Somatic Cough Syndrome (Previously Referred to as Psychogenic Cough) and Tic Cough (Previously Referred to as Habit Cough) in Adults and Children: CHEST Guideline and Expert Panel Report

BACKGROUND: We conducted a systematic review on the management of psychogenic cough, habit cough, and tic cough to update the recommendations and suggestions of the 2006 guideline on this topic.

METHODS: We followed the American College of Chest Physicians (CHEST) methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework. The Expert Cough Panel based their recommendations on data from the systematic review, patients' values and preferences, and the clinical context. Final grading was reached by consensus according to Delphi methodology.

RESULTS: The results of the systematic review revealed only low-quality evidence to support how to define or diagnose psychogenic or habit cough with no validated diagnostic criteria. With respect to treatment, low-quality evidence allowed the committee to only suggest therapy for children believed to have psychogenic cough. Such therapy might consist of nonpharmacologic trials of hypnosis or suggestion therapy, or combinations of reassurance, counseling, and referral to a psychologist, psychotherapy, and appropriate psychotropic medications. Based on multiple resources and contemporary psychologic, psychiatric, and neurologic criteria (Diagnostic and Statistical Manual of Mental Disorders, 5th edition and tic disorder guidelines), the committee suggests that the terms psychogenic and habit cough are out of date and inaccurate.

CONCLUSIONS: Compared with the 2006 CHEST Cough Guidelines, the major change in suggestions is that the terms psychogenic and habit cough be abandoned in favor of somatic cough syndrome and tic cough, respectively, even though the evidence to do so at this time is of low quality.

Metformin use and survival after colorectal cancer: A population-based cohort study.

Preclinical evidence suggests that metformin could delay cancer progression. Previous epidemiological studies however have been limited by small sample sizes and certain time-related biases. This study aimed to investigate whether colorectal cancer patients with type 2 diabetes who were exposed to metformin had reduced cancer-specific mortality. We conducted a retrospective cohort study of 1,197 colorectal cancer patients newly diagnosed from 1998 to 2009 (identified from English cancer registries) with type 2 diabetes (based upon Clinical Practice Research Datalink, CPRD, prescription and diagnosis records). In this cohort 382 colorectal cancer-specific deaths occurred up to 2012 from the Office of National Statistics (ONS) mortality data. Metformin use was identified from CPRD prescription records. Using time-dependent Cox regression models, unadjusted and adjusted hazard ratios (HR) and 95% CIs were calculated for the association between post-diagnostic exposure to metformin and colorectal cancer-specific mortality. Overall, there was no evidence of an association between metformin use and cancer-specific death before or after adjustment for potential confounders (adjusted HR 1.06, 95% CI 0.80, 1.40). In addition, after adjustment for confounders, there was also no evidence of associations between other diabetic medications and cancer-specific mortality including sulfonylureas (HR 1.14, 95% CI 0.86, 1.51), insulin use (HR 1.35, 95% CI 0.95, 1.93) or other anti-diabetic medications including thiazolidinediones (HR 0.73, 95% CI 0.46, 1.14). Similar associations were observed by duration of use and for all-cause mortality. This population-based study, the largest to date, does not support a protective association between metformin and survival in colorectal cancer patients.

Regular medication reviews for children and young people with ADHD

The National Institute for Health and Care Excellence's (2008) guidelines for the diagnosis and management of attention deficit hyperactivity disorder (ADHD) recommend a full clinical and psychological assessment by an appropriately trained clinician; this should include a detailed developmental and psychiatric history. Stimulant medications, which are Schedule II controlled drugs, are the most commonly prescribed medicines in the UK and across the world for the management of ADHD. Children and young people with a diagnosis of ADHD receiving these stimulant medications are required to attend regular review appointments with a consultant child and adolescent psychiatrist or specialist nurse under shared care guidelines with general practices, and it has long been recognized that appropriately educated nurses can assist in the management of ADHD. Owing to the pharmacological action of the stimulant medication on neurotransmission, there is potential for misuse and dependence. A growing body of evidence suggests that adolescents with ADHD can become involved in drug diversion and that the topic should be explored during assessment. The level of misuse of prescribed stimulants is increasing, and adolescents and young people with ADHD may misuse to enhance cognitive function for academic purposes. The following scenario highlights some of the challenges and opportunities for independent nurse prescribers working in child and adolescent mental health services.

