Advances in Device and Formulation Technologies for Pulmonary Drug Delivery

Inhaled pharmaceuticals are formulated and delivered differently according to the therapeutic indication. However, specific device-formulation coupling is often fickle, and new medications or indications also demand new strategies. The discontinuation of chlorofluorocarbon propellants has seen replacement of older metered dose inhalers with dry powder inhaler formulations. High-dose dry powder inhalers are increasingly seen as an alternative dosage form for nebulised medications. In other cases, new medications have completely bypassed conventional inhalers and been formulated for use with unique inhalers such as the Staccato® device. Among these different devices, integration of software and electronic assistance has become a shared trend. This review covers recent device and formulation advances that are forming the current landscape of inhaled therapeutics.     

Market penetration of new drugs in one United Kingdom region: implications for general practitioners and administrators.

OBJECTIVE--To determine the use of new drugs in one United Kingdom region. DESIGN--Examination of data on prescribing of angiotensin converting enzyme inhibitors, new broad spectrum antibiotics, and H2 receptor antagonists. Calculation of number of defined daily doses prescribed each month. SETTING--All general practices in Northern Ireland. MAIN OUTCOME MEASURES--Drug use index and market share of each drug. RESULTS--During 1988-91 prescribing of angiotensin converting enzyme inhibitors increased by 126%, of H2 receptor antagonists by 46%, and of new antibiotics by 207%. The first drug on the market usually retained the largest market share. Use of oral antibiotics increased threefold irrespective of the reporting policy of the general practitioners'' local laboratory. CONCLUSIONS--The increase in prescribing of these drugs seems to be greater than can be accounted for by an increase in patients with specific indications for these drugs. This suggests that the profession has not instituted effective checks to ensure that the legitimate promotion of new products does not lead to inappropriate and wasteful use.     

Impact of a New Reimbursement Program on Hepatitis B Antiviral Medication Cost and Utilization in Beijing,China

Background

Hepatitis B virus (HBV) infection is a significant clinical and financial burden for chronic hepatitis B (CHB) patients. In Beijing, China, partial reimbursement on antiviral agents was first implemented for the treatment of CHB patients in July 1, 2011.

Aims

In this study, we describe the medical cost and utilization rates of antiviral therapy for CHB patients to explore the impact of the new partial reimbursement policy on the medical care cost, the composition, and antivirals utilization.

Methods

Clinical and claims data of a retrospective cohort of 92,776 outpatients and 2,774 inpatients with non-cirrhotic CHB were retrieved and analyzed from You''an Hospital, Beijing between February 14, 2008 and December 31, 2012. The propensity score matching was used to adjust factors associated with the annual total cost, including age, gender, medical insurance type and treatment indicator.

Results

Compared to patients who paid out-of-pocket, medical cost, especially antiviral costs increased greater among patients with medical insurance after July 1, 2011, the start date of reimbursement policy. Outpatients with medical insurance had 16% more antiviral utilization; usage increased 3% among those who paid out-of-pocket after the new partial reimbursement policy was implemented.

Conclusions

Direct medical costs and antiviral utilization rates of CHB patients with medical insurance were higher than those from paid out-of-pocket payments, even after adjusting for inflation and other factors. Thus, a new partial reimbursement program may positively optimize the cost and standardization of antiviral treatment.     

Impact of counselling on careseeking behaviour in families with sick children: cluster randomised trial in rural India

Objective To assess whether training doctors in counselling improves careseeking behaviour in families with sick children.Design Pair matched, community randomised trial conducted in 12 primary health centres (six pairs). Doctors in intervention centres were trained in counselling, communication, and clinical skills, using the integrated management of childhood illness approach.Setting Rural district in Rajasthan, India.Participants Children aged under 5 years presenting for curative care and their mothers were recruited and visited monthly at home for six months. A total of 2460 children were recruited (1248 intervention, 1212 control).Main outcome measures Careseeking behaviour of mothers for sick children; mothers'' knowledge and perceptions of seeking care; counselling performance of doctors.Results For episodes of illness with at least one reported danger sign, 15% of intervention group mothers and 10% of control group mothers reported having sought care from an appropriate provider promptly; this difference was not statistically significant (relative risk reduction 5%, 95% confidence interval -0.4% to 11%; P = 0.07). One month after training, intervention site doctors counselled more effectively than control group doctors, but at six months their performance had declined. A greater proportion of mothers in the intervention group than in the control group recalled having had at least one danger sign explained (45% v 8%; P = 0.02).Conclusions Mothers'' appreciation of the need to seek prompt and appropriate care for severe episodes of childhood illness increased, but their careseeking behaviour did not improve significantly.     

