Efficiency of Original versus Generic Intravenous Iron Formulations in Patients on Haemodialysis

Aims

The appropriate use of intravenous (IV) iron is essential to minimise the requirements for erythropoiesis-stimulating agents (ESAs). The clinical efficacy of generic IV iron compared to the original formulation is controversial. We evaluated the changes that were induced after switching from a generic IV iron to an original formulation in a stable, prevalent haemodialysis (HD) population.

Methods

A total of 342 patients were included, and the follow-up period was 56 weeks for each formulation. Anaemia parameters and doses of ESA and IV iron were prospectively recorded before and after the switch from generic to original IV iron.

Results

To maintain the same haemoglobin (Hb) levels after switching from the generic to the original formulation, the requirements for IV iron doses were reduced by 34.3% (from 52.8±33.9 to 34.7±31.8mg/week, p<0.001), and the ESA doses were also decreased by 12.5% (from 30.6±23.6 to 27±21μg/week, p<0.001). The erythropoietin resistance index declined from 8.4±7.7 to 7.4±6.7 IU/kg/week/g/dl after the switch from the generic to the original drug (p = 0.001). After the switch, the transferrin saturation ratio (TSAT) and serum ferritin levels rose by 6.8%(p<0.001) and 12.4%(p = 0.001), respectively. The mortality rate was similar for both periods.

Conclusions

The iron and ESA requirements are lower with the original IV iron compared to the generic drug. In addition, the uses of the original formulation results in higher ferritin and TSAT levels despite the lower dose of IV iron. Further studies are necessary to analyse the adverse effects of higher IV iron dosages.     

Determinants of Adherence to Treatment in Hypertensive Patients of African Descent and the Role of Culturally Appropriate Education

Background

In Western countries, better knowledge about patient-related determinants of treatment adherence (medication and lifestyle) is needed to improve treatment adherence and outcomes among hypertensive ethnic minority patients of African descent.

Objective

To identify patient-related determinants of adherence to lifestyle and medication recommendations among hypertensive African Surinamese and Ghanaian patients with suboptimal treatment results (SBP≥140) living in the Netherlands and how culturally appropriate hypertension education (CAHE) influenced those determinants.

Methods

This study analysed data of 139 patients who participated in the CAHE trial. Univariate logistic regression analysis was used to measure the association between patient-related determinants (medication self-efficacy, beliefs about medication and hypertension, social support, and satisfaction with care) and treatment adherence. We also tested whether CAHE influenced the determinants.

Results

Medication self-efficacy and social support were associated with medication adherence at baseline. At six months, more medication self-efficacy and fewer concerns about medication use were associated with improved medication adherence. Self-efficacy was also associated with adherence to lifestyle recommendations at baseline. CAHE influenced patients’ illness perceptions by creating more understanding of hypertension, its chronic character, and more concerns about the associated risks.

Conclusion

In this high-risk population, health care providers can support medication adherence by paying attention to patients’ medication self-efficacy, the concerns they may have about medication use and patients’ perceptions on hypertension. The CAHE intervention improved patients’ perception on hypertension.     

Switching multiple sclerosis patients with breakthrough disease to second-line therapy

Background

Multiple sclerosis (MS) patients with breakthrough disease on immunomodulatory drugs are frequently offered to switch to natalizumab or immunosuppressants. The effect of natalizumab monotherapy in patients with breakthrough disease is unknown.

Methods

This is an open-label retrospective cohort study of 993 patients seen at least four times at the University of California San Francisco MS Center, 95 had breakthrough disease on first-line therapy (60 patients switched to natalizumab, 22 to immunosuppressants and 13 declined the switch [non-switchers]). We used Poisson regression adjusted for potential confounders to compare the relapse rate within and across groups before and after the switch.

Results

In the within-group analyses, the relapse rate decreased by 70% (95% CI 50,82%; p<0.001) in switchers to natalizumab and by 77% (95% CI 59,87%; p<0.001) in switchers to immunosuppressants; relapse rate in non-switchers did not decrease (6%, p = 0.87). Relative to the reduction among non-switchers, the relapse rate was reduced by 68% among natalizumab switchers (95% CI 19,87%; p = 0.017) and by 76% among the immunosuppressant switchers (95% CI 36,91%; p = 0.004).