Improving appropriate polypharmacy for older people in primary care: selecting components of an evidence-based intervention to target prescribing and dispensing.

Background
The use of multiple medicines (polypharmacy) is increasingly common in older people. Ensuring that patients receive the most appropriate combinations of medications (appropriate polypharmacy) is a significant challenge. The quality of evidence to support the effectiveness of interventions to improve appropriate polypharmacy is low. Systematic identification of mediators of behaviour change, using the Theoretical Domains Framework (TDF), provides a theoretically robust evidence base to inform intervention design. This study aimed to (1) identify key theoretical domains that were perceived to influence the prescribing and dispensing of appropriate polypharmacy to older patients by general practitioners (GPs) and community pharmacists, and (2) map domains to associated behaviour change techniques (BCTs) to include as components of an intervention to improve appropriate polypharmacy in older people in primary care.

Methods
Semi-structured interviews were conducted with members of each healthcare professional (HCP) group using tailored topic guides based on TDF version 1 (12 domains). Questions covering each domain explored HCPs’ perceptions of barriers and facilitators to ensuring the prescribing and dispensing of appropriate polypharmacy to older people. Interviews were audio-recorded and transcribed verbatim. Data analysis involved the framework method and content analysis. Key domains were identified and mapped to BCTs based on established methods and discussion within the research team.

Results
Thirty HCPs were interviewed (15 GPs, 15 pharmacists). Eight key domains were identified, perceived to influence prescribing and dispensing of appropriate polypharmacy: ‘Skills’, ‘Beliefs about capabilities’, ‘Beliefs about consequences’, ‘Environmental context and resources’, ‘Memory, attention and decision processes’, ‘Social/professional role and identity’, ‘Social influences’ and ‘Behavioural regulation’. Following mapping, four BCTs were selected for inclusion in an intervention for GPs or pharmacists: ‘Action planning’, ‘Prompts/cues’, ‘Modelling or demonstrating of behaviour’ and ‘Salience of consequences’. An additional BCT (‘Social support or encouragement’) was selected for inclusion in a community pharmacy-based intervention in order to address barriers relating to interprofessional working that were encountered by pharmacists.

Conclusions
Selected BCTs will be operationalised in a theory-based intervention to improve appropriate polypharmacy for older people, to be delivered in GP practice and community pharmacy settings. Future research will involve development and feasibility testing of this intervention.

Single nucleotide polymorphisms in the APCS gene influence geographic atrophy secondary to VEGF inhibition therapy in neovascular macular degeneration.

