Factors Related to Non-recovery from Whiplash. The Nord-Trøndelag Health Study (HUNT)

Background

Whiplash injuries show a variable prognosis which is difficult to predict. Most individuals experiencing whiplash injuries rapidly recover but a significant proportion develop chronic symptoms and ongoing disability.

Purpose

By employing longitudinal data, we investigated how psychological and physical symptoms, self-rated health, use of health services and medications, health behavior and demographic factors predict recovery from whiplash.

Method

Data from two waves of a large, Norwegian, population-based study (The Nord-Trøndelag Health Study: HUNT2 and HUNT3) were used. Individuals reporting whiplash in HUNT2 (baseline) were identified in HUNT3 11 years later. The characteristics of individuals still suffering from whiplash in HUNT3 were compared with the characteristics of individuals who had recovered using Pearson’s chi-squared test, independent sample t-tests and logistic regression.

Results

At follow-up, 31.6 % of those reporting whiplash at baseline had not recovered. These individuals (n?=?199) reported worse health at baseline than recovered individuals (n?=?431); they reported poorer self-rated health (odds ratio [OR]?=?3.12; 95 % confidence interval [CI], 2.20–4.43), more symptoms of anxiety (OR?=?1.70; 95 % CI, 1.15–2.50), more diffuse somatic symptoms (OR?=?2.38; 95 % CI, 1.61–3.51) and more musculoskeletal symptoms (OR?=?1.21; 95 % CI, 1.13–1.29). Individuals still suffering from whiplash also visited more health practitioners at baseline (OR?=?1.18; 95 % CI, 1.06–1.32) and used more medications (OR?=?1.24; 95 % CI, 1.09–1.40).

Conclusion

Poor self-rated health seems to be a strong risk factor for whiplash injuries becoming chronic. Diffuse somatic symptoms, musculoskeletal symptoms and symptoms of anxiety at baseline are important prognostic risk factors. Knowledge of these maintaining risk factors enables identification of individuals at risk of non-recovery, facilitating adequate treatment for this vulnerable group.     

IgA Deficiency,Autoimmunity & Pregnancy: A Population-Based Matched Cohort Study

Background

Several autoimmune disorders have been linked to adverse pregnancy outcome. IgA deficiency shares many autoimmune traits, but its association with pregnancy outcome is unknown.

Methods

Prospective population-based cohort study in Sweden of 613 mothers with IgA deficiency (IgA levels?IgA deficiency was matched on maternal age, parity, early pregnancy smoking status, education level, and delivery year with up to 5 control births (n?=?5,758).

Results

Offspring to women with IgA deficiency had 79 g lower birth weight than controls (mean?±?SD: 3,457?±?559 vs 3,537?±?553 g, P?P?=?0.001). No difference in preterm birth (<37 weeks) could be detected in deliveries to women with IgA deficiency vs control deliveries (5.8 % vs 5.2 %; odds ratio (OR)?=?1.13, 95%CI?=?0.85–1.49), but small for gestational age birth was more common (4.3 % vs 2.8 %; OR?=?1.48, 95%CI?=?1.04–2.10). Women with IgA deficiency also delivered more often by caesarean section (16.9 % vs 11.9 %; OR?=?1.51, 95%CI?=?1.26–1.82), while no difference was observed regarding low Apgar score (<7 at 5 min; 1.1 % vs 1.0 %; OR?=?1.18; 95%CI?=?0.62–2.27). When excluding women with autoimmune diseases, the excess risks of adverse pregnancy outcome diminished.

Conclusion

There is a small excess risk of certain adverse delivery and perinatal outcomes among offspring to women with IgA deficiency. These excess risks are attenuated when considering the presence of autoimmune diseases.     

Asthma and Hypogammaglobulinemia: an Asthma Phenotype with Low Type 2 Inflammation

Purpose

Little is known about hypogammaglobulinemia (HGG) in asthma patients. No data are available on the characteristics of adult patients with asthma and HGG.

