Patent foramen ovale and cryptogenic stroke: contemporary evidence and treatment

Introduction: Patent foramen ovale (PFO) is a common anatomical variant in the adult circulation. It is a channel allowing communication between the left and right atria and is a remnant of the foetal circulation. In approximately 25% of the population, this channel persists into adulthood. PFO has been proposed as a potential pathophysiological mechanism for cryptogenic stroke.

Areas covered: This review will examine the contemporary evidence for both the association between cryptogenic stroke and PFO and the management of this condition. The authors hope to provide a comprehensive overview of the current evidence and best practice in relation to PFO closure. In addition, the authors will propose some potential avenues for future research in this controversial area and try to predict how PFOs in cryptogenic stroke will be managed in the near future.

Expert commentary: In carefully selected patients with cryptogenic stroke, PFO closure represents an evidence based treatment option for the prevention of further ischemic neurological events. A multidisciplinary approach is necessary to ensure appropriate patient selection for the procedure. This should include a vascular neurologist/stroke physician and an interventional cardiologist with an interest in PFO closure.     

Closing the gap on patent foramen ovale and cryptogenic stroke

Introduction: The treatment options for prevention of recurrent of cryptogenic stroke in patients with patent foramen ovale (PFO) have been intensely debated in the recent decades. The suggested options were percutaneous closure of PFO versus medical therapy. However, up to these date there is a controversy regarding the indication of percutaneous closure. Multiple meta-analysis and recent randomized control trials showed the benefit of PFO closure when compared with medical therapy alone.

Areas covered: The article reviews the prevalence, physiology, diagnosis and treatment options of PFO after cryptogenic stroke. Furthermore, it will discuss the results of randomized control trials that compared the PFO closure to medical therapy.

Expert opinion: The association between PFO and unexplained cryptogenic stroke has been well established in the multiple studies. The diagnosis and management of PFO might be challenging in some cases. Although multiple studies showed that PFO closure is associated with lower rates of recurrent stroke in patients presenting with cryptogenic stroke, the indication and patient selection for this intervention are not well established yet in the guidelines.     

Premature atrial complexes in an ischemic stroke population and risk of recurrent stroke: a systematic review

Introduction: Premature atrial complexes (PACs) have been proposed as a possible mediator between normal sinus rhythm and atrial fibrillation (AF). The aim of this study was to summarize the available knowledge of association between PACs and recurrent stroke or transient ischemic attack (TIA) in ischemic stroke patients.

Areas covered: In this systematic review, we investigated the risk of recurrent events in patients who experienced ischemic stroke or TIA. Occurrence of PACs in electrocardiographic monitoring after index stroke/TIA was required. We identified and included three observational cohort studies, investigating in total 1005 patients. The studies reported that a significant burden of PACs occurred in a high proportion of stroke and TIA patients. More PACs were independently associated with an increased risk of recurrent stroke or TIA or the composite of recurrent stroke/TIA or death. Definition of PACs cut-off as well as patient characteristics differed between groups.

Expert Commentary: This review supports an association between higher burden of PACs and recurrent stroke, and stresses the need for studies on PACs in stroke patients. A special awareness of stroke patients with a high PACs load is recommendable particularly for assessing the intensity and duration toward AF progression, and possible future treatment recommendations.     

The relationship between insurance claim closure and recovery after traffic injuries for individuals with whiplash associated disorders

Purpose: The purpose of this study was to determine if time to claim closure was similar to time to self-reported recovery in a no fault motor vehicle collision insurance system.

Method: A prospective cohort of traffic injured adults with a whiplash-associated disorder (WAD) was assembled. We excluded participants who applied for benefits after 42 days of the collision, who were in hospital for more than two days and participants who were not followed up at least once after their injury. Questionnaires were completed at baseline, six weeks, three-, six-, nine- and 12-months after the collision.

Results: The mean age of the cohort was 39 years and 66% were female. The mean number of days until claim closure and for self-reported recovery was 291days and 134 days, respectively. We found those who had their claim closed at each follow-up period had lower levels of disability and were more likely to report they were recovered than participants with open claims.

Conclusion: We conclude that time to claim closure could be used as an outcome measure in traffic collision; however, this measure should be used with caution since it over-estimates the true time to recovery.