Introduction: Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly mostly due to the development of neovascular AMD (nAMD) or geographic atrophy (GA). Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are an effective therapeutic option for nAMD. Following anti-VEGF treatments, increased atrophy of the retinal pigment epithelium (RPE) and choriocapillaries that resembles GA has been reported. We sought to evaluate the underlying genetic influences that may contribute to this process. Methods: We selected 68 single nucleotide polymorphisms (SNPs) from genes previously identified as susceptibility factors in AMD, along with 43 SNPs from genes encoding the VEGF protein and its cognate receptors as this pathway is targeted by treatment. We enrolled 467 consecutive patients (Feb 2009 to October 2011) with nAMD who received anti-VEGF therapy. The acutely presenting eye was designated as the study eye and retinal tomograms graded for macular atrophy at study exit. Statistical analysis was performed using PLINK to identify SNPs with a P value < 0.01. Logistic regression models with macular atrophy as dependent variable were fitted with age, gender, smoking status, common genetic risk factors and the identified SNPs as explanatory variables. Results: Grading for macular atrophy was available in 304 study eyes and 70% (214) were classified as showing macular atrophy. In the unadjusted analysis we observed significant associations between macular atrophy and two independent SNPs in the APCS gene: rs6695377: odds ratio (OR) = 1.98; 95% confidence intervals (CI): 1.23, 3.19; P = 0.004; rs1446965: OR = 2.49, CI: 1.29, 4.82; P = 0.006 and these associations remained significant after adjustment for covariates. Conclusions: VEGF is a mitogen and growth factor for choroidal blood vessels and the RPE and its inhibition could lead to atrophy of these key tissues. Anti-VEGF treatment can interfere with ocular vascular maintenance and may be associated with RPE and choroidal atrophy. As such, these medications, which block the effects of VEGF, may influence the development of GA. The top associated SNPs are found in the APCS gene, a highly conserved glycoprotein that encodes Serum amyloid P (SAP) which opsonizes apoptotic cells. SAP can bind to and activate complement components via binding to C1q, a mechanism by which SAP may remove cellular debris, affecting regulation of the three complement pathways.

Protocol-driven adjustment of ocular hypotensive medication in patients at low risk of conversion to glaucoma

AIM: To investigate the safety and potential savings of decreasing medication use in low-risk patients with ocular hypertension (OH).
METHODS: Patients with OH receiving pressure-lowering medication identified by medical record review at a university hospital underwent examination by a glaucoma specialist with assessment of visual field (VF), vertical cup-to-disc ratio (vCDR), central corneal thickness and intraocular pressure (IOP). Subjects with estimated 5-year risk of glaucoma conversion <15% were asked to discontinue ≥1 medication, IOP was remeasured 1 month later and risk was re-evaluated at 1 year.
RESULTS: Among 212 eyes of 126 patients, 44 (20.8%) had 5-year risk >15% and 14 (6.6%) had unreliable baseline VF. At 1 month, 15 patients (29 eyes, 13.7%) defaulted follow-up or refused to discontinue medication and 11 eyes (5.2%) had risk >15%. The remaining 69 patients (107 eyes, 50.7%) successfully discontinued 141 medications and completed 1-year follow-up. Mean IOP (20.5±2.65 mm Hg vs 20.3±3.40, p=0.397) did not change, though mean VF pattern SD (1.58±0.41 dB vs 1.75±0.56 dB, p=0.001) and glaucoma conversion risk (7.31±3.74% vs 8.76±6.28%, p=0.001) increased at 1 year. Mean defect decreased (-1.42±1.60 vs -1.07±1.52, p=0.022). One eye (0.47%) developed a repeatable VF defect and 13 eyes (6.1%) had 5-year risk >15% at 1 year. The total 1-year cost of medications saved was US$4596.
CONCLUSIONS: Nearly half (43.9%) of low-risk OH eyes in this setting could safely reduce medications over 1 year, realising substantial savings.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Phacoemulsification combined with posterior capsulorhexis and anterior vitrectomy in the management of malignant glaucoma in phakic eyes

Purpose: To describe sequential phacoemulsification-intraocular lens (IOL) implantation-posterior capsulorhexis-anterior vitrectomy in the management of phakic malignant glaucoma. Methods: Twenty consecutive patients (25 eyes) with phakic malignant glaucoma were enrolled at the Zhongshan Ophthalmic Center, Sun Yat-sen University. All patients underwent phacoemulsification, IOL implantation and posterior capsulorhexis together with anterior vitrectomy via a clear corneal paracentesis. Visual acuity, intraocular pressure (IOP), anterior chamber depth (ACD), surgical complications and medications required after the surgery were recorded. Results: After surgery, the mean LogMAR visual acuity and ACD increased significantly (visual acuity from -1.56 ± 1.17 to -0.54 ± 0.81, p < 0.001; ACD from 0.367 ± 0.397 mm to 2.390 ± 0.575 mm, p < 0.001), and mean IOP decreased significantly (from 39.6 ± 10.6 mm Hg to 14.5 ± 4.1 mmHg, p < 0.001). No serious perioperative complications occurred, and only five eyes required topical glaucoma medications after surgery. Conclusion: Combined phacoemulsification-IOL implantation-posterior capsulorhexis-anterior vitrectomy surgery is a safe and effective method for treating patients with phakic malignant glaucoma. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

