International Journal of Medicine and Medical Sciences ISSN: 2167-0404 Vol. 2 (11), pp.256-262, November, 2012. © International Scholars Journals

Full Length Research Paper 

 

Long-term trends and determinants of myocardial infarction morbidity, mortality, and lethality in Russian population

Valery. V. Gafarov^1,2* and Almira. V. Gafarova^1,2

¹Federal State Budgetary Institution the Interdepartmental Laboratory of Cardiovascular Disease Epidemiology of Siberian Branch of the Russian Academy of Medical Sciences, Russia.

²Federal State Budgetary Institution the Research Institute of Internal Medicine of Siberian Branch of the Russian Academy of Medical Sciences, Russia.

*Corresponding author. E-mail: [email protected]  

Received 18 July, 2012; Accepted 08 November, 2012

Abstract

The objective of the study was to elucidate 33-year trends and determinants in myocardial infarction (MI) morbidity, mortality, and lethality in Russia in 1977 to 2009. Data of WHO studies (Acute Myocardial Infarction Register and MONICA) were analyzed in three districts of Novosibirsk. MI morbidity in 25 to 64-year-old population in Russia was found to be one of the highest in the world. MI morbidity rates remained steady for the entire period of study except for 1988, 1994, 1998 (increase), 2002 to 2004, and 2006 (decrease). Changes in mortality and lethality were similar to changes in morbidity except for 1977 to 1978 and 2002 to 2005. Prehospital mortality and lethality rates significantly exceeded the rates of in-hospital deaths. MI mortality rates exceeded death rates caused by alcohol abuse by 2 to 3 times. Mortality and lethality decrease during period of unchanged morbidity suggested improvement in cardiac care; increase in mortality and lethality at a time of decreased morbidity indicated disorganization of medical services. Prevalence of psychosocial risk factors significantly increased over time, whereas levels of behavioral and somatic risk factors remained unchanged. MI morbidity, mortality, and lethality rates were markers of increasing social stress in population. MI deaths were the main component of increase in mortality in Russia.

Key words: Myocardial infarction, epidemiology, morbidity, mortality, risk factors.

International Journal of Medicine and Medical Sciences ISSN: 2167-0404 Vol. 2 (11), pp. 263-268, November, 2012. © International Scholars Journals

Full Length Research Paper

Τhe role of exercise in the breast cancer related lymphedema

Panagiotou A., Nastoulis E., Bakirtzis D., Papadopoulos P., Tsonga TH., Fiska A. and Kapetanakis S.*

Department of Anatomy Medical School of Alexandroupolis, Democritus University of Thrace, Greece, 68100.

*Corresponding author. E-mail: [email protected]

Received 07 August, 2012; Accepted November 09, 2012

Abstract

The upper extremity breast cancer related lymphedema is a result of the surgery and /or radiation in the axillary lymph node due to interference of the lymphatic drainage of the affected area. Lymphedema is presented as a chronic swelling of the limb followed by pain, changes in the appearance of the skin, difficulty in moving of the joints and infections. These symptoms significantly affect the quality of life of the patient. The main risk factors for developing lymphedema include stage of cancer, the type of surgery, the surgical removal or/and radiation of axillary lymph nodes, the number of retrieved lymph nodes, the exposure to high temperatures and obesity. Lymphedema is irreversible so it is imperative to inform patients about risk factors and how to prevent and control it when is installed. In this point exercise can have significant benefits for breast cancer survivors during and after treatment. Furthermore participation in an upper body exercise program caused no changes in arm circumference or arm volume in women with lymphedema after breast cancer and exercise generally encourages skeletal muscle contractions to provide the primary pumping mechanism for lymphatic and venous drainage and therefore stimulates the contraction of lymph vessels.

Key words: Lymphedema, exercise, breast cancer, aerobic exercise.  

International Journal of Medicine and Medical Sciences ISSN: 2167-0404 Vol. 2 (11), pp. 245-250, November, 2012. © International Scholars Journals

Full Length Research Paper

 

Volitional single fiber electromyography of the masseter muscle; normative values and in myasthenia gravis

Saly. H. Elkholy¹*, Hatem. S. Shehata², Hebatallah Raafat¹, Amani. M. Nawito¹ and Rania. A. Almahdy¹

¹Clinical Neurophysiology Unit, Faculty of Medicine, Cairo University, Egypt.