Conclusions

Switching to natalizumab or immunosuppressants in patients with breakthrough disease is effective in reducing clinical activity of relapsing MS. The magnitude of the effect and the risk-benefit ratio should be evaluated in randomized clinical trials and prospective cohort studies.     

The Influence of Socioeconomic Status on Selection of Anticoagulation for Atrial Fibrillation

Importance

Without third-party insurance, access to marketed drugs is limited to those who can afford to pay. We examined this phenomenon in the context of anticoagulation for patients with nonvalvular atrial fibrillation (NVAF).

Objective

To determine whether, among older Ontarians receiving anticoagulation for NVAF, patients of higher socioeconomic status (SES) were more likely to switch from warfarin to dabigatran prior to its addition to the provincial formulary.

Design, Setting and Participants

Population-based retrospective cohort study of Ontarians aged 66 years and older, between 2008 and 2012.

Exposure

Socioeconomic status, as approximated by median neighborhood income.

Main Outcomes and Measure

We identified two groups of older adults with nonvalvular atrial fibrillation: those who appeared to switch from warfarin to dabigatran after its market approval but prior to its inclusion on the provincial formulary (“switchers”), and those with ongoing warfarin use during the same interval (“non-switchers”).

Results

We studied 34,797 patients, including 3183 “switchers” and 31,614 “non-switchers”. We found that higher SES was associated with switching to dabigatran prior to its coverage on the provincial formulary (p<0.0001). In multivariable analysis, subjects in the highest quintile were 50% more likely to switch to dabigatran than those in the lowest income quintile (11.3% vs. 7.3%; adjusted odds ratio 1.50; 95% CI 1.32 to 1.68). Following dabigatran’s addition to the formulary, the income gradient disappeared.

Conclusions and Relevance

We documented socioeconomic inequality in access to dabigatran among patients receiving warfarin for NVAF. This disparity was eliminated following the drug’s addition to the provincial formulary, highlighting the importance of timely reimbursement decisions.     

Food Preference and Appetite after Switching between Sweet and Savoury Odours in Women

Background

Exposure to food odours increases the appetite for congruent foods and decreases the appetite for incongruent foods. However, the effect of exposure to a variety of food odours, as often occurs in daily life, is unknown.

Objective

Investigate how switching between sweet and savoury odours affects the appetite for sweet and savoury products.

Design

Thirty women (age: 18-45y; BMI: 18.5-25kg/m²) intensely smelled the contents of cups filled with banana, meat or water (no-odour) in a within-subject design with four combinations: no-odour/banana, no-odour/meat, meat/banana and banana/meat. Participants received one combination per test day. In each combination, two cups with different fillings were smelled for five minutes after each other. Treatment order was balanced as much as possible. The effects of previous exposure and current odour on the appetite for (in)congruent sweet and savoury products, and odour pleasantness were analysed. A change from meat to banana odour or banana to meat odour was referred to as switch, whereas a change from no-odour to meat odour or no-odour to banana odour was no-switch.

Results

The current odour (P<0.001), as opposed to the previous exposure (P = 0.71), determined the appetite for (in)congruent sweet and savoury products, already one minute after a switch between sweet and savoury odours. The pleasantness of the odour decreased during odour exposure (P = 0.005).

Conclusions

After a switch, the appetite for specific products quickly adjusted to the new odour and followed the typical pattern as found during odour exposure in previous studies. Interestingly, the appetite for the smelled food remained elevated during odour exposure, known as sensory-specific appetite, whereas the pleasantness of the odour decreased over time, previously termed olfactory sensory-specific satiety. This seeming contradiction may result from different mechanisms underlying the odour-induced anticipation of food intake versus the decrease in hedonic value during prolonged sensory stimulation.     

