Interstitial laser photocoagulation as a treatment for breast cancer

Conservative surgery is a safe alternative to mastectomy for some patients with breast cancer. A survey of surgeons in this thesis has shown that more surgeons would now undertake conservative surgery than they have done in the past. Recently a new technique, interstitial laser photocoagulation(ILP) has been described which is capable of in situ tissue necrosis with safe healing. The idea of ILP takes the concept of conservative surgery for breast cancer a step further. The main purpose of this thesis was to investigate the potential value of ILP as a future method of destroying breast cancers in situ leaving the area to heal via resorption and fibrosis. The aims of this thesis were to study the biology of laser interactions with breast cancers scheduled for surgery(and not to completely destroy the tumour), to optimise the laser parameters of power and exposure for a particular tumour and to find an imaging technique which will accurately predict the extent of laser damage. Forty five patients were treated with ILP prior to surgery(median 7 days). Tumour necrosis varied from 2-25mm. No laser damage was noted in 4 patients. Two patients developed minor complications and treatment was abandoned early due to pain in a further 4 patients. The presence of charring within the tumour was associated with larger diameters of necrosis than when charring was absent(median 13 vs 6 mm, p=0.002) and use of a precharred fibre produced similar lesions(median 14mm) which were more predictable.The histological features in the tumour following ILP were of coagulative necrosis which appeared to heal by the formation of fibrous tissue. An area of heat fixed, morphologically preserved tissue was noted within the zone of coagulative necrosis which was thought to be non-viable. Ultrasonography, Com puterised Tomography(CT) and M agnetic Resonace Imaging(MRI) were all used to monitor necrosis. Ultrasound was unable to predict the extent of necrosis as measured in the resected specimen(r=0.3, p=N.S.) but was reasonable at predicting tumour size(r=0.6, p=0.001). CT and MRI show some promise but were only investigated in small numbers of patients. This study has shown that ILP is simple and safe and when using a pre-charred fibre, predictable. If the initial results of imaging using CT and MRI are confirmed in larger studies then ILP could possibly have a role in the treatment of small breast cancers

The clinical value of new diagnostic tools for tuberculosis

Barriers to global tuberculosis (TB) control include multidrug resistance, HIV infection, and weak health systems. Case detection is critical to TB control and is affected by all three of these. Currently, most low- and middle-income countries (LMICs) rely on direct sputum smear microscopy for diagnosis. Modern culture methods and molecular tests, previously considered too complex or too expensive for implementation in LMICs, are now being introduced there in parallel with a global effort to strengthen laboratories. It remains to be seen whether services based on these tools can be made widely accessible to patients. New point-of-care tests for TB are urgently needed but cannot be expected in the near future. In the meantime, diagnostic tools based on optimized smear microscopy, although less sensitive than reference laboratory tests, may be more accessible and have more impact on case finding. It is a matter of urgency that these improved microscopy services be integrated with services based on rapid methods that can identify multidrug-resistant cases

A public health approach to hepatitis C control in low- and middle-income countries.

In light of new treatment regimens for hepatitis C, Amitabh Suthar and Anthony Harries outline a wider public health approach for tackling the disease

Risk Factors for High Early Mortality in Patients on Antiretroviral Treatment in a Rural District of Malawi.