Methods

We conducted a retrospective monocentric study between January 2006 and December 2012. Asthma patients with a serum immunoglobulin (Ig) quantitative analysis were included and classified into two groups depending on their serum IgG concentration: presence or absence of HGG. Clinical, biological, functional, and radiologic characteristics were compared in univariate and multivariate analysis, using a logistic regression model.

Results

In univariate analysis, asthma patients with HGG (n?=?25) were older (58 years old?±?18 vs 49?±?18, p?=?0.04) and more frequently active or former smokers as compared to patients with normoglobulinemia (n?=?80) (56.0 vs 35.0 %, p?=?0.01). Total IgE?<?30 kUI/L was more frequently observed in patients with HGG (53.0 vs 18.3 %, p?=?0.01). HGG asthma patients had lower fraction of exhaled nitric oxide (p?=?0.02), blood eosinophilia (p?=?0.0009), and presented with more severe composite score for bronchiectasis (p?=?0.01). In multivariate analysis, asthma patients with HGG had increased risk of being smokers [OR?=?6.11 (IC 95 %?=?1.16–32.04)], having total IgE concentration?<?30 kUI/L [OR?=?12.87 (IC 95 %?=?2.30–72.15)], and a more severe composite score of bronchiectasis [OR?=?20.65 (IC 95 %?=?2.13–199.74)].

Conclusion

Asthma patients with HGG are older and more often tobacco smoker than asthma patients without HGG. These patients have low type-2 inflammation markers.

     

Simultaneous Positivity for Anti-DNA, Anti-Nucleosome and Anti-Histone Antibodies is a Marker for More Severe Lupus Nephritis

Objective

The purpose of this study is to examine autoantibody profile of systemic lupus erythematosus (SLE) patients with lupus nephritis (LN) and to establish the correlation between the antibody reactivity and disease activity of LN.

Methods

Autoantibodies and serological parameters were measured and analyzed in 589 SLE patients. The associations of the co-positivity of anti-dsDNA, -nucleosome and –histone antibodies (3-pos) with clinical, serological and outcome parameters were analyzed.

Results

At the study entry, the prevalence for anti-dsDNA (61.52 % vs. 34.11 %, P?<?0.0001), anti-nucleosome (56.09 % vs. 37.21 %, P?=?0.0002) and anti-histone (49.35 % vs. 33.33 %, P?=?0.0013) antibodies in patients with LN were significantly higher than that in patients without LN. Patients with 3-pos had a higher proportion of proliferative renal lesions (class III?+?IV). The incidence of a poor renal outcome (7.14 % vs. 2.52 %, P?=?0.0174) in LN patients with 3-pos was significantly higher than those without 3-pos. Moreover, the rate of remission (73.63 % vs. 82.37 %, P?=?0.0245) was significantly reduced and recurrence increased (58.90 % vs. 23.44 %, P?<?0.0001) in 3-pos patients as compared to that in non 3-pos within the LN group.

Conclusion

Our data indicate a strong association between the 3-pos and renal disease activities, especially proliferative glomerulonephritis. The ability of 3-pos to predict renal flares may lead to major additional benefits in the follow-up of these patients.     

Predictors of a Functional Somatic Syndrome Diagnosis in Patients with Persistent Functional Somatic Symptoms

Background

Functional somatic syndromes (FSS) are characterized by the existence of multiple persistent functional somatic symptoms. Not many patients fulfilling the criteria for an FSS, receive a formal diagnosis, and it is unknown which factors explain this discrepancy. Patients that tend to worry and patients that gather more health information may have an increased chance of an FSS diagnosis. We hypothesized that high intelligence and high neuroticism increase the probability of an FSS diagnosis in patients with persistent functional somatic symptoms.

Purpose

This study aims to investigate patient factors that might be important in the process of syndrome labeling.