²Neurology Department, Faculty of Medicine, Cairo University, Egypt.

Corresponding author. E-mail: [email protected]

Received 07 July, 2012; Accepted 22 November, 2012

 Abstract

This study was aimed at establishing normative values for volitional single fiber electromyography (SFEMG) of the masseter muscle in Egyptians and evaluating the sensitivity of this test in the diagnosis of generalized myasthenia gravis. Twenty two patients with myasthenia gravis (mean age of 37.72 years; range, 20 to 59; mean duration of illness, 4 years; range, 1 months to 16 years) where enrolled in the study to assess for SFEMG of the masseter muscle and of the extensor digitorum communis (EDC) muscle. Twenty normal individuals (mean age 34.3; range 22 to 55 years) where similarly studied to determine the normative values of SFEMG of the masseter muscle. The mean jitter of the masseter in the patients’ group was 63.4 ± 9.98 us, compared to 21.3 ± 4.9 us in the control group. Examination of the masseter muscle yielded 100% sensitivity in this study, compared to 90% sensitivity for EDC. We suggested a normal upper limit of masseter’s mean jitter of 26 microsecond/ study (mean +/- 1 SD) and 28 us / individual fiber pair (The 95th upper percentile was 27.51 us). Volitional SFEMG of the masseter muscle is highly sensitive test to diagnose generalized MG that is not related to weakness of this particular muscle but correlated to the degree of the disease’s severity.

Key words: Single fiber electromyography (SFEMG), masseter muscle, extensor digitorum communis, myasthenia gravis, repetitive nerve stimulation, neostigmine test.

International Journal of Medicine and Medical Sciences ISSN: 2167-0404 Vol. 2 (11), pp.251-255, November, 2012. © International Scholars Journals

Full Length Research Paper

Feasibility of using World Health Organization (WHO) pain ladder in the management of pain at a secondary healthcare center

Obaro S. Michael¹* and Joseph A. Badejo²

¹Department of Pharmacology and Therapeutics, College of Medicine, Bowen University, Iwo, Nigeria.

²Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Oyo State, Nigeria.

*Corresponding author. E-mail: [email protected]

Received 08 July, 2012; Accepted 07 November, 2012

Abstract

The objectives of this report were to determine the feasibility of adhering to World Health Organization (WHO) three-step pain management guidelines in a secondary healthcare institution and to identify areas where improvements are needed. The study was carried out in January, 2012. Descriptive analysis of available analgesics and adjuvants was done and the cost implications were also evaluated. Analgesic options for the 3 rungs of the WHO pain ladder were available. However, 11/14 (78.6%) of all the analgesics were nonsteroidal antiinflammatory drugs (NSAIDS). No Cox-2 inhibitor was available. Tramadol and Dihydrocodeine were the only agents available for second level treatment of pain, while parenteral pentazocine was the only agent available for the treatment of severe pain. All the agents were affordable. Managing pain using the WHO pain ladder is feasible at secondary healthcare hospitals. However, there is a need to expand analgesic options at the second and third rungs of the ladder.

Key words: World Health Organization (WHO) pain ladder, analgesics, cost, Nigeria.

Immune reconstitution inflammatory syndrome (IRIS) is a clinical syndrome that has been described in HIV infected patients after initiation of highly active anti-retroviral therapy (HAART) and measurable viral suppression,  and

Abbreviations: AIDS, Acquired immune deficiency syndrome; ART, anti-retroviral therapy; cART, combined ART; HAART, highly active anti-retroviral therapy; HIV, human immunodeficiency virus; IRIS, immune reconstitution inflammatory syndrome; KS IRIS- Kaposi’s sarcoma immune reconstitution inflammatory syndrome, NSAIDs, non-steroidal anti-inflammatory drugs; OI, opportunistic infection. 

