Detection and Management of Deep Vein Thrombosis

The accuracy of diagnosis of deep venous thrombosis is significantly improved by combining clinical evaluation with other adjunctive methods, especially fibrinogen uptake tests, technetium scans, Doppler techniques and phlebography. Using these studies, early treatment with intravenous administration of heparin can be begun and in selected cases with long-term risks, warfarin is often useful. These same drugs, in different dosage schedules, may also be helpful as prophylaxis. With these methods of treatment, thrombectomy and caval interruption are required less often. If interruption of inferior vena cava flow becomes necessary, several new methods utilizing intracaval filters are proving to be very useful.     

Cholinergic modulation of amyloid precursor protein processing with emphasis on M1 muscarinic receptor: perspectives and challenges in treatment of Alzheimer's disease

The prescribed drugs for treatment of cognitive deficits in Alzheimer's disease (AD) patients are regarded as symptomatic drugs. Effective disease modifying therapies are not yet prescribed in AD patients. Three major hallmarks of AD (e.g. cholinergic hypofunction, Aβ and tau neuropathologies) are closely linked raising the expectation that restoring the cholinergic hypofunction to normal, in particular via selective activation of M1 muscarinic receptors, may alter the onset or progression of AD dementia. This review is focused mainly on modulation of amyloid precursor processing and Aβ levels in the brain via cholinergic treatment strategies based on M1 muscarinic agonists versus other cholinergic treatments (e.g. cholinesterase inhibitors prescribed for treatment of AD, M2 antagonists and nicotinic agonists). Advantages and potential drawbacks of these treatment modalities are reviewed versus the notion that due to an elusive etiology of AD, future disease modifiers should address comprehensively most of these AD hallmarks (e.g. Aβ pathology, tau and tangle pathologies, as well as the cholinergic hypofunction and cognitive impairments). This major requirement may be fulfilled with M1-selective muscarinic agonists and less with other reviewed cholinergic treatments.     

Bisphosphonates and the risk of atrial fibrillation

Osteoporosis is a growing problem in an ageing society. It affects women of post-menopausal age, as well as elderly subjects of both sexes, often with dysfunction of the cardiovascular system or with an increased risk of circulation disorders. It has been found that the mortality rate of subjects with osteoporosis is comparable to that of patients suffering from such diseases as obturative pulmonary disease or myocardial ischaemia. Bisphosphonates are the most thoroughly studied group of drugs prescribed for the treatment of osteoporosis. Their administration is, however, associated with a risk of adverse symptoms, which can occur as gastro-intestinal tract disturbances, muscular-osseous pains, mandible necrosis, atypical fractures and other symptoms. Recently, there has been discussion about an increased risk of atrial fibrillation in bisphosphonate-using female patients. This paper focuses on this particular problem, while summing up the actual status of knowledge regarding possible associations of bisphosphonates with cardiac rhythm disturbances.     

Bisphosphonates and the risk of atrial fibrillation

Osteoporosis is a growing problem in an ageing society. It affects women of post-menopausal age, as well as elderly subjects of both sexes, often with dysfunction of the cardiovascular system or with an increased risk of circulation disorders. It has been found that the mortality rate of subjects with osteoporosis is comparable to that of patients suffering from such diseases as obturative pulmonary disease or myocardial ischaemia. Bisphosphonates are the most thoroughly studied group of drugs prescribed for the treatment of osteoporosis. Their administration is, however, associated with a risk of adverse symptoms, which can occur as gastro-intestinal tract disturbances, muscular-osseous pains, mandible necrosis, atypical fractures and other symptoms. Recently, there has been discussion about an increased risk of atrial fibrillation in bisphosphonate-using female patients. This paper focuses on this particular problem, while summing up the actual status of knowledge regarding possible associations of bisphosphonates with cardiac rhythm disturbances.     

Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review

ObjectiveTo assess the effects of oral mucolytics in adults with stable chronic bronchitis and chronic obstructive pulmonary disease.DesignSystematic review of randomised controlled trials that compared at least two months of regular oral mucolytic drugs with placebo.StudiesTwenty three randomised controlled trials in outpatients in Europe and United States.ResultsCompared with placebo, the number of exacerbations was significantly reduced in subjects taking oral mucolytics (weighted mean difference −0.07 per month, 95% confidence interval −0.08 to −0.05, P<0.0001). Based on the annualised rate of exacerbations in the control subjects of 2.7 a year, this is a 29% reduction. The number needed to treat for one subject to have no exacerbation in the study period would be 6. Days of illness also fell (weighted mean difference −0.56, −0.77 to −0.35, P<0.0001). The number of subjects who had no exacerbations in the study period was greater in the mucolytic group (odds ratio 2.22, 95% confidence interval 1.93 to 2.54, P<0.0001). There was no difference in lung function or in adverse events reported between treatments.ConclusionsIn chronic bronchitis and chronic obstructive pulmonary disease, treatment with mucolytics is associated with a reduction in acute exacerbations and days of illness. As these drugs have to be taken long term, they could be most useful in patients who have repeated, prolonged, or severe exacerbations of chronic obstructive pulmonary disease.

What is already know on this topic

Mucolytic drugs have properties that may be beneficial in chronic obstructive pulmonary diseaseThese drugs are not prescribed in the United Kingdom and Australasia, although they are widely used in many other countriesDrugs that reduce exacerbations may reduce the morbidity and healthcare costs associated with progressively severe disease

What this study adds

Regular use of mucolytic drugs for at least two months significantly reduces exacerbations and days of illness compared with placebo in patients with chronic bronchitis and chronic obstructive pulmonary diseaseExacerbations that do occur may not be as severe, and the benefit may be greater in those with more severe diseaseReductions are modest and treatment may not be cost effective     

Immune hemolytic anemia associated with drug therapy

Drug-induced immune hemolytic anemia (DIIHA) is considered a rare condition. Nonsteroidal anti-inflammatory drugs and antineoplastic drugs are the main causes of DIIHA. An 86-year-old male patient with pulmonary infection was admitted to the 960^th Hospital of the PLA Joint Logistics Support Force. The patient was treated with ceftazidime in addition to supportive treatment. A history of antibiotics intake and clinical and laboratory hemolysis features were considered to be key bases for DIIHA diagnosis. Clinicians need to be aware of and accurately diagnose this rare complication caused by commonly prescribed drugs to stop the use of causative drugs in time, and therefore, to prevent serious and sometimes fatal consequences.     

Candidosis of the central nervous system in children of the first year--one of the problems in nosocomial fungal infections]

CNS candidosis is a severe disease, one of the nosocomial fungal infections, with often lethal issue or invalidation of the patient. Specific signs are absent and early diagnosis is very difficult. Risk factors are the following: prematurity, candidal carriage, prolonged hospitalization, treatment with broad spectrum antibiotics and immunosupressors, artificial pulmonary ventilation. No single effective antifungal agent exists. In the case of acute fungal CNS infection the drug of choice is fluconazole (diflucan) characterized by high efficacy and CSF sanitation rate, the drug is used intravenously with possible switching off to oral form. If the pathogen is not susceptible to the drug (C. crusel, C. glabrata and C. tropicalis) amphotericin B is recommended (C. lusitaniae is not susceptible). In the case of renal or hepatic failure AmBisome may be used as less toxic form. If the case of prolonged disease antifungal drugs are used in a long-term regime, drugs combinations are also recommended. Complex therapy with granulocyte colony stimulating factor may be used if the previous regime was not effective.     

