Primary health care response to noncommunicable diseases: an assessment of Wellness Clinics in Ghana.

BACKGROUND: Globally, there is a significant unmet need for the rapidly growing burden of Non-Communicable Diseases (NCDs). Ghana has adopted and implemented Wellness Clinics (WC) nationwide to respond to the rising burden of NCDs. Regrettably, very little is known about WCs, including their structure and the services they offer. This study explores the concept of WC, their structure, position within the hospital environment, and services from the perspectives of healthcare providers and clients. METHODS: An exploratory qualitative study was conducted with health professionals (n = 12) and clients (n = 26) of Wellness Clinics in two district hospitals and one regional hospital in a deprived region of Ghana where NCDs are rising. Using the WHO-PEN approach, an interview guide was purposely designed for this study. The data were analysed thematically using Atlas.ti. RESULTS: All three Wellness Clinics were sub-units under the outpatient department. The WC was created by the facilities to respond to the increase in NCDs and to meet annual performance review requirements. The Wellness Clinics provided NCD diagnosis, counselling, and treatment services to approximately 300 clients per week at the facility level. Only one of the WCs provided NCD prevention services at the community level. Integrated NCD care was also provided at the WC, despite the health system and individual-level challenges reported by the health workers and clients. CONCLUSION: The implementation of the Wellness Clinic demonstrates the government's commitment to addressing the increasing burden of NCDs in Ghana through the primary health system. To maximise the impact of the wellness clinics, we recommend developing best practices, providing logistics, and addressing health insurance challenges.

Antibiotic exposure in a low-income country: screening urine samples for presence of antibiotics and antibiotic resistance in coagulase negative staphylococcal contaminants.

Development of antimicrobial resistance has been assigned to excess and misuse of antimicrobial agents. Staphylococci are part of the normal flora but are also potential pathogens that have become essentially resistant to many known antibiotics. Resistances in coagulase negative staphylococci (CoNS) are suggested to evolve due to positive selective pressure following antibiotic treatment. This study investigated the presence of the nine most commonly used antimicrobial agents in human urine from outpatients in two hospitals in Ghana in relation to CoNS resistance. Urine and CoNS were sampled (n = 246 and n = 96 respectively) from patients in two hospitals in Ghana. CoNS were identified using Gram staining, coagulase test, and MALDI-TOF/MS, and the antimicrobial susceptibility to 12 commonly used antimicrobials was determined by disk diffusion. Moreover an analytical method was developed for the determination of the nine most commonly used antimicrobial agents in Ghana by using solid-phase extraction in combination with HPLC-MS/MS using electron spray ionization. The highest frequency of resistance to CoNS was observed for penicillin V (98%), trimethoprim (67%), and tetracycline (63%). S. haemolyticus was the most common isolate (75%), followed by S. epidermidis (13%) and S. hominis (6%). S. haemolyticus was also the species displaying the highest resistance prevalence (82%). 69% of the isolated CoNS were multiple drug resistant (≧ 4 antibiotics) and 45% of the CoNS were methicillin resistant. Antimicrobial agents were detected in 64% of the analysed urine samples (n = 121) where the most frequently detected antimicrobials were ciprofloxacin (30%), trimethoprim (27%), and metronidazole (17%). The major findings of this study was that the prevalence of detected antimicrobials in urine was more frequent than the use reported by the patients and the prevalence of resistant S. haemolyticus was more frequent than other resistant CoNS species when antimicrobial agents were detected in the urine.

Fluorescence versus white-light bronchoscopy for detection of preneoplastic lesions: a randomized study.