OBJECTIVES: Among adults started on antiretroviral treatment (ART) in a rural district hospital (a) to determine the cumulative proportion of deaths that occur within 3 and 6 months of starting ART, and (b) to identify risk factors that may be associated with such mortality. DESIGN AND SETTING: A cross-sectional analytical study set in Thyolo district, Malawi. METHODS: Over a 2-year period (April 2003 to April 2005) mortality within the first 3 and 6 months of starting ART was determined and risk factors were examined. RESULTS: A total of 1507 individuals (517 men and 990 women), whose median age was 35 years were included in the study. There were a total of 190 (12.6%) deaths on ART of which 116 (61%) occurred within the first 3 months (very early mortality) and 150 (79%) during the first 6 months of initiating ART. Significant risk factors associated with such mortality included WHO stage IV disease, a baseline CD4 cell count under 50 cells/mul and increasing grades of malnutrition. A linear trend in mortality was observed with increasing grades of malnutrition (chi for trend = 96.1, P </= 0.001) and decreasing CD4 cell counts (chi for trend = 72.4, P </= 0.001). Individuals who were severely malnourished [body mass index (BMI) < 16.0 kg/m] had a six times higher risk of dying in the first 3 months than those with a normal nutritional status. CONCLUSIONS: Among individuals starting ART, the BMI and clinical staging could be important screening tools for use to identify and target individuals who, despite ART, are still at a high risk of early death

Operational research in low-income countries: what, why, and how?

Operational research is increasingly being discussed at institutional meetings, donor forums, and scientific conferences, but limited published information exists on its role from a disease-control and programme perspective. We suggest a definition of operational research, clarify its relevance to infectious-disease control programmes, and describe some of the enabling factors and challenges for its integration into programme settings. Particularly in areas where the disease burden is high and resources and time are limited, investment in operational research and promotion of a culture of inquiry are needed so that health care can become more efficient. Thus, research capacity needs to be developed, specific resources allocated, and different stakeholders (academic institutions, national programme managers, and non-governmental organisations) brought together in promoting operational research

Scaling up antiretroviral therapy in Malawi-implications for managing other chronic diseases in resource-limited countries.

The national scale-up of antiretroviral therapy (ART) in Malawi is based on the public health approach, with principles and practices borrowed from the successful DOTS (directly observed treatment, short course) tuberculosis control framework. The key principles include political commitment, free care, and standardized systems for case finding, treatment, recording and reporting, and drug procurement. Scale-up of ART started in June 2004, and by December 2008, 223,437 patients were registered for treatment within a health system that is severely underresourced. The Malawi model for delivering lifelong ART can be adapted and used for managing patients with chronic noncommunicable diseases, the burden of which is already high and continues to grow in low-income and middle-income countries. This article discusses how the principles behind the successful Malawi model of ART delivery can be applied to the management of other chronic diseases in resource-limited settings and how this paradigm can be used for health systems strengthening

The timing of death in patients with tuberculosis who die during anti-tuberculosis treatment in Andhra Pradesh, South India

Background: India has 2.0 million estimated tuberculosis (TB) cases per annum with an estimated 280,000 TBrelated deaths per year. Understanding when in the course of TB treatment patients die is important for determining the type of intervention to be offered and crucially when this intervention should be given. The objectives of the current study were to determine in a large cohort of TB patients in India:- i) treatment outcomes including the number who died while on treatment, ii) the month of death and iii) characteristics associated with “early” death, occurring in the initial 8 weeks of treatment. Methods: This was a retrospective study in 16 selected Designated Microscopy Centres (DMCs) in Hyderabad, Krishna and Adilabad districts of Andhra Pradesh, South India. A review was performed of treatment cards and medical records of all TB patients (adults and children) registered and placed on standardized anti-tuberculosis treatment from January 2005 to September 2009. Results: There were 8,240 TB patients (5183 males) of whom 492 (6%) were known to have died during treatment. Case-fatality was higher in those previously treated (12%) and lower in those with extra-pulmonary TB (2%). There was an even distribution of deaths during anti-tuberculosis treatment, with 28% of all patients dying in the first 8 weeks of treatment. Increasing age and new as compared to recurrent TB disease were significantly associated with “early death”. Conclusion: In this large cohort of TB patients, deaths occurred with an even frequency throughout anti-TB treatment. Reasons may relate to i) the treatment of the disease itself, raising concerns about drug adherence, quality of anti-tuberculosis drugs or the presence of undetected drug resistance and ii) co-morbidities, such as HIV/ AIDS and diabetes mellitus, which are known to influence mortality. More research in this area from prospective and retrospective studies is needed