is characterized by paradoxical or unmasked acute worsening of an underlying opportunistic infection (OI) or AIDS-defining illness (Shelburne et al., 2002; Manabe et al., 2007; Haddow et al., 2010). It is a serious condition that can occur shortly after a person starts HIV therapy for the first time. It happens when one’s immune system recovers too quickly. Highly active antiretroviral therapy can start to restore immune cell function and respond to other infections that may or may not have been diagnosed before starting therapy, even the ones that may have already been under control. Because clinical deterioration occurs during immune recovery, this phenomenon has been described in different terms as immune restoration disease, immune reconstitution syndrome, Immune recovery disease, immune reconstitution disease, immune rebound illness, steroid-withdrawal disease, immune response reactions and paradoxical reactions (Cheng  et  al.,  2000;  Cooney,  2002; French et al., 2000; Shelburne et al., 2002).

There are two common clinical scenarios in IRIS: unmasking IRIS and paradoxical IRIS. In unmasking IRIS, the infection is newly identified after the initiation of antiretroviral treatment (ART), and usually the provoking pathogen is viable (French, 2009). In paradoxical IRIS, the infection was previously treated but worsened clinically after ART initiation and the causative pathogens can be either viable or non-viable (French, 2009).

It is a paradoxical deterioration in clinical status after ART initiation despite improved immune function due to inflammatory response against infectious antigen, which may or may not have been diagnosed at initiation of ART. Immune reconstitution inflammatory syndrome most often occurs in patients with low initial CD4 (usually <50/µl) and rapid decline in viral load; onset usually within 6 weeks of ART initiation, but sometimes several months later (Musey et al., 1999; Rosenberg et al., 2000). Although IRIS that is seen even in late-stage disease, is more prominent in patients who commence treatment during early HIV infection before substantial damage to the immune system, where robust responses are often seen after treatment (Oxenius et al., 2001).

It is speculated that IRIS results from the restoration of immunity to pathogen-specific antigens present at the time of ART initiation. Following ART, a quantitative increase in peripheral T cells occur which partially restores activity to recall antigens as a result of suppression of HIV viral replication in lymphoid tissue and reductions in immune activation (Bucy et al., 1999; Autran et al., 1997). Therefore, the aim of this review is to compile and provide the available information on the epidemiology, clinical presentation and pathogenesis and present treatment options of IRIS.

EPIDEMIOLOGY AND RISK FACTORS OF IRIS

Despite numerous descriptions of the infectious and noninfectious causes of IRIS, the overall incidence of the syndrome itself remains largely unknown. The incidence of IRIS observed in HIV infected patients following initiation of HAART is variable (Li et al., 1998; Palella et al., 1998). The proportion of patients starting ART who develop IRIS is not well known, with estimates ranging from less than 10% to more than 50% in several studies (Kumarasamy et al., 2004; Narita et al., 1998; Lawn et al., 2005a; Ortega-Larrocea et al., 2005), but not all have reported an increased risk of the syndrome in patients starting ART who have advanced immunodeficiency (French et al., 2004; Colebunders et al., 2006; French et al., 2000; Jevtović et al., 2005; Bourgarit et al., 2006).

In a single study conducted in Ethiopia, the proportion of IRIS was 17.2% among 186 HIV/AIDS patients receiving HAART. According to the study, the mean number of days of IRIS occurrence for different diseases ranged from 26 to 122 days was 80 days.

Opportunistic diseases associated with IRIS were tuberculosis (68.8%), herpes zoster rash (12.5%), cryptococcosis (9.4%), toxoplasmosis (6.3%) and bacterial pneumonia (3.1%) (Huruy et al., 2008).

A retrospective study showed that among 47 patients on combined ART (cART) at a TB clinic, 11 (23%) experienced unmasking IRIS (Valin et al., 2010). The patients had lower CD4%, higher HIV-RNA load at baseline and a stronger CD4% increase with HIV-RNA decline after one month on cART than the 36 remaining patients without unmasking IRIS (Valin et al., 2010).