BACKGROUND: There are no currently approved methods for the screening and early detection of lung cancer. We compared the ability of conventional white-light bronchoscopy (WLB) and laser-induced fluorescence endoscopy (LIFE) to detect preneoplastic lung lesions in a randomized trial in which both the order of the procedures and the bronchoscopists were randomly assigned. METHODS: The study included high-risk subjects enrolled because of a cigarette smoking history of at least 30 pack-years, an air-flow obstruction, and either an abnormal sputum cytology (n = 48) or a previous or suspected lung cancer (n = 7). LIFE and WLB were performed on all patients. Biopsy specimens were assessed for histologic abnormalities, including the presence of angiogenic squamous dysplasia. All statistical tests were two-sided. RESULTS: A total of 391 biopsy specimens were taken from the 55 patients. Thirty-two patients (58%; 95% confidence interval [CI] = 44% to 71%) had at least one biopsy with moderate or severe dysplasia, and 19 (59%; 95% CI = 41% to 76%) of these patients could be diagnosed based solely on the results of LIFE. LIFE was statistically significantly more sensitive than WLB for detecting moderate dysplasia or worse (68.8% versus 21.9%, respectively) (difference = 46.9%; 95% CI = 25% to 68%; P< .001). The relative sensitivities (WLB = 1.0) were 3.1 (95% CI = 1.6 to 6.3) for LIFE and 3.7 (95% CI = 1.9 to 7.3) for LIFE and WLB combined. LIFE was less specific than WLB (69.6% versus 78.3%, respectively; P = .45), but the difference was not statistically significant. The relative specificities (WLB = 1.0) were 0.9 for LIFE (95% CI = 0.6 to 1.3) and 0.6 (95% CI = 0.4 to 1.0) for LIFE and WLB combined. The results were similar regardless of the order of the procedures or the order of the bronchoscopists. Also, LIFE was better at identifying angiogenic squamous dysplasia lesions than WLB (detection ratio [DR], which indicates the relative likelihood of getting a positive result in a sample with dysplasia compared with one without, for LIFE = 1.39 [95% CI = 1.17 to 1.65] versus DR for WLB = 0.67 [95% CI = 0.38 to 1.21]). CONCLUSION: LIFE was more sensitive than WLB in detecting preneoplastic bronchial changes in high-risk subjects. The prognostic implication of this finding is not yet clear.

Review of recent advances in fluorescence bronchoscopy in early localization of central airway lung cancer.

Centrally located lung cancers are radiologically occult until so far advanced as to have a low cure rate or require extensive resection for cure, but at a cost of high morbidity. These cancers represent about one-fifth of new lung cancers. Autofluorescence bronchoscopy appears to be an important tool in localizing premalignant and early malignant lesions in the large central airways, particularly when applied to high-risk patients. Applications include studies of molecular biology of premalignancy and early malignancy, chemoprevention studies, endobronchial therapy studies, localization of synchronous tumors, estimation of the extent of field cancerization, and better estimation of resection margins. Autofluorescence bronchoscopy appears to be significantly more sensitive than white light examination but has low specificity. This technology is likely to gain widespread use when evaluation of sputum for malignant changes is both more sensitive and specific, and when its application is demonstrated to reduce mortality in this important subgroup of non-small cell lung cancer patients.

Angiogenic squamous dysplasia in bronchi of individuals at high risk for lung cancer.

Lung carcinogenesis is assumed to be a multistep process, but detailed understanding of the sequential morphological and molecular changes preceding invasive lung cancer remains elusive. To better understand early lung carcinogenesis, we initiated a program of fluorescence bronchoscopy in smokers at high risk for lung cancer. In the bronchial biopsies from these subjects, we observed a unique lesion consisting of capillary blood vessels closely juxtaposed to and projecting into metaplastic or dysplastic squamous bronchial epithelium, angiogenic squamous dysplasia (ASD). Serial sections of the capillary projections confirmed that they represent intramucosal capillary loops. Microvessel density in ASD was elevated in comparison to normal mucosa (P = 0.0003) but not in comparison to other forms of hyperplasia or dysplasia. ASD thus represents a qualitatively distinct form of angiogenesis in which there is architectural rearrangement of the capillary microvasculature. Genetic analysis of surface epithelium in a random subset of lesions revealed loss of heterozygosity at chromosome 3p in 53% of ASD lesions. No confirmed p53 mutations were identified. Compared with normal epithelium, proliferative activity was markedly elevated in ASD lesions. ASD occurred in 54 of 158 (34%) high-risk smokers without carcinoma and in 6 of 10 patients with squamous carcinoma who underwent fluorescence bronchoscopy. One early-stage invasive carcinoma was noteworthy for the occurrence of ASD juxtaposed to invasive tumor. Seventy-seven (59%) of the ASD lesions were detected by abnormal fluorescence alone. Twenty bronchial sites (11 patients) were rebiopsied 1 year after the initial diagnosis. At nine (45%) of these sites, the lesion was found to persist. The lesion was not present in biopsies from 16 normal nonsmoker control subjects. The presence of this lesion in high-risk smokers suggests that aberrant patterns of microvascularization may occur at an early stage of bronchial carcinogenesis.

Screening for lung cancer revisited and the role of sputum cytology and fluorescence bronchoscopy in a high-risk group.

