among POAG cases and controls, respectively. In addition, specific clinical indices used to assess severity of glaucoma such as intraocular pressure (IOP), cup/disc ratio and number of anti-glaucoma medication also did not show any significant genotype distribution in POAG cases.

Conclusion

Polymorphism rs547984 is neither associated with any clinical indices important for POAG such as IOP and cup/disc ratio nor is a risk factor for POAG in the Saudi cohort.

     

<Emphasis Type="Bold">Risk Compensation Following Medical Male Circumcision: Results from a 1-Year Prospective Cohort Study of Young School-Going Men in KwaZulu-Natal,South Africa</Emphasis>

Purpose

This study sought to assess risk compensation following voluntary medical male circumcision of young school-going men. Risk compensation is defined as an inadvertent increase in sexual risk behaviors and a corresponding decrease in self-perceived risk for contracting HIV following the application of a risk reduction technology.

Methods

This study documented the sexual practices of circumcised (n = 485) and uncircumcised (n = 496) young men in 42 secondary schools at three time points (baseline and 6 and 12 months) in a sub-district of KwaZulu-Natal, South Africa. Study participants were aged from 16 to 24 years old.

Results

At the end of the study period, there was no significant difference between the two cohorts concerning learners’ perceptions of being at risk of contracting HIV (interaction effect: b = ?0.12, p = 0.40). There was also no significant difference in the number of sexual partners in the previous month (interaction effect: b = ?0.23, p = 0.15). The proportion of learners who have never used a condom decreased significantly over time (time effect: b = ?0.27, p = 0.01), and there was no difference between the circumcised and uncircumcised learners (interaction effect: b = ?0.09, p = 0.91).

Conclusions

Risk compensation, as evidenced in this study over a 1-year period, was not associated with undergoing voluntary medical male circumcision (VMMC) in our sample of young school-going men. However, it is of concern that at the end of this study, less than half of the sexually active sample in a high-HIV-prevalence community used condoms consistently in the previous month (39% for both study cohorts). The latter underscores the need to view VMMC as a potential entry point for planned HIV and sexuality education interventions targeting young men in this community.

     

Low radiation dose computed tomography coronary angiography: evaluation of the variations in coronary arteries

Objective

Despite attempts to decrease the radiation dose, coronary computed tomography angiography (CCTA) generally uses higher doses than computed tomography scans of other organs. The purpose of this study was to evaluate the incidence of the variations of the coronary arteries using the adaptive statistical iterative reconstruction technique to perform low-dose coronary computed tomography (CTA).

Methods

Diagnostic CCTA scans were performed in 3433 patients (from November 2010 to January 2015) using an Optima CT660 (GE Healthcare, USA) 64-slice and analyzed retrospectively.

Results

The mean effective dose was 2.1 mSv (1.2–4.9 mSv) for prospective and 4.5 mSv (3.6–9.1 mSv) for retrospective ECG-gated scans. The variations of the coronary arteries (CA) excluding myocardial bridge (MB) were detected in 76 (2.2 %) of the 3433 patients. A myocardial bridge was the most common variation (n = 288, 8.3 %). The second most common variation (n = 13, 17.1 %) was an absence of the left main coronary artery (LMCA) with separate starting points for the left anterior descending (LAD) and left circumflex (LCX) arteries. In addition, there was a rare variation (n = 1, 1.3 %) consisting of the LAD artery originating from the right coronary artery (RCA).

Conclusions

The present retrospective study was conducted using CCTA on patients with a coronary artery variations in Turkey (n = 3433). Our data show that low-dose CCTA can be used to detect common coronary variations.

     

Work-focused cognitive behavioral intervention for psychological complaints in patients on sick leave due to work-related stress: Results from a randomized controlled trial

Background

Work-related stress is a global problem with negative implications for individuals and society. The purpose of the current study was to evaluate a stress management intervention for patients on sick leave due to work-related stress complaints using a three-armed randomized controlled design.

Methods

Participants were patients referred from three municipalities to the regional Department of Occupational Medicine. Inclusion criteria were: 1) sick leave due to work-related stress complaints, 2) a diagnosis of adjustment disorder or reactions to severe stress (ICD 10 code: F43,2 – F 43,9 not PTSD) or mild depressive episode (F 32.0). Through a double randomization procedure patients (n = 163) were randomized to either an intervention group (n = 58), a ‘control group A’ receiving a clinical examination (n = 56), or ‘control group B’ (n = 49) receiving no offers at the department. The intervention comprised six sessions of individual cognitive behavioral therapy and the offer of a small workplace intervention. Questionnaire data were analyzed with multivariate repeated measurements analysis. Primary outcomes assessed were perceived stress and general mental health. Secondary outcomes were sleep quality and cognitive failures. Follow-up was at four and 10 months after baseline.