Monitoring antioxidant enzymes in red cells during allergen immunotherapy

The aim of this report was to answer the question how specific immunotherapy influences the antioxidant enzyme system in patients with respiratory allergy and in longer perspective to find markers suitable to assess the efficacy of treatment. In open prospective randomised study 28 patients (18 females and 10 males, age 14–48 years) with seasonal respiratory allergy were treated with allergen immunotherapy. Subjects received subcutaneous therapy with allergens absorbed on calcium phosphate or aluminium hydroxide and were analyzed by the established protocol at the beginning, after three and 12 month of the treatment. In all treatment group red cell superoxide dismutase and glutathione peroxidase activities were in the normal range in allergic patients both before and during the treatment. Catalase activity in the allergic patients was lower as compared with controls and a significant increase of the enzyme activity occurred during and at the end of the treatment. In patients treated with calcium phosphate adsorbed allergen there was a continous increase of catalase activity from beginning up to the end of observation. In the case of the aluminium hydroxide treatment there was an increase from the baseline values up in the third month of the treatment and a decrease on the 12^th month. In summary, the present results open the question that allergen immunotherapy may cause imbalance of oxidants and antioxidants. To support our findings larger controlled field studies are needed.     

Extracorporeal life support in cardiogenic shock: indications and management in current practice

Veno-arterial extracorporeal life support (VA-ECLS) provides circulatory and respiratory stabilisation in patients with severe refractory cardiogenic shock. Although randomised controlled trials are lacking, the use of VA-ECLS is increasing and observational studies repeatedly have shown treatment benefits in well-selected patients. Current clinical challenges in VA-ECLS relate to optimal management of the individual patient on extracorporeal support given its inherent complexity. In this review article we will discuss indications, daily clinical management and complications of VA-ECLS in cardiogenic shock refractory to conventional treatment strategies.     

Lack of effect of oral magnesium on high blood pressure: a double blind study.

Seventeen unselected patients with mild to moderate essential hypertension and whose average supine blood pressure after two months'' observation with no treatment was 154/100 mm Hg were entered into a double blind randomised crossover study of one month''s treatment with magnesium aspartate (15 mmol magnesium/day) and treatment with placebo for a further month. This preparation of magnesium was well tolerated and did not cause diarrhoea. Despite a significant increase in plasma magnesium concentration and a significant increase in urinary excretion of magnesium while taking magnesium aspartate there was no fall in blood pressure compared with either treatment with placebo or values before treatment. The results provide no evidence for a role of dietary magnesium in the regulation of high blood pressure and are contrary to recent speculations.     

Has time come for a re-assessment of spa therapy? The NAIADE survey in Italy

Goal of this study was to investigate whether appropriately applied spa therapy in several indications could be associated with a subsequent fall in the need for costly health services and missed working days due to sick-leave. The Naiade project was a multicenter observational, longitudinal, questionnaire-based study comparing an “entry” inquiry addressed to patients before an entry thermal cycle, and a “return” inquiry after 1 year. Routine statistical methods were used for comparisons. The study was carried out in 297 of the 340 certified Italian spa centers. Inquiries were managed by the spa doctor(s), with the collaboration of family doctors, and when necessary, hospitals, other health services, labour offices and employers. After exclusion of regular customers and of patients with acute disease phases or severe health conditions, 39,943 patients divided into eight diseases subgroups (rheumatic, respiratory, dermatologic, gynaecologic, otorhynologic, urinary, vascular and gastroenteric) underwent entry inquiry and appropriate spa treatment. Patients who returned for treatment after 1 year (“index year”) were 23,680 (59.2%) and received return inquiry. Outcomes considered were: frequency and duration of hospitalisation periods; missed working days; regular use of disease-specific drugs; and resort to “non-spa” rehabilitation therapies. The data collected at return inquiry were compared with those of entry inquiry. All the considered outcomes appeared to be significantly reduced in the index year in seven of the eight disease subgroups in comparison with the previous year. In conclusion, disease-appropriate spa treatments were followed by a reduction in the need of subsequent health interventions in most disease subgroups. The health promoting value of spa treatments should therefore undergo more rigorous assessment with randomised controlled studies.     

Problems of care in a private nursing home.

To assess problems of care in a private nursing home an observational study was carried out over two months, during which a research nurse worked as a member of the staff in a home caring for 25 patients aged 62-90. During the second month a consultant physician visited the home weekly to hold case conferences and assess each patient''s functional ability and drug regimen. Various problems in medical, nursing, and bureaucratic matters were identified--for example, staff failed to understand the appropriate response to various medical symptoms; no clear policy existed for managing pressure sores; and one patient''s anticoagulant state could not be assessed when industrial action meant that transport to take him to hospital was not available--and several changes in drug treatments were recommended. The problems that were identified were mainly due to poor communication between the home and general practitioners and hospitals and to the lack of guidance policy on common issues that arise in long term care. Such a policy could be produced by health authority staff, general practitioners, and representatives of nursing homes.     

Trial of three-day and ten-day courses of amoxycillin in otitis media.

A randomised double-blind controlled trial compared three-day and 10-day courses of amoxycillin (25 mg/kg daily) in children with otitis media. Seventeen doctors from five centres admitted 84 children between the ages of 2 and 10 years. Symptoms and signs were measured on admission to the trial, on day 3, and on day 15. Mother''s observations were recorded daily for 10 days. Audiograms were performed at four and 12 weeks after the end of the trial. The treatment groups showed little difference in the speed of resolution of symptoms and signs, the numbers of primary treatment failures, or the frequency of recurrent ear infections. There were no complications in either group. Most children with otitis media can probably be successfully and safely treated with no more than a three-day course of amoxycillin providing their progress is reviewed about the fifth or sixth day after treatment started. This policy could save over 1 million pounds annually in antibiotic costs.     