Methods

Our study was performed in a large, representative population cohort (n?=?976) in Groningen, The Netherlands, and included two assessment waves. Intelligence was measured using the General Aptitude Test Battery version B 1002-B. Neuroticism was measured using the 12-item neuroticism scale of the Eysenck Personality Questionnaire-Revised. Functional somatic symptoms were measured with the somatization section of the Composite International Diagnostic Interview. Current FSS diagnosis was assessed with a questionnaire. We performed multivariable logistic regression analyses including sum scores of neuroticism, intelligence scores, sex, number of functional somatic symptoms, and age as potential predictors of having an FSS diagnosis.

Results

From the 976 participants that completed measurements at follow-up, 289 (26.4 %) participants reported at least one persistent functional somatic symptom, and these subjects were included in the main analyses (38.4 % males, mean age of 55.2 years (SD?=?10.7), 36–82 years). High numbers of functional somatic symptoms ((OR)?=?1.320; 95 % (CI)?=?1.097–1.588), female sex (OR?=?9.068; 95 % CI?=?4.061–20.251), and high intelligence (OR?=?1.402; 95 % CI?=?1.001–1.963) were associated with an FSS diagnosis, while age (OR?=?0.989; 95 % CI?=?960–1.019) and neuroticism (OR?=?0.956; 95 % CI?=?0.872–1.048) were not.

Conclusion

This study suggests that high intelligence, but not high neuroticism, increases the chance of syndrome labeling in patients with persistent functional somatic symptoms.     

Immunoglobulin Dosage and Switch from Intravenous to Subcutaneous Immunoglobulin Replacement Therapy in Patients with Primary Hypogammaglobulinemia: Decreasing Dosage Does Not Alter Serum IgG Levels

Objective

The impact of reducing immunoglobulin dosage while switching from intravenous to subcutaneous replacement therapy was evaluated.

Methods

Sixty-five patients with primary hypogammaglobulinemia on stable intravenous replacement therapy were included in a monocentric longitudinal trial. IgG trough levels were measured at baseline and during 1 year following the switch to the subcutaneous route.

Results

Mean IgG trough level after 12 months of subcutaneous therapy was increased by 5.4% (8.37–8.82 g/l, p?=?0.3), while immunoglobulin dosage had been reduced by 28.3% (151–108 mg/kg/week, p?<?0.0001). For the patients with the lowest serum IgG level upon intravenous infusions, serum IgG level rose by 37% (5.33–7.33 g/l, p?=?0.003), while mean immunoglobulin dosage was reduced by 36% (170–109 mg/kg/week, p?=?0.04).

Conclusion

The present study shows that sustained serum IgG levels can be achieved after switching towards subcutaneous replacement despite using reduced immunoglobulin doses.     

Cancer Survival Through Lifestyle Change (CASTLE): a Pilot Study of Weight Loss

Background

Excess weight is a strong predictor of incident breast cancer (BC) and survivorship. A limited number of studies comparing strategies for promoting successful weight loss in women with remitted BC exist.

Purpose

CASTLE was a pilot study comparing the effectiveness/feasibility of in-person and telephonic behavioral-based lifestyle weight loss interventions in BC survivors.

Method

Fifty-two overweight/obese women (BMI?=?25–45 kg/m²) with remitted BC (stages I–IIIa) who recently completed cancer treatment were assigned to either an in-person group (n?=?24) or an individual telephone-based condition (n?=?11). Both interventions focused on increasing physical activity and reducing caloric intake. The phase I intervention lasted 6 months. The in-person condition received 16 group-based sessions, and the telephone condition received intervention calls approximately weekly. Phase II lasted 6 months (e.g., months 6–12), and all participants received monthly intervention calls via telephone.

Results

Participants were predominately Caucasian (80 %) with a mean age of 52.8 (8.0) years and BMI of 31.9 (5.4) kg/m². Mixed models ANOVAs showed significant within group weight loss after 6 months for both the in-person (?3.3 kg?±?4.4, p?=?0.002) and the telephonic (?4.0 kg?±?6.0, p?=?0.01) conditions with no between group differences. During phase II, the in-person group demonstrated significant weight regain (1.3 kg?±?1.7, p?=?0.009).