Results

Complaints were significantly reduced in all groups over time. No group effects were observed between the intervention group and control group A that was clinically assessed. Significant group effects were found for perceived stress and memory when comparing the intervention group to group B, but most likely not due to an intervention effect.

Conclusion

Psychological complaints improved substantially over time in all groups, but there was no significant treatment effect on any outcomes when the intervention group was compared to control group A that received a clinical assessment.

Trial registration

ISRCTN ISRCTN91404229. Registered 03 August 2012 (retrospectively registered).

     

The <Emphasis Type="Italic">PTPN22</Emphasis> R263Q polymorphism confers protection against systemic lupus erythematosus and rheumatoid arthritis,while <Emphasis Type="Italic">PTPN22</Emphasis> R620W confers susceptibility to Graves’ disease in a Mexican population

Objective

The functional PTPN22 R620W polymorphism (rs2476601) is clearly associated with susceptibility to several autoimmune diseases (ADs). However, the PTPN22 R263Q polymorphism (rs33996649) has been scarcely explored in different ADs. Here we aimed to examine the associations of the PTPN22 R620W and R263Q polymorphisms with susceptibility to or protection against rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Graves’ disease (GD) among Mexican patients.

Methods

We conducted a case–control study including 876 patients (405 with SLE, 388 with RA, and 83 with GD) and 336 healthy control individuals. PTPN22 genotypes were determined using the TaqMan 5′ allele discrimination assay.

Results

PTPN22 R620W was associated with GD susceptibility (OR 4.3, p = 0.004), but was not associated with SLE (OR 1.8, p = 0.19). We previously demonstrated that this polymorphism is associated with RA susceptibility (OR 4.17, p = 0.00036). Moreover, PTPN22 R263Q was associated with protection against SLE (OR 0.09, p = 004) and RA (OR 0.28, p = 0.045), but was not associated with GD.

Conclusions

Our data provide the first demonstration that PTPN22 R620W confers GD susceptibility among Latin-American patients. Moreover, this is the second report documenting the association of PTPN22 R263Q with protection against SLE and RA.

     

The suprascapular notch narrows with aging: a preliminary solution of the old conjecture based on a 3D-CT evaluation

Purpose

The purpose of this study was to describe the morphology of the suprascapular notch in terms of age distribution. We hypothesized that the notch narrows with aging.

Methods

Seven hundred and sixty consecutive patients (465 men and 295 women) scheduled for a shoulder surgery were retrospectively reviewed. A 3D-CT of the shoulder was taken to evaluate the shape of the notch according to the Rengachary classification. The six types of Rengachary classification were arranged into three major categories according to transverse scapular ligament ossification and notch size as follows: the wide notch (type 1 and type 2); the narrow notch (type 3 and type 4); and the ossified notch (type 5 and type 6). Comparisons between categories were done with a one-way analysis of variance.

Results

There was a statistically significant difference among the three categories (P < .01): the narrow notch group (n = 442, 63.4 ± 12.8 years) and the ossified notch group (n = 66, 65.9 ± 10.6 years) were significantly older than the wide notch group (n = 252, 57.5 ± 17.8 years), respectively. In patients with Rengachary type 5 shoulders, ossification was dominant on the medial side of the notch in 37 of 39 shoulders (92.3 %).

Conclusion

The current study showed that morphological changes of the scapular notch are related to aging. The narrow notch and the ossified notch are seemed to be developed from the wide notch in terms of the ossification starting from the medial side.

     

The Use of Salmonella Typhim Vaccine to Diagnose Antibody Deficiency

Purpose

The specific antibody response to the unconjugated 23-valent pneumococcal polysaccharide vaccine is one of the most common tests used to assess for possible humoral immunodeficiency. The results can be difficult to interpret because most people have been immunized with one or more of the pneumococcal vaccines and there is controversy regarding what constitutes a normal response. To circumvent this problem, we developed an ELISA to measure IgG-specific antibodies to the Salmonella Vi Typhim (S. Typhim) vaccine, a pure polysaccharide vaccine, which is a neoantigen for the vast majority of people in the USA.

Methods

We compared the pre- and post-vaccination serum titers to the Vi Typhim vaccine in healthy controls (n = 22), patients previously diagnosed with a primary immunodeficiency (n = 30), and patients referred for possible humoral immune deficiency (n = 29). We also determined if the S. Typhim vaccine could be used to assess specific antibody responses in people on antibody replacement therapy.