Increased Risk of Depressive Disorder following Cholecystectomy for Gallstones

Background

Prior studies indicate a possible association between depression and cholecystectomy, but no study has compared the risk of post-operative depressive disorders (DD) after cholecystectomy. This retrospective follow-up study aimed to examine the relationship between cholecystectomy and the risk of DD in patients with gallstones in a population-based database.

Methods

Using ambulatory care data from the Longitudinal Health Insurance Database 2000, 6755 patients who received a first-time principal diagnosis of gallstones at the emergency room (ER) were identified. Among them, 1197 underwent cholecystectomy. Each patient was then individually followed-up for two years to identify those who were later diagnosed with DD. Cox proportional hazards regressions were performed to estimate the risk of developing DD between patients with gallstone who did and those who did not undergo cholecystectomy.

Results

Of 6755 patients with gallstones, 173 (2.56%) were diagnosed with DD during the two-year follow-up. Among patients who did and those who did not undergo cholecystectomy, 3.51% and 2.36% later developed depressive disorder, respectively. After adjusting for the patient’s sex, age and geographic location, the hazard ratio (HR) of DD within two years of gallstone diagnosis was 1.43 (95% CI, 1.02–2.04) for patients who underwent cholecystectomy compared to those who did not. Females, but not males, had a higher the adjusted HR of DD (1.61; 95% CI, 1.08–2.41) for patients who underwent cholecystectomy compared to those who did not.

Conclusions

There is an association between cholecystectomy and subsequent risk of DD among females, but not in males.     

Disparities between Ophthalmologists and Patients in Estimating Quality of Life Associated with Diabetic Retinopathy

Background

This study aimed to evaluate and compare the utility values associated with diabetic retinopathy (DR) in a sample of Chinese patients and ophthalmologists.

Methods

Utility values were evaluated by both the time trade-off (TTO) and rating scale (RS) methods for 109 eligible patients with DR and 2 experienced ophthalmologists. Patients were stratified by Snellen best-corrected visual acuity (BCVA) in the better-seeing eye. The correlations between the utility values and general vision-related health status measures were analyzed. These utility values were compared with data from two other studies.

Results

The mean utility values elicited from the patients themselves with the TTO (0.81; SD 0.10) and RS (0.81; SD 0.11) methods were both statistically lower than the mean utility values assessed by ophthalmologists. Significant predictors of patients’ TTO and RS utility values were both LogMAR BCVA in the affected eye and average weighted LogMAR BCVA. DR grade and duration of visual dysfunction were also variables that significantly predicted patients’ TTO utility values. For ophthalmologists, patients’ LogMAR BCVA in the affected eye and in the better eye were the variables that significantly predicted both the TTO and RS utility values. Patients’ education level was also a variable that significantly predicted RS utility values. Moreover, both diabetic macular edema and employment status were significant predictors of TTO and RS utility values, whether from patients or ophthalmologists. There was no difference in mean TTO utility values compared to our American and Canadian patients.

Conclusions

DR caused a substantial decrease in Chinese patients’ utility values, and ophthalmologists substantially underestimated its effect on patient quality of life.     

Borderline Personality and the Detection of Angry Faces

Background

Many studies have assessed emotion recognition in patients with Borderline Personality Disorder and considerable evidence has been accumulated on patients’ ability to categorize emotions. In contrast, their ability to detect emotions has been investigated sparsely. The only two studies that assessed emotion detection abilities found contradictory evidence on patients’ ability to detect angry faces.

Methods

To clarify whether patients with Borderline Personality Disorder show enhanced detection of angry faces, we conducted three experiments: a laboratory study (n = 53) with a clinical sample and two highly powered web studies that measured Borderline features (n₁ = 342, n₂ = 220). Participants in all studies completed a visual search paradigm, and the reaction times for the detection of angry vs. happy faces were measured.

Results

Consistently, data spoke against enhanced detection of angry faces in the Borderline groups, indicated by non-significant group (Borderline vs. healthy control) × target (angry vs. happy) interactions, despite highly satisfactory statistical power to detect even small effects.

Conclusions

In contrast to emotion categorization, emotion detection appears to be intact in patients with Borderline Personality Disorder and individuals high in Borderline features. The importance of distinguishing between these two processes in future studies is discussed.     