• Implications for Rehabilitation

• Time to claim closure as an outcome measure for whiplash-associated disorders has been criticized in the literature because it is thought that closure is not reflective of the health status of the individual.

• We found that claim closure was associated with lower levels of disability, but the time to claim closure was significantly longer than the time to self-reported recovery.

• Time to claim closure may be used with caution as a “proxy” measure of recovery from an injury; however, it must be noted that it over-estimates the true time of recovery

     

Development and validation of a prediction model for long-term sickness absence based on occupational health survey variables

Purpose: The purpose of this study is to develop and validate a prediction model for identifying employees at increased risk of long-term sickness absence (LTSA), by using variables commonly measured in occupational health surveys.

Materials and methods: Based on the literature, 15 predictor variables were retrieved from the DAnish National working Environment Survey (DANES) and included in a model predicting incident LTSA (≥4 consecutive weeks) during 1-year follow-up in a sample of 4000 DANES participants. The 15-predictor model was reduced by backward stepwise statistical techniques and then validated in a sample of 2524 DANES participants, not included in the development sample. Identification of employees at increased LTSA risk was investigated by receiver operating characteristic (ROC) analysis; the area-under-the-ROC-curve (AUC) reflected discrimination between employees with and without LTSA during follow-up.

Results: The 15-predictor model was reduced to a 9-predictor model including age, gender, education, self-rated health, mental health, prior LTSA, work ability, emotional job demands, and recognition by the management. Discrimination by the 9-predictor model was significant (AUC = 0.68; 95% CI 0.61–0.76), but not practically useful.

Conclusions: A prediction model based on occupational health survey variables identified employees with an increased LTSA risk, but should be further developed into a practically useful tool to predict the risk of LTSA in the general working population.

• Implications for rehabilitation

• Long-term sickness absence risk predictions would enable healthcare providers to refer high-risk employees to rehabilitation programs aimed at preventing or reducing work disability.

• A prediction model based on health survey variables discriminates between employees at high and low risk of long-term sickness absence, but discrimination was not practically useful.

• Health survey variables provide insufficient information to determine long-term sickness absence risk profiles.

• There is a need for new variables, based on the knowledge and experience of rehabilitation professionals, to improve long-term sickness absence risk profiles.

     

“Whenever I can I push myself to go to work”: a qualitative study of experiences of sickness presenteeism among workers with rheumatoid arthritis

Purpose: UK government policy emphasizes the importance of continuing to work for recovery from poor health, yet sickness presenteeism (going to work whilst ill) is commonly regarded as having negative consequences for organizations and individuals. Our study explores experiences of working after onset of rheumatoid arthritis (RA), a chronic musculoskeletal disorder characterized by high rates of work disability.

Materials and methods: An exploratory qualitative study consisting of in-depth interviews and six-month follow-up with 11 men and women with RA employed at disease onset.

Results: We expand upon previous models of sickness presenteeism by distinguishing between presenteeism that occurs voluntarily (wanting to work despite illness) and involuntarily (feeling pressured to work when ill). RA onset affected participants’ ability to work, yet motivation to remain working remained high. The implementation of workplace adjustments enabled participants to stay working and restore their work capacity. Conversely, managers’ misinterpretation of organizational sickness absence policies could lead to involuntary presenteeism or delayed return to work, conflicting with the notion of work as an aid to recovery.

Conclusion: Workplace adjustments can facilitate voluntary sickness presenteeism. To reduce work disability and sickness absence, organizational policies should be sufficiently flexible to accommodate the needs of workers with fluctuating conditions.

• Implications for rehabilitation

• Individuals with rheumatoid arthritis (RA) are at high risk of work disability.

• Individuals’ motivation to remain in work following onset of RA remains high, yet sickness presenteeism (working while ill) has received largely negative attention.

• It is important to distinguish between voluntary and involuntary forms of sickness presenteeism.

• Workplace adjustments facilitate voluntary sickness presenteeism (wanting to work despite illness) and improve job retention and productivity among workers with RA.

• Involuntary presenteeism (feeling pressured to work while ill) may occur if organizational policies are not sufficiently flexible to accommodate the needs of workers with RA.