Results

Following immunization with the S. Typhim vaccine, we found that a 2-fold increase in titers is 100% sensitive and specific in detecting known humoral immune deficiencies as determined by ROC curve analysis. This cut-off value was successfully applied to possible immune deficiency patients (n = 29), resulting in the diagnosis of seven subjects with humoral immunodeficiency. The use of immunoglobulin replacement therapy did not affect the median response ratios compared to subjects not receiving gammaglobulin.

Conclusion

This study suggests that measurement of the specific antibody response to the S. Typhim vaccine may have advantages over pneumococcal vaccination in the evaluation of the humoral immune response.

     

Replaced common hepatic artery from the superior mesenteric artery: multidetector computed tomography (MDCT) classification focused on pancreatic penetration and the course of travel

Purpose

We categorize the subtypes of the replaced common hepatic artery (RCHA) and evaluate the clinical implications.

Methods

Thirty-four cases of the RCHA were evaluated retrospectively using multidetector computed tomography. We categorized them into the three RCHA subtypes according to pancreatic penetration and the passing routes. The distance between the orifice of the superior mesenteric artery (SMA) and RCHA bifurcation (D _SMA-RCHA) was measured using advanced 3D imaging software. Analysis of variance was used to evaluate the difference in D _SMA-RCHA according to the RCHA subtype.

Results

Type A (n = 17, 50 %) referred to RCHA penetrating the pancreatic parenchyma, all crossing the dorsal aspect of the superior mesenteric vein (SMV). Among them, three cases were accompanied by the circumportal pancreas. Type B (n = 10, 29 %) referred to RCHA without penetration of the pancreatic parenchyma and crossing of the dorsal aspect of the main portal vein (MPV) or SMV. Type C (n = 7, 21 %) referred to RCHA without penetration of the pancreas parenchyma and crossing of the ventral aspect of the MPV or SMV. The mean D _SMA-RCHA of each subtype was as follows: type A, 3.13 cm [95 % confidence interval (CI) 2.70–3.57]; type B, 2.04 cm [95 % CI 1.40–2.68]; and type C, 2.14 cm [95 % CI 2.23–2.92]. The D _SMA-RCHA of the penetrating pancreatic parenchyma of the RCHA was significantly longer than that of the non-penetrating pancreatic parenchyma (P = 0.007).

Conclusion

Half of RCHA show penetrating the pancreatic parenchyma, which was categorized as type A, and this type A takes off from the SMA more distally than RCHA without intrapancreatic penetration.

     

Public support for pictorial warnings on cigarette packs: an experimental study of US smokers

Background

Understanding factors that influence public support for “nudging” policies, like pictorial cigarette pack warnings, may offer insight about how to increase such support. We sought to examine factors that influence smokers’ support for requiring pictorial warnings on cigarette packs.

Methods

In 2014 and 2015, we randomly assigned 2149 adult US smokers to receive either pictorial warnings or text-only warnings on their cigarette packs for 4 weeks. The outcome examined in the current study was support for a policy requiring pictorial warnings on cigarette packs in the US.

Results

Support for pictorial warnings was high at baseline (mean: 3.2 out of 4). Exposure to pictorial warnings increased policy support at week 4 (β = .05, p = .03). This effect was explained by increases in perceived message effectiveness (p < .001) and reported conversations about policy support (p < .001). Message reactance (i.e., an oppositional reaction to the warning) partially diminished the impact of pictorial warnings on policy support (p < .001).

Conclusions

Exposing people to a new policy through implementation could increase public support for that policy by increasing perceived effectiveness and by prompting conversations about the policy. Reactance may partially weaken the effect of policy exposure on public support.

     

Work-Family Conflict Modifies the Association of Smoking and Periodontal Disease

Purpose

The aims of the study were to assess the association of periodontal loss of attachment with smoking and work-family conflict and assess whether work-family conflict modifies the association of smoking and periodontal disease.

Method

A random sample of 45–54 year olds from metropolitan Adelaide, South Australia, was surveyed by mailed self-complete questionnaire during 2004–2005. Oral examinations were performed on persons who responded to the questionnaire, providing an assessment of periodontal status.

Results

A total of 879 responded (participation rate = 43.8 %), with n = 709 oral examinations (completion rate = 80.7 %). Prevalence of periodontal loss of attachment (LOA) of 6+ mm was higher (p < 0.05) for smokers (23.8 %) compared to non-smokers (7.8 %) among employed adults. The adjusted prevalence ratio for LOA 6+ mm was prevalence ratio (PR) = 4.9 (95 % CI 2.2–8.8) for smokers, and there was a significant interaction (p < 0.05) between smoking status and work-family conflict.