Factors Predicting Difficulty of Laparoscopic Low Anterior Resection for Rectal Cancer with Total Mesorectal Excision and Double Stapling Technique

Background

Laparoscopic sphincter-preserving low anterior resection for rectal cancer is a surgery demanding great skill. Immense efforts have been devoted to identifying factors that can predict operative difficulty, but the results are inconsistent.

Objective

Our study was conducted to screen patients’ factors to build models for predicting the operative difficulty using well controlled data.

Method

We retrospectively reviewed records of 199 consecutive patients who had rectal cancers 5–8 cm from the anal verge. All underwent laparoscopic sphincter-preserving low anterior resections with total mesorectal excision (TME) and double stapling technique (DST). Data of 155 patients from one surgeon were utilized to build models to predict standardized endpoints (operative time, blood loss) and postoperative morbidity. Data of 44 patients from other surgeons were used to test the predictability of the built models.

Results

Our results showed prior abdominal surgery, preoperative chemoradiotherapy, tumor distance to anal verge, interspinous distance, and BMI were predictors for the standardized operative times. Gender and tumor maximum diameter were related to the standardized blood loss. Temporary diversion and tumor diameter were predictors for postoperative morbidity. The model constructed for the operative time demonstrated excellent predictability for patients from different surgeons.

Conclusions

With a well-controlled patient population, we have built a predictable model to estimate operative difficulty. The standardized operative time will make it possible to significantly increase sample size and build more reliable models to predict operative difficulty for clinical use.     

Adolescent Pregnancy and Attained Height among Black South African Girls: Matched-Pair Prospective Study

Importance

The impact of adolescent pregnancy on offspring birth outcomes has been widely studied, but less is known about its impact on the growth of the young mother herself.

Objective

To determine the association between adolescent pregnancy and attained height.

Design

Prospective birth cohort study.

Setting

Cohort members followed from birth to age 20 y in Soweto, South Africa.

Participant

From among 840 Black females with sufficient data, we identified 54 matched pairs, in which a girl who became pregnant before the age of 17 years was matched with a girl who did not have a pregnancy by age 20 y. Pairs were matched on age at menarche and height-for-age z scores in the year before the case became pregnant (mean 15.0 y).

Main Outcome Measures

The two groups were compared with respect to attained height, measured at mean age 18.5 y.

Results

Mean age at conception was 15.9 years (range: 13.7 to 16.9 y). Mean height at matching was 159.4 cm in the adolescent pregnancy group and 159.3 cm in the comparison group (p = 0.3). Mean attained height was 160.4 cm in the adolescent pregnancy group and 160.3 cm in the comparison group (p = 0.7).

Conclusions

Among Black females in Soweto, South Africa, adolescent pregnancy was not associated with attained height.     

Is Patent “Evergreening” Restricting Access to Medicine/Device Combination Products?

Background

Not all new drug products are truly new. Some are the result of marginal innovation and incremental patenting of existing products, but in such a way that confers no major therapeutic improvement. This phenomenon, pejoratively known as “evergreening”, can allow manufacturers to preserve market exclusivity, but without significantly bettering the standard of care. Other studies speculate that evergreening is especially problematic for medicine/device combination products, because patents on the device component may outlast expired patents on the medicine component, and thereby keep competing, possibly less-expensive generic products off the market.

Materials and Methods

We focused on four common conditions that are often treated by medicine/device product combinations: asthma and chronic obstructive pulmonary disease (COPD), diabetes, and severe allergic reactions. The patent data for a sample of such products (n = 49) for treating these conditions was extracted from the United States Food and Drug Administration’s Orange Book. Additional patent-related data (abstracts, claims, etc) were retrieved using LexisNexis TotalPatent. Comparisons were then made between each product’s device patents and medicine patents.

Results

Unexpired device patents exist for 90 percent of the 49 medicine/device product combinations studied, and were the only sort of unexpired patent for 14 products. Overall, 55 percent of the 235 patents found by our study were device patents. Comparing the last-to-expire device patent to that of the last-to-expire active ingredient patent, the median additional years of patent protection afforded by device patents was 4.7 years (range: 1.3–15.2 years).

