Trends and associated factors for Covid-19 hospitalisation and fatality risk in 2.3 million adults in England.

The Covid-19 mortality rate varies between countries and over time but the extent to which this is explained by the underlying risk in those infected is unclear. Using data on all adults in England with a positive Covid-19 test between 1st October 2020 and 30th April 2021 linked to clinical records, we examined trends and risk factors for hospital admission and mortality. Of 2,311,282 people included in the study, 164,046 (7.1%) were admitted and 53,156 (2.3%) died within 28 days of a positive Covid-19 test. We found significant variation in the case hospitalisation and mortality risk over time, which remained after accounting for the underlying risk of those infected. Older age groups, males, those resident in areas of greater socioeconomic deprivation, and those with obesity had higher odds of admission and death. People with severe mental illness and learning disability had the highest odds of admission and death. Our findings highlight both the role of external factors in Covid-19 admission and mortality risk and the need for more proactive care in the most vulnerable groups.

Influence of the first wave of COVID-19 on asthma inhaler prescriptions.

In the beginning of the COVID-19 pandemic, there were major concerns regarding the huge demand for asthma inhalers. Using the primary-care medical records for 614,700 asthma patients between January and June 2020, we found that there was a substantial increase in inhalers solely in March 2020. Patients significantly associated with receiving higher inhaled corticosteroid prescriptions were younger, of higher socioeconomic status, and had milder asthma.

Changes in COPD inhaler prescriptions in the United Kingdom, 2000 to 2016.

BACKGROUND: Over the past two decades, there have been significant changes in the pharmacological management of COPD, due to an explosion of inhaler trials, and timely updation of national and international guidelines. We sought to describe temporal changes in prescribing practices in the United Kingdom, and some of the factors that may have influenced them. PATIENTS AND METHODS: COPD patients were identified from UK primary care nationally representative electronic healthcare records (Clinical Practice Research Datalink), between 2000 and 2016. Prescription data were described by the three maintenance inhaled medication classes used, inhaled corticosteroids (ICS), long-acting beta agonist (LABA), long-acting muscarinic antagonist (LAMA), and their combinations, dual LABA-ICS, dual LAMA-LABA, or triple therapy LABA-ICS-LAMA. Differing patient characteristics across the six different therapy regimens were measured in 2016. RESULTS: COPD patients were identified: 187,588 prevalent and incident inhaler users and 169,511 incident inhaler users. Since 2002, LAMA showed increasing popularity, while ICS alone exhibited an inverse trend. Triple therapy prescriptions rapidly increased as the first-line therapy until 2014 when LAMA-LABA prescriptions started to increase. By 2014, 41% of all COPD patients were maintained on triple therapy, and 13% were maintained on LAMA only. Characterizing the patients in 2016 revealed that those on triple therapy were more likely to have more severe disease, yet, over a third of patients on triple therapy had only mild disease. CONCLUSION: UK prescribing practices were not in keeping with national guidelines but did appear to align with evidence from major drug trials and updated international guidelines. There has been a huge upsurge in triple therapy but incident data show this trend is beginning to reverse for initial management.

A histomorphometric study of cortical bone of the iliac crest in patients treated with glucocorticoids.

The effects of glucocorticoids on cancellous bone remodeling and structure are well documented but there are no reported histomorphometric studies in human cortical bone in glucocorticoid-treated patients. We have performed a histomorphometric analysis of iliac crest cortical bone in 14 patients treated with glucocorticoids, 9 females and 5 males, aged 18 to 48 years (34.1 +/- 7 years) (mean +/- standard deviation [SD]). The underlying disease was cystic fibrosis in 8 patients; asthma 3; and nephrotic syndrome; Crohn disease and inflammatory pseudotumor of the liver in one patient each. Results were compared with an age-matched control group of 10 premenopausal women and 4 men aged 22 to 38 years (30.1 +/- 4.8 years) who were not, however matched for underlying disease. Cortical bone indices were assessed by image analysis. Cortical width and area were similar in the two groups. However, cortical porosity, Haversian canal number, and density were higher in patients treated with glucocorticoids compared with controls (8.4 +/- 8.9% vs. 5.1 +/- 3.9%; P = 0.03) (45.9 +/- 23.2 vs. 31.9 +/- 24.4; P =0.003) (13.7 +/- 9.4 vs. 6.7 +/- 3.3/mm2; P = 0.00005). Haversian canal area did not differ significantly between groups. The mean wall width of the osteons, bone formation rate (microm2/microm/day) and mineral apposition rate (microm/day) were lower in treated patients compared to controls (48.8 +/- 7.1 microm vs. 59.8 +/- 12.9 microm; P = 0.01) (0.056 +/- 0.040 vs. 0.095 +/- 0.058; P = 0.05) and (0.59 +/- 0.12 vs. 0.75 +/- 0.11; P = 0.002). The proportion of canals with an eroded surface was lower in the treated compared with the control group, although this difference was not statistically significant. These results demonstrate that cortical porosity is increased in patients treated with long-term glucocorticoid therapy, due mainly to an increase in the number rather than size of Haversian canals. This may be because of increased bone resorption during the early stages of glucocorticoid therapy, in combination with long-term impairment of bone formation. Effects of the underlying disease on bone remodeling may also contributed to these changes and could not be excluded in the present study; since control subjects were not matched in terms of disease status.