Conclusion

Our pilot study findings demonstrated that telephone-based behavioral weight loss programs are effective and feasible in BC survivors and that telephonic programs may have advantages in promoting weight loss maintenance.     

Interleukin-18 promoter polymorphisms and plasma levels are associated with increased risk of periodontitis: a meta-analysis

Objective

Emerging evidence has showed that interleukin-18 (IL-8) promoter polymorphisms and plasma IL-18 levels may be associated with increased risk of periodontitis, but individually published results are inconclusive. The aim of this meta-analysis was to derive a more precise estimation of these associations.

Methods

A literature search of PubMed, Cochrane Library, Embase, Web of Science, SpringerLink, China BioMedicine and China National Knowledge Infrastructure databases was conducted on articles published before April 1st, 2013. Crude odds ratio (OR) or standardized mean difference (SMD) with 95 % confidence intervals (CI) were calculated.

Results

Nine case–control studies were included with a total of 576 periodontitis patients and 458 healthy controls. Two common polymorphisms (?607A > C and ?137G>C) in the IL-18 gene were addressed. Our meta-analysis results indicated that the C variant of IL-18 ?607A>C polymorphism was associated with increased periodontitis risk (C allele vs. A allele: OR = 1.86, 95 % CI: 1.30–2.65, P = 0.001; AC+CC vs. AA: OR = 2.64, 95 % CI: 1.34–5.21, P = 0.005). There was also a significant association between the C variant of IL-18 ?137G>C polymorphism and an increased periodontitis risk (C allele vs. G allele: OR = 1.47, 95 % CI: 1.13–1.91, P = 0.004; GC+CC vs. GG: OR = 1.66, 95 % CI: 1.21–2.29, P = 0.002). Furthermore, the mean levels of plasma IL-18 of periodontitis patients were also higher than those of healthy controls (SMD = 1.18, 95 % CI: 0.51–1.85, P = 0.001).

Conclusion

The current meta-analysis suggests that IL-18 promoter polymorphisms and plasma IL-18 levels are associated with increased risk of periodontitis. IL-18 promoter polymorphisms and elevated plasma IL-18 levels may be useful biomarkers for predicting the development of periodontitis.     

Weight Perception and Dietary Intake among Chinese Youth, 2004–2009

Background

Little is known on the extent of weight misperception and its relation with dietary intake among Chinese youth.

Purpose

The study aimed to investigate extent and correlates of weight misperception and its relation with dietary intake among Chinese youth.

Method

Data pertaining to Chinese youth, 6–17 years of age, from the 2004–2009 China Health and Nutrition Survey (N?=?3,923) were analyzed using STATA version 12.1. The heights and weights of the participants were measured by well-trained health workers at the participants' homes or a local clinic following the reference protocol recommended by the World Health Organization. The dietary intake data of the participants were collected on three consecutive days at both the household and individual levels.

Results

Of the children 6–11 years of age, 18.9 % were underweight and 15.3 % were overweight. Among the children 12–17 years of age, 18.3 % were underweight and 8.1 % were overweight. Less than 60 % of Chinese youth accurately estimated their weight status. Nutrition knowledge was positively related to a perception of being overweight (adjusted odds ratio [AOR]?=?1.98, p?=?.007) among children 12–17 years of age. A perception of being overweight was positively associated with fat and protein intake among children 6–11 years of age (p?<?.05).

Conclusions

A discrepancy exists between the actual and perceived weight status of Chinese youth. Efforts are needed in China to promote accurate weight perception, healthy weight, and eating behaviors.     

Disagreement in doctor's and patient's rating about medically unexplained symptoms and health care use

Background

Medically unexplained (somatoform) symptoms (MUS) are highly prevalent in primary care. It remains unclear to what extent patients and their general practitioners (GPs) agree upon the etiology of physical symptoms as well as on the number of visits to the GP.

Purpose

The purpose of this study is to determine patient–physician agreement on reported symptoms.