Conclusion

Incremental, patentable innovation in devices to extend the overall patent protection of medicine/device product combinations is very common. Whether this constitutes “evergreening” depends on whether these incremental innovations and the years of extra patent protection they confer are proportionately matched by therapeutic improvements in the standard of care, which is highly debatable.     

Essential Medicines in a High Income Country: Essential to Whom?

Objective

To explore the perspectives of a diverse group of stakeholders engaged in medicines decision making around what constitutes an “essential” medicine, and how the Essential Medicines List (EML) concept functions in a high income country context.

Methods

In-depth qualitative semi-structured interviews were conducted with 32 Australian stakeholders, recognised as decision makers, leaders or advisors in the area of medicines reimbursement or supply chain management. Participants were recruited from government, pharmaceutical industry, pharmaceutical wholesale/distribution companies, medicines non-profit organisations, academic health disciplines, hospitals, and consumer groups. Perspectives on the definition and application of the EML concept in a high income country context were thematically analysed using grounded theory approach.

Findings

Stakeholders found it challenging to describe the EML concept in the Australian context because many perceived it was generally used in resource scarce settings. Stakeholders were unable to distinguish whether nationally reimbursed medicines were essential medicines in Australia. Despite frequent generic drug shortages and high prices paid by consumers, many struggled to describe how the EML concept applied to Australia. Instead, broad inclusion of consumer needs, such as rare and high cost medicines, and consumer involvement in the decision making process, has led to expansive lists of nationally subsidised medicines. Therefore, improved communication and coordination is needed around shared interests between stakeholders regarding how medicines are prioritised and guaranteed in the supply chain.

Conclusions

This study showed that decision-making in Australia around reimbursement of medicines has strayed from the fundamental utilitarian concept of essential medicines. Many stakeholders involved in medicine reimbursement decisions and management of the supply chain did not consider the EML concept in their approach. The wide range of views of what stakeholders considered were essential medicines, challenges whether the EML concept is out-dated or underutilised in high income countries.     

Plasma Matrix Metalloproteinase-9 Levels Predict First-Time Coronary Heart Disease: An 8-Year Follow-Up of a Community-Based Middle Aged Population

Background

The enzyme in matrix metalloproteinase (MMP)-9 has been suggested to be an important determinant of plaque degradation. While several studies have shown elevated levels in patients with coronary heart disease, results in prospective population based studies evaluating MMP-9 in relation to first time coronary events have been inconclusive. As of today, there are four published studies which have measured MMP-9 in serum and none using plasma. Measures of MMP-9 in serum have been suggested to have more flaws than measures in plasma.

Aim

To investigate the independent association between plasma levels of MMP-9 and first-time incidence of coronary events in an 8-year follow-up.

Material and Methods

428 men and 438 women, aged 45–69 years, free of previous coronary events and stroke at baseline, were followed-up. Adjustments were made for sex, age, socioeconomic position, behavioral and cardiovascular risk factors, chronic disease at baseline, depressive symptoms, interleukin-6 and C-reactive protein.

Results

53 events were identified during a risk-time of 6 607 person years. Hazard ratio (HR) for MMP-9 after adjustment for all covariates were HR = 1.44 (1.03 to 2.02, p = 0.033). Overall, the effect of adjustments for other cardiovascular risk factors was low.

Conclusion

Levels of plasma MMP-9 are independently associated with risk of first-time CHD events, regardless of adjustments. These results are in contrast to previous prospective population-based studies based on MMP-9 in serum. It is essential that more studies look at MMP-9 levels in plasma to further evaluate the association with first coronary events.     

Primary Care Physicians’ Attitudes and Beliefs towards Chronic Low Back Pain: An Asian Study

Background

Chronic low back pain is a serious global health problem. There is substantial evidence that physicians’ attitudes towards and beliefs about chronic low back pain can influence their subsequent management of the condition.