Lung cancer is an epidemic disease that is underrepresented in the research funding for early detection and chemoprevention arenas. Screening programs have been discouraged for both financial and political reasons. Yet, increasing evidence suggests that screening and early detection may improve outcome in lung cancer. Sputum cytology examination has been shown in several studies to lead to detection of lung cancer at an earlier stage, resulting in an improved 5-year survival rate. Monoclonal antibody detection, fluorescence bronchoscopy, and low-dose spiral CT increase diagnostic sensitivity and improve the ability to localize early-stage lesions. Utilizing these new techniques and improving the definition of high-risk groups may improve the success and cost-effectiveness of early detection based on sputum cytology. The ultimate goal of improving long-term survival in lung cancer will be achieved only when cancer can be detected in its early stages and lesions can be localized in large numbers. Advances in the last 15 years offer an encouraging vision for the value of early detection and effective treatment for lung cancer.

Analysis of immune system gene expression in small rheumatoid arthritis biopsies using a combination of subtractive hybridization and high-density cDNA arrays.

Subtractive hybridization of cDNAs generated from synovial RNA which had been isolated from patients with rheumatoid arthritis (RA) or normal controls was used in conjunction with high-density array hybridization to identify genes of immunological interest. The method was designed to detect gene expression in small needle biopsy specimens by means of a prior amplification of nanogram amounts of total RNA to full-length cDNA using PCR. The latter was cut with Rsa I, ligated with adapters, hybridized with unmodified driver cDNA, and subjected to suppression subtraction PCR. Differentially expressed products were cloned into E. coli and picked into 384 well plates. Inserts were obtained by PCR across the multiple cloning site, and the products arrayed at high density on nylon filters. The subtracted cDNAs were also labelled by random priming for use as probes for library screening. The libraries chosen were the subtracted one described above and a set of 45,000 ESTs from the I.M. A.G.E consortium. Clones showing positive hybridization were identified by sequence analysis and homology searching. The results showed that the subtracted hybridization approach could identify many gene fragments expressed at different levels, the most abundant being immunoglobulins and HLA-DR. The expression profile was characteristic of macrophage, B cell and plasma cell infiltration with evidence of interferon induction. In addition, a significant number of sequences without matches in the nucleotide databases were obtained, this demonstrates the utility of the method in finding novel gene fragments for further characterisation as potential members of the immune system. Although RA was studied here, the technology is applicable to any disease process even in cases where amounts of tissue may be limited.

Efficacy of two sputum collection techniques in patients with air flow obstruction.

OBJECTIVE: To compare the efficacy of two sputum collection techniques in patients with chronic obstructive pulmonary disease (COPD) in order to diagnose dysplasia or neoplasia. STUDY DESIGN: This was a crossover study design comparing induced sputum with sputum collected at home. One hundred seven patients with COPD were enrolled. Fifty-six were randomized to collect induced sputum first followed by sputum collection at home. Fifty-one randomly assigned patients collected the sputum in reverse order. RESULTS: The second sputum collection technique for both random assignments gave the greatest yield of adequate sputum. There was no significant difference in efficacy between the collection of the two sputum collection techniques in the presence of the learning (period) effect. CONCLUSION: Sputum collection is equally efficacious by the induced method and the home collection method. A learning effect was responsible for the increased yield of sputum abnormalities in the second collection session. Sputum collection at home may facilitate the amount of dysplasic and neoplastic bronchial epithelial changes in heavy smokers with COPD.

Novel inhibitors of fungal protein synthesis produced by a strain of Graphium putredinis. Isolation, characterisation and biological properties.

The isolation and structure determination of 6 analogues of the fungal protein synthesis inhibitor GR135402, from Graphium putredinis, is described. The relative potencies of the compounds as protein synthesis inhibitors and as in vitro antifungal agents provide interesting insights into the structure-activity relationships in this series.

Cytopathological analysis of sputum in patients with airflow obstruction and significant smoking histories.