The worldwide epidemic of diabetic retinopathy

Diabetic retinopathy (DR), a major microvascular complication of diabetes, has a significant impact on the world′s health systems. Globally, the number of people with DR will grow from 126.6 million in 2010 to 191.0 million by 2030, and we estimate that the number with vision-threatening diabetic retinopathy (VTDR) will increase from 37.3 million to 56.3 million, if prompt action is not taken. Despite growing evidence documenting the effectiveness of routine DR screening and early treatment, DR frequently leads to poor visual functioning and represents the leading cause of blindness in working-age populations. DR has been neglected in health-care research and planning in many low-income countries, where access to trained eye-care professionals and tertiary eye-care services may be inadequate. Demand for, as well as, supply of services may be a problem. Rates of compliance with diabetes medications and annual eye examinations may be low, the reasons for which are multifactorial. Innovative and comprehensive approaches are needed to reduce the risk of vision loss by prompt diagnosis and early treatment of VTDR.

Surgical strategies for coexisting glaucoma and cataract: an evidence-based update.

OBJECTIVE:

To assess short- and long-term control of intraocular pressure (IOP) with different surgical treatment strategies for coexisting cataract and glaucoma.

DESIGN:

Systematic literature review and analysis.

METHOD:

We performed a search of the published literature to identify all eligible articles pertaining to the surgical management of coexisting cataract and glaucoma in adults. One investigator abstracted the content of each article onto a custom-designed form. A second investigator corroborated the findings. The evidence supporting different approaches was graded by consensus as good, fair, weak, or insufficient.

MAIN OUTCOME MEASURES:

Short-term (24 hours or fewer) and long-term (more than 24 hours) IOP control.

RESULTS:

The evidence was good that long-term IOP is lowered more by combined glaucoma and cataract operations than by cataract operations alone. On average, the IOP was 3 to 4 mmHg lower in the combined groups with fewer medications required. The evidence was weak that extracapsular cataract extraction (ECCE) alone results in short-term increase in IOP and was insufficient to determine the short-term impact of phacoemulsification cataract extraction (PECE) on IOP in glaucoma patients. The evidence was weak that short-term IOP control was better with ECCE or PECE combined with an incisional glaucoma procedure compared with ECCE or PECE alone. The evidence was also weak (but consistent) that long-term IOP is lowered by 2 to 4 mmHg after ECCE or PECE. Finally, there was weak evidence that combined PECE and trabeculectomy produces slightly worse long-term IOP control than trabeculectomy alone, and there was fair evidence that the same is true for ECCE combined with trabeculectomy.

CONCLUSIONS:

There is strong evidence for better long-term control of IOP with combined glaucoma and cataract operations compared with cataract surgery alone. For other issues regarding surgical treatment strategies for cataract and glaucoma, the available evidence is limited or conflicting.

Nuclear cataract shows significant familial aggregation in an older population after adjustment for possible shared environmental factors.