Lithium vs. valproate vs. olanzapine vs. quetiapine as maintenance monotherapy for bipolar disorder: a population‐based UK cohort study using electronic health records

It is unclear which maintenance treatment for bipolar disorder is superior in clinical practice. Randomized controlled head‐to‐head trials of available drugs either do not exist or are inconclusive. We aimed to compare rates of monotherapy treatment failure in individuals prescribed lithium, valproate, olanzapine or quetiapine by a population‐based cohort study using electronic health records. 5,089 patients with bipolar disorder were prescribed lithium (N=1,505), valproate (N=1,173) olanzapine (N=1,366) or quetiapine (N=1,075) as monotherapy. Treatment failure was defined as time to stopping medication or add‐on of another mood stabilizer, antipsychotic, antidepressant or benzodiazepine. In unadjusted analyses, the duration of successful monotherapy was longest in individuals treated with lithium. Treatment failure had occurred in 75% of those prescribed lithium by 2.05 years (95% CI: 1.63‐2.51), compared to 0.76 years (95% CI: 0.64‐0.84) for those prescribed quetiapine, 0.98 years (95% CI: 0.84‐1.18) for those prescribed valproate, and 1.13 years for those prescribed olanzapine (95% CI: 1.00‐1.31). Lithium's superiority remained in a propensity score matched analysis; when treatment failure was defined as stopping medication or add‐on of a mood stabilizer or antipsychotic; and when treatment failure was restricted to more than three months after commencing the study drug. Lithium appears to be more successful as monotherapy maintenance treatment than valproate, olanzapine or quetiapine. Lithium is often avoided because of its side effect profile, but alternative treatments may reduce the time to being prescribed more than one drug, with potential additive side effects of these treatments.     

EMOTIONAL PROBLEMS IN CHILDREN—The Uses of Drugs in Therapeutic Management

Emotional disturbances in children may be due to an anxiety state, to obsessive-compulsive neurosis, to schizophrenia or to a brain injury causing a behavior disorder. Children in an anxiety state have difficulty in school because anxiety interferes with concentration, impairs memory and makes decisions difficult. Consequently, these children often fear school and express their anxiety by behavior disturbances which alienate them from parents and teachers.There are a number of chemotherapeutic agents physicians can use as a part of the treatment of emotionally disturbed children. Phenobarbital is valuable for short-term therapy for the anxious child. Meprobamate also may be prescribed for anxiety reactions. It is of limited value for the hyperkinetic and obsessive-compulsive child and of no value in the schizophrenic child. Atarax (hydroxyzine dihydrochloride) is beneficial for the neurotic and hyperkinetic brain-injured child. Children with severe anxiety reactions and schizophrenic disorders respond best to chlorpromazine or reserpine.It must be emphasized that drug therapy is a part of the total therapeutic attack on the emotional problems of children.     

Drugs That Cause Weight Gain

Among drugs which cause weight gain, the tricyclic antidepressant medications are a drug class producing persistent and problematic body weight gain in many treated patients. Major depressive illness is often associated with reductions in appetite and body weight, and treatment with antidepressants effectively restores mood, appetite and weight. However, a frequent complaint of patients treated with tricyclic drugs is of excessive and unwanted weight gain, oftentimes resulting in medication noncompliance. The incidence of weight gain during acute and chronic treatment with different, frequently prescribed antidepressant drugs will be reviewed, as will the possible mechanisms by which such drugs alter caloric intake and expenditure, contributing to drug-induced weight gain.     

Percutaneous Aspiration Lung Biopsy

A total of 182 percutaneous trans-thoracic aspiration biopsies were performed in 164 patients over a three-year period. In malignant neoplasms arising in the lung the diagnostic accuracy rate was 84%. In the non-malignant localized parenchymal lesions the accuracy drops considerably unless the lesion is cystic or cavitary. Some patients with non-parenchymal lesions were selected to assess further the value of this procedure. It proved much less rewarding in lesions of the chest wall, diaphragm and also in diffuse parenchymal disease. These lesions may be more accurately identified by other methods of biopsy. Lesions presenting as a mediastinal mass are an intermediate group and in selected cases helpful information can often be obtained by small-bore needle aspiration, particularly if a pericardial, bronchogenic or thymic cyst is suspected. Recent reports have shown that the aspiration of pulmonary lesions can be utilized to obtain viable tumour cells for chemosensitivity testing. The aspiration of nodular pulmonary lesions should be considered when a diagnosis is not forthcoming from the usual investigative means, since there has been little morbidity and no mortality in the series.     