Vertebral deformities and low bone mineral density in adults with cystic fibrosis: a cross-sectional study.

Patients with cystic fibrosis (CF) have low bone mineral density (BMD). The clinical relevance of this is not clearly established. The aim of this study was to determine the prevalence of low BMD and vertebral deformities in CF adults with varied disease severity. One hundred and seven patients (58 men) aged 18-60 years underwent dual-energy X-ray absorptiometry scanning of the lumbar spine and hip, radiology of the spine and biochemical studies. Thirty-eight percent had a Z-score of < -1, with 13% having Z-scores < -2. Seventeen percent had evidence of vertebral deformity on radiography, mostly in the thoracic spine. Thirty-five percent reported past fractures, of which 9% were rib fractures. Percent predicted forced expiratory volume in 1 second (FEV1) and the amount of daily physical activity were positively related to BMD. The number of intravenous antibiotic courses in the previous 5 years was negatively related to BMD. Patients with a history of rib fracture and CF-related diabetes had significantly lower femoral neck BMD (p < 0.02). The median serum 25-hydroxyvitamin D was 28 nmol/l, with 36% of patients having levels below 25 nmol/l despite vitamin D supplementation. Forty-four percent had raised levels of urinary pyridinium crosslinks (NTx). In conclusion, fragility fractures and hypovitaminosis D occur commonly in adult patients with CF. Low BMD occurs in patients with more severe disease and significantly relates to FEV1, infective exacerbations and daily energy expended in physical activity.

Desquamative interstitial pneumonia and respiratory bronchiolitis-associated interstitial lung disease.

Our understanding of the various types and patterns of diffuse lung disease that might result in fibrosis has evolved considerably over the last 50 years. Many entities now regarded as distinct had been previously "lumped'' together as a single disease, "lung fibrosis,'' and more recently misdiagnosed as idiopathic pulmonary fibrosis (IPF, synonymous with cryptogenic fibrosing alveolitis). In 1965 desquamative interstitial pneumonia (DIP) was first described, and later it was clearly demonstrated that the clinical and pathological features of DIP and IPF were different, particularly in terms of survival and response to therapy. They are not part of the same disease spectrum nor does DIP evolve into usual interstitial pneumonia (UIP). Later, in the mid-1980s, RBILD was described as a distinct clinicopathologic syndrome with features consistent with an interstitial lung disease among current or former smokers. In the recent histopathological classification of idiopathic interstitial pneumonia (IIP), DIP and RBILD have been included as separate entities, although there is some evidence that suggests they may lie at the two ends of a single spectrum. The debate bears similarities with the debate about DIP and UIP and is as yet unresolved. This article will give a broad and current overview of these two rarer forms of IIP, including issues that relate to diagnosis, imaging, histopathology, treatment, and prognosis.

Substitute decision-making and personal control: implications for self-determination.

Levels of personal control exercised by 76 adults with mental retardation were contrasted by substitute decision-making status. Individuals with no guardian or conservator exercised more personal control than did those with a conservator, who exerted more personal control than did participants with a guardian. Similar group differences in self-determination competencies were also observed. When self-determination competencies were controlled statistically, significant group differences in exercise of personal control remained. Restrictive substitute decision-making status, inappropriate to current competencies, may have constrained individuals' levels of personal control. Reviewing substitute decision-making status on a regular basis and limiting or removing guardianship/conservatorship when it is not appropriate, may enhance personal control.