PURPOSE: To quantify the association between siblings in age-related nuclear cataract, after adjusting for known environmental and personal risk factors. METHODS: All participants (probands) in the Salisbury Eye Evaluation (SEE) project and their locally resident siblings underwent digital slit lamp photography and were administered a questionnaire to assess risk factors for cataract including: age, gender, lifetime sun exposure, smoking and diabetes history, and use of alcohol and medications such as estrogens and steroids. In addition, blood pressure, body mass index, and serum antioxidants were measured in all participants. Lens photographs were graded by trained observers masked to the subjects' identity, using the Wilmer Cataract Grading System. The odds ratio for siblings for affectedness with nuclear cataract and the sibling correlation of nuclear cataract grade, after adjusting for covariates, were estimated with generalized estimating equations. RESULTS: Among 307 probands (mean age, 77.6 +/- 4.5 years) and 434 full siblings (mean age, 72.4 +/- 7.4 years), the average sibship size was 2.7 per family. After adjustment for covariates, the probability of development of nuclear cataract was significantly increased (odds ratio [OR] = 2.07, 95% confidence interval [CI], 1.30-3.30) among individuals with a sibling with nuclear cataract (nuclear grade > or = 3.0). The final fitted model indicated a magnitude of heritability for nuclear cataract of 35.6% (95% CI: 21.0%-50.3%) after adjustment for the covariates. CONCLUSIONS: Findings in this study are consistent with a genetic effect for age-related nuclear cataract, a common and clinically significant form of lens opacity.

A study of initial therapy for glaucoma in southern India: India Glaucoma Outcomes and Treatment (INGOT) Study.

PURPOSE: To compare initial glaucoma therapy with medications and trabeculectomy in southern India. METHODS: Patients aged ≥ 30 years newly diagnosed with glaucoma were randomized to trabeculectomy with 5-fluorouracil or medical therapy. Subjects with best-corrected vision <6/18 due to cataract underwent phacoemulsification (phaco/intraocular lens, IOL). Intraocular pressure (IOP), vision and visual function were assessed at 12 months. RESULTS: Patients assigned to medications and surgery received the expected therapy in 86% (172/199) and 64% (126/199) of cases, respectively. Forty patients (20%) assigned to surgery refused any treatment and 33 (17%) received medications. Among 199 patients randomized to medications, 52 (26.1%) underwent phaco/IOL, as did 89/199 (43.7%) of patients randomized to trabeculectomy. Baseline parameters of the two groups did not differ, nor did 1-year follow-up rates (medication 65%, trabeculectomy 58%, P = 0.15). Final IOP was lower with randomization to trabeculectomy (16.3 ± 5.1 mmHg) than medication (18.8 ± 6.7 mmHg, P < 0.0001). In regression models, randomization to trabeculectomy (P < 0.0001) was associated with lower IOP, and simultaneous trabeculectomy and cataract surgery was associated with higher IOP (P = 0.008) than trabeculectomy alone. Subjects receiving Phaco/IOL had significantly better final acuity (P < 0.0001) and visual function (P = 0.035), despite concurrent glaucoma treatment. Final visual acuity was worse in those receiving trabeculectomy in addition to cataract surgery, but this was of borderline significance (P = 0.06). CONCLUSIONS: Trabeculectomy lowered IOP significantly more than medical treatment, but with slightly greater loss of visual acuity. Combined phaco/IOL and trabeculectomy improved visual acuity with substantial IOP lowering.

Potentially inappropriate prescribing among people with dementia in primary care: a retrospective cross-sectional study using the Enhanced Prescribing Database

Background: Little is known about prescribing appropriateness for community-dwelling people with dementia (PWD).
Objective To estimate potentially inappropriate prescribing (PIP) prevalence among PWD in primary care in Northern Ireland, and to investigate associations between PIP and polypharmacy, age and gender.

Methods: A retrospective cross-sectional study was conducted, using data from the Enhanced Prescribing Database. Patients were eligible if a medicine indicated for dementia management was dispensed to them during 01/01/2013 – 31/12/2013. Polypharmacy was indicated by use of ≥4 repeat medications from different drug groups. A subset of the Screening Tool of Older Persons Potentially Inappropriate Prescriptions (STOPP) criteria, comprising 36 indicators, was applied to the dataset. Overall prevalence of PIP and the prevalence per each STOPP criterion was calculated as a proportion of all eligible persons in the dataset. Logistic regression was used to investigate associations between PIP, polypharmacy, age and gender.