Method

A sample of 103 persons provided information on MUS and health care utilization (HCU) during the previous 12 months. The persons' GPs (n?=?103) were asked for the same information. By determining patient–physician agreement on reported symptoms, the sample was subdivided into a concordance group (high agreement: Pt?=?GP) and two discordance groups (substantial disagreement: Pt?>?GP, Pt?<?GP).

Results

Patients and their GPs showed substantial disagreement concerning physical symptom reports for the prior 12 months. On means, patients named 3.26 (SD?=?3.23; range 0–21) physical complaints of which 71.6% were considered to be medically unexplained (MUS), whereas GPs only determined 1.77 (SD?=?1.94; range 0–11) symptoms of which 57.5% were MUS. Substantial patient–physician agreement regarding the number of reported MUS was detected in 29.1% of the cases (Pt?=?GP). Patients of all groups underestimated their HCU.

Conclusion

Since patients' and GPs' reports differ substantially concerning the etiology of symptoms and concerning HCU, both sources of data gathering should be treated carefully in primary care research.     

Repeated core temperature elevation induces conduit artery adaptation in humans

Purpose

Shear stress is a known stimulus to vascular adaptation in humans. However, it is not known whether thermoregulatory reflex increases in blood flow and shear can induce conduit artery adaptation.

Methods

Ten healthy young volunteers therefore underwent 8 weeks of 3 × weekly bouts of 30 min lower limb heating (40 °C) during which the upper body was not directly heated. Throughout each leg heating session, a pneumatic cuff was placed on one forearm and inflated to unilaterally restrict reflex-mediated blood flow responses.

Results

Each bout of leg heating significantly increased brachial artery shear rate in the uncuffed arm (96 ± 97 vs 401 ± 96 l/s, P < 0.01), whereas no change was apparent in the cuffed arm (83 ± 69 vs 131 ± 76 l/s, P = 0.67). Repeated episodic exposure to leg heating enhanced brachial artery endothelial function (measured by flow-mediated dilation) in the uncuffed arm from week 0 (5.2 ± 1.9 %) to week 4 (7.7 ± 2.6 %, P < 0.05), before returning to baseline levels by week 8. No adaptation was evident in the cuffed arm.

Conclusions

We conclude that repeated increases in core temperature, induced via lower limb heating, resulted in upper limb conduit artery vascular adaptation which was dependent upon increases in shear stress. To our knowledge this is the first study to establish a beneficial systemic impact of thermoregulatory reflexes on conduit artery function in humans.     

Risk of Infections Among 2100 Individuals with IgA Deficiency: a Nationwide Cohort Study

Purpose

To explore the risk of infections in individuals with IgA deficiency compared to general population controls.

Methods

In this nationwide prospective population-based cohort study, we used data on IgA levels (<0.07 g/L) from six university hospitals in Sweden to identify 2100 individuals with IgA deficiency. Individuals were diagnosed between 1980 and 2010. For each patient with IgA deficiency we identified 10 controls from the general population, matched on age, sex, and place of residence (n?=?18,653). Data on infections were obtained from the Swedish National Patient Register (including inpatient and hospital-based outpatient care) between 2001 and 2010. We defined infections as having a record of a relevant international classification of disease (ICD) code. Prevalences and prevalence ratios (PRs) were calculated.

Results

Individuals with IgA deficiency were more likely to have a record of any infection (36.1 vs. 18.8 % in controls) corresponding to a PR of 2.4 (95%CI 2.2-2.6). We also noted statistically significant associations with IgA deficiency (all P-values <0.05) and respiratory tract infections (17.8 vs. 6.3 % in controls; PR?=?3.2), gastrointestinal infections (6.0 vs. 1.8 % in controls; PR?=?3.5), skin infections (4.1 vs. 2.2 % in controls; PR?=?1.9), joint infections (0.48 vs. 0.24 % in controls; PR?=?2.0; P?=?0.052), sepsis (1.5 vs. 0.45 % in controls; PR?=?3.4), meningitis (0.38 vs. 0.12 %, PR?=?3.2), mastoiditis/otitis (2.1 vs. 1.1 % in controls; PR?=?2.0), and urinary tract infections (6.1 vs. 3.4 % in controls; PR?=?1.8).