NONSURGICAL TREATMENT OF CONVERGENT STRABISMUS

It is generally agreed that surgical treatment of convergent strabismus should be withheld until all other less traumatic approaches have proved ineffectual. There are four categories of nonsurgical treatment.One is psychiatric. Too often psychiatric problems in the causation of convergent strabismus are either overlooked or unrecognized.Another is the proper employment of optical devices. For example, spectacle lenses to eliminate the need for excessive accommodation with its associated convergence excess, and the employment of prisms in the lenses to permit the two eyes to see as a unit even though they may not be properly anatomically oriented.Another kind of treatment is orthoptics, the use of exercises and rather complex optical equipment in a laboratory to train the patient in coordination between the two eyes.Treatment with drugs is based on the fact that certain drugs reduce the effort necessary for accommodation (much as eye-glasses do) and therefore lessen the stimulus toward convergence which may possibly tend toward the development of convergent strabismus.     

Drug users in contact with general practice.

A group of heroin users who are in contact with a general practice in north west Edinburgh are described. The study group was younger and included more women than previous studies. These people used a large variety of drugs and mainly purchased them locally. Frequent and often prolonged abstinent periods occurred with no prescribed opiate treatment. The group had experienced a high rate of drug related medical disorders. All these points raise the possibility that opiate users who are known to general practitioners may be a distinctly different population from those who attend drug dependency clinics. The frequency of remission and the prevalence of polydrug use have profound implications for planning and evaluating an effective medical response.     

Evidence for decreased tubular reabsorption of calcium in glucocorticoid-treated asthmatics

Fasting urine calcium excretion was measured in 15 asthmatic patients receiving long-term glucocorticoid therapy (steroid group) and in age- and sex-matched asthmatics not receiving these drugs. In the steroid group, the mean urinary calcium/creatinine ratio and the mean calcium excretion per liter of glomerular filtrate (CaE) were both approximately twice the control values (p less than 0.005). When CaE was plotted as a function of serum calcium it more often exceeded the mean normal value in the steroid-treated patients than in the controls (p less than 0.05), suggesting a reduction in tubular calcium reabsorption. Calculation of the tubular maximum for calcium reabsorption confirmed a significant reduction in the glucocorticoid-treated patients (p less than 0.005). It is concluded that glucocorticoid drugs probably inhibit the tubular reabsorption of calcium and that this is likely to contribute to the development of osteoporosis in patients receiving this treatment.     

Self-poisoning with Drugs: A Worsening Situation

The incidence of self-poisoning with drugs has doubled in Sheffield in the past 10 years. It now causes almost 1 in 10 of all medical admissions and one in five of all medical emergencies; it is the second most common reason for emergency admission to medical beds.The average age of the patients has fallen; one in five has previously been admitted to hospital with self-poisoning. The drugs used are normally prescribed by a doctor and the types employed reflect national prescribing trends. It is estimated that over 70,000 self-poisoning cases may be admitted to hospitals in the United Kingdom each year.     

Treatment of Hypertension with Propranolol

When used in the treatment of hypertension propranolol is at least of similar potency to bethanidine, guanethidine, and methyldopa. Propranolol does not produce postural or exercise hypotension and it seems that it is often more acceptable to patients than conventional drugs. It usually produces the best control of the supine blood pressure.A series of 109 hypertensive patients was treated with propranolol; in nine the drug was withdrawn. In 92 of the patients a supine or standing blood pressure of 100 mm. Hg or less was achieved. Eighty of the patients had previously been treated with other potent drugs, and close comparisons and prolonged follow-up in 17 patients showed that diastolic pressures of 100 mm. Hg or less were achieved in more patients after propranolol than with guanethidine, bethanidine, or methyldopa.Sensitivity to propranolol varies widely, and dosage should be increased gradually. The hypotensive effect often takes six to eight weeks to reach its maximum. Propranolol reduces cardiac output but may also act by reducing the cardiac component of pressor stimuli; as a result the baroreceptors gradually regulate the blood pressure at a lower level. It is contraindicated in patients with obstructive airways disease or in uncompensated heart failure.