Results: The study population comprised 6826 patients. Polypharmacy was observed in 81.5% (n=5564) of patients. PIP prevalence during the study period was 64.4% (95% CI 63.2 – 65.5; n=4393). The most common instance of PIP was the use of anticholinergic/antimuscarinic medications (n=1718; 25.2%; 95% CI 24.2 – 26.2). In multivariable analyses, both polypharmacy and gender (being female) were associated with PIP, with odds ratios of 7.6 (95% CI 6.6 – 8.7) and 1.3 (95% CI 1.2 – 1.4) respectively. No association was observed between PIP and age, after adjustments for gender and polypharmacy.

Conclusion: This study identified a high prevalence of PIP in community-dwelling PWD. Future interventions may need to focus on certain therapeutic categories and polypharmacy.

Medication regimen complexity in institutionalized elderly people in an aging society

Background Complex medication regimens may adversely affect compliance and treatment outcomes. Complexity can be assessed with the medication regimen complexity index (MRCI), which has proved to be a valid, reliable tool, with potential uses in both practice and research. Objective To use the MRCI to assess medication regimen complexity in institutionalized elderly people. Setting Five nursing homes in mainland Portugal. Methods A descriptive, cross-sectional study of institutionalized elderly people (n = 415) was performed from March to June 2009, including all inpatients aged 65 and over taking at least one medication per day. Main outcome measure Medication regimen complexity index. Results The mean age of the sample was 83.9 years (±6.6 years), and 60.2 % were women. The elderly patients were taking a large number of drugs, with 76.6 % taking more than five medications per day. The average medication regimen complexity was 18.2 (±SD = 9.6), and was higher in the females (p < 0.001). The most decisive factors contributing to the complexity were the number of drugs and dosage frequency. In regimens with the same number of medications, schedule was the most relevant factor in the final score (r = 0.922), followed by pharmaceutical forms (r = 0.768) and additional instructions (r = 0.742). Conclusion Medication regimen complexity proved to be high. There is certainly potential for the pharmacist’s intervention to reduce it as part as the medication review routine in all the patients.

Inappropriate medication use in long-term care facility residents with advanced Alzheimer’s disease and other dementias

Les personnes atteintes de démence sévère, résidant dans un centre d’hébergement et de soins de longue durée (CHSLD) et approchant la fin de leur vie, ne reçoivent pas systématiquement des soins palliatifs, malgré que ce niveau de soins soit le plus approprié. La plupart de ces personnes reçoivent également un grand nombre de médicaments dont les effets indésirables peuvent contribuer à des souffrances évitables. Une approche axée sur les soins palliatifs serait possiblement associée à une réduction de la charge médicamenteuse et, du même coup, à une prescription plus appropriée. Les objectifs de ce projet de recherche étaient de décrire l’usage des médicaments chez les résidents atteints de démence sévère en CHSLD, de comparer leur usage de médicaments à des critères de pertinence et d’évaluer si la mise en œuvre d’une approche axée sur les soins palliatifs était associée aux médicaments prescrits. Cette étude décrit l’usage des médicaments chez 215 sujets atteints de démence sévère et en fin de vie qui ont participé à une étude d’intervention quasi expérimentale menée dans quatre CHSLD du Québec sur la mise en œuvre d’une approche axée sur les soins palliatifs. L’utilisation des médicaments a été comparée à trois listes de critères pertinents publiés, soit ceux de Holmes, Rancourt et Kröger, en utilisant des statistiques descriptives. Les analyses sur l’usage de 412 médicaments différents chez 120 sujets du groupe expérimental et 95 sujets du groupe témoin ont montré que cette approche axée sur les soins palliatifs n’est pas associée à une prescription plus appropriée des médicaments chez ces personnes particulièrement vulnérables.

Does Cost-Effectiveness Analysis Have a Role in US Managed Care Drug Formularies? An Empirical Study of Utilization, Costs, Outcomes, and Elasticity of Demand of a Value-Based Formulary

Thesis (Ph.D.)--University of Washington, 2015