Conclusion

Work-family conflict modified the association of smoking with periodontal disease. Higher levels of work interfering with family were associated with higher levels of periodontal LOA for smokers compared with non-smokers.

     

Cadaveric study of anterior and posterior elbow endoscopy portals for endoscopic distal biceps repair: comparative anatomy-at-risk

Purpose

The purpose of this study was to describe neurovascular structures-at-risk during establishment of five portals for access to distal biceps tendon (DBT) in cubital fossa, and to establish relative safety of these portal sites for such access. We hypothesized that all five portals are safe for endoscopic DBT exploration.

Methods

Ten fresh frozen cadaveric elbows were dissected after placement of portals at five potential sites (four anterior, one posterior). Nine neurovascular structures (CV, cephalic vein; LCN, lateral cutaneous nerve; LV, leash of vessels; RN, radial nerve; SRN, superficial radial nerve; PIN, posterior interosseous nerve; RA, radial artery; BA, brachial artery; MN, median nerve) were dissected, and their distances from portal sites were measured. Statistical analysis was performed to determine relative portal safety, and risk of injury to neurovascular structures in relation to each portal was analyzed.

Results

Structures that were significantly “at risk” were RA (p = 0.006), SRN (p = 0.002), and PIN (p = 0.004). RA was significantly “at risk” of injury from portal 4 (p = 0.009). Similarly, SRN was “at risk” from portal 3 (p = 0.036), and the PIN was “at risk” from portal 2 (p = 0.003).

Conclusions

Portal 1 (parabiceps portal) was safe for all neurovascular structures, however, portals 2–4 were significantly closer to neurovascular structures. RA, SRN, and PIN were significantly “at risk” as compared to other structures amongst the portals studied. Portal 5 was relatively safe for SRN and PIN.

Clinical relevance

Portals 1 (parabiceps portal) and 5 (distal posterior) can be safely placed for endoscopic access to the DBT. Portal 4 (open distal anterior) may be used after careful open dissection and under direct vision. Portals 2 and 3 are not recommended for elbow endoscopy.

     

Effekte einer adaptiven Servoventilation auf Herzrhythmusstörungen bei Patienten mit chronischer Herzinsuffizienz und schlafbezogenen Atmungsstörungen

Background

In patients with chronic heart failure with reduced left ventricular ejection fraction (HFrEF) sleep-disordered breathing (SDB) is linked with an increased risk for nocturnal cardiac arrhythmias. SDB can be effectively treated with adaptive servo-ventilation (ASV). Therefore, we tested the hypothesis that ASV therapy reduces nocturnal arrhythmias and heart rate in patients with HFrEF and SDB.

Methods

In a non-prespecified subanalysis of a multicenter randomized-controlled trial (ISRCTN04353156) twenty consecutive patients with stable HFrEF (age 67 ± 9 y; left ventricular ejection fraction 32 ± 7?%) and SDB (apnea-hypopnea index, AHI 48 ± 20/h) were randomized to either ASV (n = 10; Philips Respironics, Murrysville, PA, USA) or optimal medical treatment alone (control, n = 10). Polysomnography (PSG) with centralized scoring and blinded analysis where obtained at baseline and 12 weeks. The electrocardiograms (ECG) of the PSGs were analyzed with 24 h-Holter electrocardiography software (Pulse Biomedical Inc., QRS-Card^TM Cardiology Suite, USA).

Results

There was a decrease in ventricular ectopic beats (VEBs) per hour recording time in the ASV-group compared to the control group (?8.1 ± 42.4 versus +9.8 ± 63.7/h, p = 0.356). ASV reduced the number of ventricular couplets as well as non-sustained ventricular tachycardias (nsVT) compared to the control-group (?2.3 ± 6.9 versus +2.1 ± 12.7/h, p = 0.272, and ?0.1 ± 0.5 versus +0.1 ± 1.1/h, p = 0.407, respectively). Mean nocturnal heart rate decreased in the ASV group compared to the control-group (?2.0 ± 2.7 versus +3.9 ± 11.5/minute, p = 0,169). Described changes were not significantly different between groups.

Conclusions

In HFrEF patients with SDB ASV treatment may reduce nocturnal ventricular ectopic beats, couplets, nsVT and mean nocturnal heart rate. Findings underscore the need for further analyses in larger studies.

     

The Association Between Social Support,Body Mass Index and Increased Risk of Prediabetes: the Cardiovascular Risk in Young Finns Study

Purpose

The psychosocial determinants of prediabetes are poorly understood. The aims of our study were (1) to analyse the association between perceived social support in young adulthood and fasting glucose levels and prediabetes in mid-adulthood in a cohort of healthy Finns, (2) to explore whether body mass index (BMI), inflammation or depression mediate this relationship, (3) and to examine the association between social support trajectory groups and fasting glucose.