     

Repetition of intentional drug overdose: a population-based study

Context: Intentional overdose is a leading method of self-harm and suicide, and repeat attempts strongly predict eventual death by suicide.

Objectives: To determine the risk of recurrence after a first intentional overdose. Secondary objectives included characterization of the temporal course and potential predictors of repeat overdose, a strong risk factor for death from suicide.

Methods: Design: Population-based cohort study.

Setting: Ontario, Canada, from 1 April 2002 to 31 March 2013.

Participants: All Ontario residents presenting to an emergency department after a first intentional overdose.

Main outcome measures: The incidence and timing of recurrent overdose.

Results: We followed 81,675 patients discharged from hospital after a first intentional overdose. Overall, 13,903 (17.0%) returned with a repeat overdose after a median interval of 288 (inter-quartile range: 62 to 834) days. Of these, 4493 (5.5%) had multiple repeat episodes. Factors associated with repeat self-poisoning included psychiatric care in the preceding year (adjusted hazard ratio [aHR] 1.55; 95% confidence interval [CI] 1.50 to 1.61), alcohol dependence (aHR 1.41; 95% CI 1.35 to 1.46) and documented depression (aHR 1.39; 95% CI 1.34 to 1.44). Female sex, rural residence, lower socioeconomic status, ingestion of psychoactive drugs and younger age were also weakly associated with repeat overdose.

Discussion: Hospital presentation for repetition of intentional overdose is common, with recurrent episodes often far removed from the first. While several factors predict overdose repetition, none is particularly strong.

Conclusion: Secondary prevention initiatives should be implemented for all individuals who present to the emergency department and survive intentional overdose.     

Factors associated with self-rated health in primary care

Background: Self-rated health (SRH) measures one’s current general health and is a widely used health indicator. Sleep problems, somatic health complaints, and unmet needs in interpersonal relationships are suspected to influence SRH, but studies in primary health care settings are sparse.

Objective: To examine the associations between patients’ self-rated health and their sleep problems, somatic health complaints, and unmet needs in interpersonal relationships.

Design: We collected data via questionnaires for this cross-sectional study from general practice.

Setting: Primary health care in Norway.

Subjects: 1302 consecutive patients participated.

Main outcome measures: The questionnaire included a single question about SRH, the Bergen Insomnia Scale (BIS), five questions on somatic health complaints, and three questions from the Basic Psychological Needs Scale (BPNS) pertaining to the relationships domain. We analyzed our data using ordinal logistic regression models.

Results: Our response rate was 74%. The prevalence of fair/poor SRH was 26%, with no gender differences. We revealed a significant association between increasing age and reduced SRH. The study showed that sleep problems and somatic health complaints were strongly associated with SRH, and unmet needs in relationships were also significantly and independently associated with reduced SRH in a full model analysis.

Conclusion: Sleep problems, somatic health complaints, and unmet needs in interpersonal relationships were all associated with reduced SRH. These factors are all modifiable and could be managed both within and outside a primary care setting in order to improve SRH.

• Key Points

• There was a high prevalence of reduced SRH in clinical general practice

• Sleep problems, somatic health complaints, and unmet needs in interpersonal relationships were all associated with reduced SRH

• These predictors are all modifiable with a potential to improve SRH

     

A double-blind placebo-controlled clinical investigation into pain reduction effect of placing the pain spot outside the intersection area of the two currents of interferential therapy compared to traditional method

Background: Interferential therapy (IFT) is applied to intersect in the painful area but no confirmed effect with this method. Experimentally, the highest voltage of IFT is induced outside the intersection of the two currents. Placing the painful area outside the intersection point (external application) would reveal a better effect.

Objectives: To examine the effect of external application in pain compared to traditional method.

Design: A double-blind placebo-controlled clinical investigation.

Setting: A public hospital.

Participants: 168 LBP subjects.

Interventions: Assignment: (1) external IFT, (2) placebo external IFT, (3) traditional IFT and (4) placebo traditional IFT. Groups 1 and 3 received 20 min of IFT at 100 Hz and groups 2 and 4 received sham IFT.