A study in sub-Saharan Africa and United Kingdom showed that 58 patients (13.9%) experienced Kaposi’s sarcoma (KS-IRIS) among 436 patients during the first 3 months on cART. Independent predictors of KS-IRIS development were found to be having an advance KS-stage at KS diagnosis and having a pre-cART HIV viral load higher than 5 log10 copies/ml (Letang, 2011).

Essentially, any pathogen that can cause an opportunistic infection as a result of impaired cellular immune responses can provoke IRIS after pathogen-specific immune responses are restored by ART (French, 2009).

The risks of unmasking and paradoxical forms of IRIS in HIV infected patients starting ART are fuelled by a combination of the late presentation of patients with advanced immunodeficiency, the associated high rates of OIs and the need for rapid initiation of ART to minimize overall mortality risk. Risk factors identified for the development of IRIS in one cohort study included male sex, a shorter interval between initiating treatment for OI and starting ART, rapid fall in HIV-1 RNA after ART, and being ART-naïve at the time of OI diagnosis (Dhasmana et al., 2008; Manabe et al., 2007; Shelburne et al., 2005). Other significant predictors have also included younger age, a lower baseline CD4 cell percentage, a lower CD4 cell count at ART initiation, and a lower CD4 to CD8 cell ratio at baseline (Ratnam et al., 2006). The four principal factors associated with an increased risk of developing IRIS are: (1) Low baseline CD4+ T-cell count, (2) Excellent virologic response to ART, (3) Increased antigen burden of an OI and (4) Early initiation of ART in close proximity to starting therapy for an OI (Valin et al., 2010; French, 2009; Dhasmana et al., 2008; Manabe et al., 2007; Shelburne et al., 2005; Ratnam et al., 2006). These factors have been identified in different studies done; however, these risk factors are by any means universal. For example, extrapolating from a case series on TB-IRIS may not be informative for defining the risk of hepatitis B IRIS (Shuli et al., 2008).

CLINICAL PRESENTATION AND DIAGNOSIS OF IRIS

Almost any organ or system may be affected by IRIS, and the clinical spectrum of IRIS depends on the site affected, the pathogen involved, and the host-parasite inter­action and manifestations  are  worsened  than  other conditions. IRIS may be targeted at viable infective antigens, dead or dying infective antigens, host antigens, tumour antigens and other antigens, giving rise to a heterogeneous range of clinical manifestations. The commonest forms of IRIS are associated with mycobacterial infections, fungi and herpes viruses (Dhasmana et al., 2008). Tuberculosis, Mycobacterium avium complex, Cryptococcus, Cytomegalovirus, Hepatitis B or C, Progressive multifocal leukoencephalopathy, Kaposi’s sarcoma, Autoimmune diseases, Herpes simplex virus, varicella zoster virus, a number of dermatologic manifestations, such as folliculitis and oral and genital warts, may appear or worsen during immune reconstitution (New York State Department of Health AIDS Institute, 2009).

Definition of IRIS is described as follows as stated by French et al. (2000) and must meet both major A and B criteria, or major A and any two minor criteria.

Major criteria A

a) Atypical presentation of OIs or tumors in patients responding to ART.

b) Localized disease (for example, lymph nodes, liver, spleen).

c) Exaggerated inflammatory reaction (for example, severe fever, painful lesions).

d) A typical inflammatory response in affected tissues (for example, granulomas, suppuration, necrosis, perivascular lymphocytic inflammatory cell infiltrate).

e) Progression of organ dysfunction or enlargement of preexisting lesions after definite clinical improvement with pathogen-specific therapy before ART and exclusion of treatment toxicity and new diagnoses.

Major criteria B

a) Decrease in viral load greater than one log.

Minor criteria

a) Increased CD4 T-cell count after ART.

b) Increase in an immune response specific to the relevant pathogen (for example, delayed-type hypersensitivity response to mycobacterial antigens).

c) Spontaneous resolution of disease without specific antimicrobial therapy or tumor chemotherapy with continuation of ART (French et al., 2004).