Asthma in primary schools.

Seven schools in the Lewes area were visited to identify which children were using inhalational treatment for asthma. The attitudes of the parents and schools were assessed, as was the children''s skill in using inhalers. Five per cent of all children were receiving inhalational treatment with bronchodilator drugs. On average they had missed seven school days in the past year. The opinions of the parents about treatment appeared to be determined by the severity of the child''s asthma. Most schools coped well with giving bronchodilators, though there was no real understanding of the nature of the disease or treatment. Most children who had received pressurised inhalers could not use them satisfactorily.     

Multicentre study of cancer pain and its treatment in France.

OBJECTIVE--To describe the treatment of cancer pain in France and to evaluate the predictive factors for inadequate management. DESIGN--Multicentre, representative cross sectional survey. SETTING--20 treatment centres, including cancer centres, university hospitals, state hospitals, private clinics, and one homecare setting (in which patients are supported at home). SUBJECTS--605 patients with cancer. MAIN MEASURES--Patients rated prevalence and severity of pain and functional impairment related to pain. Doctors reported patients'' cancer characteristic, performance status, pain severity, and analgesic drugs ordered. RESULTS--57% (340/601) of patients with cancer reported pain due to their disease, and, of those with pain, 69% (224/325) rated their worst pain at a level that impaired their ability to function. 30% (84/279) were reported as receiving no drugs for their pain. Of the 270 patients in pain for whom information on treatment was available 51% (137/270) were not receiving adequate pain relief, according to an index based on the World Health Organisation''s guidelines. French doctors were found to underestimate the severity of their patients'' pain. Younger patients, patients without metastatic disease, patients with a better performance status, and patients who rated their pain as more severe than their doctors did were at greater risk for undertreatment of their pain. CONCLUSIONS--In the light of the high prevalence and the severity of pain among patients with cancer, the assessment and treatment of cancer pain in France remain inadequate, emphasising the need for changes in patient care.     

Randomised controlled trial of computer assisted management of hypertension in primary care.

The hypothesis that general practitioners would obtain better outcomes for patients with hypertension using a computer than doctors not using a computer was tested. Sixty family physicians were randomised to two treatment strategies. "Test" physicians completed a data collection form after each visit from a patient with hypertension and mailed the forms to the test centre for processing. Computer feedback on management was mailed to the doctors. This encouraged doctors to apply the "stepped care" protocol, supplied charts of diastolic blood pressure v time, and ranked patients'' diastolic blood pressures by percentile. Letters were mailed to patients to remind them of appointments. "Control" doctors filled out the same data collection forms as test physicians, but neither doctors nor patients received computer feedback. Physicians who used the computer saw more patients per practice than control doctors (test 50 patients, control 40). For all patients the length of follow up was significantly longer in test practices (test 199 days, control 167), and a smaller percentage dropped out of active treatment in test practices (test 37.5%, control 42.1%). For patients with "moderate" hypertension of a baseline diastolic pressure of greater than 104 mm Hg the mean score of the last recorded pressure was below the goal of 90 mm Hg in test practices (88.5 mm Hg), but it failed to reach this goal in control practices (93.3 mm Hg). A greater average reduction of diastolic pressure was achieved in test practices (test 21.7 mm Hg, control 16.7 mm Hg). Though patients with "moderate" hypertension were better controlled in test practices than in control practices, the patients in test practices visited their doctors less often (test 13.3 visits per patient-year, control 17.4 visits). Among patients with newly detected hypertension test practices achieved a greater reduction in diastolic pressure than control practices (test 15.1 mm Hg v control 11.3 mm Hg) and more sustained control of hypertension (test 323 days per patient-year with a diastolic pressure of 90 mm Hg or less v control 259 days).     

Randomised comparison of procedures for obtaining informed consent in clinical trials of treatment for cancer.

Methods of obtaining informed consent have evolved differently in Western countries without substantive information on the impact of these different practices on the patients. A randomised study was performed to compare two commonly adopted methods of seeking consent to randomised treatment: an individual approach at the discretion of each doctor and a uniform policy of total disclosure of all relevant information. The impact of both consent procedures on the patient''s understanding and anxiety levels and on the doctor-patient relationship was assessed by means of a questionnaire given soon after the consent interview. Fifty seven patients were assigned at random to two groups: to 29 patients an individual approach to seeking consent was adopted and to 28 patients all relevant information was given. Seven patients refused consent to randomised treatment, with slightly more refusals by patients in the total disclosure group (5 v 2, p = 0.25). The main effects of total disclosure of all information compared with an individual approach to seeking consent were: a better understanding of treatment and side effects and of research aspects of the treatments; less willingness to agree to randomised treatment; and increased anxiety. No significant differences were found in patients'' perceptions of the doctor-patient relationship. A repeat questionnaire given three to four weeks later no longer showed significant differences between the two groups.