Main outcome measures: Before and after IFT session, pain severity (VAS), pressure threshold (PPT), pain distribution and ROM were assessed.

Results: IFT changed all outcomes similarly. VAS and ROM improved statistically, P < 0.03. A trend of better VAS reduced with active IFTs.

Conclusions: No therapeutic difference between the two methods.     

Social disparities in diabetes care: a general population study in Denmark

Objective: We investigated the association between socioeconomic factors and the attainment of treatment goals and pharmacotherapy in patients with type 2 diabetes in Denmark.

Design: A cross-sectional population study.

Setting: The municipality of Naestved, Denmark.

Subjects: We studied 907 patients with type 2 diabetes identified from a random sample of 21,205 Danish citizens.

Main outcome measures: The proportion of patients who were not achieving goals for diabetes care based on their HbA_1c, LDL-cholesterol, blood pressure, and lifestyle, and the proportion of patients who were treated with antihypertensive and cholesterol- and glucose-lowering medication.

Methods: We investigated the association of the socioeconomic factors such as age, gender, education, occupation, income, and civil status and attainment of treatment goals and pharmacotherapy in logistic regression analyses. We investigated effect modification of cardiovascular disease and kidney disease.

Results: Middle age (40–65 years), low education level (i.e. basic schooling), and low household income (i.e. less than 21,400 € per year) were associated with nonattainment of goals for diabetes care. The association of socioeconomic factors with attainment of individual treatment goals varied. Patients with low socioeconomic status were more often obese, physically inactive, smoking, and had elevated blood pressure. Socioeconomic factors were not associated with treatment goals for hyperglycemia. Socioeconomic factors were inconsistently associated with pharmacotherapy. There was no difference in contacts to general practitioners according to SES.

Conclusions: In a country with free access to health care, the socioeconomic factors such as middle age, low education, and low income were associated with nonattainment of goals for diabetes care.

• KEY POINTS

• Middle age, low education, and low income were associated with nonattainment of goals for diabetes care, especially for lifestyle goals.

• Patients with low socioeconomic status were more often obese, physically inactive, smoking, and had elevated blood pressure.

• Association of socioeconomic factors with pharmacotherapy was inconsistent.

     

Reprogramming T-cells for adoptive immunotherapy of ovarian cancer

Introduction: Epithelial ovarian cancer (EOC) is the most common cause of death among gynecological malignancies. Despite surgical and pharmacological efforts to improve patients’ outcome, persistent and recurrent EOC remains an un-eradicable disease.

Chimeric associated antigens (CAR) T cells are T lymphocytes expressing an engineered T cell receptor that activate the immune response after an MHC unrestricted recognition of specific antigens, including tumor associated antigens (TAAs).

CART cells have been shown to be effective in the treatment of hematologic tumors even if frequently associated with potentially severe toxicity and high production costs.

Areas covered: In this review, we will focus on preclinical and clinical studies evaluating CART activity in EOC in order to identify possible difficulties and advantages of their use in this particular setting.

Expert Opinion: The pattern of diffusion within the peritoneal cavity, the tumor microenvironment and the high rate of TAAs make EOC a particularly interesting model for CART cells use. Data from preclinical studies indicate a potential activity of CARTs in EOC, but robust clinical data are still awaited. Further studies are needed to determine the best methods of administration and the most effective CAR type to treat EOC patients.     

Resolution of cannabis hyperemesis syndrome with topical capsaicin in the emergency department: a case series

Background: Cannabinoid hyperemesis syndrome (CHS) is characterized by symptoms of cyclic abdominal pain, nausea, and vomiting in the setting of prolonged cannabis use. The transient receptor potential vanilloid 1 (TRPV1) receptor may be involved in this syndrome. Topical capsaicin is a proposed treatment for CHS; it binds TRPV1 with high specificity, impairing substance P signaling in the area postrema and nucleus tractus solitarius via overstimulation of TRPV1. This may explain its apparent antiemetic effect in this syndrome.

Purpose: We describe a series of thirteen cases of suspected cannabis hyperemesis syndrome treated with capsaicin in the emergency departments of two academic medical centers.

Methods: A query of the electronic health record at both centers identified thirteen patients with documented daily cannabis use and symptoms consistent with CHS who were administered topical capsaicin cream for symptom management.