Possible differential diagnoses in patients experiencing clinical deterioration after initiating ART

a) IRIS—paradoxical reaction (deterioration of known condition that would otherwise be expected to improve).

b) IRIS—unmasking (new clinical presentation of undiagnosed but preexisting condition).

c) Failure of OI treatment because of drug-resistant organism.

d) Failure of OI treatment because of non adherence to OI treatment or prophylaxis.

e) Failure of ART because of drug resistance.

f) Failure of ART because of non adherence to ART.

g) Failure of OI treatment or ART for other reasons (for example, malabsorption).

h) Newly acquired OI or other condition.

i) Expected course of preexisting OI or other condition.

j) Adverse drug reaction.

There is no diagnostic test for IRIS and the differential diagnosis is complex as mentioned before. Therefore it is important to note that IRIS is a diagnosis per exclusion which means that first all other possible causes of clinical worsening should be ruled out before we can conclude that the patient has IRIS (Haddow et al., 2009).

IMMUNOPATHOGENESIS OF IRIS

The immunopathogenesis of IRIS remains incompletely defined or poorly understood but studies have shown associations with T-cell expansion, proinflammatory cytokine release and diminished regulatory T-cell activity (Dhasmana et al., 2008). The vast majority of cases of IRIS develop in the first 3 months of ART (Shelburne and Hamill, 2003; Lawn et al., 2005b) corresponding to the first phase of immune reconstitution in which there is a very rapid increase in both the number of circulating CD45RO+ memory cells as well as CD4 cell function (Autran et al., 1997). Delayed development of IRIS in minority of cases might be due to delayed immune recovery after ART is commenced.

Most cases of IRIS are associated with chronic bacterial infections, viral infections and deep fungal infections, which typically trigger immunopathology via cell-mediated T-helper type 1 (TH1) cytokine-secreting immune responses (Bourgarit et al., 2006; Shelburne and Hamill, 2003; Lawn et al., 2005b; Havlir and Barnes, 1999). Many different pathogens have been associated with the development of IRIS. The leading pathogens include: Mycobacterium tuberculosis, Mycobacterium avium complex, Cytomegalovirus, Cryptococcus, Pneumocystis, Herpes simplex virus, Hepatitis B virus and Human herpes virus 8 (associated with Kaposi’s sarcoma). Some case reports have also documented IRIS associated with: hepatitis C virus, parvovirus B19 (Nolan et al., 2003), herpes simplex, Bartonella henselae, Histoplasma capsulatum (Breton et al., 2006), dermatophytosis (Van Hal et al., 2005), leprosy (Couppié et al., 2004; Lawn et al., 2003; Bower et al., 2005; Menezes et al., 2009), bacillus Calmette-Guérin (BCG) (Puthanakit et al., 2005), Penicillium marneffei (Gupta et al., 2007), Schistosoma mansoni (De  Silva  et  al.,  2006) and Molluscum  contagiosum  virus.  In addition, some patients with Kaposi's sarcoma have developed an IRIS-like syndrome when  HAART  was  initiated  (Murdoch  et  al.,

2008; Shelburne et al., 2005; Connick et al., 2004) and other patients have developed grave's thyrotoxicosis or recurrence of sarcoidosis after starting HAART.

The development of IRIS requires advanced HIV infection with severe immune damage, improving immunity in response to ART, the presence of inciting antigens that trigger an immune response and the apparent loss of normal homeostatic control of immune responses, resulting in an over exuberant inflammatory response. The strongest predictor for the development of IRIS, however, is a low CD4+ T-cell count prior to starting ART (French et al., 2000; Ratnam et al., 2006).

In AIDS patients, damage to homeostatic control mechanisms followed by rapid ART-restoration of pathogen-specific immune responses, could promote exaggerated inflammatory responses, especially if viable pathogens or pathogen debris are present at high concentrations. Nevertheless, it is intriguing that restoration of pathogen specific immunity is uneventful in some patients but leads to severe immunopathology in others (Munier and Kelleher, 2007). Highly active anti-retroviral therapy induced metabolic derangements are being described for IRIS related to autoimmune disease (Calabrese et al., 2005). 