Conclusions

Individuals with IgA deficiency are at an increased risk of infections requiring hospital care.

     

A Randomized Controlled Trial Evaluating the Efficacy of a Theory-based Intervention Promoting Condom Use Among Chinese Monogamous Female Sexually Transmitted Infection Patients

Background

Chinese monogamous women may contract sexually transmitted diseases (STD) from their sole male sex partner, but these women do not have high self-efficacy in negotiating about condom use with their regular sex partners.

Purpose

We aim to investigate the relative efficacy of a theory-based and clinic-based cognitive behavioral intervention versus a control intervention in increasing prevalence of condom use with their male sex partner among Chinese monogamous female sexually transmitted disease patients.

Methods

A randomized controlled trial (RCT) was conducted. Participants were randomly allocated into the intervention group (n?=?88) or the control group (n?=?88). All participants were phone interviewed at baseline and at 2 and 3 months after completion of the baseline survey. The three-session group intervention was based on the information–motivation–behavioral skills (IMB) model. Participants of the control group were provided with educational pamphlets. The primary outcome was consistent condom use in the last month. Relative risks were calculated, and multiple logistic regression models were fit.

Results

As compared to the control group, the intervention group reported higher prevalence of consistent condom use with the sole male sex partner in the last month at month 2 (75.3 versus 59.8 %, RR?=?1.26, 95 % CI?=?1.01, 1.57) and month 3 (77.8 versus 54.6 %, RR?=?1.42, 95 % CI?=?1.13, 1.80), whilst the baseline between-group difference was statistically non-significant. Some other secondary outcomes such as “intention to request condom use in the next month even if the sexual partner dislikes using condoms” were also statistically significant. Furthermore, the majority (94 %) of the intervention group members were satisfied with the intervention.

Conclusions

The theory-based intervention is potentially efficacious, but the follow-up period was relatively short. Large-scale randomized clinical trials and subsequent translational research are greatly warranted in the future.     

Modern Health Worries, Subjective Health Complaints, Health Care Utilization, and Sick Leave in the Norwegian Working Population

Background

Modern health worries (concerns about aspects of modern life affecting health) heve been associated with subjective health complaints and health care utilization.

Purpose

The aim of this study was to investigate the association between modern health worries (MHW) and subjective health complaints (SHC), health care utilization, and sick leave related to such complaints in the Norwegian working population.

Methods

A sample of the Norwegian working population (N?=?569) answered a questionnaire which included the Subjective Health Complaints Inventory and a Norwegian version of the Modern Health Worries Scale.

Results

Ninety-one percent of the participants reported at least one complaint in the past 30 days, and 96 % of the participants reported concerns for at least one of the items in the MHW scale. Women reported significantly more and more severe complaints compared to men and significantly more concern about aspects of modern life affecting health. Participants who reported a high level of MHW showed nearly twice the risk of reporting a high level of SHC (odds ratio (OR)?=?1.83; 95 % confidence interval (CI)?=?1.30–2.71; p?=?0.001), and they showed twice the risk for self-certified sick leave related to SHC (OR?=?2.04; 95 % CI?=?1.01–3.92; p?=?0.048). High levels of MHW showed no significant association with health care utilization or doctor-certified sick leave.

Conclusions

Subjective health complaints and concerns about aspects of modern life affecting health are very common, even among healthy workers. Women have more complaints and more concerns compared to men. Within the health care system, it may be advantageous to pay close attention to the association between high levels of MHW and high levels of SHC.     

Differences Between Post-Authorization Adverse Drug Reactions of Biopharmaceuticals and Small Molecules

Background

The nature of adverse drug reactions observed post-authorization for biopharmaceuticals differs from that observed for chemically synthesized, small molecules (SMs). However, it remains unclear how much of the observed differences can be attributed to differences in authorized indications of the two product groups.