Method

A prospective design was used with an analytic sample of 1250 participants aged 3–18 years at baseline (1980) and aged 12–39 years when social support was measured. Fasting glucose and prediabetes were assessed 32 years after baseline. Linear and logistic regression was used to examine the association between social support and the outcome measures. A bootstrapping technique was used to examine mediation effects.

Results

Social support was associated with future glucose levels in women after adjusting for childhood socioeconomic status (SES) and youth depression (β = ?0.136, p = 0.001) and also predicted prediabetes in women after adjusting for childhood SES (β = 1.31, 95 % CI 1.02 to 1.69, p = 0.031). Both associations were attenuated after adjusting for BMI in mid-adulthood. BMI was found to mediate the relationship between social support and prediabetes in women (β for indirect effect β = 0.09, SE = 0.03, CI = 0.03 to 0.16).

Conclusion

Low perceived social support in young adulthood is associated with high fasting glucose and prediabetes in mid-adulthood in women but not men. The association between social support and prediabetes in women can be partly explained by BMI.

     

Hyper IgM Syndrome: a Report from the USIDNET Registry

Purpose

The United States Immunodeficiency Network (USIDNET) patient registry was used to characterize the presentation, genetics, phenotypes, and treatment of patients with Hyper IgM Syndrome (HIGM).

Methods

The USIDNET Registry was queried for HIGM patient data collected from October 1992 to July 2015. Data fields included demographics, criteria for diagnosis, pedigree analysis, mutations, clinical features, treatment and transplant records, laboratory findings, and mortality.

Results

Fifty-two physicians entered data from 145 patients of ages 2 months to 62 years (median 12 years); 131 were males. Using patients’ age at last entry, data from 2072 patient years are included. Mutations were recorded for 85 subjects; 82 were in CD40LG. Eighteen subjects had non-X-linked HIGM. 40 % had a normal serum IgM and 15 %, normal IgA. Infections were reported for 91 %, with pulmonary, ear, and sinus infections being the most common. 42 % had Pneumocystis jirovecii pneumonia; 6 % had Cryptosporidium. 41 % had neutropenia. 78 % experienced non-infectious complications: chronic diarrhea (n?=?22), aphthous ulcers (n?=?28), and neoplasms (n?=?8) including colon cancer, adrenal adenoma, liver adenocarcinoma, pancreatic carcinoid, acute myeloid leukemia, hepatoma, and, in a female with an autosomal dominant gain of function mutation in PIK3CD, an ovarian dysgerminoma. Thirteen patients had a hematopoietic marrow or stem cell transplant; three had solid organ transplants. Thirteen were known to have died (median age?=?14 years).

Conclusions

Analysis of the USIDNET Registry provides data on the common clinical features of this rare syndrome, and in contrast with previously published data, demonstrates longer survival times and reduced gastrointestinal manifestations.

     

Motivational and Volitional Correlates of Physical Activity in Participants Reporting No,Past, and Current Hypertension: Findings from a Cross-Sectional Observation Study

Purpose

The study investigated differences in motivational and volitional correlates of physical activity in persons who reported currently having hypertension, had hypertension in the past, or had no hypertension by using the health action process approach as a theoretical background.

Method

Self-reported data from 512 participants (71.9% women; M _age = 46.83 years; SD _age = 13.77; M _BMI = 24.89; SD _BMI = 4.71) were analyzed using multivariate analysis of variance (MANOVA), analysis of variance (ANOVA), and post hoc comparisons of groups to determine differences in motivational and volitional correlates for physical activity between groups followed by analysis of covariance (ANCOVA). Additionally, χ ² statistic was used to analyze differences in the distribution of behavioral stages between groups.

Results

Participants with hypertension reported a higher perceived vulnerability (d = 0.99) and lower action planning (d = 0.32) and self-efficacy (d = 0.30) compared to those who indicated no hypertension. Their perceived vulnerability was also higher compared to those who indicated past hypertension on the mean level (d = 0.60). Significant main effects for all independent variables were found when controlling for gender and HAPA stages with main effects for perceived vulnerability, action planning, and self-efficacy. Participants with current hypertension were more prominent in the intender stage, whereas participants with past hypertension were more likely to be in the actor stage. Participants with no hypertension at all were equally distributed across the intender and actor stages.

Conclusion

The study contributes to the understanding of differences in motivational and volitional correlates of physical activity in persons who reported different hypertension statuses.