Conditions for IRIS require: antigen, restoration of antigen-specific immunity, dysregulated immune response which is hypothesized to be functional imbalance in pro-inflammatory (Th1, Th17) versus anti-inflammatory (Treg) T-cell populations. Cytokine profiles of IRIS events are heterogeneous based on the inciting pathogen (for example, viral, fungal, mycobacterial, etc) with marked individual variation. Pro-inflammatory cytokines are generated at time of mycobacterial and fungal IRIS events, such as IL-6, IL-17, IFN-γ, and TNF-α (Shuli et al., 2008).

When comparing cytokine levels between IRIS cases and non-IRIS controls by the type of IRIS presentation, different cytokine expression patterns were observed and most IRIS cases showed an increase in IL-6 and IFN-g in comparison to non-IRIS controls (Catherine et al., 2010).

During HAART and immune reconstitution, pathogen derived antigens are processed and presented to CD4+ T-cells leading to T-cell activation and secretion of macrophage-activating interferon-γ. Vitamin D inhibits this IFN-γ production. In case of low vitamin D levels prior to HAART, a defective clearing of pathogens and a delayed negative feedback on macrophage activation due to low vitamin D production, can lead to excessive granuloma formation and an exacerbated inflammatory response described as IRIS (Baeke et al., 2007).

One possible mechanism that illustrates the immunology of IRIS in a subject with HIV/TB co-infection shows that compromised gut immunity leads to increased translocation of luminal gram negative bacterial lipopolysaccharides into the systemic circulation. Initiation of HAART in the subject leads to abrupt restoration of CD4+ T-cells and almost any  pathogen-specific  immune response. IRIS developers have a high burden of lipopolysaccharids and pro-inflammatory cytokines produced against lipopolysaccharids could result in an exaggerated, nonspecific attack on latent mycobacterial antigens that are presented in the local lymph nodes leading to localized inflammation (Esaki et al., 2007).

Higher pre-ART levels of interleukin (IL)-4 and IL-17 as well as lower tumor necrosis factor (TNF)-a, granulocyte colony-stimulating factor (GCSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) predicted future IRIS. After ART was initiated, increasing levels of C-reactive protein (CRP), D-dimer, IL-6, IL-7, IL-13, G-CSF, or IL-1RA were associated with increasing hazard of IRIS (David et al., 2010).

Patients who had experienced an IRIS demonstrated increased levels of bioavailable IL-6 and increased expression of CCR5 and CCR3 on monocytes and granulocytes, but numbers of γδT-cells were similar to patients with similar CD4 T cell counts without an IRIS. Carriage of HLA-A2, HLA-B44 was associated with a history of Cytomegalovirus (CMV) retinitis and/or encephalomyelitis as an IRIS, but not with IRIS initiated by Mycobacterium spp., cutaneous varicella zoster or herpes simplex infections or hepatitis c virus (HCV). It also identified that a patient with graves’ thyrotoxicosis and pronounced lymphadenopathy after HAART, demonstrated that thyroid stimulating hormone receptor antibody production was associated with an increase in serum soluble CD30, suggesting acquired immune dysregulation (Priceab et al., 2001).

Genetic polymorphisms of IL-6, IL-12, and TNF-α have been also implicated as possible factors in risk and protection from IRIS. Differences in gene expression exist prior to beginning HIV therapy which may predict the risk of subsequent IRIS. The genes differentially expressed involve immune activation and anti-viral responses (Shuli et al., 2008).

CD4 T-cells are involved in mycobacterial and other granulomatous IRIS whereas CD8+ T cells are more frequently associated with viral IRIS. Immune reconstitution disease could be the consequence of unbalanced reconstitution of over activated T cells and regulatory T cells (Tregs). Direct activation of monocytes and dendritic cells during immune reconstitution, in particular by living or dead mycobacteria or antigenic debris could be a possibility. Antigen load during immune restoration may be a determining factor as well. Finally, the cytokine environment during immune restoration, IL-7 and IL-10 in particular, both important in T-cell homeostasis, could have a pivotal role in the development of IRIS (Kestens et al., 2008).