Relationship of skeletal muscle mass, muscle strength and bone mineral density in adults with cystic fibrosis.

Few studies have investigated peripheral muscle strength and quality in patients with cystic fibrosis (CF). The present study tested the isometric and isokinetic strength of the quadriceps and hamstrings using an isokinetic dynamometer and a strength-testing chair in 25 CF adults and 25 controls. Total body and leg muscle mass were determined by dual-energy X-ray absorptiometry, and bone mineral density (BMD) was also measured. Both muscle strength and muscle mass (total body and leg) were decreased in the CF group. In both groups there was a highly significant relationship between quadriceps strength and leg muscle mass (CF, r=0.7, P=0.0002; controls, r=0.6, P=0.0013). When strength was normalized for muscle size, there was no significant difference between the two groups. Total body and leg BMD were significantly reduced in CF subjects compared with controls. However, when corrected for height, the differences disappeared. There was a significant relationship found between leg muscle mass and leg BMD. We conclude that CF adults are significantly weaker than controls. This is due to lower muscle mass, and not to a reduced force-generating capacity of the muscle, implying that there is no decrease in the quality of CF muscle. BMD is also reduced in CF subjects, and this appears to be related to shorter stature in this group.

Pulmonary artery occlusion by tuberculous mediastinal lymphadenopathy.

Two cases of tuberculous mediastinal lymphadenopathy are presented in which the clinical features mimicked those of pulmonary embolism, causing striking abnormalities on radionuclide scintigraphy. It is concluded that tuberculous mediastinal lymphadenopathy should be included in the differential diagnosis of reduced lung perfusion due to proximal pulmonary artery occlusion.

Clarithromycin therapy for bacteremic Mycobacterium avium complex disease. A randomized, double-blind, dose-ranging study in patients with AIDS. AIDS Clinical Trials Group Protocol 157 Study Team.

OBJECTIVE: To determine the antimicrobial activity and tolerability of clarithromycin for treating bacteremic Mycobacterium avium complex disease in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A randomized, double-blind, dose-ranging study. SETTING: Outpatient clinics. PATIENTS: 154 patients with human immunodeficiency virus (HIV) infection and blood cultures positive for M. avium complex who had symptomatic disease. INTERVENTIONS: Random assignment to clarithromycin at dosages of 500 mg, 1000 mg, or 2000 mg twice daily for 12 weeks. MAIN OUTCOME MEASURE: Median number of colony-forming units of M. avium complex per milliliter of blood. RESULTS: Clarithromycin decreased mycobacterial CFUs from 2.7 to 2.8 log 10/mL of blood at baseline to less than 0 log 10/mL during follow-up (P < 0.0001). After 2 weeks, patients receiving 500 mg twice daily were less likely to be culture negative than were patients receiving 1000 or 2000 mg twice daily (11% compared with 33% or 29%; P = 0.08). At 6 weeks, the median number of CFUs of M. avium complex/mL of blood was 0 or 1 for all three groups. Clarithromycin-resistant isolates of M. avium complex developed in 46% of patients at a median of 16 weeks. Median survival was longer in patients assigned to 500 mg twice daily (median, 249 days) than in patients assigned to 1000 mg or 2000 mg. Death in the first 12 weeks was lowest in the 500-mg group (P = 0.007). CONCLUSIONS: Clarithromycin therapy acutely decreased M. avium complex bacteremia in patients with HIV infection by more than 99%. Clarithromycin, 500 mg twice daily, was well tolerated and associated with better survival. Emergence of clarithromycin-resistant organisms was an important problem.

Determinants of the choice of rural practice: a study of Yugoslav general practitioners.

A questionnaire study of Yugoslav general practitioners was undertaken to document reasons for the unpopularity of rural practice and to characterize better the GPs who do choose rural practice. Responses indicated that rural GPs were significantly more overworked, had less opportunity for continuing education, had poorer medical facilities, and had less adequate schools for their children than urban GPs. On the other hand, rural work was felt to be more interesting and to provide closer contact with patients. GPs who were happy in rural practice were more likely to have urban backgrounds, to have planned to be rural physicians before entering medical school, and to have undergone GP specialization training than were other GPs in the sample. Relative importances attributed to the various practice location determinants are noted. Possible applications of the study in alleviating rural doctor shortages are discussed.