Objectives

(1) to evaluate the attitudes and beliefs towards chronic low back pain among primary care physicians in Asia; (2) to study the cultural differences and other factors that are associated with these attitudes and beliefs.

Method

A cross sectional online survey was sent to primary care physicians who are members of the Hong Kong College of Family Physician (HKCFP). The Pain Attitudes and Beliefs Scale for Physiotherapist (PABS-PT) was used as the questionnaire to determine the biomedical and biopsychosocial orientation of the participants.

Results

The mean Biomedical (BM) score was 34.8+/-6.1; the mean biopsychosocial (BPS) score was 35.6 (+/- 4.8). Both scores were higher than those of European doctors. Family medicine specialists had a lower biomedical score than General practitioners. Physicians working in the public sector tended to have low BM and low BPS scores; whereas physicians working in private practice tended to have high BM and high BPS scores.

Conclusion

The lack of concordance in the pain explanatory models used by private and public sector may have a detrimental effect on patients who are under the care of both parties. The uncertain treatment orientation may have a negative influence on patients’ attitudes and beliefs, thus contributing to the tension and, perhaps, even ailing mental state of a person with chronic LBP.     

Pattern of Drug Resistance and Risk Factors Associated with Development of Drug Resistant Mycobacterium tuberculosis in Pakistan

Background

Drug resistant tuberculosis (DR-TB) is a major public health problem in developing countries such as Pakistan.

Objective

The current study was conducted to assess the frequency of drug resistant tuberculosis including multi drug resistance (MDR- TB) as well as risk factors for development of DR-TB, in Punjab, Pakistan.

Methodology

Drug susceptibility testing (DST) was performed, using proportion method, for 2367 culture positive Mycobacterium tuberculosis (MTB) cases that were enrolled from January 2012 to December 2013 in the province of Punjab, Pakistan, against first-line anti-tuberculosis drugs. The data was analyzed using statistical software; SPSS version 18.

Results

Out of 2367 isolates, 273 (11.5%) were resistant to at least one anti-TB drug, while 221 (9.3%) showed MDR- TB. Risk factors for development of MDR-TB were early age (ranges between 10–25 years) and previously treated TB patients.

Conclusion

DR-TB is a considerable problem in Pakistan. Major risk factors are previous history of TB treatment and younger age group. It emphasizes the need for effective TB control Program in the country.     

Intranasal Volume Changes Caused by the Endoscopic Endonasal Transsphenoidal Approach and Their Effects on Nasal Functions

Objective

We evaluated postoperative changes in nasal cavity volume and their effects on nasal function and symptoms after endoscopic endonasal transsphenoidal approach for antero-central skull base surgery.

Study Design

Retrospective chart review at a tertiary referral center.

Methods

We studied 92 patients who underwent binostril, four-hand, endoscopic endonasal transsphenoidal approach surgery using the bilateral modified nasoseptal rescue flap technique. Pre- and postoperative paranasal computed tomography and the Mimics^® program were used to assess nasal cavity volume changes at three sections. We also performed several pre- and postoperative tests, including the Connecticut Chemosensory Clinical Research Center test, Cross-Cultural Smell Identification Test, Nasal Obstruction Symptoms Evaluation, and Sino-Nasal Outcome Test-20. In addition, a visual analog scale was used to record subjective symptoms. We compared these data with the pre- and postoperative nasal cavity volumes.

Results

Three-dimensional, objective increases in nasal passage volumes were evident between the inferior and middle turbinates (p<0.001) and between the superior turbinate and choana (p = 0.006) postoperatively. However, these did not correlate with subjectively assessed symptoms (NOSE, SNOT-20 and VAS; all nasal cavity areas; p≥0.05) or olfactory dysfunction (CCCRC and CCSIT test; all nasal cavity areas; p≥0.05).

Conclusion

Skull base tumor surgery via an endoscopic endonasal transsphenoidal approach altered the patients’ nasal anatomy, but the changes in nasal cavity volumes did not affect nasal function or symptoms. These results will help surgeons to appropriately expose the surgical field during an endoscopic endonasal transsphenoidal approach.