Objective

To investigate if the nature of adverse drug reactions identified post-authorization for biopharmaceuticals differs from those of SMs within the same anatomical therapeutic chemical (ATC) group.

Methods

We analyzed safety issues included in post-authorization, changes to the Summary of Product Characteristics of centrally approved products in the European Union classified in the ATC main group of ‘antineoplastic and immunomodulating agents’. Generics and biosimilars were excluded. All issues identified during 2004–2011 were analyzed for differences in nature and timing between biopharmaceutical and SM products, at different ATC levels.

Results

A total of 747 adverse drug reactions were identified; 361 for biopharmaceuticals and 386 for SMs. Within the sub group of immunosuppressants, neoplasms (20 % vs 2 %, p < 0.01) and infections and infestations (22 % vs 9 %, p < 0.01) occurred significantly more frequent for biopharmaceuticals. Adverse drug reactions of SMs were more often renal and urinary disorders (7 % vs 0 %, p < 0.01), blood and lymphatic system disorders (10 % vs 3 %, p = 0.04), and vascular disorders (7 % vs 1 %, p = 0.02). In the subgroup of antineoplastics, immune system disorders occurred more frequently for biopharmaceuticals, (6 % vs 1 %, p = 0.04). With the exception of immune system disorders and renal disorders, the overall differences between biopharmaceuticals and SMs were mostly caused by products authorized as immunosuppressants. For the subset of products authorized after 2004, the median time to the first safety issue was 18 months (95 % CI 12.4–21.5) for biopharmaceuticals and 17 months (95 % CI 12.5–21.5) for SMs and did not differ significantly within subgroups.

Conclusion

Even within a group of medicinal products approved in the same indication, differences were observed in the nature of adverse drug reactions between biopharmaceuticals and SMs. The considerable differences in the nature of adverse drug reactions between biopharmaceuticals and SMs were not associated with differences in the timing of regulatory actions.     

Randomized trial of primaquine hypnozoitocidal efficacy when administered with artemisinin-combined blood schizontocides for radical cure of <Emphasis Type="Italic">Plasmodium vivax</Emphasis> in Indonesia

Background

Safety and efficacy of primaquine against repeated attacks of Plasmodium vivax depends upon co-administered blood schizontocidal therapy in radical cure. We assessed primaquine (PQ) as hypnozoitocide when administered with dihydroartemisinin-piperaquine (Eurartesim®, DHA-PP) or artesunate-pyronaridine (Pyramax®, AS-PYR) to affirm its good tolerability and efficacy. A third arm, artesunate followed by primaquine, was not intended as therapy for practice, but addressed a hypothesis concerning primaquine efficacy without co-administration of blood schizontocide.

Methods

During March to July 2013, an open-label, randomized trial enrolled Indonesian soldiers with vivax malaria at Sragen, Central Java, after six months duty in malarious Papua, Indonesia. No malaria transmission occurred at the study site and P. vivax recurrences in the 12 months following therapy were classified as relapses. A historic relapse control derived from a cohort of soldiers who served in the same area of Papua was applied to estimate risk of relapse among randomized treatment groups. Those were: 1) AS followed 2d later by PQ (0.5 mg/kg daily for 14d); 2) co-formulated AS-PYR concurrent with the same regimen of PQ; or 3) co-formulated DHA-PP concurrent with the same regimen of PQ.

Results

Among 532 soldiers, 219 had vivax malaria during the four months following repatriation to Java; 180 of these were otherwise healthy and G6PD-normal and enrolled in the trial. Subjects in all treatment groups tolerated the therapies well without untoward events and cleared parasitemia within three days. First relapse appeared at day 39 post-enrollment, and the last at day 270. Therapeutic efficacy of PQ against relapse by incidence density analysis was 92 % (95 %CI?=?83–97 %), 94 %(95 %CI?=?86–97 %), and 95 %(95 %CI?=?88–98 %) when combined with AS, AS-PYR, or DHA-PP, respectively.