PREVENTION OF IRIS

To prevent development of IRIS, initiation of  ART  before advanced immunosuppression would be expected to reduce the risk of IRIS because advanced immunosuppression increases the risk for opportunistic infections, which is a risk factor for IRIS (Bonham et al., 2008). Recognize that the highest risk occurs in patients with CD4<50 and HIV viral load >100,000 who have a rapid response to ARV (Shuli et al., 2008; Beishuizen et al., 2009). To prevent unmasking IRIS, a thorough screening for active opportunistic infections before ART initiation is critical, because patients with advanced immunosuppression may have atypical or minimal symptoms owing to the absence of an inflammatory response (Dhasmana et al., 2008; Meintjes and Lynen, 2008). For paradoxical IRIS, a shorter delay between starting treatment for tuberculosis and cryptococcosis and ART has been identified as a risk factor (Navas et al., 2002; Breen et al., 2004). However, delaying ART to the end of tuberculosis treatment may reduce the risk of tuberculosis-IRIS occurrence, but is likely to come at the cost of advancing immunosup- pression, other opportunistic infections and increased AIDS-related mortality (Lawns and Woods, 2007).

TREATMENT OF IRIS

The evidence base for producing guidelines on the treatment of IRIS is very limited and relies heavily on clinical observations and expert opinion (Meintjes and Lynen, 2008). Basically, treatment of IRIS should be started after all other alternatives are ruled out which can be used as mono or combination therapy. The treatment approaches are: temporary ART discontinuation until the clinical condition has improved, use of non-steroidal anti-inflammatory drugs (NSAIDs) or corticosteroids, pathogen-specific therapy or other therapy (Battegay and Drechsler, 2006). ART interruption should be recommended only for patients with severe, life-threatening symptoms until their condition is established. Immune reconstitution inflammatory syndrome can recur during re-initiation of ART, so this has to be monitored carefully. However, stopping ART in the setting of incompletely suppressed HIV replication may be associated with an increased risk of antiretroviral resistance (Meintjes et al., 2008).

Anti-inflammatory therapy may be effective but should be reserved for the most severe cases; this is especially true of corticosteroid therapy, which can increase the risk of reactivating other latent infections. Anti-retroviral therapy should only be ceased if disease is life threatening. In cases of paradoxical IRIS, treatment of the opportunistic infection should be continued to suppress replication of the provoking pathogen and to reduce antigen load (French, 2009).

Non-steroidal anti-inflammatory drugs are advised for the management of mild and moderate cases, and corticosteroids    for    the    individuals    with   severe   or life-threatening disorders. On the other hand, corticosteroids have been shown to be associated with an excess of Kaposi’s sarcoma and herpes virus reactivation in HIV-infected patients with low CD4 counts but not in patients with increasing CD4 counts after initiation of ART. Pathogen-specific therapy should be started or continued in the case of unmasking or paradoxical IRIS (Meintjes and Lynen, 2008). Prednisone reduced the need for hospitalization and therapeutic procedures and hastened improvements in symptoms, performance, and quality of life (Meintjes et al., 2010).

CONCLUSION

Immune reconstitution inflammatory syndrome is the result of an exaggerated cellular immune response to living or dead pathogens or debris. It is associated with restoration of pathogen-specific effector T cells and regulatory T cells. T regulatory cells may be suppressed; however, by the disrupted cytokine environment because of impairment of the homeostatic control mechanisms. A part from this fact, it is not clear which factors or combination of factors trigger IRIS. These factors could be pathogen related (antigen load), genetic or immune related such as for instance the diversity of pathogen-specific T cells during immune restoration. Clinicians treating patients with AIDS need to be aware that HAART-engendered immune recovery may result in pathological inflammation in a subset of patients. Vigilance needs to be especially high during the first several months of therapy where the incidence of IRIS peaks, but cases continues to occur even after 1 or 2 years of therapy. Early monitoring of CD4 counts in HIV patients is needed so that cART should not be delayed in patients with AIDS defining diseases. The lack of appropriate treatment guidelines poses challenges in the management of these patients hence provision of treatment guidelines and performing more research regarding immunopathogenesis, diagnosis and treatment of IRIS.

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Table 2. SCAN Diagnoses of the 20 interviewees and socio-demographic variables, ZDS and PHQ-9 scores.

Table 3. Agreement between ZDSSF, PHQ, and SCAN.