Results: All 13 patients experienced symptom relief after administration of capsaicin cream.

Conclusion: Topical capsaicin was associated with improvement in symptoms of CHS after other treatments failed.     

Safety profile of snake antivenom (use) in Hong Kong – a review of 191 cases from 2008 to 2015

Introduction: The mainstay of treatment for significant envenoming from snakebites is antivenom. However, there is insufficient data regarding the safety of antivenom used in Hong Kong. We describe the incidence of hypersensitivity reactions from antivenom use and review the frequency and reasons for intensive care unit (ICU) admission.

Methods: The Hong Kong Poisons Information Centre database was reviewed. All patients given snake antivenom between 2008 and 2015 were included. Patient demographics, species of snake involved, details of antivenom used, treatment location, use of pre-treatment, reasons for ICU admission (where applicable) and details of early and late antivenom reactions were extracted.

Results: There were 191 patients who received snake antivenom. Most (93%) were treated with either the green pit viper antivenom from Thailand or the Agkistrodon halys antivenom from China. The incidences of early hypersensitivity reactions to green pit viper antivenom and Agkistrodon Halys antivenom were 4.7% and 1.4%, respectively. Most patients (69%) were managed in the ED observation ward or general ward. There were 59 patients managed in ICU, most (90%) of whom were admitted for close monitoring during antivenom administration. There were no cases of significant morbidity from antivenom administration. Eight patients (5.6%) had features suggestive of mild serum sickness.

Conclusions: The incidence of immediate hypersensitivity reaction to antivenom commonly used in Hong Kong is low. Majority of patients were managed safely in the emergency department observation ward or general ward. Serum sickness appears to be uncommon and possible cases presented with mild features.     

The effect on the patient flow in a local health care after implementing reverse triage in a primary care emergency department: a longitudinal follow-up study

Objective: Reverse triage means that patients who are not considered to be in need of medical services are not placed on the doctor’s list in an emergency department (ED) but are sent, after face-to-face evaluation by a triage nurse, to a more appropriate health care unit. It is not known how an abrupt application of such reverse triage in a combined primary care ED alters the demand for doctors’ services in collaborative parts of the health care system.

Design: An observational study.

Setting: Register-based retrospective quasi-experimental longitudinal follow-up study based on a before–after setting in a Finnish city.

Subjects: Patients who consulted different doctors in a local health care unit.

Main outcome measures: Numbers of monthly visits to different doctor groups in public and private primary care, and numbers of monthly referrals to secondary care ED from different sources of primary care were recorded before and after abrupt implementation of the reverse triage.

Results: The beginning of reverse triage decreased the number of patient visits to a primary ED doctor without increasing mortality. Simultaneously, there was an increase in doctor visits in the adjacent secondary care ED and local private sector. The number of patients who came to secondary care ED without a referral or with a referral from the private sector increased.

Conclusions: The data suggested that the reverse triage causes redistribution of the use of doctors’ services rather than a true decrease in the use of these services.     

Pay for performance associated with increased volume of medication reviews but not with less inappropriate use of medications among the elderly – an observational study

Objective: A pay for performance programme was introduced in 2009 by a Swedish county with 1.6 million inhabitants. A process measure with payment linked to coding for medication reviews among the elderly was adopted. We assessed the association with inappropriate medication for five years after baseline.

Design and setting: Observational study that compared medication for elderly patients enrolled at primary care units that coded for a high or low volume of medication reviews.

Patients: 144,222 individuals at 196 primary care centres, age 75 or older.

Main outcome measures: Percentage of patients receiving inappropriate drugs or polypharmacy during five years at primary care units with various levels of reported medication reviews.

Results: The proportion of patients with a registered medication review had increased from 3.2% to 44.1% after five years. The high-coding units performed better for most indicators but had already done so at baseline. Primary care units with the lowest payment for coding for medication reviews improved just as well in terms of inappropriate drugs as units with the highest payment – from 13.0 to 8.5%, compared to 11.6 to 7.4% and from 13.6 to 7.2% vs 11.8 to 6.5% for polypharmacy.