Conclusions

This trial offers evidence of good tolerability and efficacy of PQ against P. vivax relapse when administered concurrently with DHA-PP or AS-PYR. These offer alternative partner drugs for radical cure with primaquine. The AS arm demonstrated efficacy with a total dose of 7 mg/kg PQ without concurrently administered blood schizontocide, another option when primaquine therapy is removed in time from the treatment of the acute malaria or applied presumptively without an attack.

Trial registration

Current Controlled Trials ISRCTN82366390, assigned 20 March 2013.

     

Extracorporeal photochemotherapy in mycosis fungoides

Objectives

Extracorporeal photo-chemotherapy (ECP, photopheresis) is an approved treatment modality for mycosis fungoides (MF). Our aim is to present our ECP data for MF.

Negative Affect Differentiation and Adherence During Treatment for Thalassemia

Background

Although research has demonstrated the detrimental effects of excessive negative affect on treatment adherence and morbidity in chronic illness, rarely have researchers investigated the benefits of awareness of negative emotional experiences during treatment.

Purpose

In this investigation, we examined the association of negative affect differentiation (the ability to report negative emotional experiences as separate and distinct from each other,) to treatment adherence in adult patients with the congenital blood disorder thalassemia.

Method

Negative affect differentiation was assessed during a 12–16-week treatment-based diary and adherence was operationalized as attendance at routine screenings over 12 months. Participants were adult patients (n?=?32; age M?=?31.63, SD?=?7.72; 72 % female) with transfusion-dependent thalassemia in treatment in a large metropolitan hospital in the Northeastern USA.

Results

The results indicate that negative affect differentiation is significantly associated with greater adherence to treatment, even when controlling for disease burden and level of psychological distress.

Conclusion

Although preliminary, this investigation suggests that differentiated processing of negative emotional experiences during illness can lead to adaptive treatment-related behavior. As such, it may present a new avenue for research and intervention targeting the improvement of adherence during treatment for chronic illness.     

The effects of aerobic exercise training at two different intensities in obesity and type 2 diabetes: implications for oxidative stress, low-grade inflammation and nitric oxide production

Aims

To investigate the effect of 16 weeks of aerobic training performed at two different intensities on nitric oxide (tNOx) availability and iNOS/nNOS expression, oxidative stress (OS) and inflammation in obese humans with or without type 2 diabetes mellitus (T2DM).

Methods

Twenty-five sedentary, obese (BMI > 30 kg/m²) males (52.8 ± 7.2 years); 12 controls versus 13 T2DM were randomly allocated to four groups that exercised for 30 min, three times per week either at low (Fat-Max; 30–40 % VO_2max) or moderate (T _vent; 55–65 % VO_2max) intensity. Before and after training, blood and muscle samples (v. lateralis) were collected.

Results

Baseline erythrocyte glutathione was lower (21.8 ± 2.8 vs. 32.7 ± 4.4 nmol/ml) and plasma protein oxidative damage and IL-6 were higher in T2DM (141.7 ± 52.1 vs. 75.5 ± 41.6 nmol/ml). Plasma catalase increased in T2DM after T _vent training (from 0.98 ± 0.22 to 1.96 ± 0.3 nmol/min/ml). T2DM groups demonstrated evidence of oxidative damage in response to training (elevated protein carbonyls). Baseline serum tNOx were higher in controls than T2DM (18.68 ± 2.78 vs. 12.34 ± 3.56 μmol/l). Training at T _vent increased muscle nNOS and tNOx in the control group only. Pre-training muscle nNOS was higher in controls than in T2DMs, while the opposite was found for iNOS. No differences were found after training for plasma inflammatory markers.

Conclusion

Exercise training did not change body composition or aerobic fitness, but improved OS markers, especially when performed at T _vent. Non-diabetics responded to T _vent training by increasing muscle nNOS expression and tNOx levels in skeletal muscle while these parameters did not change in T2DM, perhaps due to higher insulin resistance (unchanged after intervention).