Advances in the understanding of lung cancer biology have led to observations that specific genetic changes occur in premalignant dysplasia. These observations have occurred predominantly in molecular studies of resected lung tumors and consequently, they may not be fully representative of those biological abnormalities characterizing premalignant lesions in individuals without overt lung cancer. Studies of premalignant epithelial cell biology and chemoprevention are needed in this patient subgroup. Such an initiative is now underway through the lung cancer Specialized Program of Research Excellence (SPORE) grant awarded to the University of Colorado Cancer Center (and affiliated institutions) by the National Cancer Institute. To identify participants for the early detection and chemoprevention trials of the Colorado SPORE, we initiated a sputum cytology screening program targeting persons with chronic obstructive pulmonary disease and smoking histories of 40 or more pack-years. During the first 26 months after activation of the screening program, sputum samples from 632 participants were evaluated. Of these, 533 (84%) of the subjects submitted specimens deemed adequate for cytopathological interpretation; 99 (16%) provided sputum samples unsuitable for cytodiagnosis. Of those participants who submitted adequate samples, 48% had cytodiagnoses of mild dysplasia, 26 % had moderate to severe dysplasia, and 2% presented with carcinoma in situ or invasive carcinoma. Logistic regression modeling was pursued to determine whether selected demographic and/or clinical status variables could be identified as statistically significant predictors of the specific cytological outcome to be expected (mild dysplasia, moderate dysplasia, and so forth). The only apparent associations found from both univariate and multivariate analyses were that the total number of pack-years of smoking history decreased with severity of cytodiagnosis and that those individuals with mild or moderate dysplasia were more likely to be ex-smokers than those with grades of regular metaplasia or lower. Based on the initial results of the Colorado SPORE sputum cytology screening program, we conclude that persons with chronic obstructive pulmonary disease and 40 or more pack-years of smoking history have a high prevalence of premalignant dysplasia detectable through sputum cytology and should be targeted for research programs focusing on lung cancer prevention, early detection, and exploratory biomarker studies.

Pulmonary hypertension associated with long-term inhalation of "crank" methamphetamine.

We present the case of a 33-year-old white male truck driver with a ten-year history of 3.5-g/wk "crank" and "peanut butter methamphetamine" inhalation (methamphetamine and propylhexedrine, respectively). This patient developed marked pulmonary hypertension as a probable consequence of abuse of these drugs. Proposed mechanisms of disease invoke toxic endothelial injury, hypoxic insult, direct spasm, vasculitis, and dysregulation of mediators of vascular tone. The possible role of genetics is discussed in reference to variability of human response to sympathomimetic challenge.

Unexplained pulmonary infiltrates in the compromised patient. An invasive investigation in a consecutive series.

A series of 51 consecutive unexplained pulmonary infiltrates were reviewed retrospectively, in a group of 48 patients in whom invasive procedures were performed. Fifty-two percent of these patients had leukemia or lymphoma and 40% had solid tumors. All patients had lung tissue obtained premortem either by transbronchial biopsy through the flexible fiberoptic bronchoscope or by open lung biopsy. There was a 27% complication rate in these invasive procedures including bleeding, pneumothorax, and ventilatory support. Infectious agents were found in only 13 cases (25%) with a mortality rate of 62%. The pathologic finding of the underlying malignant disease or organizing pneumonia portended a poor prognosis with 100% and 80% mortality, respectively. Twenty-one patients had biopsy tissue revealing only nonspecific pathologic changes and were associated with the lowest mortality (19%). It was found that 50% of the solid tumor patients with unexplained pulmonary infiltrates had nonspecific pathologic changes. The biopsy findings resulted in a change in the therapy in 29% of the cases and in 19% of the cases the subsequent change in therapy resulted in marked improvement. The lung biopsy is useful to diagnose treatable infectious disease, as well as for prognostic guidance in caring for critically ill compromised patients.

Effect of aging alone on mechanical properties of the normal adult human lung.

For plethysmographic studies of respiratory mechanics, we selected, from a general population, 51 subjects, aged 25-75 yr, who had never smoked, had no present or past cardiorespiratory symptoms or disease, were alpha1-antitrypsin MM phenotypes, and were normal by physical examination, vectorcardiography, and chest roentgenography. Approximately equal numbers of men and women were represented in each of three age groups; 25-35, 36-64, and 65-75. Both sexes demonstrated loss of lung elastic recoil with age, most significant at high lung volumes, but the rate of loss was less than previously reported. Males had higher lung recoil than females of comparable age, but if lung size was taken into account, there were no sex differences in bulk elastic properties. Maximum expiratory flow diminished with age only at low volumes, suggesting that equal pressure points are more centrally located at low lung volumes in the elderly.

Exercise-aggravated hypoxemia and orthodeoxia in cirrhosis.

A syndrome characterized by hypoxemia aggravated by exercise, orthodeoxia, hypocapnia, and evidence of hyperdynamic circulation, but otherwise normal indices of pulmonary air flow, volume, and distribution of ventilation has been observed as an infrequent complication of hepatic cirrhosis. An illustrative case is described, the features of which support the presence of a shunt or shunt-like mechanism consisting of low-resistance vascular communications within the lung. We suggest that this may represent the existence of a hepatopulmonary syndrome analogous to the hepatorenal syndrome.