Conclusions: Payment linked to coding for medication reviews was associated with an increase in the percentage of patients for whom a medication review had been registered. However, the impact of payment on quality improvement is uncertain, given that units with the lowest payment for medication reviews improved equally well as units with the highest payment.     

Pain pattern classification and directional preference for patients with neck pain

Objectives:

Pain Pattern Classification (PPC) and Directional Preference (DP) have been shown to be predictive of health care outcomes and serve to guide orthopedic clinical decision making. We conducted a prospective, observational cohort study to verify the association between PPC, DP, and clinical outcomes.

Methods:

Clinical outcome measures including pain intensity and disability were completed at first examination and follow-up by 335 patients. A Pearson’s chi-squared test was used to determine differences in prevalence rates for the categorical variables, and two-sample t-tests were used to determine differences in rates for the continuous variables. A Tukey’s range test was used to determine differences in follow-up pain intensity and disability for neck pain dual-classification schemes.

Results:

The prevalence of DP was 82.4%. The prevalence of CEN, Non-CEN, and Non-Classifiable (NC) was 15.2%, 42.1%, and 25.1%, respectively. The prevalence of DP was lowest for patients with sub-acute symptoms and who were <45 years old. Patients classified as DP CEN had, on average 2.62 NDI units less than patients classified as Non-DP. Patients classified as DP CEN had, on average, 0.90 pain intensity units less than patients classified as Non-DP at follow-up. Patients who demonstrated DP CEN did not have clinically significant lower pain intensity or disability at follow-up than patients who demonstrated Non-DP.

Discussion:

The results of this investigation need to be interpreted with caution with respect to the study design and it’s subsequent strengths and limitations.

Level of Evidence:

1b.     

Quality indicators for the diagnosis and antibiotic treatment of acute respiratory tract infections in general practice: a RAND Appropriateness Method

Objective: To develop quality indicators for the diagnosis and antibiotic treatment of acute respiratory tract infections, tailored to the Danish general practice setting.

Design: A RAND/UCLA Appropriateness Method was used.

Setting: General practice.

Subjects: A panel of nine experts, mainly general practitioners, was asked to rate the relevance of 64 quality indicators for the diagnosis and antibiotic treatment of acute respiratory tract infections based on guidelines. Subsequently, a face-to-face meeting was held to resolve misinterpretations and to achieve consensus.

Main outcome measures: The experts were asked to rate the indicators on a nine-point Likert scale. Consensus of appropriateness for a quality indicator was reached if the overall panel median rating was 7–9 with agreement.

Results: A total of 50 of the 64 proposed quality indicators attained consensus. Consensus was achieved for 12 indicators focusing on the diagnostic process and 19 indicators focusing on the decision about antibiotic treatment and choice of antibiotics, respectively.

Conclusion: These newly developed quality indicators may be used to strengthen Danish general practitioners’ focus on their management of patients with acute respiratory tract infections and to identify where there is a need for future quality improvements.     

Patient trajectories in a Norwegian unit of municipal emergency beds

Objective: The Coordination reform was implemented in Norway from 2012, aiming at seamless patient trajectories. All municipalities are required to establish emergency care beds (MEBs) to avoid unnecessary hospital admissions. We aimed to examine occupancy rate, patient characteristics, diagnoses and discharge level of municipal care in a small MEB unit.

Design: Cross-sectional, observational study.

Setting: A two-bed emergency care unit.

Subjects: All patients admitted to the unit during one year.

Main outcome measures: Patients’ age and gender, comorbidity, main diagnoses and municipal care level on admission and discharge, diagnostic and therapeutic initiatives, occupancy rate.

Results: Sixty admissions were registered, with total bed occupancy 194 days, and an occupancy rate of 0.27. The patients (median age 83 years, 57% women) had mostly infections, musculoskeletal symptoms or undefined conditions. Some 48% of the stays exceeded three days and 43% of the patients were subsequently transferred to nursing homes or hospitals.

Conclusion: Occupancy rate was low. Patient selection was not according to national standards, and stays were longer. Many patients were transferred to nursing homes, indicating that the unit was an intermediate pathway or a short cut to institutional care. It is unclear whether the unit avoided hospital admissions.