DISCUSSION

The current study found that ZDS-SF had good response stability over two week interval (ICC = 0.66). There was an excellent agreement between ZDS-SF and SCAN on whether the participant was depressed or not depressed for 95% of cases (Kappa = 0.89). The ZDS-SF showed a good sensitivity and specificity (100 and 93%), with a positive predictive value of 83%.

The completion of self-rated depression scales needs a good level of education, co-operation of the respondents and may be more likely to be affected by cultural bias or illness presentation. But, they are cost-effective in time and resources especially in case of mass screening surveys (Jenkins and Dillman, 1995). On the other hand, clinical interview is considered the gold standard for depression diagnosis as it is more objective than subjective and it is carried out by well-trained physicians who can rate the symptoms accurately. However it is time consuming and costly (Wing et al., 1990). The aforementioned highlights the importance of validating self-rating scales using a gold-standard clinical interview (for example, SCAN). It has been proposed that ZDS-SF is a relatively constant over two week period. Thus, test robustness can be measured over a relatively short time (Ibrahim et al., 2011a).

As predicted the result of the test-retest reliability was moderate because ZDS-SF scale was primarily intended to measure current mental state (over the past two weeks). Symptoms are expected to change over time but these changes are more likely to be cyclic in some individuals. Moreover, test-retest analysis has some methodological bias that is, time interval was variable and totally dependent on the participant’s availability. It has been assumed that shorter intervals will produce higher correlations than longer intervals. If there was more information about what happened to participants during the time interval then the test results should be better differentiated.   In   particular,   adverse   life events   are expected to introduce variability in the mood profile of participants and thus modify the test outcome (Valentin et al., 2002).

The concurrent validity of the scale was tested against the PHQ and the SCAN. ZDS-SF scores were strongly correlated with both PHQ scores and SCAN diagnostic results (rs = 0.76, p < 0.001 and rs = 0.88, p < 0.001 respectively). Also, using the Kappa analysis, ZDS-SF demonstrated a very good agreement with the SCAN (0.89, p < 0.001) which is a ‘gold standard’. This was stronger than the agreement with PHQ (0.74, p < 0.001). Additionally, ZDS-SF as a screening tool for depression was tested against the SCAN and showed 100% sensitivity, nearly 93% specificity, and an overall accuracy of 95%. The SCAN interview probes persistent symptoms experienced over the past month which explains the perfect agreement between the ZDS-SF classification of depression at time 1 and the clinical diagnosis of depression two weeks later, providing further evidence of the ZDS-SF validity. 

This was in accordance with other studies; in general population studies where the validity of the ZDS-SF has been examined against the HDRS which found that it was a valid measure and could be used as a useful screening measure for both clinical and research studies (Fawzi et al., 1982; Fawzy, 1982; Shaheen and Fawzi, 1985). Moreover, in two student sample studies the ZDS-SF was tested against PHQ revealing good concurrent validity against this well-established screening tool (Ibrahim et al., 2010, 2011a). These results demonstrated that ZDS-SF is good screening tool for depression in university students. Although longer than the PHQ we believe that the more comprehensive and the wider range of symptom domains assessed makes it particularly useful for screening for emotional difficulties in well-educated populations across both developed and developing countries.

The strength of the present study was the use of a well validated self-administered scale (PHQ) in addition to a gold-standard depression semi-structured interview (SCAN), administered blind to ZDS-SF scores, in order to validate the ZDS-SF. However the study encountered the following limitations; the small number of participants (n=20), and the use of a convenience approach for student recruitment.

In conclusion, ZDS-SF scale is a valid measure of depression with very good psychometric properties in a university student cohort. Further research is planned to establish the psychometric properties of the ZDS-SF in a Chinese student population.

ACKNOWLEDGEMENTS

The authors are very grateful for the Ministry of Higher Education,    Egyptian    Government    specially    Assiut University for sponsoring my whole studies. It is a pleasure to express my deepest gratitude and grateful appreciation to the University of Nottingham for supporting this study. Last but not least, my special thanks and gratitude to the students who took part in this study. It would not have been possible without their help.

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